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Brain Studies



A continuing education course for 30 ces

APA, BRN, CA BBS, FL, NAADAC, NBCC, TX SBEPC, TXBSWE

As the field of psychology understands the importance of neuroscience, www.psychceu.com is pleased to announce a course on the brain, written by leading researchers.

Click on the links below to jump to specific sections:

Introduction:

Brain Basics:

Know Your Brain
The Life and Death of a Neuron
National Institute of Neurological Disorders and Stroke

The Neuroscience of Mental Health
Department of Health and Human Services

Development:


Stress and the Developing Brain

National Institute of Mental Health

Excessive Stress Disrupts the Architecture of the Developing Brain
National Scientific Council on the Developing Child

The Teenage Brain: a work in progress
National Institute of Mental Health

Attack of the Teenage Brain!!
Dennis Palumbo, MFT

Specific Neurological Conditions:


Amyotrophic Lateral Sclerosis 
National Institute of Neurological Disorders and Stroke

Brain and Spinal Tumors
National Institute of Neurological Disorders and Stroke

Cerebral Aneurysm
National Institute of Neurological Disorders and Stroke

Cerebral Palsy
National Institute of Neurological Disorders and Stroke

Chronic Pain
National Institute of Neurological Disorders and Stroke

Dementia
National Institute of Neurological Disorders and Stroke

Huntington's Disease
National Institute of Neurological Disorders and Stroke

Migraines & Headaches
National Institute of Neurological Disorders and Stroke

Mild Traumatic Brain Injury
Heads Up! Facts for Physicians About Mild Traumatic Brain Injury
U.S. Department of Health and Human Services

Mild Traumatic Brain Injury
Acute Management of Mild Traumatic Brain Injury in Military Operational Settings:
Clinical Practice Guidelines and Recommendations
The Defense and Veterans Brain Injury Center Working Group

Multiple Sclerosis
National Institute of Neurological Disorders and Stroke

Muscular Dystrophy
National Institute of Neurological Disorders and Stroke

Neuropathy:
National Institute of Neurological Disorders and Stroke

Diabetic Neuropathy
Hereditary Neuropathies
Charcot-Marie-Tooth Disease
Peripheral Neuropathy

Parkinson's Disease
National Institute of Neurological Disorders and Stroke

Restless Legs Syndrome
National Institute of Neurological Disorders and Stroke

Seizures and Epilepsy
National Institute of Neurological Disorders and Stroke

Shingles
National Institute of Neurological Disorders and Stroke

Spinal Cord Injury
National Institute of Neurological Disorders and Stroke

Stroke
National Institute of Neurological Disorders and Stroke

Tourette Syndrome
National Institute of Neurological Disorders and Stroke

Traumatic Brain Injury

Traumatic Brain Injury
National Institute of Neurological Disorders and Stroke

Talk and Die Syndrome
Scott LaFee

Sandplay Therapy With Traumatic Brain Injured Adults:
An Exploratory Qualitative Study
Lorraine Razzi Freedle, Ph.D.


Introduction


Brain Basics: Know Your Brain

Introduction

The brain is the most complex part of the human body. This three-pound organ is the seat of intelligence, interpreter of the senses, initiator of body movement, and controller of behavior. Lying in its bony shell and washed by protective fluid, the brain is the source of all the qualities that define our humanity. The brain is the crown jewel of the human body.

For centuries, scientists and philosophers have been fascinated by the brain, but until recently they viewed the brain as nearly incomprehensible. Now, however, the brain is beginning to relinquish its secrets. Scientists have learned more about the brain in the last 10 years than in all previous centuries because of the accelerating pace of research in neurological and behavioral science and the development of new research techniques. As a result, Congress named the 1990s the Decade of the Brain. At the forefront of research on the brain and other elements of the nervous system is the National Institute of Neurological Disorders and Stroke (NINDS), which conducts and supports scientific studies in the United States and around the world.

This fact sheet is a basic introduction to the human brain. It may help you understand how the healthy brain works, how to keep it healthy, and what happens when the brain is diseased or dysfunctional.

Image 1


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The Architecture of the Brain

The brain is like a committee of experts. All the parts of the brain work together, but each part has its own special properties. The brain can be divided into three basic units: the forebrain, the midbrain, and the hindbrain.

The hindbrain includes the upper part of the spinal cord, the brain stem, and a wrinkled ball of tissue called the cerebellum (1). The hindbrain controls the body’s vital functions such as respiration and heart rate. The cerebellum coordinates movement and is involved in learned rote movements. When you play the piano or hit a tennis ball you are activating the cerebellum. The uppermost part of the brainstem is the midbrain, which controls some reflex actions and is part of the circuit involved in the control of eye movements and other voluntary movements. The forebrain is the largest and most highly developed part of the human brain: it consists primarily of the cerebrum (2) and the structures hidden beneath it (see "The Inner Brain").

When people see pictures of the brain it is usually the cerebrum that they notice. The cerebrum sits at the topmost part of the brain and is the source of intellectual activities. It holds your memories, allows you to plan, enables you to imagine and think. It allows you to recognize friends, read books, and play games.

The cerebrum is split into two halves (hemispheres) by a deep fissure. Despite the split, the two cerebral hemispheres communicate with each other through a thick tract of nerve fibers that lies at the base of this fissure. Although the two hemispheres seem to be mirror images of each other, they are different. For instance, the ability to form words seems to lie primarily in the left hemisphere, while the right hemisphere seems to control many abstract reasoning skills.

For some as-yet-unknown reason, nearly all of the signals from the brain to the body and vice-versa cross over on their way to and from the brain. This means that the right cerebral hemisphere primarily controls the left side of the body and the left hemisphere primarily controls the right side. When one side of the brain is damaged, the opposite side of the body is affected. For example, a stroke in the right hemisphere of the brain can leave the left arm and leg paralyzed.

The Forebrain ------- The Midbrain -------- The Hindbrain

  

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The Geography of Thought

Each cerebral hemisphere can be divided into sections, or lobes, each of which specializes in different functions. To understand each lobe and its specialty we will take a tour of the cerebral hemispheres, starting with the two frontal lobes (3), which lie directly behind the forehead. When you plan a schedule, imagine the future, or use reasoned arguments, these two lobes do much of the work. One of the ways the frontal lobes seem to do these things is by acting as short-term storage sites, allowing one idea to be kept in mind while other ideas are considered. In the rearmost portion of each frontal lobe is a motor area (4), which helps control voluntary movement. A nearby place on the left frontal lobe called Broca’s area (5) allows thoughts to be transformed into words.

When you enjoy a good meal—the taste, aroma, and texture of the food—two sections behind the frontal lobes called the parietal lobes (6) are at work. The forward parts of these lobes, just behind the motor areas, are the primary sensory areas (7). These areas receive information about temperature, taste, touch, and movement from the rest of the body. Reading and arithmetic are also functions in the repertoire of each parietal lobe.

As you look at the words and pictures on this page, two areas at the back of the brain are at work. These lobes, called the occipital lobes (8), process images from the eyes and link that information with images stored in memory. Damage to the occipital lobes can cause blindness.

The last lobes on our tour of the cerebral hemispheres are the temporal lobes (9), which lie in front of the visual areas and nest under the parietal and frontal lobes. Whether you appreciate symphonies or rock music, your brain responds through the activity of these lobes. At the top of each temporal lobe is an area responsible for receiving information from the ears. The underside of each temporal lobe plays a crucial role in forming and retrieving memories, including those associated with music. Other parts of this lobe seem to integrate memories and sensations of taste, sound, sight, and touch.

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The Cerebral Cortex

Coating the surface of the cerebrum and the cerebellum is a vital layer of tissue the thickness of a stack of two or three dimes. It is called the cortex, from the Latin word for bark. Most of the actual information processing in the brain takes place in the cerebral cortex. When people talk about "gray matter" in the brain they are talking about this thin rind. The cortex is gray because nerves in this area lack the insulation that makes most other parts of the brain appear to be white. The folds in the brain add to its surface area and therefore increase the amount of gray matter and the quantity of information that can be processed.

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The Inner Brain

Deep within the brain, hidden from view, lie structures that are the gatekeepers between the spinal cord and the cerebral hemispheres. These structures not only determine our emotional state, they also modify our perceptions and responses depending on that state, and allow us to initiate movements that you make without thinking about them. Like the lobes in the cerebral hemispheres, the structures described below come in pairs: each is duplicated in the opposite half of the brain.

The hypothalamus (10), about the size of a pearl, directs a multitude of important functions. It wakes you up in the morning, and gets the adrenaline flowing during a test or job interview. The hypothalamus is also an important emotional center, controlling the molecules that make you feel exhilarated, angry, or unhappy. Near the hypothalamus lies the thalamus (11), a major clearinghouse for information going to and from the spinal cord and the cerebrum.

An arching tract of nerve cells leads from the hypothalamus and the thalamus to the hippocampus (12). This tiny nub acts as a memory indexer—sending memories out to the appropriate part of the cerebral hemisphere for long-term storage and retrieving them when necessary. The basal ganglia (not shown) are clusters of nerve cells surrounding the thalamus. They are responsible for initiating and integrating movements. Parkinson’s disease, which results in tremors, rigidity, and a stiff, shuffling walk, is a disease of nerve cells that lead into the basal ganglia.

Image 5

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Making Connections

The brain and the rest of the nervous system are composed of many different types of cells, but the primary functional unit is a cell called the neuron. All sensations, movements, thoughts, memories, and feelings are the result of signals that pass through neurons. Neurons consist of three parts. The cell body (13) contains the nucleus, where most of the molecules that the neuron needs to survive and function are manufactured. Dendrites (14) extend out from the cell body like the branches of a tree and receive messages from other nerve cells. Signals then pass from the dendrites through the cell body and may travel away from the cell body down an axon (15) to another neuron, a muscle cell, or cells in some other organ. The neuron is usually surrounded by many support cells. Some types of cells wrap around the axon to form an insulating sheath (16). This sheath can include a fatty molecule called myelin, which provides insulation for the axon and helps nerve signals travel faster and farther. Axons may be very short, such as those that carry signals from one cell in the cortex to another cell less than a hair’s width away. Or axons may be very long, such as those that carry messages from the brain all the way down the spinal cord.

Image 6

Scientists have learned a great deal about neurons by studying the synapse—the place where a signal passes from the neuron to another cell. When the signal reaches the end of the axon it stimulates tiny sacs (17). These sacs release chemicals known as neurotransmitters (18) into the synapse (19). The neurotransmitters cross the synapse and attach to receptors (20) on the neighboring cell. These receptors can change the properties of the receiving cell. If the receiving cell is also a neuron, the signal can continue the transmission to the next cell.

Image 7

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Some Key Neurotransmitters at Work

Acetylcholine is called an excitatory neurotransmitter because it generally makes cells more excitable. It governs muscle contractions and causes glands to secrete hormones. Alzheimer’s disease, which initially affects memory formation, is associated with a shortage of acetylcholine.

GABA (gamma-aminobutyric acid) is called an inhibitory neurotransmitter because it tends to make cells less excitable. It helps control muscle activity and is an important part of the visual system. Drugs that increase GABA levels in the brain are used to treat epileptic seizures and tremors in patients with Huntington’s disease.

Serotonin is an inhibitory neurotransmitter that constricts blood vessels and brings on sleep. It is also involved in temperature regulation. Dopamine is an inhibitory neurotransmitter involved in mood and the control of complex movements. The loss of dopamine activity in some portions of the brain leads to the muscular rigidity of Parkinson’s disease. Many medications used to treat behavioral disorders work by modifying the action of dopamine in the brain.

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Neurological Disorders

When the brain is healthy it functions quickly and automatically. But when problems occur, the results can be devastating. Some 50 million people in this country—one in five—suffer from damage to the nervous system. The NINDS supports research on more than 600 neurological diseases. Some of the major types of disorders include: neurogenetic diseases (such as Huntington’s disease and muscular dystrophy), developmental disorders (such as cerebral palsy), degenerative diseases of adult life (such as Parkinson’s disease and Alzheimer’s disease), metabolic diseases (such as Gaucher’s disease), cerebrovascular diseases (such as stroke and vascular dementia), trauma (such as spinal cord and head injury), convulsive disorders (such as epilepsy), infectious diseases (such as AIDS dementia), and brain tumors.

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The National Institute of Neurological Disorders and Stroke

Since its creation by Congress in 1950, the NINDS has grown to become the leading supporter of neurological research in the United States. Most research funded by the NINDS is conducted by scientists in public and private institutions such as universities, medical schools, and hospitals. Government scientists also conduct a wide array of neurological research in the more than 20 laboratories and branches of the NINDS itself. This research ranges from studies on the structure and function of single brain cells to tests of new diagnostic tools and treatments for those with neurological disorders.

For information on other neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
www.ninds.nih.gov Top

 

NIH Publication No.01-3440a

Last updated May 01, 2007


 

The Life and Death of a Neuron

Table of Contents

Introduction

Until recently, most neuroscientists thought we were born with all the neurons we were ever going to have. As children we might produce some new neurons to help build the pathways - called neural circuits - that act as information highways between different areas of the brain. But scientists believed that once a neural circuit was in place, adding any new neurons would disrupt the flow of information and disable the brain’s communication system.

In 1962, scientist Joseph Altman challenged this belief when he saw evidence of neurogenesis (the birth of neurons) in a region of the adult rat brain called the hippocampus. He later reported that newborn neurons migrated from their birthplace in the hippocampus to other parts of the brain. In 1979, another scientist, Michael Kaplan, confirmed Altman’s findings in the rat brain, and in 1983 he found neural precursor cells in the forebrain of an adult monkey.

These discoveries about neurogenesis in the adult brain were surprising to other researchers who didn’t think they could be true in humans. But in the early 1980s, a scientist trying to understand how birds learn to sing suggested that neuroscientists look again at neurogenesis in the adult brain and begin to see how it might make sense. In a series of experiments, Fernando Nottebohm and his research team showed that the numbers of neurons in the forebrains of male canaries dramatically increased during the mating season. This was the same time in which the birds had to learn new songs to attract females.

Why did these bird brains add neurons at such a critical time in learning? Nottebohm believed it was because fresh neurons helped store new song patterns within the neural circuits of the forebrain, the area of the brain that controls complex behaviors. These new neurons made learning possible. If birds made new neurons to help them remember and learn, Nottebohm thought the brains of mammals might too.

Other scientists believed these findings could not apply to mammals, but Elizabeth Gould later found evidence of newborn neurons in a distinct area of the brain in monkeys, and Fred Gage and Peter Eriksson showed that the adult human brain produced new neurons in a similar area.

For some neuroscientists, neurogenesis in the adult brain is still an unproven theory. But others think the evidence offers intriguing possibilities about the role of adult-generated neurons in learning and memory.

The image of neuron

Neuron

The Architecture of the Neuron

The central nervous system (which includes the brain and spinal cord) is made up of two basic types of cells: neurons (1) and glia (4) & (6). Glia outnumber neurons by a substantial amount -- some scientists have estimated it to be as large as nine to one -- but in spite of their smaller numbers, neurons are the key players in the brain.

Neurons are information messengers. They use electrical impulses and chemical signals to transmit information between different areas of the brain, and between the brain and the rest of the nervous system. Everything we think and feel and do would be impossible without the work of neurons and their support cells, the glial cells called astrocytes (4) and oligodendrocytes (6).

Neurons have three basic parts: a cell body and two extensions called an axon (5) and a dendrite (3). Within the cell body is a nucleus (2), which controls the cell’s activities and contains the cell’s genetic material. The axon looks like a long tail and transmits messages from the cell. Dendrites look like the branches of a tree and receive messages for the cell. Neurons communicate with each other by sending chemicals, called neurotransmitters, across a tiny space, called a synapse, between the axons and dendrites of adjacent neurons.

The image of Neuron Architecture

The architecture of the neuron.

There are three classes of neurons:

  1. Sensory neurons carry information from the sense organs (such as the eyes and ears) to the brain.
  2. Motor neurons have long axons and carry information from the central nervous system to the muscles and glands of the body.
  3. Interneurons have short axons and communicate only within their immediate region.

Scientists think that neurons are the most diverse kind of cell in the body. Within these three classes of neurons are hundreds of different types, each with specific message-carrying abilities.

How these neurons communicate with each other by making connections is what makes each of us unique in how we think, and feel, and act.

Birth

The extent to which new neurons are generated in the brain is a controversial subject among neuroscientists. Although the majority of neurons are already present in our brains by the time we are born, there is evidence to support that neurogenesis (the scientific word for the birth of neurons) is a lifelong process.

Neurons are born in areas of the brain that are rich in concentrations of neural precursor cells (also called neural stem cells). These cells have the potential to generate most, if not all, of the different types of neurons and glia found in the brain.

Neuroscientists have observed how neural precursor cells behave in the laboratory. Although this may not be exactly how these cells behave when they are in the brain, it gives us information about how they could be behaving when they are in the brain’s environment.

The science of stem cells is still very new, and could change with additional discoveries, but researchers have learned enough to be able to describe how neural stem cells generate the other cells of the brain. They call it a stem cell’s lineage and it is similar in principle to a family tree.

Neural stem cells increase by dividing in two and producing either two new stem cells, or two early progenitor cells, or one of each.

When a stem cell divides to produce another stem cell, it is said to self-renew. This new cell has the potential to make more stem cells.

When a stem cell divides to produce an early progenitor cell, it is said to differentiate. Differentiation means that the new cell is more specialized in form and function. An early progenitor cell does not have the potential of a stem cell to make many different types of cells. It can only make cells in its particular lineage.

Early progenitor cells can self-renew or go in either of two ways. One type will give rise to astrocytes. The other type will ultimately produce neurons or oligodendrocytes.

Migration

Once a neuron is born it has to travel to the place in the brain where it will do its work.

How does a neuron know where to go? What helps it get there?

Scientists have seen that neurons use at least two different methods to travel:

  1. Some neurons migrate by following the long fibers of cells called radial glia. These fibers extend from the inner layers to the outer layers of the brain. Neurons glide along the fibers until they reach their destination.
  2. Neurons also travel by using chemical signals. Scientists have found special molecules on the surface of neurons -- adhesion molecules -- that bind with similar molecules on nearby glial cells or nerve axons. These chemical signals guide the neuron to its final location.

Not all neurons are successful in their journey. Scientists think that only a third reach their destination. The rest either never differentiate, or die and disappear at some point during the two to three week phase of migration.

Some neurons survive the trip, but end up where they shouldn’t be. Mutations in the genes that control migration create areas of misplaced or oddly formed neurons that can cause disorders such as childhood epilepsy or mental retardation. Some researchers suspect that schizophrenia and the learning disorder dyslexia are partly the result of misguided neurons.

The image of Neuron Migration

Some neurons migrate by riding along extensions (radial glia) until they reach their final destinations.

Differentiation

Once a neuron reaches its destination, it has to settle in to work. This final step of differentiation is the least well-understood part of neurogenesis.

Neurons are responsible for the transport and uptake of neurotransmitters - chemicals that relay information between brain cells.

Depending on its location, a neuron can perform the job of a sensory neuron, a motor neuron, or an interneuron, sending and receiving specific neurotransmitters.

In the developing brain, a neuron depends on molecular signals from other cells, such as astrocytes, to determine its shape and location, the kind of transmitter it produces, and to which other neurons it will connect. These freshly born cells establish neural circuits - or information pathways connecting neuron to neuron - that will be in place throughout adulthood.

But in the adult brain, neural circuits are already developed and neurons must find a way to fit in. Researchers suspect that astrocytes play a similar role in the adult brain, actively regulating the function and synapse formation of new neurons.

As a new neuron settles in, it starts to look like surrounding cells. It develops an axon and dendrites and begins to communicate with its neighbors.

The image of neuron differentiation

Stem cells differentiate to produce different types of nerve cells.

Death

Although neurons are the longest living cells in the body, large numbers of them die during migration and differentiation.

The lives of some neurons can take abnormal turns. Some diseases of the brain are the result of the unnatural deaths of neurons.

- In Parkinson’s disease, neurons that produce the neurotransmitter dopamine die off in the basal ganglia, an area of the brain that controls body movements. The brain can no longer control the body and people shake and jerk in spasms.

- In Huntington’s disease, a genetic mutation causes over-production of a neurotransmitter called glutamate, which kills neurons in the basal ganglia. As a result, people twist and writhe uncontrollably.

- In Alzheimer’s disease, unusual proteins build up in and around neurons in the neocortex and hippocampus, parts of the brain that control memory. When these neurons die, people lose their capacity to remember and their ability to do everyday tasks. Physical damage to the brain and other parts of the central nervous system can also kill or disable neurons.

- Blows to the brain, or the damage caused by a stroke, can kill neurons outright or slowly starve them of the oxygen and nutrients they need to survive.

- Spinal cord injury can disrupt communication between the brain and muscles when neurons lose their connection to axons located below the site of injury. These neurons may still live, but they lose their ability to communicate.

The image of a diseased neuron

One method of cell death results from the release of excess glutamate.

The image of a dying neuron

Macrophages (green) eat dying neurons in order to clear debris.

Hope Through Research

Scientists hope that by understanding more about the life and death of neurons they can develop new treatments, and possibly even cures, for brain diseases and disorders that affect the lives of millions of Americans.

The most current research suggests that neural stem cells can generate many, if not all, of the different types of neurons found in the brain and the nervous system. Learning how to manipulate these stem cells in the laboratory into specific types of neurons could produce a fresh supply of brain cells to replace those that have died or been damaged.

Therapies could also be created to take advantage of growth factors and other signaling mechanisms inside the brain that tell precursor cells to make new neurons. This would make it possible to repair, reshape, and renew the brain from within.

For information on other neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
www.ninds.nih.gov

Top

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.


 

The Neuroscience of Mental Health
Department of Health and Human Services

A vast body of research on mental health and, to an even greater extent, on mental illness constitutes the foundation of this Surgeon General’s report. To understand and better appreciate the content of the chapters that follow, readers outside the mental health field may desire some background information. Thus, this chapter furnishes a“primer” on topics that the report addresses.

The chapter begins with an overview of research under way today that is focused on the neuroscience of mental health. Modern integrative neuroscience offers a means of linking research on broad“systems level” aspects of brain function with the remarkably detailed tools and findings of molecular biology. The report begins with a discussion of the brain because it is central to what makes us human and provides an understanding of mental health and mental illness. All of human behavior is mediated by the brain. Consider, for example, a memory that most people have from childhood—that of learning to ride a bicycle with the help of a parent or friend. The fear of falling, the anxiety of lack of control, the reassurances of a loved one, and the final liberating experience of mastery and a newly extended universe create an unforgettable combination. For some, the memories are not good ones: falling and being chased by dogs have left marks of anxiety and fear that may last a lifetime. Science is revealing how the skill learning, emotional overtones, and memories of such experiences are put together physically in the brain. The brain and mind are two sides of the same coin. Mind is not possible without the remarkable physical complexity that is built into the brain, but, in addition, the physical complexity of the brain is useless without the sculpting that environment, experience, and thought itself provides. Thus the brain is now known to be physically shaped by contributions from our genes and our experience, working together. This strengthens the view that mental disorders are both caused and can be treated by biological and experiential processes, working together. This understanding has emerged from the breathtaking progress in modern neuroscience that has begun to integrate knowledge from biological and behavioral sciences.

An overview of mental illness follows the section on modern integrative brain science. The section highlights topics including symptoms, diagnosis, epidemiology (i.e., research having to do with the distribution and determinants of mental disorders in population groups, including various racial and ethnic minority groups), and cost, all of which are discussed in greater and more pointed detail in the chapters that follow. Etiology is the study of the origins and causes of disease, and that section reviews research that is seeking to define, with ever greater precision, the causes of mental disorders. As will be seen, etiology research examines fundamental biological, behavioral, and sociocultural processes, as well as a necessarily broad array of life events. The section on development of temperament reveals how mental health science has attempted over much of the past century to understand how biological, psychological, and sociocultural factors meld in health as well as in illness. The chapter then reviews research approaches to the prevention and treatment of mental disorders and provides an overview of mental health services and their delivery. Final sections cover the growing influence on the mental health field of the need for attention to cultural diversity, the importance of the consumer movement, and new optimism about recovery from mental illness—that is, the possibility of recovering one’s life.

The Neuroscience of Mental Health1

Complexity of the Brain I: Structural

As befits the organ of the mind, the human brain is the most complex structure ever investigated by our science. The brain contains approximately 100 billion nerve cells, or neurons, and many more supporting cells, or glia. In and of themselves, the number of cells in this 3-pound organ reveal little of its complexity. Yet most organs in the body are composed of only a handful of cell types; the brain, in contrast, has literally thousands of different kinds of neurons, each distinct in terms of its chemistry, shape, and connections (Figure 2-1 depicts the structural variety of neurons). To illustrate, one careful, recent investigation of a kind of interneuron that is a small local circuit neuron in the retina, called the amacrine cell, found no less than 23 identifiable types.

But this is only the beginning of the brain’s complexity.

The workings of the brain depend on the ability of nerve cells to communicate with each other. Communication occurs at small, specialized structures called synapses. The synapse typically has two parts. One is a specialized presynaptic structure on a terminal portion of the sending neuron that contains packets of signalling chemicals, or neurotransmitters. The second is a postsynaptic structure on the dendrites of the receiving neuron that has receptors for the neurotransmitter molecules.

The typical neuron has a cell body, which contains the genetic material, and much of the cell’s energy-producing machinery. Emanating from the cell body are dendrites, branches that are the most important receptive surface of the cell for communication. The dendrites of neurons can assume a great many shapes and sizes, all relevant to the way in which incoming messages are processed. The output of neurons is carried along what is usually a single branch called the axon. It is down this part of the neuron that signals are transmitted out to the next neuron. At its end, the axon may branch into many terminals. (Figure 2-2.)

The usual form of communication involves electrical signals that travel within neurons, giving rise to chemical signals that diffuse, or cross, synapses, which in turn give rise to new electrical signals in the postsynaptic neuron. Each neuron, on average, makes more than 1,000 synaptic connections with other neurons. One type of cell—a Purkinje cell—may make between 100,000 and 200,000 connections with other neurons. In aggregate, there may be between 100 trillion and a quadrillion synapses in the brain. These synapses are far from random. Within each region of the brain, there is an exquisite architecture consisting of layers and other anatomic substructures in which synaptic connections are formed. Ultimately, the pattern of synaptic connections gives rise to what are called circuits in the brain. At the integrative level, large- and small-scale circuits are the substrates of behavior and of mental life. One of the most awe-inspiring mysteries of brain science is how neuronal activity within circuits gives rise to behavior and, even, consciousness.

The complexity of the brain is such that a single neuron may be part of more than one circuit. The organization of circuits in the brain reveals that the brain is a massively parallel, distributed information processor. For example, the circuits involved in vision receive information from the retina. After initial processing, these circuits analyze information into different streams, so that there is one stream of information describing what the visual object is, and another stream is concerned with where the object is in space. The information stream having to do with the identity of the object is actually broken down into several more refined parallel streams. One, for example, analyzes shape while another analyzes color. Ultimately, the visual world is resynthesized with information about the tactile world, and the auditory world, with information from memory, and with emotional coloration. The massively parallel design is a great pattern recognizer and very tolerant of failure in individual elements. This is why a brain of neurons is still a better and longer-lasting information processor than a computer.

The specific connectivity of circuits is, to some degree, stereotyped, or set in expected patterns within the brain, leading to the notion that certain places in the brain are specialized for certain functions (Figure 2-3). Thus, the cerebral cortex, the mantle of neurons with its enormous surface area increased by outpouchings, called gyri, and indentations, called sulci, can be functionally subdivided. The back portion of the cerebral cortex (i.e., the occipital lobe), for example, is involved in the initial stages of visual processing. Just behind the central sulcus is the part of the cerebral cortex involved in the processing of tactile information (i.e., parietal lobe). Just in front of the central sulcus is a part of the cerebral cortex involved in motor behavior (frontal lobe). In the front of the brain is a region called the prefrontal cortex, which is involved with some of the highest integrated functions of the human being, including the ability to plan and to integrate cognitive and emotional streams of information.

Beneath the cortex are enormous numbers of axons sheathed in the insulating substance, myelin. This subcortical “white matter,” so named because of its appearance on freshly cut brain sections, surrounds deep aggregations of neurons, or“gray matter,” which, like the cortex, appears gray because of the presence of neuronal cell bodies. It is within this gray matter that the brain processes information. The white matter is akin to wiring that conveys information from one region to another. Gray matter regions include the basal ganglia, the part of the brain that is involved in the initiation of motion and thus profoundly affected in Parkinson’s disease, but that is also involved in the integration of motivational states and, thus, a substrate of addictive disorders. Other important gray matter structures in the brain include the amygdala and the hippocampus. The amygdala is involved in the assignment of emotional meaning to events and objects, and it appears to play a special role in aversive, or negative, emotions such as fear. The hippocampus includes, among its many functions, responsibility for initially encoding and consolidating explicit or episodic memories of persons, places, and things.

In summary, the organization of the brain at the cellular level involves many thousands of distinct kinds of neurons. At a higher integrative level, these neurons form circuits for information processing determined by their patterns of synaptic connections. The organization of these parallel distributed circuits results in the specialization of different geographic regions of the brain for different functions. It is important to state at this point, however, that, especially in younger individuals, damage to a particular brain region may yield adaptations that permit circuits spared the damage and, therefore, other regions of the brain, to pick up some of the functions that would otherwise have been lost.

Figure 2-1. Structural variety of neurons

Structural Variety of Neurons Graphic
Click to enlarge

Source: Fischbach, 1992, p. 53. (Permission granted: Patricia J. Wynne.)

1Special thanks to Steven E. Hyman, M.D., Director, National Institute of Mental Health, and Gerald D. Fischbach, M.D., Director, National Institute of Neurological Diseases and Stroke, for their contributions to this section.

Figure 2-2. How neurons communicate

How Neurons Communicate Graphic
Click to enlarge

Source: Fischbach, 1992, p. 52. (Permission granted: Tomo Narashima.)

Figure 2-3. The brain: Organ of the mind
The brain: Organ of the Mind Graphic
Click to enlarge

Source: Fischbach, 1992, p. 51. (Permission granted: Carol Donner.)

Complexity of the Brain II: Neurochemical

Superimposed on this breathtaking structural complexity is the chemical complexity of the brain. As described above, electrical signals within neurons are converted at synapses into chemical signals which then elicit electrical signals on the other side of the synapse. These chemical signals are molecules called neurotransmitters. There are two major kinds of molecules that serve the function of neurotransmitters: small molecules, some quite well known, with names such as dopamine, serotonin, or norepinephrine, and larger molecules, which are essentially protein chains, called peptides. These include the endogenous opiates, Substance P, and corticotropin releasing factor (CRF), among others. All told, there appear to be more than 100 different neurotransmitters in the brain (Table 2-1 contains a selected list).

A neurotransmitter can elicit a biological effect in the postsynaptic neuron by binding to a protein called a neurotransmitter receptor. Its job is to pass the information contained in the neurotransmitter message from the synapse to the inside of the receiving cell. It appears that almost every known neurotransmitter has more than one different kind of receptor that can confer rather different signals on the receiving neuron. Dopamine has 5 known neurotransmitter receptors; serotonin has at least 14.

Table 2-1. Selected neurotransmitters important in psychopharmacology

Excitatory amino acid
Glutamate

Inhibitory amino acids
Gamma aminobutyric acid
Glycine

Monoamines and related neurotransmitters
Norepinephrine
Dopamine
Serotonin
Histamine
Acetylcholine (quarternary amine)

Purine
Adenosine

Neuropeptides

    Opioids
    Enkephalins
    Beta-endorphin
    Dynorphin

    Tachykinin
    Substance P

    Hypothalamic-releasing factors
    Corticotropin-releasing hormone

Although there are many kinds of receptors with many different signaling functions, we can divide most neurotransmitter receptors into two general classes. One class of neurotransmitter receptor is called a ligand-gated channel, where“ligand” simply means a molecule (i.e., a neurotransmitter) that binds to a receptor. When neurotransmitters interact with this kind of receptor, a pore within the receptor molecule itself is opened and positive or negative charges enter the cell. The entry of positive charge may activate additional ion channels that allow more positive charge to enter. At a certain threshold, this causes a cell to fire an action potential—an electrical event that leads ultimately to the release of neurotransmitter. By definition, therefore, receptors that admit positive charge are excitatory neurotransmitter receptors. The classic excitatory neurotransmitter receptors in the brain utilize the excitatory amino acids glutamate and, to a lesser degree, aspartate as neurotransmitters. Conversely, inhibitory neurotransmitters act by permitting negative charges into the cell, taking the cell farther away from firing. The classic inhibitory neurotransmitters in the brain are the amino acids gamma amino butyric acid, or GABA, and, to a lesser degree, glycine.

Most of the other neurotransmitters in the brain, such as dopamine, serotonin, and norepinephrine, and all of the many neuropeptides constitute the second major class. These are neither precisely excitatory nor inhibitory but rather act to produce complex biochemical changes in the receiving cell. Their receptors do not contain intrinsic ion pores but rather interact with signaling proteins, called“G proteins” found inside the cell membrane. These receptors thus are called G protein-linked receptors. The details are less important than understanding the general scheme. Stimulation of G protein-linked receptors alters the way in which receiving neurons can process subsequent signals from glutamate or GABA. To use a metaphor of a musical instrument, if glutamate, the excitatory neurotransmitter, is puffing wind into a flute or clarinet, it is the modulatory neurotransmitters such as dopamine or serotonin that might be seen as playing the keys and, thus, altering the melody via G protein-linked receptors.

The architecture of these systems drives home this point. The precise brain circuits that carry specific information about the world and that are involved in precise point-to-point communication within the brain use excitatory or inhibitory neurotransmission. Examples of such circuits, which are massively parallel, can be found in the visual and auditory cortex. Overlying this pattern of precise, rapid (timing in the range of milliseconds) neurotransmission are the modulatory systems in the brain that use norepinephrine, serotonin, and dopamine. In each case, the neurotransmitter in question is made by a very small number of nerve cells clustered in a limited number of areas in the brain. Of the hundred billion neurons in the brain, only about 500,000, for example, make dopamine—that is, for every 200,000 cells in the brain, only one makes dopamine. Even fewer make norepinephrine. The cell bodies of the dopamine neurons are clustered in a few brain regions, most importantly, regions deep in the brain, in the midbrain, called the substantia nigra, and the ventral tegmental area. Norepinephrine neurons are made in the nucleus locus coeruleus even farther down in the brain stem in a structure called the pons. Serotonin is made by a somewhat larger number of nuclei but, still, not by many cells. Nuclei called the raphe nuclei spread along the brain stem. While each of these neurotransmitters is made by a small number of neurons with clustered cell bodies, each sends its axons branching throughout the brain, so that in each case a very small number of neurons, which largely appear to fire in unison when excited, influence almost the entire brain. This is not the picture of systems that are communicating precise bits of information about the world but rather are intrinsic modulatory systems that act via other G protein-linked receptors to alter the overall responsiveness of the brain. These neurotransmitters are responsible for brain states such as degree of arousal, ability to pay attention, and for putting emotional color or significance on top of cold cognitive information provided by precise glutaminergic circuits. It is no wonder that these modulatory neurotransmitters and their receptors are critical targets of medications used to treat mental disorders—for example, the antidepressant and antipsychotic drugs—and also are the targets of drugs of abuse.

Complexity of the Brain III: Plasticity

The preceding paragraphs have illustrated the chemical and anatomic structure of the brain and, in so doing, provided some picture of its complexity as well as some picture of its function. The crowning complexity of the brain, however, is that it is not static. The brain is always changing. People learn so much and have so many distinct types of memory: conscious, episodic memory of the sort that is encoded initially in the hippocampus; memory of motor programs or procedures that are encoded in the striatum; emotional memories that can initiate physiologic and behaviorally adaptive repertoires encoded, for example, in the amygdala; and many other kinds. Every time a person learns something new, whether it is conscious or unconscious, that experience alters the structure of the brain. Thus, neurotransmission in itself not only contains current information but alters subsequent neurotransmission if it occurs with the right intensity and the right pattern. Experience that is salient enough to cause memory creates new synaptic connections, prunes away old ones, and strengthens or weakens existing ones. Similarly, experiences as diverse as stress, substance abuse, or disease can kill neurons, and current data suggest that new neurons continue to develop even in adult brains, where they help to incorporate new memories. The end result is that information is now routed over an altered circuit. Many of these changes are long-lived, even permanent. It is in this way that a person can look back 10 or 20 or 50 years and remember family, a home or school room, or friends. The general theme is that to really understand the kind of memory—indeed, any brain function—one must think at least at two levels: one, the level of molecular and cellular alterations that are responsible for remodeling synapses, and, two, the level of information content and behavior which circuits and synapses serve.

To summarize this section, scientists are truly beginning to learn about the structure and function of the brain. Its awe-inspiring complexity is fully consistent with the fact that it supports all behavior and mental life. Implied in the foregoing, is the fact that brains are built not only by genes—and again, it is the lion’s share of the 80,000 or so human genes that are involved in building a structure so complex as the brain. Genes are not by themselves the whole story. Brains are built and changed through life through the interaction of genes with environment, including experience. It is true that a set of genes might create repetitive multiples of one type of unit, yet the brain appears far more complex than that. It stands to reason that if 50,000 or 60,000 genes are involved in building a brain that may have 100 trillion or a quadrillion synapses, additional information is needed, and that information comes from the environment. It is this fundamental realization that is beginning to permit an understanding of how treatment of mental disorders works—whether in the form of a somatic intervention such as a medication, or a psychological“talk” therapy—by actually changing the brain.

Imaging the Brain

There are many exciting developments in brain science. Of great relevance to the study of mental function and mental illness is the ability to image the activity of the living human brain with technologies developed in recent decades, such as positron emission tomography scanning or functional magnetic resonance imaging. Such approaches can exploit surrogates of neuronal firing such as blood flow and blood oxygenation to provide maps of activity. As science learns more about brain circuitry and learns more from cognitive and affective neuroscience about how to activate and examine the function of particular brain circuits, differences between health and illness in the function of particular circuits certainly will become evident. We will be able to see the action of psychotropic drugs and, perhaps most exciting, we will be able to see the impact of that special kind of learning called psychotherapy, which works after all because it works on the brain.

Different brain chemicals, brain receptors, and brain structures will come up in the discussion of particular illnesses throughout this document. This section is meant to provide a panoramic, not a detailed, introduction and also to provide certain overarching lessons. When something is referred to as biological or brain-based, that is not shorthand for saying it is genetic and, thus, predetermined; similarly, references to “psychological” or even“social” phenomena do not exclude biological processes. The brain is the great integrator, bringing together genes and environment. The study of the brain requires reducing problems initially to bite-sized bits that will allow investigators to learn something, but ultimately, the agenda of neuroscience is not reductionist; the goal is to understand behavior, not to put blinders on and try to explain it away. As the foregoing discussion illustrates, the brain also is complex. Thus, having a disease that affects one or even many critical circuits does not overthrow, except in extreme cases, such as advanced Alzheimer’s disease, all aspects of a person. Typically, people retain their personality and, in most cases, their ability to take responsibility for themselves.

In retrospect, early biological models of the mind seem impoverished and deterministic—for example, models that held that “levels” of a neurotransmitter such as serotonin in the brain were the principal influence on whether one was depressed or aggressive. Neuroscience is far beyond that now, working to integrate information coming “bottom-up” from genes and molecules and cells, with information flowing“top-down” from interactions with the environment and experience to the internal workings of the mind and its neuronal circuits. Ultimately, however, the goal is not only human self-understanding. In knowing eventually precisely what goes wrong in what circuits and what synapses and with what chemical signals, the hope is to develop treatments with greater effectiveness and with fewer side effects. Indeed, as the following chapters indicate, the hope is for cures and ultimately for prevention. There is every reason to hope that as our science progresses, we will achieve those goals.

 



Development

Stress and the Developing Brain
National Institute of Mental Health

 

Download the pdf file:
Stress and the Developing Brain

 

Excessive Stress Disrupts the Architecture of the Developing Brain.
National Scientific Council on the Developing Child

 

Download the pdf file:
Excessive Stress Disrupts the Architecture of the Developing Brain

Used with express permission from the
Center on the Developing Child
www.developingchild.harvard.edu

 

The Teenage Brain: a work in progress
National Institute of Mental Health

Part 1:

First, download the pdf file:

The Teenage Brain: a work in progress

 

Part 2:

Attack of the Teenage Brain!!
by Dennis Palumbo, MFT
Huffington Report


From the pages of medical journals to feature stories on the network news, there's been a swell of media coverage the past few years concerning "the teenage brain."

Despite sounding like the title of Hollywood's latest horror-movie blockbuster, the phrase actually refers to recent neurological research on adolescent brain chemistry. To the surprise of practically no one not wearing a lab coat, it's finally been demonstrated scientifically that the teenage brain is different from that of a mature adult.

According to the data, these differences explain the average teen's inclination to stay up late, sleep until noon, and exhibit extreme mood swings (for example, from sullen and defiant to really sullen and defiant). Some researchers have even blamed these brain differences for the adolescent's devotion to high-decibel music, insistence on low-decibel mumbling, and willingness to stand in line for hours to see the midnight showing of Watchmen.

As soon as these results made national headlines, the usual social pundits weighed in: this new research, they claimed, clearly suggested that we should ban teen driving and even raise the voting age. After all, we now had proof positive that today's teens are simply too erratic to be entrusted with such responsibilities.

This may be. But what about the mid-life brain? Perhaps the next time we embark on exhaustive, heavily-funded research into what's inside the human skull, we should focus our efforts on the average middle-aged person. Because if my friends and I are at all representative, I'd argue that whatever's going on in our collective brains is equally suspect.

Though not without good reason. We're in the middle of an economic melt-down, deluged with more-bad-news-updates constantly by the media. Not to mention the Middle East crisis, global warming, and daily bulletins about the life and travails of the OctoMom. Most adults I know are over-worked, over-stressed and generally overwhelmed by their ongoing struggles with careers, child-rearing, and relationships. They're forgetful, obsessed with their health (popping pills to an extent no teenager would even contemplate), envious of their neighbors and always---always---sleep-deprived.

Frankly, even on a good day, our brains are nothing to write home about. It's everything we can do to keep our complicated, must-have Starbucks coffee orders straight in our heads.

I think it's too easy to blame all this on brain chemistry. The truth is, life is hard, no matter how old you are. Whether you're worried about making the track team or paying the mortgage; about fitting in with the cool kids or impressing your new boss, it's all about trying to cope.

Granted, your average teen's coping mechanisms rarely extend beyond junk food and video games.
But are adults' choices any better? Addicted to Internet porn, Gray's Anatomy, Tom Clancy novels and golf. Fretting over who just got voted off Dancing with the Stars. Running from yoga class to a "Parents Without Partners" meeting to the latest Donald Trump get-rich-quick seminar.

And, amidst all this, compulsively checking e-mails and sending text messages on their cellphones (while nursing fantasies of winning the Lottery or running off to Tahiti with the office manager).

Let's face it, teens have just two basic goals: having sex and getting into a good college. Both pretty laudable and straightforward aims, especially when compared with the confusing and relentless demands of contemporary life with which adults have to contend. It's no wonder, then, that at the end of a hard day, most adults just want to collapse on the sofa and channel-surf.

Sartre once said that the state of man is incomprehension and rage. Okay, maybe he was a bit of a Gloomy Gus. But isn't the bewilderment and struggle to which he alludes true at times for all of us, particularly at certain crucial stages in our life?

As a psychotherapist, I see daily the unfortunate consequences of assigning a diagnostic label to practically every kind of behavior under the sun. Instead, we need to remember that people are too complex to fit neatly into categories.

And that includes teenage people.

In fact, before we start debating whether teens should be allowed to drive and vote, we'd better be able to defend letting us adults do so. It's not as if our record in either of these endeavors is anything to brag about. (Okay, we got one right with Obama, but still...)

My point is, I think we should give kids a break. They're not responsible for the way their brains develop, any more than they are for the world in which they have to grow up.

If anything, the latter is a result of brains much older, and supposedly wiser, than theirs.

Formerly a Hollywood screenwriter (My Favorite Year; Welcome Back, Kotter, etc.), Dennis Palumbo, MA, MFT is now a licensed psychotherapist in private practice, specializing in creative issues. His newest book, a collection of mystery short stories, is called From Crime to Crime. For more information, please visit his website at www.dennispalumbo.com

Specific Neurological Conditions

Amyotrophic Lateral Sclerosis


What is amyotrophic lateral sclerosis?
Who gets ALS?
What are the symptoms?
How is ALS diagnosed?
What causes ALS?
How is ALS treated?
What research is being done?
How Can I Help Research?
Where can I get more information?

What is amyotrophic lateral sclerosis?


Amyotrophic lateral sclerosis (ALS), sometimes called Lou Gehrig's disease, is a rapidly progressive, invariably fatal neurological disease that attacks the nerve cells (neurons) responsible for controlling voluntary muscles. The disease belongs to a group of disorders known as motor neuron diseases, which are characterized by the gradual degeneration and death of motor neurons.

Motor neurons are nerve cells located in the brain, brainstem, and spinal cord that serve as controlling units and vital communication links between the nervous system and the voluntary muscles of the body. Messages from motor neurons in the brain (called upper motor neurons) are transmitted to motor neurons in the spinal cord (called lower motor neurons) and from them to particular muscles. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (atrophy), and twitch (fasciculations) . Eventually, the ability of the brain to start and control voluntary movement is lost.

ALS causes weakness with a wide range of disabilities (see section titled "What are the symptoms?"). Eventually, all muscles under voluntary control are affected, and patients lose their strength and the ability to move their arms, legs, and body. When muscles in the diaphragm and chest wall fail, patients lose the ability to breathe without ventilatory support. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. However, about 10 percent of ALS patients survive for 10 or more years.

Although the disease usually does not impair a person's mind or intelligence, several recent studies suggest that some ALS patients may have alterations in cognitive functions such as depression and problems with decision-making and memory.

ALS does not affect a person's ability to see, smell, taste, hear, or recognize touch. Patients usually maintain control of eye muscles and bladder and bowel functions, although in the late stages of the disease most patients will need help getting to and from the bathroom.

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Who gets ALS?


As many as 20,000 Americans have ALS, and an estimated 5,000 people in the United States are diagnosed with the disease each year. ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. ALS most commonly strikes people between 40 and 60 years of age, but younger and older people also can develop the disease. Men are affected more often than women.

In 90 to 95 percent of all ALS cases, the disease occurs apparently at random with no clearly associated risk factors. Patients do not have a family history of the disease, and their family members are not considered to be at increased risk for developing ALS.

About 5 to 10 percent of all ALS cases are inherited. The familial form of ALS usually results from a pattern of inheritance that requires only one parent to carry the gene responsible for the disease. About 20 percent of all familial cases result from a specific genetic defect that leads to mutation of the enzyme known as superoxide dismutase 1 (SOD1). Research on this mutation is providing clues about the possible causes of motor neuron death in ALS. Not all familial ALS cases are due to the SOD1 mutation, therefore other unidentified genetic causes clearly exist.

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What are the symptoms?


The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; slurred and nasal speech; or difficulty chewing or swallowing. These general complaints then develop into more obvious weakness or atrophy that may cause a physician to suspect ALS.

The parts of the body affected by early symptoms of ALS depend on which muscles in the body are damaged first. In some cases, symptoms initially affect one of the legs, and patients experience awkwardness when walking or running or they notice that they are tripping or stumbling more often. Some patients first see the effects of the disease on a hand or arm as they experience difficulty with simple tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Other patients notice speech problems.

Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Patients have increasing problems with moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign (the large toe extends upward as the sole of the foot is stimulated in a certain way) also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations).

To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.

Although the sequence of emerging symptoms and the rate of disease progression vary from person to person, eventually patients will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. Difficulty swallowing and chewing impair the patient's ability to eat normally and increase the risk of choking. Maintaining weight will then become a problem. Because the disease usually does not affect cognitive abilities, patients are aware of their progressive loss of function and may become anxious and depressed. A small percentage of patients may experience problems with memory or decision-making, and there is growing evidence that some may even develop a form of dementia. Health care professionals need to explain the course of the disease and describe available treatment options so that patients can make informed decisions in advance. In later stages of the disease, patients have difficulty breathing as the muscles of the respiratory system weaken. Patients eventually lose the ability to breathe on their own and must depend on ventilatory support for survival. Patients also face an increased risk of pneumonia during later stages of ALS.

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How is ALS diagnosed?


No one test can provide a definitive diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.

Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, a herniated disk in the neck, syringomyelia, or cervical spondylosis.

Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.

Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukemia virus (HTLV), and Lyme disease can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, and spinal muscular atrophy also can mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis.

Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients may wish to obtain a second neurological opinion.

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What causes ALS?


The cause of ALS is not known, and scientists do not yet know why ALS strikes some people and not others. An important step toward answering that question came in 1993 when scientists supported by the National Institute of Neurological Disorders and Stroke (NINDS) discovered that mutations in the gene that produces the SOD1 enzyme were associated with some cases of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by free radicals. Free radicals are highly reactive molecules produced by cells during normal metabolism. If not neutralized, free radicals can accumulate and cause random damage to the DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. In support of this, animal studies have shown that motor neuron degeneration and deficits in motor function accompany the presence of the SOD1 mutation.

Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid. Laboratory studies have demonstrated that neurons begin to die off when they are exposed over long periods to excessive amounts of glutamate. Now, scientists are trying to understand what mechanisms lead to a buildup of unneeded glutamate in the spinal fluid and how this imbalance could contribute to the development of ALS.

Autoimmune responses—which occur when the body's immune system attacks normal cells—have been suggested as one possible cause for motor neuron degeneration in ALS. Some scientists theorize that antibodies may directly or indirectly impair the function of motor neurons, interfering with the transmission of signals between the brain and muscles.

In searching for the cause of ALS, researchers have also studied environmental factors such as exposure to toxic or infectious agents. Other research has examined the possible role of dietary deficiency or trauma. However, as of yet, there is insufficient evidence to implicate these factors as causes of ALS.

Future research may show that many factors, including a genetic predisposition, are involved in the development of ALS.

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How is ALS treated?


No cure has yet been found for ALS. However, the Food and Drug Administration (FDA) has approved the first drug treatment for the disease—riluzole (Rilutek). Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole prolongs survival by several months, mainly in those with difficulty swallowing. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects. However, this first disease-specific therapy offers hope that the progression of ALS may one day be slowed by new medications or combinations of drugs.

Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals such as physicians; pharmacists; physical, occupational, and speech therapists; nutritionists; social workers; and home care and hospice nurses. Working with patients and caregivers, these teams can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.

Physicians can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, and constipation. Pharmacists can give advice on the proper use of medications and monitor a patient's prescriptions to avoid risks of drug interactions.

Physical therapy and special equipment can enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical therapists can recommend exercises that provide these benefits without overworking muscles. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients conserve energy and remain mobile.

ALS patients who have difficulty speaking may benefit from working with a speech therapist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech therapists can help patients develop ways for responding to yes-or-no questions with their eyes or by other nonverbal means and can recommend aids such as speech synthesizers and computer-based communication systems. These methods and devices help patients communicate when they can no longer speak or produce vocal sounds.

Patients and caregivers can learn from speech therapists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.

When the muscles that assist in breathing weaken, use of nocturnal ventilatory assistance (intermittent positive pressure ventilation [IPPV] or bilevel positive airway pressure [BIPAP]) may be used to aid breathing during sleep. Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time.

Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheostomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck. Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support.

Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Respiratory therapists can help caregivers with tasks such as operating and maintaining respirators, and home care nurses are available not only to provide medical care but also to teach caregivers about giving tube feedings and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.

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What research is being done?


The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is the Federal Government's leading supporter of biomedical research on ALS. The goals of this research are to find the cause or causes of ALS, understand the mechanisms involved in the progression of the disease, and develop effective treatment.

Scientists are seeking to understand the mechanisms that trigger selective motor neurons to degenerate in ALS and to find effective approaches to halt the processes leading to cell death. This work includes studies in animals to identify the means by which SOD1 mutations lead to the destruction of neurons. The excessive accumulation of free radicals, which has been implicated in a number of neurodegenerative diseases including ALS, is also being closely studied. In addition, researchers are examining how the loss of neurotrophic factors may be involved in ALS. Neurotrophic factors are chemicals found in the brain and spinal cord that play a vital role in the development, specification, maintenance, and protection of neurons. Studying how these factors may be lost and how such a loss may contribute to motor neuron degeneration may lead to a greater understanding of ALS and the development of neuroprotective strategies. By exploring these and other possible factors, researchers hope to find the cause or causes of motor neuron degeneration in ALS and develop therapies to slow the progression of the disease.

Researchers are also conducting investigations to increase their understanding of the role of programmed cell death or apoptosis in ALS. In normal physiological processes, apoptosis acts as a means to rid the body of cells that are no longer needed by prompting the cells to commit "cell suicide." The critical balance between necessary cell death and the maintenance of essential cells is thought to be controlled by trophic factors. In addition to ALS, apoptosis is pervasive in other chronic neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease and is thought to be a major cause of the secondary brain damage seen after stroke and trauma. Discovering what triggers apoptosis may eventually lead to therapeutic interventions for ALS and other neurological diseases.

Scientists have not yet identified a reliable biological marker for ALS—a biochemical abnormality shared by all patients with the disease. Once such a biomarker is discovered and tests are developed to detect the marker in patients, allowing early detection and diagnosis of ALS, physicians will have a valuable tool to help them follow the effects of new therapies and monitor disease progression.

NINDS-supported researchers are studying families with ALS who lack the SOD1 mutation to locate additional genes that cause the disease. Identification of additional ALS genes will allow genetic testing useful for diagnostic confirmation of ALS and prenatal screening for the disease. This work with familial ALS could lead to a greater understanding of sporadic ALS as well. Because familial ALS is virtually indistinguishable from sporadic ALS clinically, some researchers believe that familial ALS genes may also be involved in the manifestations of the more common sporadic form of ALS. Scientists also hope to identify genetic risk factors that predispose people to sporadic ALS.

Potential therapies for ALS are being investigated in animal models. Some of this work involves experimental treatments with normal SOD1 and other antioxidants. In addition, neurotrophic factors are being studied for their potential to protect motor neurons from pathological degeneration. Investigators are optimistic that these and other basic research studies will eventually lead to treatments for ALS.

Results of an NINDS-sponsored phase III randomized, placebo-controlled trial of the drug minocycline to treat ALS were reported in 2007. This study showed that people with ALS who received minocycline had a 25 percent greater rate of decline than those who received the placebo, according to the ALS functional rating scale (ALSFRS-R).

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How Can I Help Research?


The NINDS contributes to the support of the Human Brain and Spinal Fluid Resource Center in Los Angeles. This bank supplies investigators around the world with tissue from patients with neurological and other disorders. Tissue from individuals with ALS is needed to enable scientists to study this disorder more intensely. Prospective donors may contact:

Human Brain and Spinal Fluid Resource Center
Neurology Research (127A)
W. Los Angeles Healthcare Center
11301 Wilshire Blvd. Bldg. 212
Los Angeles, CA 90073
310-268-3536
24-hour pager: 310-636-5199
Email: RMNbbank@ucla.edu
http://www.loni.ucla.edu/~nnrsb/NNRSB

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

ALS Association
27001 Agoura Road
Suite 150
Calabasas Hills, CA   91301-5104
advocacy@alsa-national.org
http://www.alsa.org
Tel: 818-880-9007 800-782-4747
Fax: 818-880-9006

Les Turner ALS Foundation
5550 W. Touhy Avenue
Suite 302
Skokie, IL   60077-3254
info@lesturnerals.org
http://www.lesturnerals.org
Tel: 888-ALS-1107 847-679-3311
Fax: 847-679-9109

Muscular Dystrophy Association
3300 East Sunrise Drive
Tucson, AZ   85718-3208
mda@mdausa.org
http://www.mda.org
Tel: 520-529-2000 800-344-4863
Fax: 520-529-5300

Project ALS
900 Broadway
Suite 901
New York, NY   10003
info@projectals.org
http://www.projectals.org
Tel: 212-420-7382 800-603-0270
Fax: 212-420-7387

ALS Therapy Development Institute
215 First Street
Cambridge, MA   02142
info@als.net
http://www.als.net
Tel: 617-441-7200
Fax: 617-441-7299

 
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"Amyotrophic Lateral Sclerosis Fact Sheet," NINDS. Publication date April 2003.

NIH Publication No. 00-916



Brain and Spinal Tumors

Introduction
What are Brain and Spinal Cord Tumors?
Overview of the brain and spinal cord
CNS Tumor FAQS
What are benign and malignant tumors?
What are primary and metastatic tumors?
What causes CNS tumors?
Who is at risk?
How many people have these tumors?
How are tumors graded?
What are the possible symptoms?
How are CNS tumors diagnosed?
How are brain and spinal cord tumors treated?
Neurosurgery
Radiation Therapy
Chemotherapy
What is the prognosis?
What Research is Being Done?

Where can I get more information?
Appendix: Some CNS Tumors and Tumor-Related Conditions
Glossary

Introduction


A diagnosis of a brain or spinal cord tumor brings uncertainty and worry to you and your friends and family.  It’s easy to become overwhelmed by a new world of tests, technology, and treatments that you may know little or nothing about.

This handbook will give you a better understanding of brain and spinal cord tumors, their treatment options, and the latest research to find safer, more effective ways to diagnose and treat them.  You can take the best care of yourself by learning about your diagnosis and discussing it with your doctors.

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What are Brain and Spinal Cord Tumors?


Brain and spinal cord tumors are found in the tissue inside the skull or the bony spinal column, which makes up the central nervous system (CNS). A tumor is a mass of cells that forms a new growth or is present at birth (congenital).  Tumors occur when genes that regulate cell growth become damaged or mutated, allowing cells to grow and divide out of control.  Tumors can form anywhere in the body.

Depending on the type, a growing tumor can kill healthy cells or disrupt their function.   It can move or press on sensitive tissue and block the flow of blood and other fluid, causing pain and inflammation.  A tumor can also block the normal flow of electricity in the brain or nerve signaling to and from the brain.  Some tumors cause no trouble at all.

There are more than 120 types of brain and spinal cord tumors.  Some are named by the type of cell in which they start (such as glioma) or location (such as meningioma, which form in the lining of the brain and spinal cord).  See the Appendix at the end of this guide for a listing of some CNS tumors and tumor-related conditions and the Glossary for specific terms and their meanings.

The following overview explains how the CNS works and what happens when a tumor is present.

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Overview of the brain and spinal cord


The brain has three major parts:

  • brain stem—This lowest part of the brain (above the neck) connects to the spinal cord and relays information between the brain and the body using bundles of long nerves.  It controls basic life-sustaining functions, including blood pressure, heartbeat, breathing, consciousness, swallowing, and body temperature.
  • cerebrum—This largest and outermost part of the brain processes information from our senses to tell the body how to respond.  It controls functions including movement, touch, judgment, learning, speech, emotions, and thinking.
  • cerebellum—Located at the lower rear of the brain, above the brain stem, the cerebellum controls balance, helps maintain equilibrium, and coordinates such complex muscle movements as walking and talking.

The brain’s two halves, or hemispheres, use nerve cells (neurons) to speak with each other.  Each side of the cerebrum controls movement and function on the other side of the body.  In addition, each hemisphere has four sections, called lobes, which handle different neurological functions.

The frontal lobes manage voluntary movement, such as writing, and let us set and prioritize goals.  A frontal lobe tumor can cause changes in personality, intellect, reasoning, and behavior; affect coordination and walking, and cause speech loss.  The temporal lobes are linked to perception, memory, and understanding sounds and words.  A tumor here might cause speech and hearing problems, blackouts, seizures, or sensations such as a feeling of fear.  The parietal lobes let us simultaneously receive and understand sensations such as pressure and pain.  A parietal lobe tumor might cause difficulty understanding or speaking words, problems with coordination, seizures, and numbness or weakness on one side of the body.  The occipital lobes receive and process light and visual images, and detect motion.  An occipital lobe tumor can affect the field of vision, usually on one side of the face, and how we understand written words.

Three layers of protective tissue (called the meninges) cover the brain—the thick dura mater (outer layer), the arachnoid (middle), and the pia mater (innermost to the brain).

Brain tumors in infants and adults tend to be located in the cerebrum.  Brain tumors in children ages 1-12 years are more commonly found in the cerebellum.

The spinal cord—an extension of the brain—lies protected inside the bony spinal column.  It contains bundles of nerves that carry messages between the brain and other parts of the body, such as instructions from the brain to move an arm or information from the skin that signals pain.

A tumor that forms on or near the spinal cord can disrupt communication between the brain and the nerves or restrict the cord's supply of blood.  Because the spinal column is narrow, a tumor here—unlike a brain tumor—can cause symptoms on both sides of the body at the same time.

Most spinal cord tumors form below the neck.   Symptoms generally strike body areas at the same level or at a level below that of the tumor.  For example, a tumor midway along the spinal cord (in the thoracic spine) can cause pain that spreads over the chest and gets worse when the individual coughs, sneezes, or lies down.  A tumor that grows in the cervical spine can cause pain that seems to come from the neck or arms, and a tumor that grows in the lower, lumbar spine can trigger back or leg pain.

The three major groups of spinal cord tumor describe where they are found.  Extradural tumors grow between the inner surface of the spinal canal and the tough dura mater.  Tumors inside the dura (intradural tumors) are further divided into those outside the spinal cord (extramedullary tumors) and those inside the spinal cord (intramedullary tumors).  Other descriptors for spinal cord tumors are intrinsic, meaning the tumor forms inside the spinal cord; and extrinsic, where the tumor forms outside of and presses on the cord as it grows.

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CNS Tumor FAQS


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What are benign and malignant tumors?


No matter where they are located in the body, tumors are classified as benign or malignant.

Benign tumors are slow growing, non-cancerous cell masses that have a defined edge and do not spread to other parts of the body.  Cells in the tumor are similar to normal cells.  Often these tumors can be removed surgically and usually do not recur.

Malignant, or cancerous, tumors have cells that look different from normal cells.  They can quickly invade surrounding tissue and often have edges that are hard to define, which makes it difficult to remove the entire tumor surgically.

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What are primary and metastatic tumors?


Primary tumors of the CNS are growths that begin in the brain or spinal cord.   They can be either malignant or benign and are identified by the types of cells they contain, their location, or both.  Most primary CNS tumors occur in adults.

Metastatic, or secondary, tumors in the CNS are caused by cancer cells that break away from the primary tumor that developed in a non-CNS part of the body.  These tumors are named after the type of cancer that causes them.   Metastastic tumors (also called metastases) to the brain occur in about one-fourth of all cancers that develop in other parts of the body, such as cancer of the lung, breast, or kidneys; or melanoma, a form of skin cancer.  They are more common than primary tumors and occur more often in adults than in children.

Metastatic spine tumors usually form within the bony covering of the spinal column but may also invade the spinal canal from the chest or abdomen.

While cancers elsewhere in the body can easily cause tumors inside the brain and spinal cord, CNS tumors rarely spread outside the nervous system.

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What causes CNS tumors?


Researchers really don't know why primary brain and spinal cord tumors develop.  Possible causes under investigation include viruses, defective genes, exposure to certain chemicals and other hazardous materials, and immune system disorders.  Although smoking, alcohol consumption, and certain dietary habits are associated with some types of cancers, they have not been linked to primary CNS tumors.

In a small number of individuals, CNS tumors may result from specific genetic diseases, such as neurofibromatosis and tuberous sclerosis, or exposure to radiation. Non-ionizing radiation (radio waves) from mobile phone use does not increase the risk of developing a brain tumor.1

Brain and spinal cord tumors are not contagious or, at this time, preventable.

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Who is at risk?


Anyone can develop a primary CNS tumor, although the risk is very small.  Having one or more of the known risk factors does not guarantee that someone will develop a tumor.  Brain tumors occur more often in males than in females and are most common in middle-aged to older persons.  They also tend to occur more often in children under age 9 than in other children, and some tumors tend to run in families.  Most brain tumors in children are primary tumors.

Other risk factors for developing a primary CNS tumor include race (Caucasians are more likely to develop a CNS tumor than other races) and occupation.  Workers in jobs that require repeated contact with ionizing radiation or certain chemicals, including those used to manufacture building supplies or plastics and textiles, have a greater chance of developing a brain tumor.

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How many people have these tumors?


More than 359,000 persons in the United States are estimated to be living with a diagnosis of primary brain or central nervous system tumor.2    More than 195,000 Americans are diagnosed with a brain tumor each year.3  Brain tumors are the most common form of solid tumor in children.

Spinal cord tumors are less common than brain tumors.  Although they affect people of all ages, spinal cord tumors are most common in young and middle-aged adults.  Nearly 3,200 central nervous system tumors are diagnosed each year in children under age 20.4

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How are tumors graded?


The generally accepted scale for grading CNS tumors was approved by the World Health Organization in 1993.  Grading is based on the tumor’s cellular makeup and location.  Tumors may also be classified as low-grade (slowly growing) or high-grade (rapidly growing).  Some tumors change grades as they progress, usually to a higher grade, and can become a different type of tumor.  The tumor is graded by a pathologist following a biopsy or during surgery.

Grade I tumors grow slowly and generally do not spread to other parts of the brain.  It is often possible to surgically remove an entire grade I benign tumor, but this type of tumor may be monitored periodically, without further treatment.

Grade II tumors also grow slowly, sometimes into surrounding tissue, and can become a higher-grade tumor.  Treatment varies according to tumor location and may require chemotherapy, radiation, or surgery followed by close observation.

Grade III tumors are malignant and can spread quickly into other CNS tissue.  Tumor cells will look different than those in surrounding tissue.  Aggressive treatment, often using a combination of chemotherapy, radiation, and/or surgery, is required.

Grade IV tumors invade nearby tissue very quickly and are difficult to treat.  The cancerous tissue will look very different from surrounding tissue.  Aggressive treatment is required.

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What are the possible symptoms?


Brain and spinal cord tumors cause many diverse symptoms, which can make detection tricky.  Symptoms depend on tumor type, location, size, and rate of growth.  Certain symptoms are quite specific because they result from damage to particular areas of the brain.  Symptoms generally develop slowly and worsen as the tumor grows.

The most obvious sign of a brain tumor in infants is a rapidly widening head or bulging crown.

Common symptoms of a brain tumor in adults include headaches, seizures, problems with balance or coordination, loss of muscle control, hydrocephalus, and changes in personality or behavior.

Headaches are the most common symptom of a brain tumor.  Headaches may progressively worsen, become more frequent or constant, and recur, often at irregular intervals.  Headache pain may worsen when coughing, changing posture, or straining and may be severe upon waking.

Seizures can occur, with symptoms that may include convulsions, loss of consciousness, or loss of bladder control.  Seizures that first start in adulthood (in someone who has not been in an accident or who had an illness that causes seizures) are a key warning sign of brain tumors.

Nausea and vomiting may be more severe in the morning and may accompany headaches.

Vision or hearing problems can include blurred or double vision, partial or total loss of vision or hearing, ringing or buzzing sounds, and abnormal eye movements.

Personality, behavior, and cognitive changes can include psychotic episodes and problems with speech, language, thinking, and memory.

Motor problems can include weakness or paralysis, lack of coordination, or gradual loss of sensation or movement in an arm or leg.  A sudden, marked change in handwriting may be a sign of a tumor.

Balance problems can include dizziness, trouble with walking, clumsiness, or loss of the normal control of equilibrium.

Hydrocephalus and increased intracranial pressure are caused when a tumor blocks the flow of the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord.  Symptoms may include headaches, nausea, and vomiting.

Other symptoms may include endocrine disorders or abnormal hormonal regulation, difficulty swallowing, facial paralysis and sagging eyelid, fatigue, weakened sense of smell, or disrupted sleep and sleep pattern changes.

Common symptoms of a spinal cord tumor include pain, numbness or sensory changes, and motor problems and loss of muscle control.

Pain can feel as if it is coming from various parts of the body.  Back pain may extend to the hips, legs, feet, and arms.  This pain is often constant and may be severe.  It is often progressive and can have a burning or aching quality.

Numbness or sensory changes can include decreased skin sensitivity to temperature and progressive numbness or a loss of sensation, particularly in the legs.

Motor problems and loss of muscle control can include muscle weakness, spasticity (in which the muscles stay stiffly contracted), and impaired bladder and/or bowel control.  If untreated, symptoms may worsen to include muscle wasting, decreased muscle strength, an abnormal walking rhythm known as ataxia, and paralysis.

Symptoms may spread over various parts of the body when one or more tumors extend over several sections of the spinal cord.

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How are CNS tumors diagnosed?


A doctor, usually a neurologist, oncologist, or neuro-oncologist, can confirm a diagnosis of a brain or spinal cord tumor based on a patient’s symptoms, personal and family medical history, and results of a physical exam and specialized tests and techniques.

A neurological exam—the first test—assesses movement and sensory skills, hearing and speech, reflexes, vision, coordination and balance, mental status, and changes in mood or behavior, among other abilities.   Some tests require a specialist to perform and analyze results.

Diagnostic Imaging

The doctor will order one or more imaging techniques that show extremely detailed views of body structures, including tissues, organs, bones, and nerves.  If there is a tumor, diagnostic imaging will confirm the diagnosis and help doctors determine the tumor's type, detect swelling and other associated conditions, and, over time, check the results of treatment.

See the NINDS publication, “Neurological Diagnostic Tests and Procedures,” for a more complete description of the following tests:

Computed Tomography (CT) uses x-rays and a computer to produce fast, detailed cross-sectional images or “slices” of organs, bones, and tissues, including a tumor.  It is also good for detecting the buildup of calcium, which causes tissue to harden and can develop into a tumor.

Magnetic Resonance Imaging (MRI) uses a computer, radio waves, and a strong magnetic field to produce two-dimensional slices or a detailed three-dimensional model of tissue being scanned.  MRI takes longer to perform than does a CT but is more sensitive and gives better pictures of tumors located near bone. 

Both CT and MRI scans for tumor are usually performed before and after administration of a "contrast" agent (such as a dye) that is given into a vein.  Many tumors become much brighter on the scan taken after the contrast is given.

Functional MRI (fMRI) creates images of areas of the brain with specific functions such as movement and language.   It can assess brain damage from head injury or degenerative disorders, identify and monitor other neurological disorders such as stroke, and show the distance between specific brain functions and tumors in particular areas of the brain.

Magnetic Resonance Spectroscopy (MRS) gives doctors a chemical snapshot of tissues being studied.  It uses the MRI scanner's magnetic field and radio waves to measure and analyze the chemical make-up of the tissue sample.

Positron Emission Tomography (PET) provides computer-generated two- and three-dimensional scans of the brain’s chemical activity and cellular function.  PET traces and measures the brain’s use of glucose (sugar, used by the brain for energy) that is attached to small amounts of radioactivity and injected into the bloodstream.  Since malignant tissue uses more glucose than normal tissue, it usually shows up on the scan as brighter than surrounding tissue.  

Single Photon Emission Computed Tomography (SPECT) studies blood flow to tissue.  Certain tumors grow new blood vessels to increase their supply of blood and nutrients.  A radioactive isotope is injected intravenously and traced as it travels into the skull.  A sophisticated computer processes and stacks the data into a detailed three-dimensional image of activity within the brain.

Angiography (or arteriogram) can distinguish certain types of tumors that have a characteristic pattern of blood vessels and blood flow.  A dye that deflects x-rays is injected into a major blood vessel and a series of x-rays is taken as the dye flows to the brain.  In many situations angiography has been replaced by non-invasive tests such as CT and MRI.

Laboratory Tests

Testing blood, urine, and other substances can provide clues about the tumor and monitor levels of therapeutic drugs.

Additional tests may include an electroencephalogram, or EEG, which monitors brain activity through the skull (tumors can disrupt the normal flow of brain wave activity and cause seizures); CSF analysis, in which a small amount of the cerebrospinal fluid is removed by a special needle and examined for abnormal cells or unusual levels of various compounds that suggest a brain or spinal cord tumor; and magnetoencephalography (MEG), which studies brain function by measuring the magnetic field generated by nerve cells in the brain.   CSF fluid analysis should be performed with extreme caution on individuals with very large brain tumors.

Diagnosing the distinct type of brain tumor is often difficult.  Individuals should consider asking their primary care physician or oncologist for a second opinion, particularly from a neuro-oncologist or neurosurgeon, as there may be new information available and some tumors can change grade or recur.  Even a second opinion that confirms the original diagnosis can help people better prepare for their care and treatment.

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How are brain and spinal cord tumors treated?


A specialized team of doctors advises and assists individuals throughout treatment and rehabilitation.  These doctors may include:

A neurologist is a specialist in nervous system disorders.

A medical oncologist is a specialist in cancer.

A neuro-oncologist is a neurologist who specializes in nervous system tumors.

A neuroradiologist is a doctor trained in reading diagnostic imaging results who specializes in the CNS.

A pathologist is a clinical physician who diagnoses diseases of tissues or cells using a variety of laboratory tests.

A neurosurgeon is a brain or spinal cord surgeon.

A radiation oncologist is a doctor who specializes in using radiation to treat individuals with cancer.

This team will recommend a treatment plan based on the tumor's location, type, size and aggressiveness, as well as on the individual’s medical history, age, and general health.

Initial treatment for a CNS tumor may involve a variety of drugs, including anticonvulsants to treat seizures, pain medications, steroids or other anti-inflammatory drugs to reduce swelling and improve blood flow, antidepressants to treat anxiety or ease depression that might occur following a tumor diagnosis, and drugs to fight nausea caused by various treatments.

Malignant tumors require some form of treatment, while some small benign tumors may need only periodic monitoring.  The three standard treatment options for malignant CNS tumors are neurosurgery, radiation therapy, and chemotherapy.  Some patients may receive a combination of treatments.

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Neurosurgery


Surgery is usually the first step in treating an accessible tumor—one that can be removed without unacceptable risk of neurological damage.  Surgery is aimed at removing all or as much tumor as possible (called resecting or excising) and can often slow worsening of neurological function.

An inaccessible or inoperable tumor is one that cannot be removed surgically because of the risk of severe nervous system damage during the operation.  These tumors are frequently located deep within the brain or near vital structures such as the brain stem.

A biopsy is usually performed to help doctors determine how to treat a tumor.  A brain biopsy involves surgically removing a small part of the skull to sample the tumor tissue.  Biopsies can sometimes be performed by a needle inserted through a small hole.  A small piece of tissue remains in the hollow needle when it is removed from the body.  A pathologist will stain and examine the tissue for certain changes that signal cancer and grade it to reflect the degree of malignancy.

If the sample is cancerous, the surgeons will remove as much of the tumor as possible.  For some primary brain tumors it is not possible to surgically remove all malignant cells.  Malignant brain tumors commonly recur from cells that have spread from the original tumor mass into the surrounding brain tissue.  In contrast, many benign tumors and secondary metastatic tumors can be completely removed surgically.

In some cases, a surgeon may need to insert a shunt into the skull to drain any dangerous buildup of CSF caused by the tumor.  A shunt is a flexible plastic tube that is used to divert the flow of CSF from the central nervous system to another part of the body, where it can be absorbed as part of the normal circulatory process. 

Fortunately, research has led to advances in neurosurgery that make it possible for doctors to completely remove many tumors that were previously thought to be inoperable.  These new techniques and tools let neurosurgeons operate within the tight, vulnerable confines of the CNS.  Some tools used in the operating room include a surgical microscope, the endoscope (a small viewing tube attached to a video camera), and miniature precision instruments that allow surgery to be performed through a small incision in the brain or spine.

Intraoperative MRI uses a special type of MRI to provide a real-time evaluation of the surgery.   Constantly updated images that are provided during surgery let doctors see how much tumor material has been removed.  Intraoperative MRI can also help doctors choose the best surgical approaches and monitor any complications during surgery.

Navigation equipment used in computer-guided, or stereotactic, neurosurgery gives doctors a precise, three-dimensional map of an individual’s spine or brain as the operation progresses.  A computer uses pre-operative diagnostic images of the individual to reduce the risk of damage to surrounding tissue.

Intraoperative nerve monitoring tests such as evoked potentials use real-time recordings of nerve cell activity to determine the role of specific nerves and monitor brain activity as the surgery progresses.  Small electrodes are used to stimulate a nerve and measure its electrical response (or evoked potential).  Some surgeries may be done while the individual is awake under monitored anesthesia care, rather than under general anesthesia.  This allows doctors to monitor the individual’s speech and motor functions as a tumor is being removed.

A possible side effect of surgery is swelling around the site of the tumor, and can be treated with steroids.  Bleeding into the tumor site or infection are other serious risks of brain surgery.

In the cae of metastatic tumors, doctors usually treat the original cancer.  However, if there are only one or two metastases to the brain or if a metastatic tumor causes serious disability or pain, doctors may recommend surgery—even if the original cancer has not been controlled.

Surgery may be the beginning and end of your treatment if the biopsy shows a benign tumor.  If the tumor is malignant, doctors often recommend additional treatment, including radiation and chemotherapy, or one of several experimental treatments.

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Radiation Therapy


Radiation therapy usually involves repeated doses of x-rays or other forms of radiation to kill cancer cells or keep them from multiplying.  When successful, this therapy shrinks the tumor mass but does not actually remove it.  Radiation therapy can be used to treat surgically inaccessible tumors or tumor cells that may remain following surgery.

Depending on tumor type and stage, radiation treatment might be delivered externally, using focused beams of energy or charged particles that are directed at the tumor, or internally, using a surgically implanted device.  The stronger the radiation, the deeper it can penetrate to the target site.  Healthy cells may also be damaged by radiation therapy but most are able to repair themselves, while the damaged tumor cells cannot.

A radiation oncologist will explain the therapy and how much radiation is needed.  Treatment often begins a week after surgery and may continue for several weeks.  Depending on tumor type and location, individuals may be able to receive a modified form of therapy to lessen damage to healthy cells and improve the overall treatment.

Externally-delivered radiation therapy poses no risk of radioactivity to the patient or family and friends.  Types of external radiation therapy include:

Whole brain radiation is generally used to shrink multiple cancerous tumors, rather than to target individual tumors.  It may be given as the sole form of treatment or in advance of other forms of radiation therapy and microsurgery.  Whole brain radiation is generally used for metastatic tumors and rarely for primary tumors.

Conventional external beam radiation aims a uniform dose of high-energy radiation at the tumor and surrounding tissue from outside the body.  It is used to treat large tumors or those that may have spread into surrounding tissue.

Three-dimensional conformal radiotherapy (3D-CRT) uses diagnostic imaging to prepare an accurate, computer-generated three-dimensional image of the tumor and surrounding tissue.  The computer then coordinates and sends multiple beams of radiation to the tumor’s exact shape, sparing nearby organs and surrounding tissue.

Intensity modulated radiation therapy (IMRT) is similar to 3D-CRT but varies the intensity of the hundreds of individual radiation beams to deliver more precise doses to the tumor or to specific areas within it.  IRMT can provide a highly effective dose of radiation to the tumor, with less exposure to surrounding tissue.

Hyperfractionation involves giving two or more smaller amounts of radiation a day instead of a larger, single dose.  It can deliver more radiation to certain tumors and reduce damage to normal cells.

Radiosurgery is usually a one-time treatment involving a large amount of sharply focused radiation that is aimed at the brain tumor.  Stereotactic radiosurgery uses computer imaging to direct precisely focused radiation into the tumor from multiple angles.  It does not actually cut into the person but, like other forms of radiation therapy, harms a tumor cell’s ability to grow and divide.  Stereotactic radiosurgery is commonly used to treat surgically inaccessible tumors.  It also may be used at the end of conventional radiation treatment.  Two common stereotactic radiosurgery procedures are:

  • Linear-accelerated radiosurgery (LINAC) uses radar-like technology to prepare and fire a single beam of high-energy x-rays into the tumor.  Also called high linear-energy transfer radiation, LINAC forms the beam to match the tumor’s shape, avoiding surrounding tissue.  A special machine that rotates around the head then fires a uniform dose of radiation into the tumor.
  • Gamma knife® radiosurgery focuses more than 200 beams of gamma radiation into one intersecting beam that is fired into the tumor.  It also uses computer imaging to prepare a model of the tumor.  This single treatment takes between one and four hours and is often recommended for inaccessible or hard to treat tumors.

Both procedures may be given on an outpatient basis but an overnight stay in the hospital is often recommended.

Proton beam therapy directs a beam of high-energy protons directly at the tumor site, leaving surrounding healthy tissue and organs intact.  It is best used to treat tumors that are solid and have not spread to other parts of the body.  Proton beam therapy can be used as a stand-alone treatment or in combination with chemotherapy or as follow-up to surgery.

Internal tumor radiation therapy, also called brachytherapy or interstitial radiation therapy, involves placing a small amount of radioactive material into or near the tumor (or its cavity, if the tumor has been surgically removed).  In most cases, the radiation is inserted at the time of surgery or using imaging and a catheter.  The radiation may be left in place for several days and, if more than one treatment is needed, the doctor may leave the catheter in place for a longer period.

Individuals may need to be hospitalized for a few days following this procedure as the radiation may extend outside their body and could possibly harm others.  The radiation becomes less active each day until it is safe for individuals who have been treated to be around others.

Side effects of radiation therapy vary from person to person and are usually temporary.  They typically begin about two weeks after treatment starts and may include fatigue, nausea, vomiting, reddened or sore skin in the area receiving treatment, headache, hearing loss, problems with sleep, and hair loss (although the hair usually grows back once the treatment has stopped).  Radiation therapy in young children, particularly those children age three or younger, can cause problems with learning, processing information, thinking, and growing.

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Chemotherapy


Chemotherapy uses powerful drugs to kill cancer cells or stop them from growing or dividing.  These drugs are usually given by pill or injection and travel through the body to the brain, or can be inserted surgically using dissolvable wafers that have been soaked in a chemotherapeutic drug.   These wafers slowly release a high concentrate of the drug to kill any remaining malignant cells.  Chemotherapy may also be given to kill cancer cells in the spinal column.

Chemotherapy is given in cycles to more effectively harm cancer cells and give normal cells time to recover from any damage.  The oncologist will base the treatment on the type of cancer, drug(s) to be used, the frequency of administration, and the number of cycles needed.

Individuals might receive chemotherapy to shrink the tumor before surgery (called neo-adjuvant therapy), in combination with radiation therapy, or after radiation treatment (called adjuvant therapy) to destroy any remaining cancer cells.  Metronomic therapy involves giving continuous low-dose chemotherapy to block mechanisms that stimulate the growth of new blood vessels needed to feed the tumor.  Chemotherapy is also used to treat CNS lymphoma and inaccessible tumors or tumors that do not respond to radiation therapy.

Not all tumors are vulnerable to the same anticancer drugs, so a person’s treatment may include a combination of drugs.  Common CNS chemotherapeutics include temozolomide, carmustine (also called BCNU), lomustine, tamoxifen, carboplatin, methotrexate, procarbazine, and vincristine.  Individuals should be sure to discuss all options with their medical team.

Side effects of chemotherapy may include hair loss, nausea, digestive problems, reduced bone marrow production, and fatigue.  The treatment can also harm normal cells that are growing or dividing at the same time, but these cells usually recover and problems stop once the treatment has ended.

Alternative and complementary approaches may help tumor patients better cope with their diagnosis and treatment.  Some of these therapies, however, may be harmful if used during or after cancer treatment and should be discussed with a doctor beforehand.  Common approaches include nutritional and herbal supplements, vitamins, special diet, and mental or physical techniques to reduce stress.

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What is the prognosis?


Each person is different.  Prognosis depends greatly on prompt diagnosis and treatment, the individual’s age and general health, whether the tumor is malignant or benign, tumor size and location, tumor grade, and response to therapy.  An individual whose entire tumor has been removed successfully may recover completely.  Generally, prognosis is poorer in very young children and in older individuals.  Rehabilitation and counseling can help patients and family members better cope with the disorder and improve quality of life.

Continued monitoring and long-term follow-up is advised as many tumors resist treatment and tend to recur.

Normal tissue and nerves that may have been damaged or traumatized by the tumor or its treatment will need time to heal.  Some post-treatment symptoms will disappear over time.  Physical therapy can help people regain motor skills, muscle strength, and balance.  Some individuals may need to relearn how to swallow or speak if the brain’s cognitive areas have been affected.  Occupational therapy can teach people new ways to perform tasks.   Supportive care can help people manage any pain and other symptoms.

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What Research is Being Done?


Scientists continue to investigate ways to better understand, diagnose, and treat CNS tumors.  Several of today’s treatment regimens were experimental therapies only a decade ago.  Current clinical studies of genetic risk factors, environmental causes, and molecular mechanisms of cancers may translate into tomorrow’s treatment of, or perhaps cure for, these tumors.

Much of this work is supported by the National Institutes of Health (NIH), through the collaborative efforts of its National Institute of Neurological Disorders and Stroke (NINDS) and National Cancer Institute (NCI), as well as other agencies within the Federal government, nonprofit groups, pharmaceutical companies, and private institutions.   Some of this research is conducted through the collaborative neuroscience and cancer research community at the NIH or through research grants to academic centers throughout the United States .

The jointly sponsored NCI-NINDS Neuro-Oncology Branch coordinates research to develop and test the effectiveness and safety of novel therapies for people with CNS tumors.  These experimental treatment options may include new drugs, combination therapy, gene therapy, biologic immuno-agents, surgery, and radiation.  Information about these trials, and trials involving other disorders, can be accessed at the Federal government’s database of clinical trials, http://clinicaltrials.gov.

Part of this research involves creating a comprehensive public database of clinical, molecular, and genetic information on brain tumors to help researchers and clinicians identify and evaluate molecular targets in brain cancer.   The joint NCI-NINDS Repository for Molecular Brain Neoplasia Data (REMBRANDT) will hold genetic and molecular analysis of samples from brain tumor patients in NCI-sponsored clinical trials in what is slated to become the largest clinical/genetic corollary study ever conducted on brain tumors.   It will also store a wide array of molecular and genetic data regarding all types of brain tumors.   Understanding the biology behind these tumors will provide clues to new therapeutic approaches.

Researchers are also developing mouse models that mimic human CNS cancers, which may speed discovery of potential treatments in humans. 

Beyond their efforts to develop needed resources, scientists at the NIH and at universities across the US are are exploring a variety of approaches to treat CNS tumors.  These experimental approaches include boosting the immune system to better fight tumor cells, developing therapies that target the tumor cell while sparing normal cells, making improvements in radiation therapy, disabling the tumor using genes attached to viruses, and defining biomarkers that may predict the response of a CNS tumor to a particular treatment.

Biological therapy involves enhancing the body’s overall immune response to recognize and fight cancer cells.  The immune system is designed to attack foreign substances in the body; since cancer cells aren’t foreign, they usually do not generate much of an immune response.  Researchers are using different methods to provoke a strong immune response to tumor cells.  Such proteins as interleukin and interferon, both of which are immune system “messengers” called cytokines, and other substances can stimulate and restore the body’s natural response against proteins on the surfaces of cancer cells and thus slow tumor growth.  Other therapy uses viruses, T-cells (a major component of immune system function), and other substances to increase immune response and target the tumor cells.  Scientists are also experimenting with genetically altered T-cells from the patient’s own body, which are cultured with an antigen and injected directly into the brain following surgery.  Biological therapies to fight CNS tumors include vaccines, gene therapy, antibody therapy, and tumor growth factors.

Antibodies are proteins that are normally produced by the body to ward off bacteria and viruses.   Monoclonal antibodies are multiple copies of a single antibody that act as a homing device to fit one—and only one—type of antigen (a protein on the surface of the tumor cell that stimulates the immune system response).  Scientists at the NINDS and elsewhere are linking these antibodies to immunotoxins that seek out tumor cells with a matching antigen, bind to these tumor cells, and deliver their toxin, with minimal damage to surrounding normal cells.  Additional approaches include attaching a radioactive substance to the antibodies, which act as targeting agents to deliver radiation to the tumor cell.

Gene therapy (also called gene transfer) aims to deliver a suicide gene to the tumor cell.  It can also be used to boost the immune system.  A gene whose activity can be influenced to kill the cell is integrated into a virus that can cross the blood-brain barrier (an elaborate network of fine blood vessels and cells that filters the blood reaching the CNS) and travel to the tumor.  Delivery methods under investigation include viruses and stem cells.  Gene therapy may become an important add-on therapy for individuals who do not respond well to other treatments.

Scientists are testing the effectiveness of vaccine therapy for a variety of CNS tumors.  Vaccine therapy strengthens the immune response by inserting an antigen that the body will attack.  Some vaccines target a specific antigen, while others, using the whole tumor cell to make the vaccine, hope to target multiple antigens which the tumor may express.  Research has shown the vaccine can be genetically engineered with tumor antigens and injected into the body to induce an immune response, which increases the attack on antigens expressed on the surface of the tumor cell.  Experimental CNS tumor vaccines include those designed to stimulate an immune response to a particular protein or antigen, and dendritic cell vaccines (in which blood cells are taken from the body, processed in a laboratory and given back to the patient to break up the tumor cell outer protein into smaller pieces, which increases targeting by immune cells).  

Findings from NIH-sponsored research on adult CNS tumor development and treatment suggest the immune system and, potentially, infection with the cytomegalovirus may play a critical role in certain tumor-type risk and prognosis.  Repeated stimulation of the immune system to counter this herpes virus may serve as a tumor promotion factor.  Scientists hope to identify immune factors and develop targeted immunotherapies for this disease.

Targeted therapy uses different molecules to reduce tumor gene expression and suppress uncontrolled growth by killing or reducing the production of tumor cells.  Of particular interest to scientists is the development of tailored therapeutics—involving a combination of targeted agents—to treat tumors based on tehir genetic make-up.  Specifically, molecularly targeted drugs seek out the molecular and cellular changes that convert normal cells into cancer.  Many targeted cancer therapies are being tested in animals for use alone or in combination with other cancer treatments, such as chemotherapy.  Researchers hope to discover tumor-specific cellular or molecular pathways that can be used to increase drug delivery and to find ways to identify patients who may benefit from combined therapy.  Targeted therapies include oncogenes, growth factors, and molecules aimed at blocking gene activity.

Growth factors often govern normal cell growth.  Growth factors are released from either the cell or the surrounding tissue.  Cancer cells can either secrete these growth factors or respond to them, enabling   them to divide out of control.  A number of tumor growth factors have been identified, including those that trigger nerve tissue growth and stimulate blood vessels to grow (a process called angiogenesis).  Researchers continue to identify and develop agents that can block these factors. 

Anti-angiogenetic compounds block blood vessel growth and the flow of nutrients and oxygen to the tumor, and may also hamper cell signaling and stop tumor cells from spreading elsewhere in the body.  Clinical trials have shown that anti-angiogenetics can improve the outcome for glioblastoma multiforme tumors that recur following initial treatment with radiation and chemotherapy.  More than a dozen such compounds have been identified, including bevacizumab, interferon, and endostatin.  Researchers are studying the combination of anti-angiogenics and radiation or chemotherapy in treating newly diagnosed brain tumors.  Other research is testing angiogenic inhibitors that have had positive results in adults on children with primary CNS tumors and in patients with tumors that haven't responded well to other tumor treatment.

Oncogenes are transformed genes that are involved in cell growth and cause normal cells to divide uncontrolled and become malignant, either through mutation or over-expression.  Researchers have identified specific events that lead to this mutation and are developing diagnostic and therapeutic screening tools. 

Certain enzymes that are involved in cell division or the copying of genetic information may be over-produced in cancer cells, causing gene mutations and uncontrolled cell growth.  Several different types of kinase inhibitors—proteins that block growth-signaling enzymes without harming normal cells—have been identified and approved for cancer treatment.  Scientists are testing protein-level kinase inhibitors to see of they make CNS tumors more sensitive to chemotherapy.  Clinical trials for brain tumors are studying the safety and effectiveness of kinase inhibitors in children with CNS tumors and in other patients with recurring or hard to treat tumors.

Anti-sense oligonucleotide technology uses short fragments of nucleic acid molecules to block gene expression in specific cells and prevent tumor growth.  Unlike gene therapy, anti-sense oligonucleotide technology does not replace or substitute genetic material but inhibits the expression of select targets.  This technology (also known as RNA interference, siRNA, or shRNA) may help scientists to identify additional genes involved in tumor formation and improve drug delivery with fewer side effects.

Of particular interest are microRNAs (or miRNAs)—naturally occurring molecules that regulate gene expression and are involved in the formation and development of tumor stem cells.  Researchers are using miRNAs to switch off tumor stem cell activity.   Researchers are studying miRNAs as a possible diagnostic and therapeutic strategy for brain tumors and other forms of cancer.

Biomarkers are molecules or others substances in the blood or tissue that can be used to diagnose or monitor a particular disorder, among other functions.  As cells become cancerous, they can release unique proteins and other molecules into the body which scientists use to speed diagnosis and treatment.  Some CNS tumor biomarkers have been found, such as the epithelial growth factor receptor (EGRF) gene.  Researchers continue to search for additional clinical biomarkers of CNS tumors, to better assess risk from environmental toxins and other possible causes, and monitor and predict the outcome of CNS tumor treatment.  NINDS-funded research has recently shown that mutation analysis of EGFR can be used to predict which tumors are most likely to respond to a specific class of cancer-fighting drugs.   Identifying biomarkers may also lead to the development of new models of disease and novel therapies for tumor treatment.

Radiation therapy research incluces testing several new anticancer drugs, either independently or in combination with other drugs.  Researchers are also testing different drugs in combination with other therapies and are investigating combined therapies such as radiation and radiosurgery to effectively treat CNS tumors.  Research areas being explored include tomotherapy, boron nuclear capture therapy, liquid radiation therapy, and the use of radiosensitizers.

Radiosensitizers are drugs that make rapidly dividing tumor tissue more vulnerable to radiation.  Early studies using radiosensitizers produced mixed results.  While some trials suggested these drugs may improve survival in certain patients, other trials were found to have little benefit.  Scientists are now testing an experimental drug that increases the amount of oxygen that is released from the blood into the tissues, making cancer cells more responsive to radiation and chemotherapy.  Studies show the lack of oxygen in a tumor can make radiation therapy less effective.

Tomotherapy combines CT scanning and intensity modulated radiation therapy to deliver small beams of high-dose radiation to the tumor while greatly reducing radiation exposure to surrounding tissue.  Studies are examining the effectiveness of radiation delivery through tomotherapy and to see if long-term side effects of radiation therapy can be reduced.

Boron Neutron Capture Therapy (BNCT) is an experimental treatment that uses fission to kill tumor cells.  An amino acid or other drug that carries boron is injected into the patient, where it collects more readily in tumor cells than in regular tissue.  A beam of low-energy neutrons is directed at the tumor from outside the body, causing the boron atoms to split (called neutron capture) and send high amounts of energy into the cancerous cells.  Radiation damage to surrounding cells is extremely small.  BNCT is being tested as a post-surgery treatment for patients with certain head and neck tumors.  If successful, BNCT could someday be used to treat children with brain tumors.

Liquid radiation therapy is an experimental treatment that uses a balloon catheter to deliver internal radiation therapy to the cavity that remains following tumor surgery.  A radioactive liquid is injected into the catheter and molds the balloon to the exact edges of the cavity.  The liquid stays in the balloon for several days until it and the catheter are removed.

Chemotherapeutic drug research focuses on ways to better deliver drugs across the blood-brain barrier and into the site of the tumor.  Since chemotherapeutic drugs work in different ways to stop tumor cells from dividing, several trials are testing whether giving more than one drug, and perhaps giving them in different ways (such as staggered delivery and low-dose, long-term treatment), may kill more tumor cells without causing or lessening damaging side effects than present therapy.  Researchers are examining different levels of chemotherapeutic drugs to determine if they are less toxic to normal tissue when combined with other cancer treatments.  Other studies are investigating gene therapy as a way to make cancer cells more sensitive to chemotherapy.  Research areas include differentiating drugs, osmotic blood-brain barrier disruption, and convection enhanced delivery.

Differentiating drugs change dividing cells into non-dividing cells and can halt tumor growth.  An early study using retinoids (made from vitamin A) as an independent treatment for certain tumors showed no significant effect.  Scientists are trying retinoids in combination with other chemotherapeutic drugs or treatments to slow the growth of malignant glioma.

Researchers are testing different drugs and molecules to see if they can modulate the normal activity of the blood-brain barrier and better target tumor cells and associated blood vessels. 

Osmotic blood-brain barrier disruption uses certain drugs to open blood vessels throughout the brain.  Scientists are currently studying whether certain chemotherapeutic drugs, when given with osmotic blood-brain barrier disruption, might be an effective way to kill cancer cells without harmful side effects.

Convection enhanced delivery sends a continuous, uniform stream of toxic drugs into the tumor via catheters that are inserted during surgery.  This drug delivery system, which bypasses the blood-brain barrier, is being evaluated in children with recurring brain cancer and in patients whose tumor location prevents its total surgical removal.

Also under investigation are ways to help the body respond to improved drug delivery or other cancer treatments.  Bone marrow and stem cell transplants may replace blood-forming cells that are killed by chemotherapy, radiation treatment, or a combination of therapies.  These transplants, which are given after radiation or chemotherapy, help the patient’s bone marrow recover and produce healthy blood cells.  Researchers are studying the effectiveness of these transplants in protecting blood cells in children with certain types of CNS tumors and in other patients with recurrent or hard to treat CNS cancer, who receive higher than normal doses of chemotherapy.

Although many new approaches to treatment appear promising, it is important to remember that all potential therapies must stand the tests of well-designed, carefully controlled clinical trials and long-term follow-up of treated patients before any conclusions can be drawn about their safety or effectiveness.   New trial designs are also being developed to more quickly evaluate novel agents and may involve pre-selection of patients based on the molecular abnormality in their tumor.

Past research has led to improved tumor treatments and techniques for many individuals with CNS tumors.   Current research promises to generate further improvements.   In the years ahead, physicians and individuals who have a CNS tumor can look forward to new, more effective, less toxic forms of therapy developed through a better molecular understanding of the unique traits of CNS tumors.

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[1] Cellular Phone Use and Cancer Risk:  Update of a Danish Nationwide Cohort. Schüz et. al., Journal of the National Cancer Institute, Vol. 98, No. 23, December 6, 2006, pp. 1703-1713.

[2] Central Brain Tumor Registry of the United States, 2005-2006

[3] American Brain Tumor Foundation, 2008

[3] Central Brain Tumor Registry of the United States, 2005-2006

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at: BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

National Cancer Institute (NCI)
National Institutes of Health, DHHS
6116 Executive Boulevard, Ste. 3036A, MSC 8322
Bethesda, MD   20892-8322
cancergovstaff@mail.nih.gov
http://cancer.gov
Tel: 800-4-CANCER (422-6237) 800-332-8615 (TTY)

American Brain Tumor Association (ABTA)
2720 River Road
Suite 146
Des Plaines, IL   60018-4117
info@abta.org
http://www.abta.org
Tel: 847-827-9910 800-886-2282
Fax: 847-827-9918
Funds research for effective treatment and prevention of brain tumors and assists patients in finding and evaluating the best treatment options.

Brain Tumor Society
124 Watertown Street
Suite 2D
Watertown, MA   02472-2500
info@braintumor.org
http://www.tbts.org
Tel: 617-924-9997 800-770-TBTS (8287)
Fax: 617-924-9998
National non-profit providing resources and services to patients, survivors, friends, and professionals. Also funds basic science and translational brain tumor research.

Childhood Brain Tumor Foundation
20312 Watkins Meadow Drive
Germantown, MD   20876
cbtf@childhoodbraintumor.org
http://www.childhoodbraintumor.org
Tel: 877-217-4166 301-515-2900
Non-profit organization that raises funds for scientific and clinical research to improve both prognosis and quality of life for those affected by pediatric brain tumors. Works to heighten public awareness and provides information and resources for families and patients.

Children's Brain Tumor Foundation
274 Madison Avenue
Suite 1004
New York, NY   10016
info@cbtf.org
http://www.cbtf.org
Tel: 212-448-9494 866-CBT-HOPE (228-4673)
Fax: 212-448-1022
Works to improve the treatment, quality of life, and long-term outlook for children with brain and spinal cord tumors through research, support, education, and advocacy programs.

Katie's Kids for the Cure/ National Fund for Pediatric Brain Tumor Research
3741 Walnut Street
Box 612
Philadelphia, PA   19104
info@katieskids.org
http://www.katieskids.org
Tel: 877-KTS-KIDS (587-5437) 610-831-9026
Fax: 215-689-1454
Funds innovative and creative brain tumor research, both clinical and basic science.

National Brain Tumor Foundation (NBTF)
22 Battery Street
Suite 612
San Francisco, CA   94111-5520
nbtf@braintumor.org
http://www.braintumor.org
Tel: 415-834-9970 800-934-CURE (2873)
Fax: 415-834-9980
Non-profit organization dedicated to supporting people whose lives have been affected by brain tumors. Provides support and education for patients, their families, and friends and raises funds for research to treat and cure brain tumors.

Musella Foundation for Brain Tumor Research and Information
1100 Peninsula Blvd.
Hewlett, NY   11557
musella@virtualtrials.com
http://www.virtualtrials.com
Tel: 516-295-4740 888-295-4740
Fax: 516-295-2870
Non-profit organization dedicated to improving the quality of life and survival times for brain tumor patients by providing information to patients and their families and raising money for brain tumor research.

American Cancer Society
National Home Office
250 Williams Street, NW
Atlanta, GA   30303-1002
http://www.cancer.org
Tel: 800-ACS-2345 (227-2345)
Nationwide community-based voluntary health organization dedicated to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and service.

International RadioSurgery Association
3002 N. Second Street
Harrisburg, PA   17110
office1@irsa.org
http://www.irsa.org
Tel: 717-260-9808
Fax: 717-260-9809
Proactive patient organization providing information and referrals on Gamma Knife, Linac, and particle beam radiosurgery for brain tumors, arteriovenous malformations (AVMs), and neurological pain and movement disorders.

Cushing's Support and Research Foundation
65 East India Row
Suite 22B
Boston, MA   02110-3389
cushinfo@csrf.net
http://csrf.net
Tel: 617-723-3674
Fax: same as phone
Provides information and support for Cushing's Disease and Cushing's Syndrome patients and their families and works to increase awareness and educate the public.

Pediatric Brain Tumor Foundation
302 Ridgefield Court
Asheville, NC   28806
familysupport@pbtfus.org
http://www.pbtfus.org
Tel: 828-665-6891 800-253-6530
Fax: 828-665-6894
Committed to providing hope for the thousands of children and families affected by brain tumor.

Pituitary Network Association
P.O. Box 1958
Thousand Oaks, CA   91358
rnr@pituitary.org
http://www.pituitary.org
Tel: 805-499-9973
Fax: 805-480-0633
International non-profit organization for patients with pituitary disorders, their families, loved ones, and the physicians and health care providers who treat them.

Preuss Foundation, Inc. [For Brain Tumor Research]
2223 Avenida de la Playa
Suite 220
La Jolla, CA   92037
fari@preuss.org
Tel: 858-454-0200
Fax: 858-454-4449
Provides forums for basic brain tumor researchers in an effort to increase communication and collaboration among them.



 

Cerebral Aneurysm
What is a cerebral aneurysm?
What causes a cerebral aneurysm?
How are aneurysms classified?
Who is at risk?
What are the dangers?
What are the symptoms?
How are cerebral aneurysms diagnosed?
How are cerebral aneurysms treated?
Can cerebral aneurysms be prevented?
What is the prognosis?
What research is being done?
Where can I get more information?

What is a cerebral aneurysm?


A cerebral aneurysm (also known as an intracranial or intracerebral aneurysm) is a weak or thin spot on a blood vessel in the brain that balloons out and fills with blood.  The bulging aneurysm can put pressure on a nerve or surrounding brain tissue.  It may also leak or rupture, spilling blood into the surrounding tissue (called a hemorrhage).  Some cerebral aneurysms, particularly those that are very small, do not bleed or cause other problems.  Cerebral aneurysms can occur anywhere in the brain, but most are located along a loop of arteries that run between the underside of the brain and the base of the skull.

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What causes a cerebral aneurysm?


Most cerebral aneurysms are congenital, resulting from an inborn abnormality in an artery wall.  Cerebral aneurysms are also more common in people with certain genetic diseases, such as connective tissue disorders and polycystic kidney disease, and certain circulatory disorders, such as arteriovenous malformations.[1]

Other causes include trauma or injury to the head, high blood pressure, infection, tumors, atherosclerosis (a blood vessel disease in which fats build up on the inside of artery walls) and other diseases of the vascular system, cigarette smoking, and drug abuse.  Some investigators have speculated that oral contraceptives may increase the risk of developing aneurysms.

Aneurysms that result from an infection in the arterial wall are called mycotic aneurysms.  Cancer-related aneurysms are often associated with primary or metastatic tumors of the head and neck.  Drug abuse, particularly the habitual use of cocaine, can inflame blood vessels and lead to the development of brain aneurysms.


[1] A congenital malformation in which a snarled tangle of arteries and veins in the brain disrupts blood flow.
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How are aneurysms classified?


There are three types of cerebral aneurysm.  A saccular aneurysm is a rounded or pouch-like sac of blood that is attached by a neck or stem to an artery or a branch of a blood vessel.  Also known as a berry aneurysm (because it resembles a berry hanging from a vine), this most common form of cerebral aneurysm is typically found on arteries at the base of the brain.  Saccular aneurysms occur most often in adults.  A lateral aneurysm appears as a bulge on one wall of the blood vessel, while a fusiform aneurysm is formed by the widening along all walls of the vessel.

Aneurysms are also classified by size.  Small aneurysms are less than 11 millimeters in diameter (about the size of a standard pencil eraser), larger aneurysms are 11-25 millimeters (about the width of a dime), and giant aneurysms are greater than 25 millimeters in diameter (more than the width of a quarter).

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Who is at risk?


Brain aneurysms can occur in anyone, at any age.  They are more common in adults than in children and slightly more common in women than in men.  People with certain inherited disorders are also at higher risk.

All cerebral aneurysms have the potential to rupture and cause bleeding within the brain.  The incidence of reported ruptured aneurysm is about 10 in every 100,000 persons per year (about 27,000 patients per year in the U.S. ), most commonly in people between ages 30 and 60 years.  Possible risk factors for rupture include hypertension, alcohol abuse, drug abuse (particularly cocaine), and smoking.  In addition, the condition and size of the aneurysm affects the risk of rupture.

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What are the dangers?


Aneurysms may burst and bleed into the brain, causing serious complications including hemorrhagic stroke, permanent nerve damage, or death.  Once it has burst, the aneurysm may burst again and rebleed into the brain, and additional aneurysms may also occur.  More commonly, rupture may cause a subarachnoid hemorrhage—bleeding into the space between the skull bone and the brain.  A delayed but serious complication of subarachnoid hemorrhage is hydrocephalus, in which the excessive buildup of cerebrospinal fluid in the skull dilates fluid pathways called ventricles that can swell and press on the brain tissue.  Another delayed postrupture complication is vasospasm, in which other blood vessels in the brain contract and limit blood flow to vital areas of the brain.  This reduced blood flow can cause stroke or tissue damage.

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What are the symptoms?


Most cerebral aneurysms do not show symptoms until they either become very large or burst.  Small, unchanging aneurysms generally will not produce symptoms, whereas a larger aneurysm that is steadily growing may press on tissues and nerves.  Symptoms may include pain above and behind the eye; numbness, weakness, or paralysis on one side of the face; dilated pupils; and vision changes.  When an aneurysm hemorrhages, an individual may experience a sudden and extremely severe headache, double vision, nausea, vomiting, stiff neck, and/or loss of consciousness.  Patients usually describe the headache as “the worst headache of my life” and it is generally different in severity and intensity from other headaches patients may experience.  “Sentinel” or warning headaches may result from an aneurysm that leaks for days to weeks prior to rupture.  Only a minority of patients have a sentinel headache prior to aneurysm rupture.

Other signs that a cerebral aneurysm has burst include nausea and vomiting associated with a severe headache, a drooping eyelid, sensitivity to light, and change in mental status or level of awareness.  Some individuals may have seizures.  Individuals may lose consciousness briefly or go into prolonged coma.  People experiencing this “worst headache,” especially when it is combined with any other symptoms, should seek immediate medical attention.

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How are cerebral aneurysms diagnosed?


Most cerebral aneurysms go unnoticed until they rupture or are detected by brain imaging that may have been obtained for another condition.  Several diagnostic methods are available to provide information about the aneurysm and the best form of treatment.  The tests are usually obtained after a subarachnoid hemorrhage, to confirm the diagnosis of an aneurysm.

Angiography is a dye test used to analyze the arteries or veins.  An intracerebral angiogram can detect the degree of narrowing or obstruction of an artery or blood vessel in the brain, head, or neck, and can identify changes in an artery or vein such as a weak spot like an aneurysm.  It is used to diagnose stroke and to precisely determine the location, size, and shape of a brain tumor, aneurysm, or blood vessel that has bled.  This test is usually performed in a hospital angiography suite.  Following the injection of a local anesthetic, a flexible catheter is inserted into an artery and threaded through the body to the affected artery.  A small amount of contrast dye (one that is highlighted on x-rays) is released into the bloodstream and allowed to travel into the head and neck.  A series of x-rays is taken and changes, if present, are noted.

Computed tomography (CT) of the head is a fast, painless, noninvasive diagnostic tool that can reveal the presence of a cerebral aneurysm and determine, for those aneurysms that have burst, if blood has leaked into the brain.  This is often the first diagnostic procedure ordered by a physician following suspected rupture.  X-rays of the head are processed by a computer as two-dimensional cross-sectional images, or “slices,” of the brain and skull.  Occasionally a contrast dye is injected into the bloodstream prior to scanning.  This process, called CT angiography, produces sharper, more detailed images of blood flow in the brain arteries.  CT is usually conducted at a testing facility or hospital outpatient setting.

Magnetic resonance imaging (MRI) uses computer-generated radio waves and a powerful magnetic field to produce detailed images of the brain and other body structures.  Magnetic resonance angiography (MRA) produces more detailed images of blood vessels.  The images may be seen as either three-dimensional pictures or two-dimensional cross-slices of the brain and vessels.  These painless, noninvasive procedures can show the size and shape of an unruptured aneurysm and can detect bleeding in the brain.

Cerebrospinal fluid analysis may be ordered if a ruptured aneurysm is suspected.  Following application of a local anesthetic, a small amount of this fluid (which protects the brain and spinal cord) is removed from the subarachnoid space—located between the spinal cord and the membranes that surround it—by surgical needle and tested to detect any bleeding or brain hemorrhage.  In patients with suspected subarachnoid hemorrhage, this procedure is usually done in a hospital.

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How are cerebral aneurysms treated?


Not all cerebral aneurysms burst.  Some patients with very small aneurysms may be monitored to detect any growth or onset of symptoms and to ensure aggressive treatment of coexisting medical problems and risk factors.  Each case is unique, and considerations for treating an unruptured aneurysm include the type, size, and location of the aneurysm; risk of rupture; patient’s age, health, and personal and family medical history; and risk of treatment.

Two surgical options are available for treating cerebral aneurysms, both of which carry some risk to the patient (such as possible damage to other blood vessels, the potential for aneurysm recurrence and rebleeding, and the risk of post-operative stroke).

Microvascular clipping involves cutting off the flow of blood to the aneurysm.  Under anesthesia, a section of the skull is removed and the aneurysm is located.  The neurosurgeon uses a microscope to isolate the blood vessel that feeds the aneurysm and places a small, metal, clothespin-like clip on the aneurysm’s neck, halting its blood supply.  The clip remains in the patient and prevents the risk of future bleeding.  The piece of the skull is then replaced and the scalp is closed.  Clipping has been shown to be highly effective, depending on the location, shape, and size of the aneurysm.  In general, aneurysms that are completely clipped surgically do not return.

A related procedure is an occlusion, in which the surgeon clamps off (occludes) the entire artery that leads to the aneurysm.  This procedure is often performed when the aneurysm has damaged the artery.  An occlusion is sometimes accompanied by a bypass, in which a small blood vessel is surgically grafted to the brain artery, rerouting the flow of blood away from the section of the damaged artery.

Endovascular embolization is an alternative to surgery.  Once the patient has been anesthetized, the doctor inserts a hollow plastic tube (a catheter) into an artery (usually in the groin) and threads it, using angiography, through the body to the site of the aneurysm.  Using a guide wire, detachable coils (spirals of platinum wire) or small latex balloons are passed through the catheter and released into the aneurysm.  The coils or balloons fill the aneurysm, block it from circulation, and cause the blood to clot, which effectively destroys the aneurysm.  The procedure may need to be performed more than once during the patient’s lifetime.

Patients who receive treatment for aneurysm must remain in bed until the bleeding stops.  Underlying conditions, such as high blood pressure, should be treated.  Other treatment for cerebral aneurysm is symptomatic and may include anticonvulsants to prevent seizures and analgesics to treat headache.  Vasospasm can be treated with calcium channel-blocking drugs and sedatives may be ordered if the patient is restless.  A shunt may be surgically inserted into a ventricle several months following rupture if the buildup of cerebrospinal fluid is causing harmful pressure on surrounding tissue.  Patients who have suffered a subarachnoid hemorrhage often need rehabilitative, speech, and occupational therapy to regain lost function and learn to cope with any permanent disability.

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Can cerebral aneurysms be prevented?


There are no known ways to prevent a cerebral aneurysm from forming.  People with a diagnosed brain aneurysm should carefully control high blood pressure, stop smoking, and avoid cocaine use or other stimulant drugs.  They should also consult with a doctor about the benefits and risks of taking aspirin or other drugs that thin the blood.  Women should check with their doctors about the use of oral contraceptives.

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What is the prognosis?


An unruptured aneurysm may go unnoticed throughout a person’s lifetime.  A burst aneurysm, however, may be fatal or could lead to hemorrhagic stroke, vasospasm (the leading cause of disability or death following a burst aneurysm), hydrocephalus, coma, or short-term and/or permanent brain damage.

The prognosis for persons whose aneurysm has burst is largely dependent on the age and general health of the individual, other preexisting neurological conditions, location of the aneurysm, extent of bleeding (and rebleeding), and time between rupture and medical attention.  It is estimated that about 40 percent of patients whose aneurysm has ruptured do not survive the first 24 hours; up to another 25 percent die from complications within 6 months.  Patients who experience subarachnoid hemorrhage may have permanent neurological damage.  Other individuals may recover with little or no neurological deficit.  Delayed complications from a burst aneurysm may include hydrocephalus and vapospasm.  Early diagnosis and treatment are important.

Individuals who receive treatment for an unruptured aneurysm generally require less rehabilitative therapy and recover more quickly than persons whose aneurysm has burst.  Recovery from treatment or rupture may take weeks to months.

Results of the International Subarachnoid Aneurysm Trial (ISAT), sponsored primarily by health ministries in the United Kingdom, France, and Canada and announced in October 2002, found that outcome for patients who are treated with endovascular coiling may be superior in the short-term (1 year) to outcome for patients whose aneurysm is treated with surgical clipping.  Long-term results of coiling procedures are unknown and investigators need to conduct more research on this topic, since some aneurysms can recur after coiling.  Before treatment patients may want to consult with a specialist in both endovascular and surgical repair of aneurysms, to help provide greater understanding of treatment options.  (The American Association of Neurological Surgeons notes that most of the centers involved in the ISAT were in Europe [primarily in England], Australia, and Canada, and that results may not be applicable to patients in the United States, “where practice patterns, particularly in reference to the degree of sub-specialization of neurovascular surgeons in major centers, are different.”[1])


[1] American Association of Neurological Surgeons/Congress of Neurological Surgeons, “Position Statement on the International Subarachnoid Aneurysm Trial (ISAT),” November 5, 2002 .
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What research is being done?


The National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH) within the U.S. Department of Health and Human Services, is the nation’s primary supporter of research on the brain and nervous system.  As part of its mission, the NINDS conducts research on intracranial aneurysms and other vascular lesions of the nervous system and supports studies through grants to medical institutions across the country.

The NINDS recently sponsored the International Study of Unruptured Intracranial Aneurysms, which included more than 4,000 patients at 61 sites in the United States, Canada, and Europe.  The findings suggest that the risk of rupture for most very small aneurysms (less than 7 millimeters in size) is low.  The results also provide a more comprehensive look at these vascular defects and offer guidance to patients and physicians facing the difficult decision about whether or not to treat an aneurysm surgically.

NINDS scientists are studying the effects of an experimental drug in treating vasospasm that occurs following rupture of a cerebral aneurysm.  The drug, developed at the NIH, delivers nitric oxide to the arteries and has been shown to reverse and prevent brain artery spasms in animals. 

Other scientists hope to improve diagnosis and prediction of cerebral vasospasm by developing antibodies to molecules known to cause vasospasm.  These molecules can be detected in the cerebrospinal fluid of subarachnoid hemorrhage patients.  An additional study will compare standard treatment for subarachnoid hemorrhage to standard treatment plus transluminal balloon angioplasty immediately after severe bleeding.  Transluminal balloon angioplasty involves the insertion, via catheter, of a deflated balloon through the affected artery and into the clot.  The balloon is inflated to widen the artery and restore blood flow (the deflated balloon and catheter are then withdrawn).

Researchers are building a new, noninvasive, high-resolution x-ray detector system that can be used to guide the placement of stents (small tube-like devices that keep blood vessels open) used to modify blood flow during treatment for brain aneurysms.

Several groups of NINDS-funded researchers are conducting genetic linkage studies to identify risk factors for familial intracranial aneurysm and/or subarachnoid hemorrhage.  One study hopes to establish patterns of inheritance in patients of different ethnic backgrounds.  Another project is aimed at targeting and providing prevention and treatment strategies for persons who are genetically at high risk for the development of brain aneurysms.  And other investigators will establish a blood and tissue sampling bank for genetic linkage and molecular analyses.

Scientists are investigating the use of intraoperative hypothermia during microclip surgery as a means to improve the rate of recovery of cognitive functions and to reduce early and postoperative complications and neurological damage.  Other studies are investigating ways to improve or replace the coils used in endovascular embolization.

Additional research being funded by the NINDS includes the development of a new animal model of human saccular aneurysm, a new method for tissue processing that should allow routine evaluation of the biological response to implantation of occlusion devices, and a computer simulation model to evaluate the outcomes of neurosurgery in patients with cerebral aneurysms.

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at: BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

Brain Aneurysm Foundation
269 Hanover Street, Building 3
Hanover, MA   02339
office@bafound.org
http://www.bafound.org
Tel: 781-826-5556 888-BRAIN02 (272-4602)

American Stroke Association: A Division of American Heart Association
7272 Greenville Avenue
Dallas, TX   75231-4596
strokeassociation@heart.org
http://www.strokeassociation.org
Tel: 1-888-4STROKE (478-7653)
Fax: 214-706-5231

American Association of Neurological Surgeons
5550 Meadowbrook Drive
Rolling Meadows, IL   60008-3852
info@aans.org
http://www.aans.org
Tel: 847-378-0500/888-566-AANS (2267)
Fax: 847-378-0600

 

 

Cerebral Palsy

Introduction
What is Cerebral Palsy?
How Many People Have Cerebral Palsy?
What Are the Early Signs?
What Causes Cerebral Palsy?
What are the Risk Factors?
Can Cerebral Palsy Be Prevented?
What Are the Different Forms?
What Other Conditions Are Associated With Cerebral Palsy?
How Does a Doctor Diagnose Cerebral Palsy?
How is Cerebral Palsy Managed?
What Specific Treatments Are Available?
Drug Treatments
Surgery
Orthotic Devices
Assistive Technology
Alternative Therapies
Are There Treatments for Other Conditions Associated with Cerebral Palsy?
Do Adults with Cerebral Palsy Face Special Health Challenges?
What Research Is Being Done?
Where can I get more information?
Glossary

Introduction


 

In the 1860s, an English surgeon named William Little wrote the first medical descriptions of a puzzling disorder that struck children in the first years of life, causing stiff, spastic muscles in their legs and, to a lesser degree, in their arms. These children had difficulty grasping objects, crawling, and walking. Unlike most other diseases that affect the brain, this condition didn’t get worse as the children grew older.  Instead, their disabilities stayed relatively the same. 

The disorder, which was called Little's disease for many years, is now known as spastic diplegia. It is one of a group of disorders that affect the control of movement and are gathered under the umbrella term of “cerebral palsy.”      

Because it seemed that many of Little’s patients were born following premature or complicated deliveries, the doctor suggested their condition was the result of oxygen deprivation during birth, which damaged sensitive brain tissues controlling movement.  But in 1897, the famous psychiatrist Sigmund Freud disagreed. Noting that children with cerebral palsy often had other neurological problems such as mental retardation, visual disturbances, and seizures, Freud suggested that the disorder might have roots earlier in life, during the brain's development in the womb. "Difficult birth, in certain cases," he wrote, "is merely a symptom of deeper effects that influence the development of the fetus."

In spite of Freud’s observation, for many decades the belief that birth complications caused most cases of cerebral palsy was widespread among physicians, families, and even medical researchers.  In the 1980s, however, scientists funded by the National Institute of Neurological Disorders and Stroke (NINDS) analyzed extensive data from more than 35,000 newborns and their mothers, and discovered that complications during birth and labor accounted for only a fraction of the infants born with cerebral palsy — probably less than 10 percent. In most cases, they could find no single, obvious cause.

This finding challenged the accepted medical theory about the cause of cerebral palsy.  It also stimulated researchers to search for other factors before, during, and after birth that were associated with the disorder.      

Advances in imaging technology, such as magnetic resonance imaging (MRI), have given researchers a way to look into the brains of infants and children with cerebral palsy and discover unique structural malformations and areas of damage.  Basic science studies have identified genetic mutations and deletions associated with the abnormal development of the fetal brain.  These discoveries offer provocative clues about what could be going wrong during brain development to cause the abnormalities that lead to cerebral palsy. 

Much of this new understanding about what causes cerebral palsy is the result of research spanning the past two decades that has been sponsored by the NINDS, the federal government’s leading supporter of neurological research.  These findings from NINDS research have:

  • identified new causes and risk factors for cerebral palsy;
  • increased our understanding of how and why brain damage at critical stages of fetal development causes cerebral palsy;
  • refined surgical techniques to correct abnormalities in muscle and bone;
  • discovered new drugs to control stiff and spastic muscles and developed more precise methods to deliver them; and
  • tested the effectiveness of therapies used to treat cerebral palsy to discover which methods work best.

 

This brochure describes what cerebral palsy is, its causes, its treatments, and how it might possibly be prevented.  Medical terms in italics are defined in the glossary at the back of the booklet. 

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What is Cerebral Palsy?


 

Doctors use the term cerebral palsy to refer to any one of a number of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination but aren’t progressive, in other words, they don’t get worse over time.  The term cerebral refers to the two halves or hemispheres of the brain, in this case to the motor area of the brain’s outer layer (called the cerebral cortex), the part of the brain that directs muscle movement; palsy refers to the loss or impairment of motor function.    

Even though cerebral palsy affects muscle movement, it isn’t caused by problems in the muscles or nerves.  It is caused by abnormalities inside the brain that disrupt the brain’s ability to control movement and posture.

In some cases of cerebral palsy, the cerebral motor cortex hasn’t developed normally during fetal growth.  In others, the damage is a result of injury to the brain either before, during, or after birth.  In either case, the damage is not repairable and the disabilities that result are permanent.      

Children with cerebral palsy exhibit a wide variety of symptoms, including: 

  • lack of muscle coordination when performing voluntary movements (ataxia);
  • stiff or tight muscles and exaggerated reflexes (spasticity);
  • walking with one foot or leg dragging;
  • walking on the toes, a crouched gait, or a “scissored” gait;
  • variations in muscle tone, either too stiff or too floppy;
  • excessive drooling or difficulties swallowing or speaking;
  • shaking (tremor) or random involuntary movements; and
  • difficulty with precise motions, such as writing or buttoning a shirt.

 

The symptoms of cerebral palsy differ in type and severity from one person to the next, and may even change in an individual over time.  Some people with cerebral palsy also have other medical disorders, including mental retardation, seizures, impaired vision or hearing, and abnormal physical sensations or perceptions.   

Cerebral palsy doesn’t always cause profound disabilities.   While one child with severe cerebral palsy might be unable to walk and need extensive, lifelong care, another with mild cerebral palsy might be only slightly awkward and require no special assistance.

Cerebral palsy isn’t a disease.  It isn’t contagious and it can’t be passed from one generation to the next.  There is no cure for cerebral palsy, but supportive treatments, medications, and surgery can help many individuals improve their motor skills and ability to communicate with the world.   

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How Many People Have Cerebral Palsy?


 

The United Cerebral Palsy (UCP) Foundation estimates that nearly 800,000 children and adults in the United States are living with one or more of the symptoms of cerebral palsy. According to the federal government’s Centers for Disease Control and Prevention, each year about 10,000 babies born in the United States will develop cerebral palsy.

Despite advances in preventing and treating certain causes of cerebral palsy, the percentage of babies who develop the condition has remained the same over the past 30 years.  Improved care in neonatal intensive-care units has resulted in higher survival rates for very low birthweight babies.  Many of these infants will have developmental defects in their nervous systems or suffer brain damage that will cause the characteristic symptoms of cerebral palsy. 

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What Are the Early Signs?


 

The early signs of cerebral palsy usually appear before a child reaches 3 years of age.  Parents are often the first to suspect that their baby’s motor skills aren’t developing normally. Infants with cerebral palsy frequently have developmental delay, in which they are slow to reach developmental milestones such as learning to roll over, sit, crawl, smile, or walk.   Some infants with cerebral palsy have abnormal muscle tone as infants. Decreased muscle tone (hypotonia) can make them appear relaxed, even floppy. Increased muscle tone (hypertonia) can make them seem stiff or rigid. In some cases, an early period of hypotonia will progress to hypertonia after the first 2 to 3 months of life. Children with cerebral palsy may also have unusual posture or favor one side of the body when they move.

Parents who are concerned about their baby's development for any reason should contact their pediatrician.  A doctor can determine the difference between a normal lag in development and a delay that could indicate cerebral palsy.   

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What Causes Cerebral Palsy?


 

The majority of children with cerebral palsy are born with it, although it may not be detected until months or years later.  This is called congenital cerebral palsy.  In the past, if doctors couldn’t identify another cause, they attributed most cases of congenital cerebral palsy to problems or complications during labor that caused asphyxia (a lack of oxygen) during birth.  However, extensive research by NINDS scientists and others has shown that few babies who experience asphyxia during birth grow up to have cerebral palsy or any other neurological disorder. Birth complications, including asphyxia, are now estimated to account for only 5 to 10 percent of the babies born with congenital cerebral palsy.

A small number of children have acquired cerebral palsy, which means the disorder begins after birth.  In these cases, doctors can often pinpoint a specific reason for the problem, such as brain damage in the first few months or years of life, brain infections such as bacterial meningitis or viral encephalitis, or head injury from a motor vehicle accident, a fall, or child abuse.

What causes the remaining 90 to 95 percent?  Research has given us a bigger and more accurate picture of the kinds of events that can happen during early fetal development, or just before, during, or after birth, that cause the particular types of brain damage that will result in congenital cerebral palsy.  There are multiple reasons why cerebral palsy happens – as the result of genetic abnormalities, maternal infections or fevers, or fetal injury, for example.  But in all cases the disorder is the result of four types of brain damage that cause its characteristic symptoms:         

Damage to the white matter of the brain (periventricular leukomalacia [PVL]). The white matter of the brain is responsible for transmitting signals inside the brain and to the rest of the body.   PVL describes a type of damage that looks like tiny holes in the white matter of an infant’s brain.  These gaps in brain tissue interfere with the normal transmission of signals.  There are a number of events that can cause PVL, including maternal or fetal infection.  Researchers have also identified a period of selective vulnerability in the developing fetal brain, a period of time between 26 and 34 weeks of gestation, in which periventricular white matter is particularly sensitive to insults and injury.   

Abnormal development of the brain (cerebral dysgenesis).   Any interruption of the normal process of brain growth during fetal development can cause brain malformations that interfere with the transmission of brain signals.  The fetal brain is particularly vulnerable during the first 20 weeks of development.  Mutations in the genes that control brain development during this early period can keep the brain from developing normally.  Infections, fevers, trauma, or other conditions that cause unhealthy conditions in the womb also put an unborn baby’s nervous system at risk.    

Bleeding in the brain (intracranial hemorrhage).  Intracranial hemorrhage describes bleeding inside the brain caused by blocked or broken blood vessels.  A common cause of this kind of damage is fetal stroke.   Some babies suffer a stroke while still in the womb because of blood clots in the placenta that block blood flow.  Other types of fetal stroke are caused by malformed or weak blood vessels in the brain or by blood-clotting abnormalities.  Maternal high blood pressure (hypertension) is a common medical disorder during pregnancy that has been known to cause fetal stroke.  Maternal infection, especially pelvic inflammatory disease, has also been shown to increase the risk of fetal stroke.    

Brain damage caused by a lack of oxygen in the brain (hypoxic-ischemic encephalopathy or intrapartum asphyxia).   Asphyxia, a lack of oxygen in the brain caused by an interruption in breathing or poor oxygen supply, is common in babies due to the stress of labor and delivery.  But even though a newborn’s blood is equipped to compensate for short-term low levels of oxygen, if the supply of oxygen is cut off or reduced for lengthy periods, an infant can develop a type of brain damage called hypoxic-ischemic encephalopathy, which destroys tissue in the cerebral motor cortex and other areas of the brain.    This kind of damage can also be caused by severe maternal low blood pressure, rupture of the uterus, detachment of the placenta, or problems involving the umbilical cord.

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What are the Risk Factors?


 

Just as there are particular types of brain damage that cause cerebral palsy, there are also certain medical conditions or events that can happen during pregnancy and delivery that will increase a baby’s risk of being born with cerebral palsy.  Research scientists have examined thousands of expectant mothers, followed them through childbirth, and monitored their children’s early neurological development to establish these risk factors.  If a mother or her baby has any of these risk factors, it doesn’t mean that cerebral palsy is inevitable, but it does increase the chance for the kinds of brain damage that cause it. 

Low birthweight and premature birth.  The risk of cerebral palsy is higher among babies who weigh less than 5 ½ pounds at birth or are born less than 37 weeks into pregnancy. The risk increases as birthweight falls or weeks of gestation shorten. Intensive care for premature infants has improved dramatically over the course of the past 30 years.  Babies born extremely early are surviving, but with medical problems that can put them at risk for cerebral palsy.  Although normal- or heavier-weight babies are at relatively low individual risk for cerebral palsy, term or near-term babies still make up half of the infants born with the condition. 

Multiple births.   Twins, triplets, and other multiple births -- even those born at term -- are linked to an increased risk of cerebral palsy.   The death of a baby’s twin or triplet further increases the risk.

Infections during pregnancy.   Infectious diseases caused by viruses, such as toxoplasmosis, rubella (German measles), cytomegalovirus, and herpes, can infect the womb and placenta.  Researchers currently think that maternal infection leads to elevated levels of immune system cells called cytokines that circulate in the brain and blood of the fetus.  Cytokines respond to infection by triggering inflammation.  Inflammation may then go on to cause central nervous system damage in an unborn baby.  Maternal fever during pregnancy or delivery can also set off this kind of inflammatory response.

Blood type incompatibility.   Rh incompatibility is a condition that develops when a mother’s Rh blood type (either positive or negative) is different from the blood type of her baby.  Because blood cells from the baby and mother mix during pregnancy, if a mother is negative and her baby positive, for example, the mother’s system won’t tolerate the presence of Rh-positive red blood cells.  Her body will begin to make antibodies that will attack and kill her baby’s blood cells.  Rh incompatibility is routinely tested for and treated in the United States , but conditions in other countries continue to keep blood type incompatibility a risk factor for cerebral palsy.   

Exposure to toxic substances.   Mothers who have been exposed to toxic substances during pregnancy, such as methyl mercury, are at a heightened risk of having a baby with cerebral palsy. 

Mothers with thyroid abnormalities, mental retardation, or seizures.   Mothers with any of these conditions are slightly more likely to have a child with cerebral palsy.

There are also medical conditions during labor and delivery, and immediately after delivery, that act as warning signs for an increased risk of cerebral palsy.  Knowing these warning signs helps doctors keep a close eye on children who face a higher risk.  However, parents shouldn’t become too alarmed if their baby has one or more of these conditions at birth. Most of these children will not develop cerebral palsy. Warning signs include: 

Breech presentation.   Babies with cerebral palsy are more likely to be in a breech position (feet first) instead of head first at the beginning of labor.

Complicated labor and delivery.   A baby who has vascular or respiratory problems during labor and delivery may already have suffered brain damage or abnormalities.

Small for gestational age.   Babies born smaller than normal for their gestational age are at risk for cerebral palsy because of factors that kept them from growing naturally in the womb.

Low Apgar score.   The Apgar score is a numbered rating that reflects a newborn's condition.   To determine an Apgar score, doctors periodically check a baby's heart rate, breathing, muscle tone, reflexes, and skin color during the first minutes after birth. They then assign points; the higher the score, the more normal a baby's condition. A low score at 10-20 minutes after delivery is often considered an important sign of potential problems such as cerebral palsy.

Jaundice.  More than 50 percent of newborns develop jaundice after birth when bilirubin, a substance normally found in bile, builds up faster than their livers can break it down and pass it from the body.  Severe, untreated jaundice can cause a neurological condition known as kernicterus, which kills brain cells and can cause deafness and cerebral palsy. 

Seizures.   An infant who has seizures faces a higher risk of being diagnosed later in childhood with cerebral palsy.

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Can Cerebral Palsy Be Prevented?


 

Cerebral palsy related to genetic abnormalities is not preventable, but a few of the risk factors for congenital cerebral palsy can be managed or avoided.  For example, rubella, or German measles, is preventable if women are vaccinated against the disease before becoming pregnant.   Rh incompatibilities can also be managed early in pregnancy.  But there are still risk factors that can’t be controlled or avoided in spite of medical intervention. 

For example, the use of electronic fetal monitoring machines to keep track of an unborn baby’s heartbeat during labor, and the use of emergency cesarean section surgery when there are significant signs of fetal distress, haven’t lowered the numbers of babies born with cerebral palsy.  Interventions to treat other prenatal causes of cerebral palsy, such as therapies to prevent prenatal stroke or antibiotics to cure intrauterine infections, are either difficult to administer or haven’t yet been proven to lower the risk of cerebral palsy in vulnerable infants.    

Fortunately, acquired cerebral palsy, often due to head injury, is preventable using common safety tactics, such as using car seats for infants and toddlers, and making sure young children wear helmets when they ride bicycles.  In addition, common sense measures around the household, such as supervising babies and young children closely when they bathe, can reduce the risk of accidental injury.

Despite the best efforts of parents and physicians, however, children will still be born with cerebral palsy. Since in many cases the cause or causes of cerebral palsy aren’t fully known, little can currently be done to prevent it. As investigators learn more about the causes of cerebral palsy through basic and clinical research, doctors and parents will know more about how to prevent this disorder.

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What Are the Different Forms?


 

The specific forms of cerebral palsy are determined by the extent, type, and location of a child’s abnormalities.  Doctors classify cerebral palsy according to the type of movement disorder involved -- spastic (stiff muscles), athetoid (writhing movements), or ataxic (poor balance and coordination) -- plus any additional symptoms.   Doctors will often describe the type of cerebral palsy a child has based on which limbs are affected. The names of the most common forms of cerebral palsy use Latin terms to describe the location or number of affected limbs, combined with the words for weakened (paresis) or paralyzed (plegia).    For example, hemiparesis (hemi = half) indicates that only one side of the body is weakened.  Quadriplegia (quad = four) means all four limbs are paralyzed. 

Spastic hemiplegia/hemiparesis.   This type of cerebral palsy typically affects the arm and hand on one side of the body, but it can also include the leg.  Children with spastic hemiplegia generally walk later and on tip-toe because of tight heel tendons.  The arm and leg of the affected side are frequently shorter and thinner.  Some children will develop an abnormal curvature of the spine (scoliosis).  Depending on the location of the brain damage, a child with spastic hemiplegia may also have seizures.  Speech will be delayed and, at best, may be competent, but intelligence is usually normal.    

Spastic diplegia/diparesis.   In this type of cerebral palsy, muscle stiffness is predominantly in the legs and less severely affects the arms and face, although the hands may be clumsy.  Tendon reflexes are hyperactive.  Toes point up.  Tightness in certain leg muscles makes the legs move like the arms of a scissor.  Children with this kind of cerebral palsy may require a walker or leg braces.  Intelligence and language skills are usually normal. 

Spastic quadriplegia/quadriparesis.   This is the most severe form of cerebral palsy, often associated with moderate-to-severe mental retardation.  It is caused by widespread damage to the brain or significant brain malformations.   Children will often have severe stiffness in their limbs but a floppy neck.  They are rarely able to walk.  Speaking and being understood are difficult.  Seizures can be frequent and hard to control. 

Dyskinetic cerebral palsy (also includes athetoid, choreoathetoid, and dystonic cerebral palsies).  This type of cerebral palsy is characterized by slow and uncontrollable writhing movements of the hands, feet, arms, or legs.  In some children, hyperactivity in the muscles of the face and tongue makes them grimace or drool.  They find it difficult to sit straight or walk.  Children may also have problems coordinating the muscle movements required for speaking.  Intelligence is rarely affected in these forms of cerebral palsy.    

Ataxic cerebral palsy.   This rare type of cerebral palsy affects balance and depth perception. Children will often have poor coordination and walk unsteadily with a wide-based gait, placing their feet unusually far apart.  They have difficulty with quick or precise movements, such as writing or buttoning a shirt. They may also have intention tremor, in which a voluntary movement, such as reaching for a book, is accompanied by trembling that gets worse the closer their hand gets to the object. 

Mixed types.  It is common for children to have symptoms that don’t correspond to any single type of cerebral palsy.  Their symptoms are a mix of types.  For example, a child with mixed cerebral palsy may have some muscles that are too tight and others that are too relaxed, creating a mix of stiffness and floppiness.

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What Other Conditions Are Associated With Cerebral Palsy?


 

Many individuals with cerebral palsy have no additional medical disorders. However, because cerebral palsy involves the brain and the brain controls so many of the body’s functions, cerebral palsy can also cause seizures, impair intellectual development, and affect vision, hearing, and behavior.  Coping with these disabilities may be even more of a challenge than coping with the motor impairments of cerebral palsy. 

These additional medical conditions include:   

Mental retardation.  Two-thirds of individuals with cerebral palsy will be intellectually impaired.  Mental impairment is more common among those with spastic quadriplegia than in those with other types of cerebral palsy, and children who have epilepsy and an abnormal electroencephalogram (EEG) or MRI are also more likely to have mental retardation. 

Seizure disorder.   As many as half of all children with cerebral palsy have seizures.   Seizures can take the form of the classic convulsions of tonic-clonic seizures or the less obvious focal (partial) seizures, in which the only symptoms may be muscle twitches or mental confusion.

Delayed growth and development.   A syndrome called failure to thrive is common in children with moderate-to-severe cerebral palsy, especially those with spastic quadriparesis.   Failure to thrive is a general term doctors use to describe children who lag behind in growth and development.  In babies this lag usually takes the form of too little weight gain.  In young children it can appear as abnormal shortness, and in teenagers it may appear as a combination of shortness and lack of sexual development.

In addition, the muscles and limbs affected by cerebral palsy tend to be smaller than normal. This is especially noticeable in children with spastic hemiplegia because limbs on the affected side of the body may not grow as quickly or as long as those on the normal side.   

Spinal deformities.  Deformities of the spine -- curvature (scoliosis), humpback (kyphosis), and saddle back (lordosis) -- are associated with cerebral palsy.  Spinal deformities can make sitting, standing, and walking difficult and cause chronic back pain. 

Impaired vision, hearing, or speech.  A large number of children with cerebral palsy have strabismus, commonly called “cross eyes,” in which the eyes are misaligned because of differences between the left and right eye muscles. In an adult, strabismus causes double vision. In children, the brain adapts to the condition by ignoring signals from one of the misaligned eyes. Untreated, this can lead to poor vision in one eye and can interfere with the ability to judge distance. In some cases, doctors will recommend surgery to realign the muscles.   

Children with hemiparesis may have hemianopia, which is defective vision or blindness that blurs the normal field of vision in one eye.   In homonymous hemianopia, the impairment affects the same part of the visual field in both eyes.

Impaired hearing is also more frequent among those with cerebral palsy than in the general population.   Speech and language disorders, such as difficulty forming words and speaking clearly, are present in more than a third of those with cerebral palsy.  

Drooling.   Some individuals with cerebral palsy drool because they have poor control of the muscles of the throat, mouth, and tongue.  Drooling can cause severe skin irritation.  Because it is socially unacceptable, drooling may also isolate children from their peers.   

Incontinence.   A common complication of cerebral palsy is incontinence, caused by poor control of the muscles that keep the bladder closed. Incontinence can take the form of bed-wetting, uncontrolled urination during physical activities, or slow leaking of urine throughout the day.   

Abnormal sensations and perceptions.   Some children with cerebral palsy have difficulty feeling simple sensations, such as touch.  They may have stereognosia, which makes it difficult to perceive and identify objects using only the sense of touch. A child with stereognosia, for example, would have trouble closing his eyes and sensing the difference between a hard ball or a sponge ball placed in his hand.

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How Does a Doctor Diagnose Cerebral Palsy?


 

Early signs of cerebral palsy may be present from birth.  Most children with cerebral palsy are diagnosed during the first 2 years of life.  But if a child’s symptoms are mild, it can be difficult for a doctor to make a reliable diagnosis before the age of 4 or 5.  Nevertheless, if a doctor suspects cerebral palsy, he or she will most likely schedule an appointment to observe the child and talk to the parents about their child’s physical and behavioral development. 

Doctors diagnose cerebral palsy by evaluating a child’s motor skills and taking a careful and thorough look at their medical history. In addition to checking for the most characteristic symptoms -- slow development, abnormal muscle tone, and unusual posture -- a doctor also has to rule out other disorders that could cause similar symptoms.  Most important, a doctor has to determine that the child's condition is not getting worse. Although symptoms may change over time, cerebral palsy by definition is not progressive. If a child is continuously losing motor skills, the problem more likely begins elsewhere – such as a genetic or muscle disease, metabolism disorder, or tumors in the nervous system. A comprehensive medical history, special diagnostic tests, and, in some cases, repeated check-ups can help confirm that other disorders are not at fault.

Additional tests are often used to rule out other movement disorders that could cause the same symptoms as cerebral palsy.  Neuroimaging techniques that allow doctors to look into the brain (such as an MRI scan) can detect abnormalities that indicate a potentially treatable movement disorder.  If it is cerebral palsy, an MRI scan can also show a doctor the location and type of brain damage.

Neuroimaging methods include:

  • Cranial ultrasound.   This test is used for high-risk premature infants because it is the least intrusive of the imaging techniques, although it is not as successful as the two methods described below at capturing subtle changes in white matter – the type of brain tissue that is damaged in cerebral palsy. 
  • Computed tomography (CT) scan.   This technique creates images that show the structure of the brain and the areas of damage.
  • Magnetic resonance imaging (MRI) scan.   This test uses a computer, a magnetic field, and radio waves to create an anatomical picture of the brain's tissues and structures.    Doctors prefer MRI imaging because it offers finer levels of detail.

On rare occasions, metabolic disorders can masquerade as cerebral palsy and some children will require additional tests to rule them out.  Most of the childhood metabolic disorders have characteristic brain abnormalities or malformations that will show up in an MRI.    

Other types of disorders can also be mistaken for cerebral palsy.  For example, coagulation disorders (which prevent blood from clotting) can cause prenatal or perinatal strokes that damage the brain and cause symptoms characteristic of cerebral palsy.  Because stroke is so often the cause of hemiplegic cerebral palsy, a doctor may find it necessary to perform diagnostic testing on children with this kind of cerebral palsy to rule out the presence of a coagulation disorder.  If left undiagnosed, coagulation disorders can cause additional strokes and more extensive brain damage. 

To confirm a diagnosis of cerebral palsy, a doctor may refer a child to additional doctors with specialized knowledge and training, such as a child neurologist, developmental pediatrician, ophthalmologist (eye doctor), or otologist (ear doctor).  Additional observations help a doctor make a more accurate diagnosis and begin to develop a specific plan for treatment.

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How is Cerebral Palsy Managed?


 

Cerebral palsy can’t be cured, but treatment will often improve a child's capabilities.   Many children go on to enjoy near-normal adult lives if their disabilities are properly managed. In general, the earlier treatment begins, the better chance children have of overcoming developmental disabilities or learning new ways to accomplish the tasks that challenge them.   

There is no standard therapy that works for every individual with cerebral palsy.  Once the diagnosis is made, and the type of cerebral palsy is determined, a team of health care professionals will work with a child and his or her parents to identify specific impairments and needs, and then develop an appropriate plan to tackle the core disabilities that affect the child’s quality of life.   

A comprehensive management plan will pull in a combination of health professionals with expertise in the following:   

physical therapy to improve walking and gait, stretch spastic muscles, and prevent deformities; 

occupational therapy to develop compensating tactics for everyday activities such as dressing, going to school, and participating in day-to-day activities; 

speech therapy to address swallowing disorders, speech impediments, and other obstacles to communication; 

counseling and behavioral therapy to address emotional and psychological needs and help children cope emotionally with their disabilities;

drugs to control seizures, relax muscle spasms, and alleviate pain;

surgery to correct anatomical abnormalities or release tight muscles;

braces and other orthotic devices to compensate for muscle imbalance, improve posture and walking, and increase independent mobility;

mechanical aids such as wheelchairs and rolling walkers for individuals who are not independently mobile; and

communication aids such as computers, voice synthesizers, or symbol boards to allow severely impaired individuals to communicate with others.  

Doctors use tests and evaluation scales to determine a child’s level of disability, and then make decisions about the types of treatments and the best timing and strategy for interventions.  Early intervention programs typically provide all the required therapies within a single treatment center.  Centers also focus on parents’ needs, often offering support groups, babysitting services, and respite care.   

The members of the treatment team for a child with cerebral palsy will most likely include the following:    

A physician, such as a pediatrician, pediatric neurologist, or pediatric physiatrist, who is trained to help developmentally disabled children. This doctor, who often acts as the leader of the treatment team, integrates the professional advice of all team members into a comprehensive treatment plan, makes sure the plan is implemented properly, and follows the child’s progress over a number of years.

An orthopedist, a surgeon who specializes in treating the bones, muscles, tendons, and other parts of the skeletal system. An orthopedist is often brought in to diagnose and treat muscle problems associated with cerebral palsy.

A physical therapist, who designs and puts into practice special exercise programs to improve strength and functional mobility.

An occupational therapist, who teaches the skills necessary for day-to-day living, school, and work.

A speech and language pathologist, who specializes in diagnosing and treating disabilities relating to difficulties with swallowing and communication.   

A social worker, who helps individuals and their families locate community assistance and education programs.

A psychologist, who helps individuals and their families cope with the special stresses and demands of cerebral palsy. In some cases, psychologists may also oversee therapy to modify unhelpful or destructive behaviors.

An educator, who may play an especially important role when mental retardation or learning disabilities present a challenge to education.

Regardless of age or the types of therapy that are used, treatment doesn’t end when an individual with cerebral palsy leaves the treatment center.  Most of the work is done at home.   Members of the treatment team often act as coaches, giving parents and children techniques and strategies to practice at home.  Studies have shown that family support and personal determination are two of the most important factors in helping individuals with cerebral palsy reach their long-term goals.

While mastering specific skills is an important focus of treatment on a day-to-day basis, the ultimate goal is to help children grow into adulthood with as much independence as possible. 

As a child with cerebral palsy grows older, the need for therapy and the kinds of therapies required, as well as support services, will likely change.   Counseling for emotional and psychological challenges may be needed at any age, but is often most critical during adolescence. Depending on their physical and intellectual abilities, adults may need help finding attendants to care for them, a place to live, a job, and a way to get to their place of employment. 

Addressing the needs of parents and caregivers is also an important component of the treatment plan.  The well-being of an individual with cerebral palsy depends upon the strength and well-being of his or her family.  For parents to accept a child’s disabilities and come to grips with the extent of their caregiving responsibilities will take time and support from health care professionals.  Family-centered programs in hospitals and clinics and community-based organizations usually work together with families to help them make well-informed decisions about the services they need.  They also coordinate services to get the most out of treatment.    

A good program will encourage the open exchange of information, offer respectful and supportive care, encourage partnerships between parents and the health care professionals they work with, and acknowledge that although medical specialists may be the experts, it’s parents who know their children best.

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What Specific Treatments Are Available?


 

Physical therapy, usually begun in the first few years of life or soon after the diagnosis is made, is a cornerstone of cerebral palsy treatment. Physical therapy programs use specific sets of exercises and activities to work toward two important goals: preventing weakening or deterioration in the muscles that aren’t being used (disuse atrophy), and keeping muscles from becoming fixed in a rigid, abnormal position (contracture).

Resistive exercise programs (also called strength training) and other types of exercise are often used to increase muscle performance, especially in children and adolescents with mild cerebral palsy.  Daily bouts of exercise keep muscles that aren’t normally used moving and active and less prone to wasting away.  Exercise also reduces the risk of contracture, one of the most common and serious complications of cerebral palsy.

Normally growing children stretch their muscles and tendons as they run, walk, and move through their daily activities.  This insures that their muscles grow at the same rate as their bones. But in children with cerebral palsy, spasticity prevents muscles from stretching.  As a result, their muscles don’t grow fast enough to keep up with their lengthening bones.  The muscle contracture that results can set back the gains in function they’ve made.  Physical therapy alone or in combination with special braces (called orthotic devices) helps prevent contracture by stretching spastic muscles.

Occupational therapy.  This kind of therapy focuses on optimizing upper body function, improving posture, and making the most of a child’s mobility.  An occupational therapist helps a child master the basic activities of daily living, such as eating, dressing, and using the bathroom alone.  Fostering this kind of independence boosts self-reliance and self-esteem, and also helps reduce demands on parents and caregivers.   

Recreational therapies.   Recreational therapies, such as therapeutic horseback riding (also called hippotherapy), are sometimes used with mildly impaired children to improve gross motor skills.  Parents of children who participate in recreational therapies usually notice an improvement in their child’s speech, self-esteem, and emotional well-being. 

Controversial physical therapies.  "Patterning" is a physical therapy based on the principle that children with cerebral palsy should be taught motor skills in the same sequence in which they develop in normal children.  In this controversial approach, the therapist begins by teaching a child elementary movements such as crawling -- regardless of age – before moving on to walking skills. Some experts and organizations, including the American Academy of Pediatrics, have expressed strong reservations about the patterning approach because studies have not documented its value.

Experts have similar reservations about the Bobath technique (which is also called “neurodevelopmental treatment”), named for a husband and wife team who pioneered the approach in England .   In this form of physical therapy, instructors inhibit abnormal patterns of movement and encourage more normal movements. 

The Bobath technique has had a widespread influence on the core physical therapies of cerebral palsy treatment, but there is no evidence that the technique improves motor control.  The American Academy of Cerebral Palsy and Developmental Medicine reviewed studies that measured the impact of neurodevelopmental treatment and concluded that there was no strong evidence supporting its effectiveness for children with cerebral palsy. 

Conductive education, developed in Hungary in the 1940s, is another physical therapy that at one time appeared to hold promise.  Conductive education instructors attempt to improve a child’s motor abilities by combining rhythmic activities, such as singing and clapping, with physical maneuvers on special equipment.  The therapy, however, has not been able to produce consistent or significant improvements in study groups. 

Speech and language therapy.  About 20 percent of children with cerebral palsy are unable to produce intelligible speech.  They also experience challenges in other areas of communication, such as hand gestures and facial expressions, and they have difficulty participating in the basic give and take of a normal conversation.  These challenges will last throughout their lives. 

Speech and language therapists (also known as speech therapists or speech-language pathologists) observe, diagnose, and treat the communication disorders associated with cerebral palsy.   They use a program of exercises to teach children how to overcome specific communication difficulties.

For example, if a child has difficulty saying words that begin with "b," the therapist may suggest daily practice with a list of "b" words, increasing their difficulty as each list is mastered. Other kinds of exercises help children master the social skills involved in communicating by teaching them to keep their head up, maintain eye contact, and repeat themselves when they are misunderstood.

Speech therapists can also help children with severe disabilities learn how to use special communication devices, such as a computer with a voice synthesizer, or a special   board covered with symbols of everyday objects and activities to which a child can point to indicate his or her wishes.          

Speech interventions often use a child’s family members and friends to reinforce the lessons learned in a therapeutic setting.  This kind of indirect therapy encourages people who are in close daily contact with a child to create opportunities for him or her to use their new skills in conversation. 

Treatments for problems with eating and drooling are often necessary when children with cerebral palsy have difficulty eating and drinking because they have little control over the muscles that move their mouth, jaw, and tongue.  They are also at risk for breathing food or fluid into the lungs.  Some children develop gastroesophageal reflux disease (GERD, commonly called heartburn) in which a weak diaphragm can’t keep stomach acids from spilling into the esophagus.  The irritation of the acid can cause bleeding and pain. 

Individuals with cerebral palsy are also at risk for malnutrition, recurrent lung infections, and progressive lung disease.  The individuals most at risk for these problems are those with spastic quadriplegia.

Initially, children should be evaluated for their swallowing ability, which is usually done with a modified barium swallow study.  Recommendations regarding diet modifications will be derived from the results of this study.

In severe cases where swallowing problems are causing malnutrition, a doctor may recommend tube feeding, in which a tube delivers food and nutrients down the throat and into the stomach, or gastrostomy, in which a surgical opening allows a tube to be placed directly into the stomach.

Although numerous treatments for drooling have been tested over the years, there is no one treatment that helps reliably.  Anticholinergic drugs – such as glycopyrolate -- can reduce the flow of saliva but may cause unpleasant side effects, such as dry mouth, constipation, and urinary retention.  Surgery, while sometimes effective, carries the risk of complications.   Some children benefit from biofeedback techniques that help them recognize more quickly when their mouths fall open and they begin to drool.  Intraoral devices (devices that fit into the mouth) that encourage better tongue positioning and swallowing are still being evaluated, but appear to reduce drooling for some children.

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Drug Treatments


 

Oral medications such as diazepam, baclofen, dantrolene sodium, and tizanidine are usually used as the first line of treatment to relax stiff, contracted, or overactive muscles.  These drugs are easy to use, except that dosages high enough to be effective often have side effects, among them drowsiness, upset stomach, high blood pressure, and possible liver damage with long-term use.  Oral medications are most appropriate for children who need only mild reduction in muscle tone or who have widespread spasticity.

Doctors also sometimes use alcohol “washes” -- injections of alcohol into muscles -- to reduce spasticity.   The benefits last from a few months to 2 years or more, but the adverse effects include a significant risk of pain or numbness, and the procedure requires a high degree of skill to target the nerve.

The availability of new and more precise methods to deliver antispasmodic medications is moving treatment for spasticity toward chemodenervation, in which injected drugs are used to target and relax muscles.  

Botulinum toxin (BT-A), injected locally, has become a standard treatment for overactive muscles in children with spastic movement disorders such as cerebral palsy.  BT-A relaxes contracted muscles by keeping nerve cells from over-activating muscle.  Although BT-A is not approved by the Food and Drug Administration (FDA) for treating cerebral palsy, since the 1990s doctors have been using it off-label to relax spastic muscles.  A number of studies have shown that it reduces spasticity and increases the range of motion of the muscles it targets. 

The relaxing effect of a BT-A injection lasts approximately 3 months.  Undesirable side effects are mild and short-lived, consisting of pain upon injection and occasionally mild flu-like symptoms.  BT-A injections are most effective when followed by a stretching program including physical therapy and splinting.    BT-A injections work best for children who have some control over their motor movements and have a limited number of muscles to treat, none of which is fixed or rigid. 

Because BT-A does not have FDA approval to treat spasticity in children, parents and caregivers should make sure that the doctor giving the injection is trained in the procedure and has experience using it in children.  

Intrathecal baclofen therapy uses an implantable pump to deliver baclofen, a muscle relaxant, into the fluid surrounding the spinal cord.  Baclofen works by decreasing the excitability of nerve cells in the spinal cord, which then reduces muscle spasticity throughout the body.  Because it is delivered directly into the nervous system, the intrathecal dose of baclofen can be as low as one one-hundredth of the oral dose.  Studies have shown it reduces spasticity and pain and improves sleep.   

The pump is the size of a hockey puck and is implanted in the abdomen.  It contains a refillable reservoir connected to an alarm that beeps when the reservoir is low.  The pump is programmable with an electronic telemetry wand.  The program can be adjusted if muscle tone is worse at certain times of the day or night.    

The baclofen pump carries a small but significant risk of serious complications if it fails or is programmed incorrectly, if the catheter becomes twisted or kinked, or if the insertion site becomes infected.  Undesirable, but infrequent, side effects include overrelaxation of the muscles, sleepiness, headache, nausea, vomiting, dizziness, and constipation. 

As a muscle-relaxing therapy, the baclofen pump is most appropriate for individuals with chronic, severe stiffness or uncontrolled muscle movement throughout the body.  Doctors have successfully implanted the pump in children as young as 3 years of age. 

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Surgery


 

Orthopedic surgery is often recommended when spasticity and stiffness are severe enough to make walking and moving about difficult or painful.  For many people with cerebral palsy, improving the appearance of how they walk – their gait – is also important.  A more upright gait with smoother transitions and foot placements is the primary goal for many children and young adults. 

In the operating room, surgeons can lengthen muscles and tendons that are proportionately too short.  But first, they have to determine the specific muscles responsible for the gait abnormalities.  Finding these muscles can be difficult.  It takes more than 30 major muscles working at the right time using the right amount of force to walk two strides with a normal gait. A problem with any of those muscles can cause an abnormal gait.  

In addition, because the body makes natural adjustments to compensate for muscle imbalances, these adjustments could appear to be the problem, instead of a compensation.   In the past, doctors relied on clinical examination, observation of the gait, and the measurement of motion and spasticity to determine the muscles involved.  Now, doctors have a diagnostic technique known as gait analysis

Gait analysis uses cameras that record how an individual walks, force plates that detect when and where feet touch the ground, a special recording technique that detects muscle activity (known as electromyography), and a computer program that gathers and analyzes the data to identify the problem muscles. Using gait analysis, doctors can precisely locate which muscles would benefit from surgery and how much improvement in gait can be expected.

The timing of orthopedic surgery has also changed in recent years.  Previously, orthopedic surgeons preferred to perform all of the necessary surgeries a child needed at the same time, usually between the ages of 7 and 10.  Because of the length of time spent in recovery, which was generally several months, doing them all at once shortened the amount of time a child spent in bed.  Now most of the surgical procedures can be done on an outpatient basis or with a short inpatient stay.  Children usually return to their normal lifestyle within a week. 

Consequently, doctors think it is much better to stagger surgeries and perform them at times appropriate to a child’s age and level of motor development.  For example, spasticity in the upper leg muscles (the adductors), which causes a “scissor pattern” walk, is a major obstacle to normal gait.  The optimal age to correct this spasticity with adduction release surgery is 2 to 4 years of age.  On the other hand, the best time to perform surgery to lengthen the hamstrings or Achilles tendon is 7 to 8 years of age.  If adduction release surgery is delayed so that it can be performed at the same time as hamstring lengthening, the child will have learned to compensate for spasticity in the adductors.  By the time the hamstring surgery is performed, the child’s abnormal gait pattern could be so ingrained that it might not be easily corrected.       

With shorter recovery times and new, less invasive surgical techniques, doctors can schedule surgeries at times that take advantage of a child’s age and developmental abilities for the best possible result.   

Selective dorsal rhizotomy (SDR) is a surgical procedure recommended only for cases of severe spasticity when all of the more conservative treatments – physical therapy, oral medications, and intrathecal baclofen -- have failed to reduce spasticity or chronic pain.  In the procedure, a surgeon locates and selectively severs overactivated nerves at the base of the spinal column.

Because it reduces the amount of stimulation that reaches muscles via the nerves, SDR is most commonly used to relax muscles and decrease chronic pain in one or both of the lower or upper limbs.  It is also sometimes used to correct an overactive bladder.  Potential side effects include sensory loss, numbness, or uncomfortable sensations in limb areas once supplied by the severed nerve. 

Even though the use of microsurgery techniques has refined the practice of SDR surgery, there is still controversy about how selective SDR actually is.  Some doctors have concerns since it is invasive and irreversible and may only achieve small improvements in function.  Although recent research has shown that combining SDR with physical therapy reduces spasticity in some children, particularly those with spastic diplegia, whether or not it improves gait or function has still not been proven.  Ongoing research continues to look at this surgery's effectiveness.  

Spinal cord stimulation was developed in the 1980s to treat spinal cord injury and other neurological conditions involving motor neurons.  An implanted electrode selectively stimulates nerves at the base of the spinal cord to inhibit and decrease nerve activity.   The effectiveness of spinal cord stimulation for the treatment of cerebral palsy has yet to be proven in clinical studies.  It is considered a treatment alternative only when other conservative or surgical treatments have been unsuccessful at relaxing muscles or relieving pain.     

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Orthotic Devices


 

Orthotic devices – such as braces and splints – use external force to correct muscle abnormalities.  The technology of orthotics has advanced over the past 30 years from metal rods that hooked up to bulky orthopedic shoes, to appliances that are individually molded from high-temperature plastics for a precise fit.   Ankle-foot orthoses are frequently prescribed for children with spastic diplegia to prevent muscle contracture and to improve gait.  Splints are also used to correct spasticity in the hand muscles.

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Assistive Technology


 

Devices that help individuals move about more easily and communicate successfully at home, at school, or in the workplace can help a child or adult with cerebral palsy overcome physical and communication limitations.   There are a number of devices that help individuals stand straight and walk, such as postural support or seating systems, open-front walkers, quadrupedal canes (lightweight metal canes with four feet), and gait poles.  Electric wheelchairs let more severely impaired adults and children move about successfully. 

The computer is probably the most dramatic example of a communication device that can make a big difference in the lives of people with cerebral palsy. Equipped with a computer and voice synthesizer, a child or adult with cerebral palsy can communicate successfully with others.   For example, a child who is unable to speak or write but can make head movements may be able to control a computer using a special light pointer that attaches to a headband.

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Alternative Therapies


 

Therapeutic (subthreshold) electrical stimulation, also called neuromuscular electrical stimulation (NES), pulses electricity into the motor nerves to stimulate contraction in selective muscle groups.  Many studies have demonstrated that NES appears to increase range of motion and muscular strength. 

Threshold electrical stimulation, which involves the application of electrical stimulation at an intensity too low to stimulate muscle contraction, is a controversial therapy.  Studies have not been able to demonstrate its effectiveness or any significant improvement with its use. 

Hyperbaric oxygen therapy.  Some children have cerebral palsy as the result of brain damage from oxygen deprivation.  Proponents of hyperbaric oxygen therapy propose that the brain tissue surrounding the damaged area can be “awakened” by forcing high concentrations of oxygen into the body under greater than atmospheric pressure. 

A recent study compared a group of children who received no hyperbaric treatment to a group that received 40 treatments over 8 weeks.  On every measure of function (gross motor, cognitive, communication, and memory) at the end of 2 months of treatment and after a further 3 months of follow up, the two groups were identical in outcome.  There was no added benefit from hyperbaric oxygen therapy.

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Are There Treatments for Other Conditions Associated with Cerebral Palsy?


 

Epilepsy.  Twenty to 40 percent of children with mental retardation and cerebral palsy also have epilepsy.  Doctors usually prescribe medications to control seizures.  The classic medications for this purpose are phenobarbital, phenytoin, carbamazepine, and valproate.  Although these drugs generally are effective in controlling seizures, their use is hampered by harmful or unpleasant side effects. 

Treatment for epilepsy has advanced significantly with the development of new medications that have fewer side effects.  These drugs include felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, and zonisamide.

In general, drugs are prescribed based on the type of seizures an individual experiences, since no one drug controls all types. Some individuals may need a combination of two or more drugs to achieve good seizure control.

Incontinence.  Medical treatments for incontinence include special exercises, biofeedback, prescription drugs, surgery, or surgically implanted devices to replace or aid muscles. Specially designed absorbent undergarments can also be used to protect against accidental leaks.   

Osteopenia.  Children with cerebral palsy who aren’t able to walk risk developing poor bone density (osteopenia), which makes them more likely to break bones.  In a study of older Americans funded by the National Institutes of Health (NIH), a family of drugs called bisphosphonates, which was recently approved by the FDA to treat mineral loss in elderly patients, also appeared to increase bone mineral density.  Doctors may choose to selectively prescribe the drug off-label to children to prevent osteopenia.   

Pain.   Pain can be a problem for people with cerebral palsy due to spastic muscles and the stress and strain on parts of the body that are compensating for muscle abnormalities.  Some individuals may also have frequent and irregular muscle spasms that can’t be predicted or medicated in advance. 

Doctors often prescribe diazepam to reduce the pain associated with muscle spasms, but it’s not known exactly how the drug works to interfere with pain signals.  The drug gabapentin has been used successfully to decrease the severity and frequency of painful spasms.  BT-A injections have also been shown to decrease spasticity and pain, and are commonly given under anesthesia to avoid the pain associated with the injections.  Intrathecal baclofen has shown good results in reducing pain, but its delivery is invasive, time intensive, and expensive.

Some children and adults have been able to decrease pain by using noninvasive and drug-free interventions such as distraction, relaxation training, biofeedback, and therapeutic massage.

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Do Adults with Cerebral Palsy Face Special Health Challenges?


 

Before the mid-twentieth century, few children with cerebral palsy survived to adulthood.  Now, because of improvements in medical care, rehabilitation, and assistive technologies, 65 to 90 percent of children with cerebral palsy live into their adult years.    This increase in life expectancy is often accompanied by a rise in medical and functional problems – some of them beginning at a relatively early age – including the following: 

Premature aging.  The majority of individuals with cerebral palsy will experience some form of premature aging by the time they reach their 40s because of the extra stress and strain the disease puts upon their bodies.  The developmental delays that often accompany cerebral palsy keep some organ systems from developing to their full capacity and level of performance.  As a consequence, organ systems such as the cardiovascular system (the heart, veins, and arteries) and pulmonary system (lungs) have to work harder and they age prematurely.

Functional issues at work.  The day-to-day challenges of the workplace are likely to increase as an employed individual with cerebral palsy reaches middle age.  Some individuals will be able to continue working with accommodations such as an adjusted work schedule, assistive equipment, or frequent rest periods.   Early retirement may be necessary for others. 

Depression.  Mental health issues can also be of concern as someone with cerebral palsy grows older.  The rate of depression is three to four times higher in people with disabilities such as cerebral palsy.  It appears to be related not so much to the severity of their disabilities, but to how well they cope with them.  The amount of emotional support someone has, how successful they are at coping with disappointment and stress, and whether or not they have an optimistic outlook about the future all have a significant impact on mental health.       

Post-impairment syndrome.  Most adults with cerebral palsy experience what is called post-impairment syndrome, a combination of pain, fatigue, and weakness due to muscle abnormalities, bone deformities, overuse syndromes (sometimes also called repetitive motion injuries), and arthritis.   Fatigue is often a challenge, since individuals with cerebral palsy use three to five times the amount of energy that able-bodied people use when they walk and move about.   

Osteoarthritis and degenerative arthritis.  Musculoskeletal abnormalities that may not produce discomfort during childhood can cause pain in adulthood.  For example, the abnormal relationships between joint surfaces and excessive joint compression can lead to the early development of painful osteoarthritis and degenerative arthritis.  Individuals with cerebral palsy also have limited strength and restricted patterns of movement, which puts them at risk for overuse syndromes and nerve entrapments.

Pain.   Issues related to pain often go unrecognized by health care providers since individuals with cerebral palsy may not be able to describe the extent or location of their pain.  Pain can be acute or chronic, and is experienced most commonly in the hips, knees, ankles, and the upper and lower back.  Individuals with spastic cerebral palsy have an increased number of painful sites and worse pain than those with other types of cerebral palsy.  The best treatment for pain due to musculoskeletal abnormalities is preventive – correcting skeletal and muscle abnormalities early in life to avoid the progressive accumulation of stress and strain that causes pain.  Dislocated hips, which are particularly likely to cause pain, can be surgically repaired.   If it is managed properly, pain does not have to become a chronic condition. 

Other medical conditions.  Adults have higher than normal rates of other medical conditions secondary to their cerebral palsy, such as hypertension, incontinence, bladder dysfunction, and swallowing difficulties.  Curvature of the spine (scoliosis) is likely to progress after puberty, when bones have matured into their final shape and size.  People with cerebral palsy also have a higher incidence of bone fractures, occurring most frequently during physical therapy sessions.  A combination of mouth breathing, poor hygiene, and abnormalities in tooth enamel increase the risk of cavities and periodontal disease.   Twenty-five percent to 39 percent of adults with cerebral palsy have vision problems; eight to 18 percent have hearing problems.

Because of their unique medical situations, adults with cerebral palsy benefit from regular visits to their doctor and ongoing evaluation of their physical status.  It is important to evaluate physical complaints to make sure they are not the result of underlying conditions.  For example, adults with cerebral palsy are likely to experience fatigue, but fatigue can also be due to undiagnosed medical problems that could be treated and reversed. 

Because many individuals with cerebral palsy outlive their primary caregiver, the issue of long-term care and support should be taken into account and planned for. 

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What Research Is Being Done?


 

Investigators from many fields of medicine and health are using their expertise to help improve the treatment and diagnosis of cerebral palsy.  Much of their work is supported through the NINDS, the National Institute of Child Health and Human Development (NICHD), other agencies within the federal government, nonprofit groups such as the United Cerebral Palsy Research and Educational Foundation, and other private institutions.

The ultimate hope for curing cerebral palsy rests with prevention. In order to prevent cerebral palsy, however, scientists have to understand normal fetal brain development so that they can understand what happens when a baby’s brain develops abnormally. 

Between conception and the birth of a baby, one cell divides to form a handful of cells, and then hundreds, millions, and, eventually, billions of cells. Some of these cells specialize to become brain cells, and then specialize even further into particular types of neurons that travel to their appropriate place in the brain (a process that scientists call neuronal migration).  Once they are in the right place, they establish connections with other brain cells.  This is how the brain develops and becomes able to communicate with the rest of the body -- through overlapping neural circuits made up of billions of interconnected and interdependent neurons.

Many scientists now think that a significant number of children develop cerebral palsy because of mishaps early in brain development. They are examining how brain cells specialize and form the right connections, and they are looking for ways to prevent the factors that disrupt the normal processes of brain development.

Genetic defects are sometimes responsible for the brain malformations and abnormalities that cause cerebral palsy.  Scientists funded by the NINDS are searching for the genes responsible for these abnormalities by collecting DNA samples from people with cerebral palsy and their families and using genetic screening techniques to discover linkages between individual genes and specific types of abnormality – primarily those associated with abnormal neuronal migration. 

Scientists are scrutinizing events in newborn babies’ brains, such as bleeding, epileptic seizures, and breathing and circulation problems, which can cause the abnormal release of chemicals that trigger the kind of damage that causes cerebral palsy.  For example, research has shown that bleeding in the brain unleashes dangerously high amounts of a brain chemical called glutamate.   Although glutamate is necessary in the brain to help neurons communicate, too much glutamate overexcites and kills neurons. Scientists are now looking closely at glutamate to detect how its release harms brain tissue.  By learning how brain chemicals that are normally helpful become dangerously toxic, scientists will have opportunities to develop new drugs to block their harmful effects.

Scientists funded by the NINDS are also investigating whether substances in the brain that protect neurons from damage, called neurotrophins, could be used to prevent brain damage as a result of stroke or oxygen deprivation.  Understanding how these neuroprotective substances act would allow scientists to develop synthetic neurotrophins that could be given immediately after injury to prevent neuron death and damage.

The relationship between uterine infections during pregnancy and the risk of cerebral palsy continues to be studied by researchers funded by the NIH.  There is evidence that uterine infections trigger inflammation and the production of immune system cells called cytokines, which can pass into an unborn baby’s brain and interrupt normal development.  By understanding what cytokines do in the fetal brain and the type of damage these immune system cells cause, researchers have the potential to develop medications that could be given to mothers with uterine infections to prevent brain damage in their unborn children. 

Approximately 10 percent of newborns are born prematurely, and of those babies, more than 10 percent will have brain injuries that will lead to cerebral palsy and other brain-based disabilities.   A particular type of damage to the white matter of the brain, called periventricular leukomalacia (PVL), is the predominant form of brain injury in premature infants.  NINDS-sponsored researchers studying PVL are looking for new strategies to prevent this kind of damage by developing safe, nontoxic therapies delivered to at-risk mothers to protect their unborn babies.

Although congenital cerebral palsy is a condition that is present at birth, a year or two can pass before any disabilities are noticed.  Researchers have shown that the earlier rehabilitative treatment begins, the better the outcome for children with cerebral palsy.  But an early diagnosis is hampered by the lack of diagnostic techniques to identify brain damage or abnormalities in infants. 

Research funded by the NINDS is using imaging techniques, devices that measure electrical activity in the brain, and neurobehavioral tests to predict those preterm infants who will develop cerebral palsy.  If these screening techniques are successful, doctors will be able to identify infants at risk for cerebral palsy before they are born.        

Noninvasive methods to record the brain activity of unborn babies in the womb and to identify those with brain damage or abnormalities would also be a valuable addition to the diagnostic tool kit.  Another NINDS-funded study focuses on the development of fetal magnetoencephalography (fMEG) – a technology that would allow doctors to look for abnormalities in fetal brain activity.

Epidemiological studies – studies that look at the distribution and causes of disease among people -- help scientists understand risk factors and outcomes for particular diseases and medical conditions.  Researchers have established that preterm birth (when a baby is born before 32 weeks’ gestation) is the highest risk factor for cerebral palsy.  Consequently, the increasing rate of premature births in the United States puts more babies at risk.  A large, long-term study funded by the NIH is following a group of more than 400 mothers and their infants born between 24 and 31 weeks’ gestation.  They are looking for relationships between preterm birth, maternal uterine infection, fetal exposure to infection, and short-term and long-term health and neurological outcomes.  The researchers are hoping to discover environmental or lifestyle factors, or particular characteristics of mothers, which might protect preterm babies from neurological disabilities.     

While this research offers hope for preventing cerebral palsy in the future, ongoing research to improve treatment brightens the outlook for those who must face the challenges of cerebral palsy today. An important thrust of such research is the evaluation of treatments already in use so that physicians and parents have valid information to help them choose the best therapy. A good example of this effort is an ongoing NINDS-supported study that promises to yield new information about which patients are most likely to benefit from selective dorsal rhizotomy, a surgical technique that is increasingly being used to reduce spasticity (see Surgery).

Similarly, although physical therapy programs are used almost universally to rehabilitate children with cerebral palsy, there are no definitive studies to indicate which techniques work best.  For example, constraint-induced therapy (CIT) is a type of physical therapy that has been used successfully with adult stroke survivors and individuals who have traumatic brain injury and are left with a weak or disabled arm on one side of the body.  The therapy involves restraining the stronger arm in a cast and forcing the weaker arm to perform 6 hours of intensive “shaping” activities every day over the course of 3 weeks.  The researchers who conducted the clinical trials in adult stroke survivors realized CIT’s potential for strengthening children’s arms weakened by cerebral palsy. 

In a randomized, controlled study of children with cerebral palsy funded by the NIH, researchers put one group of children through conventional physical therapy and another group through 21 consecutive days of CIT.   Researchers looked for evidence of improvement in the movement and function of the disabled arm, whether the improvement lasted after the end of treatment, and if it was associated with significant gains in other areas, such as trunk control, mobility, communication, and self-help skills. 

Children receiving CIT outperformed the children receiving conventional physical therapy across all measures of success, including how well they could move their arms after therapy and their ability to do new tasks during the study and then at home with their families.  Six months later they still had better control of their arm.  The results from this study are the first to prove the benefits of a physical therapy.  Additional research to determine the optimal length and intensity of CIT will allow doctors to add this therapy to the cerebral palsy treatment toolbox. 

Studies have shown that functional electrical stimulation is an effective way to target and strengthen spastic muscles, but the method of delivering the electrical pulses requires expensive, bulky devices implanted by a surgeon, or skin surface stimulation applied by a trained therapist.  NINDS-funded researchers have developed a high-tech method that does away with the bulky apparatus and lead wires by using a hypodermic needle to inject microscopic wireless devices into specific muscles or nerves.  The devices are powered by a telemetry wand that can direct the number and strength of their pulses by remote control.  The device has been used to activate and strengthen muscles in the hand, shoulder, and ankle in people with cerebral palsy as well as in stroke survivors.   

As researchers continue to explore new treatments for cerebral palsy and to expand our knowledge of brain development, we can expect significant improvements in the care of children with cerebral palsy and many other disorders that strike in early life.

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at: BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

 

 

United Cerebral Palsy (UCP)
1660 L Street, NW
Suite 700
Washington, DC   20036
national@ucp.org
http://www.ucp.org
Tel: 202-776-0406 800-USA-5UCP (872-5827)
Fax: 202-776-0414
Works to advance the independence, productivity and full citizenship of people with cerebral palsy and other disabilities, through our commitment to the principles of independence, inclusion and self-determination.

Pathways Awareness Foundation [For Children With Movement Difficulties]
150 N. Michigan Avenue
Suite 2100
Chicago, IL   60601
friends@pathwaysawareness.org
http://www.pathwaysawareness.org
Tel: 312-893-6620 800-955-CHILD (2445)
Fax: 312-893-6621
National non-profit organization dedicated to raising awareness about the value of early detection, early therapy, and inclusion for infants and children with movement differences.

March of Dimes Foundation
1275 Mamaroneck Avenue
White Plains, NY   10605
askus@marchofdimes.com
http://www.marchofdimes.com
Tel: 914-428-7100 888-MODIMES (663-4637)
Fax: 914-428-8203
Works to improve the health of babies by preventing birth defects and infant mortality through programs of research, community services, education, and advocacy.

Easter Seals
233 South Wacker Drive
Suite 2400
Chicago, IL   60606
info@easterseals.com
http://www.easterseals.com
Tel: 312-726-6200 800-221-6827
Fax: 312-726-1494
Provides services to help children and adults with disabilities and/or special needs as well as support to their families. Supports the National AgrAbility Project, a program for farmers, ranchers, and farm workers with disabilities.

Children's Neurobiological Solutions (CNS) Foundation
1726 Franceschi Road
Santa Barbara, CA   93101
info@cnsfoundation.org
http://www.cnsfoundation.org
Tel: 866-CNS-5580 (267-5580) 805-898-4442
National, non-profit organization whose mission is to accelerate the development of brain repair therapies and cures by supporting cutting-edge collaborative research on brain damage due to childhood illness, injury, or any other cause. Provides information and resources for families and health care providers.

Children's Hemiplegia and Stroke Assocn. (CHASA)
4101 West Green Oaks Blvd., Ste. 305
PMB 149
Arlington, TX   76016
info437@chasa.org
http://www.hemi-kids.org
Tel: 817-492-4325
Nonprofit organization that offers support and information to families of children who have hemiplegia due to stroke or other causes. Sponsors a number of programs for families, offers support groups and information about research studies, and sponsors conferences and a childhood stroke awareness campaign.

Cerebral Palsy International Research Foundation
1025 Connecticut Avenue
Suite 701
Washington, DC   20036
nmaher@cpirf.org
http://www.cpirf.org
Tel: 202-496-5060
Provides grants for research and training on causes and prevention of cerebral palsy and on improving the quality of life of persons with cerebral palsy.

Pedal with Pete [For Research on Cerebral Palsy]
P.O. Box 274
Kent, OH   44240
petezeid@aol.com
http://www.pedalwithpete.com
Tel: 800-304-PETE (7383)
Fax: 330-673-1240
Nonprofit organization dedicated to raising money for research to improve the quality of life for those with cerebral palsy. Aim is to help in the fight for the prevention, treatment and cure of cerebral palsy.

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Glossary

acquired cerebral palsy — cerebral palsy that occurs as a result of injury to the brain after birth or during early childhood.

Apgar score — a numbered scoring system doctors use to assess a baby's physical state at the time of birth.

anticholinergic drugs — a family of drugs that inhibit parasympathetic neural activity by blocking the neurotransmitter acetylcholine.

asphyxia — a lack of oxygen due to trouble with breathing or poor oxygen supply in the air.

ataxia (ataxic) — the loss of muscle control.

athetoid — making slow, sinuous, involuntary, writhing movements, especially with the hands.

bilirubin — a bile pigment produced by the liver of the human body as a byproduct of digestion.

bisphosphonates — a family of drugs that strengthen bones and reduce the risk of bone fracture in elderly adults. 

botulinum toxin — a drug commonly used to relax spastic muscles; it blocks the release of acetylcholine, a neurotransmitter that energizes muscle tissue. 

cerebral — relating to the two hemispheres of the human brain.

cerebral dysgenesis — defective brain development.

chemodenervation — a treatment that relaxes spastic muscles by interrupting nerve impulse pathways via a drug, such as botulinum toxin, which prevents communication between neurons and muscle tissue. 

choreoathetoid — a condition characterized by aimless muscle movements and involuntary motions.

computed tomography (CT) scan — an imaging technique that uses X-rays and a computer to create a picture of the brain's tissues and structures.

congenital cerebral palsy — cerebral palsy that is present at birth from causes that have occurred during fetal development.

contracture — a condition in which muscles become fixed in a rigid, abnormal position, which causes distortion or deformity.

cytokines — messenger cells that play a role in the inflammatory response to infection. 

developmental delay — behind schedule in reaching the milestones of early childhood development.

disuse atrophy — muscle wasting caused by the inability to flex and exercise muscles. 

dyskinetic — the impairment of the ability to perform voluntary movements, which results in awkward or incomplete movements.

dystonia (dystonic)  a condition of abnormal muscle tone.   

electroencephalogram (EEG) — a technique for recording the pattern of electrical currents inside the brain.

electromyography — a special recording technique that detects muscle activity.

failure to thrive — a condition characterized by a lag in physical growth and development.

focal (partial) seizure — a brief and temporary alteration in movement, sensation, or autonomic nerve function caused by abnormal electrical activity in a localized area of the brain.  

gait analysis — a technique that uses cameras, force plates, electromyography, and computer analysis to objectively measure an individual's pattern of walking.

gastroesophageal reflux disease (GERD) — also known as heartburn, which happens when stomach acids back up into the esophagus.  

gastrostomy — a surgical procedure that creates an artificial opening in the stomach for the insertion of a feeding tube.

gestation — the period of fetal development from the time of conception until birth.

hemianopia — defective vision or blindness that impairs half of the normal field of vision.

hemiparesis — paralysis affecting only one side of the body.

homonymous — having the same description, name, or term.  

hypertonia — increased muscle tone.

hypotonia — decreased muscle tone.

hypoxic-ischemic encephalopathy — brain damage caused by poor blood flow or insufficient oxygen supply to the brain.

intracranial hemorrhage — bleeding in the brain.   

intrapartum asphyxia — the reduction or total stoppage of oxygen circulating in a baby’s brain during labor and delivery.

intrathecal baclofen — baclofen that is injected into the cerebrospinal fluid of the spinal cord to reduce spasticity. 
intrauterine infection — infection of the uterus, ovaries, or fallopian tubes (see pelvic inflammatory disease for a more detailed explanation).

jaundice — a blood disorder caused by the abnormal buildup of bilirubin in the bloodstream.

kernicterus — a neurological syndrome caused by deposition of bilirubin into brain tissues. Kernicterus develops in extremely jaundiced infants, especially those with severe Rh incompatibility.

kyphosis — a humpback-like outward curvature of the upper spine.

lordosis — an increased inward curvature of the lower spine. 

magnetic resonance imaging (MRI) — an imaging technique that uses radio waves, magnetic fields, and computer analysis to create a picture of body tissues and structures.

nerve entrapment — repeated or prolonged pressure on a nerve root or peripheral nerve.

neuronal migration — the process in the developing brain in which neurons migrate from where they are born to where they settle into neural circuits. Neuronal migration, which occurs as early as the second month of gestation, is controlled in the brain by chemical guides and signals.

neuroprotective — describes substances that protect nervous system cells from damage or death.

neurotrophins — a family of molecules that encourage survival of nervous system cells. 

off-label drugs — drugs prescribed to treat conditions other than those that have been   approved by the Food and Drug Administration.

orthotic devices — special devices, such as splints or braces, used to treat posture problems involving the muscles, ligaments, or bones.

osteopenia — reduced density and mass of the bones. 

overuse syndrome (also called repetitive strain injury) — a condition in which repetitive movements or constrained posture cause nerve and muscle damage, which results in discomfort or persistent pain in muscles, tendons, and other soft tissues.  This can happen in various parts of the body, but is most likely to happen in the arms, legs, or hands. 

palsy — paralysis, or the lack of control over voluntary movement.

-paresis or -plegia — weakness or paralysis.   In cerebral palsy, these terms are typically combined with other phrases that describe the distribution of paralysis and weakness; for example, quadriplegia means paralysis of all four limbs. 

pelvic inflammatory disease (PID, also sometimes called pelvic infection or intrauterine infection) — an infection of the upper genital tract (the uterus, ovaries, and fallopian tubes) caused by sexually transmitted infectious microorganisms. Symptoms of PID include fever, foul-smelling vaginal discharge, abdominal pain and pain during intercourse, and vaginal bleeding.  Many different organisms can cause PID, but most cases are associated with gonorrhea and chlamydia.

periventricular leukomalacia (PVL) — “peri" means near; "ventricular" refers to the ventricles or fluid spaces of the brain; and "leukomalacia" refers to softening of the white matter of the brain.   PVL is a condition in which the cells that make up white matter die near the ventricles.  Under a microscope, the tissue looks soft and sponge-like. 

placenta — an organ that joins a mother with her unborn baby and provides nourishment and sustenance.   

post-impairment syndrome — a combination of pain, fatigue, and weakness due to muscle abnormalities, bone deformities, overuse syndromes, or arthritis.

quadriplegia — paralysis of both the arms and legs.

respite care — rest or relief from caretaking obligations.

Rh incompatibility — a blood condition in which antibodies in a pregnant woman's blood attack fetal blood cells and impair an unborn baby’s supply of oxygen and nutrients.

rubella — (also known as German measles)  a viral infection that can damage the nervous system of an unborn baby if a mother contracts the disease during pregnancy.

scoliosis — a disease of the spine in which the spinal column tilts or curves to one side of the body.

selective dorsal rhizotomy — a surgical procedure in which selected nerves are severed to reduce spasticity in the legs.

selective vulnerability — a term that describes why some neurons are more vulnerable than others to particular diseases or conditions.  For example, motor neurons are selectively vulnerable to the loss or reduction in levels of the neurotransmitter dopamine, which results in the weakness and paralysis of amyotrophic lateral sclerosis (ALS, commonly called Lou Gehrig’s disease).

spastic (or spasticity) — describes stiff muscles and awkward movements. 

spastic diplegia (or diparesis) — a form of cerebral palsy in which spasticity affects both legs, but the arms are relatively or completely spared.

spastic hemiplegia (or hemiparesis) — a form of cerebral palsy in which spasticity affects an arm and leg on one side of the body.

spastic quadriplegia (or quadriparesis) — a form of cerebral palsy in which all four limbs are paralyzed or weakened equally.

stereognosia — difficulty perceiving and identifying objects using the sense of touch.

strabismus — misalignment of the eyes, also known as cross eyes.

telemetry wand — a hand-held device that acts as a remote control, directing the dosing level of a drug via a pump implanted beneath the skin. 

tonic-clonic seizure — a type of seizure that results in loss of consciousness, generalized convulsions, loss of bladder control, and tongue biting followed by confusion and lethargy when the convulsions end. 

tremor — an involuntary trembling or quivering.

ultrasound — a technique that bounces sound waves off tissue and bone and uses the pattern of echoes to form an image, called a sonogram.

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"Cerebral Palsy: Hope Through Research," NINDS. Publication date July 2006.

NIH Publication No. 06-159



 

 

 

 

Chronic Pain

Introduction: The Universal Disorder
A Brief History of Pain
The Two Faces of Pain: Acute and Chronic
The A to Z of Pain
How is Pain Diagnosed?
How is Pain Treated?
What is the Role of Age and Gender in Pain?
Gender and Pain
Pain in Aging and Pediatric Populations: Special Needs and Concerns
A Pain Primer: What Do We Know About Pain?
What is the Future of Pain Research?
Where can I get more information?
Appendix
Spine Basics: The Vertebrae, Discs, and Spinal Cord
The Nervous Systems
Phantom Pain: How Does the Brain Feel?
Chili Peppers, Capsaicin, and Pain
Marijuana
Nerve Blocks

Introduction: The Universal Disorder


You know it at once. It may be the fiery sensation of a burn moments after your finger touches the stove. Or it's a dull ache above your brow after a day of stress and tension. Or you may recognize it as a sharp pierce in your back after you lift something heavy.

It is pain. In its most benign form, it warns us that something isn't quite right, that we should take medicine or see a doctor. At its worst, however, pain robs us of our productivity, our well-being, and, for many of us suffering from extended illness, our very lives. Pain is a complex perception that differs enormously among individual patients, even those who appear to have identical injuries or illnesses.

In 1931, the French medical missionary Dr. Albert Schweitzer wrote, "Pain is a more terrible lord of mankind than even death itself." Today, pain has become the universal disorder, a serious and costly public health issue, and a challenge for family, friends, and health care providers who must give support to the individual suffering from the physical as well as the emotional consequences of pain.

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A Brief History of Pain


Ancient civilizations recorded on stone tablets accounts of pain and the treatments used: pressure, heat, water, and sun. Early humans related pain to evil, magic, and demons. Relief of pain was the responsibility of sorcerers, shamans, priests, and priestesses, who used herbs, rites, and ceremonies as their treatments.

The Greeks and Romans were the first to advance a theory of sensation, the idea that the brain and nervous system have a role in producing the perception of pain. But it was not until the Middle Ages and well into the Renaissance-the 1400s and 1500s-that evidence began to accumulate in support of these theories. Leonardo da Vinci and his contemporaries came to believe that the brain was the central organ responsible for sensation. Da Vinci also developed the idea that the spinal cord transmits sensations to the brain.

In the 17th and 18th centuries, the study of the body-and the senses-continued to be a source of wonder for the world's philosophers. In 1664, the French philosopher René Descartes described what to this day is still called a "pain pathway." Descartes illustrated how particles of fire, in contact with the foot, travel to the brain and he compared pain sensation to the ringing of a bell.

In the 19th century, pain came to dwell under a new domain-science-paving the way for advances in pain therapy. Physician-scientists discovered that opium, morphine, codeine, and cocaine could be used to treat pain. These drugs led to the development of aspirin, to this day the most commonly used pain reliever. Before long, anesthesia-both general and regional-was refined and applied during surgery.

"It has no future but itself," wrote the 19th century American poet Emily Dickinson, speaking about pain. As the 21st century unfolds, however, advances in pain research are creating a less grim future than that portrayed in Dickinson’s verse, a future that includes a better understanding of pain, along with greatly improved treatments to keep it in check.

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The Two Faces of Pain: Acute and Chronic


What is pain? The International Association for the Study of Pain defines it as: An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

It is useful to distinguish between two basic types of pain, acute and chronic, and they differ greatly.

  • Acute pain, for the most part, results from disease, inflammation, or injury to tissues. This type of pain generally comes on suddenly, for example, after trauma or surgery, and may be accompanied by anxiety or emotional distress. The cause of acute pain can usually be diagnosed and treated, and the pain is self-limiting, that is, it is confined to a given period of time and severity. In some rare instances, it can become chronic.
  • Chronic pain is widely believed to represent disease itself. It can be made much worse by environmental and psychological factors. Chronic pain persists over a longer period of time than acute pain and is resistant to most medical treatments. It can—and often does—cause severe problems for patients.
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The A to Z of Pain


Hundreds of pain syndromes or disorders make up the spectrum of pain. There are the most benign, fleeting sensations of pain, such as a pin prick. There is the pain of childbirth, the pain of a heart attack, and the pain that sometimes follows amputation of a limb. There is also pain accompanying cancer and the pain that follows severe trauma, such as that associated with head and spinal cord injuries. A sampling of common pain syndromes follows, listed alphabetically.

Arachnoiditis is a condition in which one of the three membranes covering the brain and spinal cord, called the arachnoid membrane, becomes inflamed. A number of causes, including infection or trauma, can result in inflammation of this membrane. Arachnoiditis can produce disabling, progressive, and even permanent pain.

Arthritis. Millions of Americans suffer from arthritic conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gout. These disorders are characterized by joint pain in the extremities. Many other inflammatory diseases affect the body's soft tissues, including tendonitis and bursitis.

Back pain has become the high price paid by our modern lifestyle and is a startlingly common cause of disability for many Americans, including both active and inactive people. Back pain that spreads to the leg is called sciatica and is a very common condition (see below). Another common type of back pain is associated with the discs of the spine, the soft, spongy padding between the vertebrae (bones) that form the spine. Discs protect the spine by absorbing shock, but they tend to degenerate over time and may sometimes rupture. Spondylolisthesis is a back condition that occurs when one vertebra extends over another, causing pressure on nerves and therefore pain. Also, damage to nerve roots (see Spine Basics in the Appendix) is a serious condition, called radiculopathy, that can be extremely painful. Treatment for a damaged disc includes drugs such as painkillers, muscle relaxants, and steroids; exercise or rest, depending on the patient's condition; adequate support, such as a brace or better mattress and physical therapy. In some cases, surgery may be required to remove the damaged portion of the disc and return it to its previous condition, especially when it is pressing a nerve root. Surgical procedures include discectomy, laminectomy, or spinal fusion (see section on surgery in How is Pain Treated? for more information on these treatments).

Burn pain can be profound and poses an extreme challenge to the medical community. First-degree burns are the least severe; with third-degree burns, the skin is lost. Depending on the injury, pain accompanying burns can be excruciating, and even after the wound has healed patients may have chronic pain at the burn site.

Central pain syndrome-see "Trauma" below.

Cancer pain can accompany the growth of a tumor, the treatment of cancer, or chronic problems related to cancer's permanent effects on the body. Fortunately, most cancer pain can be treated to help minimize discomfort and stress to the patient.

Headaches affect millions of Americans. The three most common types of chronic headache are migraines, cluster headaches, and tension headaches. Each comes with its own telltale brand of pain.

  • Migraines are characterized by throbbing pain and sometimes by other symptoms, such as nausea and visual disturbances. Migraines are more frequent in women than men. Stress can trigger a migraine headache, and migraines can also put the sufferer at risk for stroke.
  • Cluster headaches are characterized by excruciating, piercing pain on one side of the head; they occur more frequently in men than women.
  • Tension headaches are often described as a tight band around the head.

Head and facial pain can be agonizing, whether it results from dental problems or from disorders such as cranial neuralgia, in which one of the nerves in the face, head, or neck is inflamed. Another condition, trigeminal neuralgia (also called tic douloureux), affects the largest of the cranial nerves (see The Nervous Systems in the Appendix) and is characterized by a stabbing, shooting pain.

Muscle pain can range from an aching muscle, spasm, or strain, to the severe spasticity that accompanies paralysis. Another disabling syndrome is fibromyalgia, a disorder characterized by fatigue, stiffness, joint tenderness, and widespread muscle pain. Polymyositis, dermatomyositis, and inclusion body myositis are painful disorders characterized by muscle inflammation. They may be caused by infection or autoimmune dysfunction and are sometimes associated with connective tissue disorders, such as lupus and rheumatoid arthritis.

Myofascial pain syndromes affect sensitive areas known as trigger points, located within the body's muscles. Myofascial pain syndromes are sometimes misdiagnosed and can be debilitating. Fibromyalgia is a type of myofascial pain syndrome.

Neuropathic pain is a type of pain that can result from injury to nerves, either in the peripheral or central nervous system (see The Nervous Systems in the Appendix). Neuropathic pain can occur in any part of the body and is frequently described as a hot, burning sensation, which can be devastating to the affected individual. It can result from diseases that affect nerves (such as diabetes) or from trauma, or, because chemotherapy drugs can affect nerves, it can be a consequence of cancer treatment. Among the many neuropathic pain conditions are diabetic neuropathy (which results from nerve damage secondary to vascular problems that occur with diabetes); reflex sympathetic dystrophy syndrome (see below), which can follow injury; phantom limb and post-amputation pain (see Phantom Pain in the Appendix), which can result from the surgical removal of a limb; postherpetic neuralgia, which can occur after an outbreak of shingles; and central pain syndrome, which can result from trauma to the brain or spinal cord.

Reflex sympathetic dystrophy syndrome, or RSDS, is accompanied by burning pain and hypersensitivity to temperature. Often triggered by trauma or nerve damage, RSDS causes the skin of the affected area to become characteristically shiny. In recent years, RSDS has come to be called complex regional pain syndrome (CRPS); in the past it was often called causalgia.

Repetitive stress injuries are muscular conditions that result from repeated motions performed in the course of normal work or other daily activities. They include:

  • writer's cramp, which affects musicians and writers and others,
  • compression or entrapment neuropathies, including carpal tunnel syndrome, caused by chronic overextension of the wrist and
  • tendonitis or tenosynovitis, affecting one or more tendons.

Sciatica is a painful condition caused by pressure on the sciatic nerve, the main nerve that branches off the spinal cord and continues down into the thighs, legs, ankles, and feet. Sciatica is characterized by pain in the buttocks and can be caused by a number of factors. Exertion, obesity, and poor posture can all cause pressure on the sciatic nerve. One common cause of sciatica is a herniated disc (see Spine Basics in the Appendix).

Shingles and other painful disorders affect the skin. Pain is a common symptom of many skin disorders, even the most common rashes. One of the most vexing neurological disorders is shingles or herpes zoster, an infection that often causes agonizing pain resistant to treatment. Prompt treatment with antiviral agents is important to arrest the infection, which if prolonged can result in an associated condition known as postherpetic neuralgia. Other painful disorders affecting the skin include:

  • vasculitis, or inflammation of blood vessels;
  • other infections, including herpes simplex;
  • skin tumors and cysts, and
  • tumors associated with neurofibromatosis, a neurogenetic disorder.

Sports injuries are common. Sprains, strains, bruises, dislocations, and fractures are all well-known words in the language of sports. Pain is another. In extreme cases, sports injuries can take the form of costly and painful spinal cord and head injuries, which cause severe suffering and disability.

Spinal stenosis refers to a narrowing of the canal surrounding the spinal cord. The condition occurs naturally with aging. Spinal stenosis causes weakness in the legs and leg pain usually felt while the person is standing up and often relieved by sitting down.

Surgical pain may require regional or general anesthesia during the procedure and medications to control discomfort following the operation. Control of pain associated with surgery includes presurgical preparation and careful monitoring of the patient during and after the procedure.

Temporomandibular disorders are conditions in which the temporomandibular joint (the jaw) is damaged and/or the muscles used for chewing and talking become stressed, causing pain. The condition may be the result of a number of factors, such as an injury to the jaw or joint misalignment, and may give rise to a variety of symptoms, most commonly pain in the jaw, face, and/or neck muscles. Physicians reach a diagnosis by listening to the patient's description of the symptoms and by performing a simple examination of the facial muscles and the temporomandibular joint.

Trauma can occur after injuries in the home, at the workplace, during sports activities, or on the road. Any of these injuries can result in severe disability and pain. Some patients who have had an injury to the spinal cord experience intense pain ranging from tingling to burning and, commonly, both. Such patients are sensitive to hot and cold temperatures and touch. For these individuals, a touch can be perceived as intense burning, indicating abnormal signals relayed to and from the brain. This condition is called central pain syndrome or, if the damage is in the thalamus (the brain's center for processing bodily sensations), thalamic pain syndrome. It affects as many as 100,000 Americans with multiple sclerosis, Parkinson's disease, amputated limbs, spinal cord injuries, and stroke. Their pain is severe and is extremely difficult to treat effectively. A variety of medications, including analgesics, antidepressants, anticonvulsants, and electrical stimulation, are options available to central pain patients.

Vascular disease or injury-such as vasculitis or inflammation of blood vessels, coronary artery disease, and circulatory problems-all have the potential to cause pain. Vascular pain affects millions of Americans and occurs when communication between blood vessels and nerves is interrupted. Ruptures, spasms, constriction, or obstruction of blood vessels, as well as a condition called ischemia in which blood supply to organs, tissues, or limbs is cut off, can also result in pain.

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How is Pain Diagnosed?


There is no way to tell how much pain a person has. No test can measure the intensity of pain, no imaging device can show pain, and no instrument can locate pain precisely. Sometimes, as in the case of headaches, physicians find that the best aid to diagnosis is the patient's own description of the type, duration, and location of pain. Defining pain as sharp or dull, constant or intermittent, burning or aching may give the best clues to the cause of pain. These descriptions are part of what is called the pain history, taken by the physician during the preliminary examination of a patient with pain.

Physicians, however, do have a number of technologies they use to find the cause of pain. Primarily these include:

  • Electrodiagnostic procedures include electromyography (EMG), nerve conduction studies, and evoked potential (EP) studies. Information from EMG can help physicians tell precisely which muscles or nerves are affected by weakness or pain. Thin needles are inserted in muscles and a physician can see or listen to electrical signals displayed on an EMG machine. With nerve conduction studies the doctor uses two sets of electrodes (similar to those used during an electrocardiogram) that are placed on the skin over the muscles. The first set gives the patient a mild shock that stimulates the nerve that runs to that muscle. The second set of electrodes is used to make a recording of the nerve's electrical signals, and from this information the doctor can determine if there is nerve damage. EP tests also involve two sets of electrodes-one set for stimulating a nerve (these electrodes are attached to a limb) and another set on the scalp for recording the speed of nerve signal transmission to the brain.
  • Imaging, especially magnetic resonance imaging or MRI, provides physicians with pictures of the body's structures and tissues. MRI uses magnetic fields and radio waves to differentiate between healthy and diseased tissue.
  • A neurological examination in which the physician tests movement, reflexes, sensation, balance, and coordination.
  • X-rays produce pictures of the body's structures, such as bones and joints.
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How is Pain Treated?


The goal of pain management is to improve function, enabling individuals to work, attend school, or participate in other day-to-day activities. Patients and their physicians have a number of options for the treatment of pain; some are more effective than others. Sometimes, relaxation and the use of imagery as a distraction provide relief. These methods can be powerful and effective, according to those who advocate their use. Whatever the treatment regime, it is important to remember that pain is treatable. The following treatments are among the most common.

Acetaminophen is the basic ingredient found in Tylenol® and its many generic equivalents. It is sold over the counter, in a prescription-strength preparation, and in combination with codeine (also by prescription).

Acupuncture dates back 2,500 years and involves the application of needles to precise points on the body. It is part of a general category of healing called traditional Chinese or Oriental medicine. Acupuncture remains controversial but is quite popular and may one day prove to be useful for a variety of conditions as it continues to be explored by practitioners, patients, and investigators.

Analgesic refers to the class of drugs that includes most painkillers, such as aspirin, acetaminophen, and ibuprofen. The word analgesic is derived from ancient Greek and means to reduce or stop pain. Nonprescription or over-the-counter pain relievers are generally used for mild to moderate pain. Prescription pain relievers, sold through a pharmacy under the direction of a physician, are used for more moderate to severe pain.

Anticonvulsants are used for the treatment of seizure disorders but are also sometimes prescribed for the treatment of pain. Carbamazepine in particular is used to treat a number of painful conditions, including trigeminal neuralgia. Another antiepileptic drug, gabapentin, is being studied for its pain-relieving properties, especially as a treatment for neuropathic pain.

Antidepressants are sometimes used for the treatment of pain and, along with neuroleptics and lithium, belong to a category of drugs called psychotropic drugs. In addition, anti-anxiety drugs called benzodiazepines also act as muscle relaxants and are sometimes used as pain relievers. Physicians usually try to treat the condition with analgesics before prescribing these drugs.

Antimigraine drugs include the triptans- sumatriptan (Imitrex®), naratriptan (Amerge®), and zolmitriptan (Zomig®)-and are used specifically for migraine headaches. They can have serious side effects in some people and therefore, as with all prescription medicines, should be used only under a doctor's care.

Aspirin may be the most widely used pain-relief agent and has been sold over the counter since 1905 as a treatment for fever, headache, and muscle soreness.

Biofeedback is used for the treatment of many common pain problems, most notably headache and back pain. Using a special electronic machine, the patient is trained to become aware of, to follow, and to gain control over certain bodily functions, including muscle tension, heart rate, and skin temperature. The individual can then learn to effect a change in his or her responses to pain, for example, by using relaxation techniques. Biofeedback is often used in combination with other treatment methods, generally without side effects. Similarly, the use of relaxation techniques in the treatment of pain can increase the patient's feeling of well-being.

Capsaicin is a chemical found in chili peppers that is also a primary ingredient in pain-relieving creams (see Chili Peppers, Capsaicin, and Pain in the Appendix).

Chemonucleolysis is a treatment in which an enzyme, chymopapain, is injected directly into a herniated lumbar disc (see Spine Basics in the Appendix) in an effort to dissolve material around the disc, thus reducing pressure and pain. The procedure's use is extremely limited, in part because some patients may have a life-threatening allergic reaction to chymopapain.

Chiropractic care may ease back pain, neck pain, headaches, and musculoskeletal conditions.  It involves "hands-on" therapy designed to adjust the relationship between the body's structure (mainly the spine) and its functioning.  Chiropractic spinal manipulation includes the adjustment and manipulation of the joints and adjacent tissues.  Such care may also involve therapeutic and rehabilitative exercises.

Cognitive-behavioral therapy involves a wide variety of coping skills and relaxation methods to help prepare for and cope with pain. It is used for postoperative pain, cancer pain, and the pain of childbirth.

Counseling can give a patient suffering from pain much needed support, whether it is derived from family, group, or individual counseling. Support groups can provide an important adjunct to drug or surgical treatment. Psychological treatment can also help patients learn about the physiological changes produced by pain.

COX-2 inhibitors may be effective for individuals with arthritis. For many years scientists have wanted to develop a drug that works as well as morphine but without its negative side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by blocking two enzymes, cyclooxygenase-1 and cyclooxygenase-2, both of which promote production of hormones called prostaglandins, which in turn cause inflammation, fever, and pain. The newer COX-2 inhibitors primarily block cyclooxygenase-2 and are less likely to have the gastrointestinal side effects sometimes produced by NSAIDs.

In 1999, the Food and Drug Administration approved a COX-2 inhibitor-celecoxib-for use in cases of chronic pain. The long-term effects of all COX-2 inhibitors are still being evaluated, especially in light of new information suggesting that these drugs may increase the risk of heart attack and stroke. Patients taking any of the COX-2 inhibitors should review their drug treatment with their doctors.

Electrical stimulation, including transcutaneous electrical stimulation (TENS), implanted electric nerve stimulation, and deep brain or spinal cord stimulation, is the modern-day extension of age-old practices in which the nerves of muscles are subjected to a variety of stimuli, including heat or massage. Electrical stimulation, no matter what form, involves a major surgical procedure and is not for everyone, nor is it 100 percent effective. The following techniques each require specialized equipment and personnel trained in the specific procedure being used:

  • TENS uses tiny electrical pulses, delivered through the skin to nerve fibers, to cause changes in muscles, such as numbness or contractions. This in turn produces temporary pain relief. There is also evidence that TENS can activate subsets of peripheral nerve fibers that can block pain transmission at the spinal cord level, in much the same way that shaking your hand can reduce pain.
  • Peripheral nerve stimulation uses electrodes placed surgically on a carefully selected area of the body. The patient is then able to deliver an electrical current as needed to the affected area, using an antenna and transmitter.
  • Spinal cord stimulation uses electrodes surgically inserted within the epidural space of the spinal cord. The patient is able to deliver a pulse of electricity to the spinal cord using a small box-like receiver and an antenna taped to the skin.
  • Deep brain or intracerebral stimulation is considered an extreme treatment and involves surgical stimulation of the brain, usually the thalamus. It is used for a limited number of conditions, including severe pain, central pain syndrome, cancer pain, phantom limb pain, and other neuropathic pains.

Exercise has come to be a prescribed part of some doctors' treatment regimes for patients with pain. Because there is a known link between many types of chronic pain and tense, weak muscles, exercise-even light to moderate exercise such as walking or swimming-can contribute to an overall sense of well-being by improving blood and oxygen flow to muscles. Just as we know that stress contributes to pain, we also know that exercise, sleep, and relaxation can all help reduce stress, thereby helping to alleviate pain. Exercise has been proven to help many people with low back pain. It is important, however, that patients carefully follow the routine laid out by their physicians.

Hypnosis, first approved for medical use by the American Medical Association in 1958, continues to grow in popularity, especially as an adjunct to pain medication. In general, hypnosis is used to control physical function or response, that is, the amount of pain an individual can withstand. How hypnosis works is not fully understood. Some believe that hypnosis delivers the patient into a trance-like state, while others feel that the individual is simply better able to concentrate and relax or is more responsive to suggestion. Hypnosis may result in relief of pain by acting on chemicals in the nervous system, slowing impulses. Whether and how hypnosis works involves greater insight-and research-into the mechanisms underlying human consciousness.

Ibuprofen is a member of the aspirin family of analgesics, the so-called nonsteroidal anti-inflammatory drugs (see below). It is sold over the counter and also comes in prescription-strength preparations.

Low-power lasers have been used occasionally by some physical therapists as a treatment for pain, but like many other treatments, this method is not without controversy.

Magnets are increasingly popular with athletes who swear by their effectiveness for the control of sports-related pain and other painful conditions. Usually worn as a collar or wristwatch, the use of magnets as a treatment dates back to the ancient Egyptians and Greeks. While it is often dismissed as quackery and pseudoscience by skeptics, proponents offer the theory that magnets may effect changes in cells or body chemistry, thus producing pain relief.

Narcotics (see Opioids, below).

Nerve blocks employ the use of drugs, chemical agents, or surgical techniques to interrupt the relay of pain messages between specific areas of the body and the brain. There are many different names for the procedure, depending on the technique or agent used. Types of surgical nerve blocks include neurectomy; spinal dorsal, cranial, and trigeminal rhizotomy; and sympathectomy, also called sympathetic blockade (see Nerve Blocks in the Appendix).

Nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin and ibuprofen) are widely prescribed and sometimes called non-narcotic or non-opioid analgesics. They work by reducing inflammatory responses in tissues. Many of these drugs irritate the stomach and for that reason are usually taken with food. Although acetaminophen may have some anti-inflammatory effects, it is generally distinguished from the traditional NSAIDs.

Opioids are derived from the poppy plant and are among the oldest drugs known to humankind. They include codeine and perhaps the most well-known narcotic of all, morphine. Morphine can be administered in a variety of forms, including a pump for patient self-administration. Opioids have a narcotic effect, that is, they induce sedation as well as pain relief, and some patients may become physically dependent upon them. For these reasons, patients given opioids should be monitored carefully; in some cases stimulants may be prescribed to counteract the sedative side effects. In addition to drowsiness, other common side effects include constipation, nausea, and vomiting.

Physical therapy and rehabilitation date back to the ancient practice of using physical techniques and methods, such as heat, cold, exercise, massage, and manipulation, in the treatment of certain conditions. These may be applied to increase function, control pain, and speed the patient toward full recovery.

Placebos offer some individuals pain relief although whether and how they have an effect is mysterious and somewhat controversial. Placebos are inactive substances, such as sugar pills, or harmless procedures, such as saline injections or sham surgeries, generally used in clinical studies as control factors to help determine the efficacy of active treatments. Although placebos have no direct effect on the underlying causes of pain, evidence from clinical studies suggests that many pain conditions such as migraine headache, back pain, post-surgical pain, rheumatoid arthritis, angina, and depression sometimes respond well to them. This positive response is known as the placebo effect, which is defined as the observable or measurable change that can occur in patients after administration of a placebo. Some experts believe the effect is psychological and that placebos work because the patients believe or expect them to work. Others say placebos relieve pain by stimulating the brain's own analgesics and setting the body's self-healing forces in motion. A third theory suggests that the act of taking placebos relieves stress and anxiety-which are known to aggravate some painful conditions-and, thus, cause the patients to feel better. Still, placebos are considered controversial because by definition they are inactive and have no actual curative value.

R.I.C.E.-Rest, Ice, Compression, and Elevation-are four components prescribed by many orthopedists, coaches, trainers, nurses, and other professionals for temporary muscle or joint conditions, such as sprains or strains. While many common orthopedic problems can be controlled with these four simple steps, especially when combined with over-the-counter pain relievers, more serious conditions may require surgery or physical therapy, including exercise, joint movement or manipulation, and stimulation of muscles.

Surgery, although not always an option, may be required to relieve pain, especially pain caused by back problems or serious musculoskeletal injuries. Surgery may take the form of a nerve block (see Nerve Blocks in the Appendix) or it may involve an operation to relieve pain from a ruptured disc. Surgical procedures for back problems include discectomy or, when microsurgical techniques are used, microdiscectomy, in which the entire disc is removed; laminectomy, a procedure in which a surgeon removes only a disc fragment, gaining access by entering through the arched portion of a vertebra; and spinal fusion, a procedure where the entire disc is removed and replaced with a bone graft. In a spinal fusion, the two vertebrae are then fused together. Although the operation can cause the spine to stiffen, resulting in lost flexibility, the procedure serves one critical purpose: protection of the spinal cord. Other operations for pain include rhizotomy, in which a nerve close to the spinal cord is cut, and cordotomy, where bundles of nerves within the spinal cord are severed. Cordotomy is generally used only for the pain of terminal cancer that does not respond to other therapies. Another operation for pain is the dorsal root entry zone operation, or DREZ, in which spinal neurons corresponding to the patient's pain are destroyed surgically. Because surgery can result in scar tissue formation that may cause additional problems, patients are well advised to seek a second opinion before proceeding. Occasionally, surgery is carried out with electrodes that selectively damage neurons in a targeted area of the brain. These procedures rarely result in long-term pain relief, but both physician and patient may decide that the surgical procedure will be effective enough that it justifies the expense and risk. In some cases, the results of an operation are remarkable. For example, many individuals suffering from trigeminal neuralgia who are not responsive to drug treatment have had great success with a procedure called microvascular decompression, in which tiny blood vessels are surgically separated from surrounding nerves.

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What is the Role of Age and Gender in Pain?


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Gender and Pain


It is now widely believed that pain affects men and women differently. While the sex hormones estrogen and testosterone certainly play a role in this phenomenon, psychology and culture, too, may account at least in part for differences in how men and women receive pain signals. For example, young children may learn to respond to pain based on how they are treated when they experience pain. Some children may be cuddled and comforted, while others may be encouraged to tough it out and to dismiss their pain.

Many investigators are turning their attention to the study of gender differences and pain. Women, many experts now agree, recover more quickly from pain, seek help more quickly for their pain, and are less likely to allow pain to control their lives. They also are more likely to marshal a variety of resources-coping skills, support, and distraction-with which to deal with their pain.

Research in this area is yielding fascinating results. For example, male experimental animals injected with estrogen, a female sex hormone, appear to have a lower tolerance for pain-that is, the addition of estrogen appears to lower the pain threshold. Similarly, the presence of testosterone, a male hormone, appears to elevate tolerance for pain in female mice: the animals are simply able to withstand pain better. Female mice deprived of estrogen during experiments react to stress similarly to male animals. Estrogen, therefore, may act as a sort of pain switch, turning on the ability to recognize pain.

Investigators know that males and females both have strong natural pain-killing systems, but these systems operate differently. For example, a class of painkillers called kappa-opioids is named after one of several opioid receptors to which they bind, the kappa-opioid receptor, and they include the compounds nalbuphine (Nubain®) and butorphanol (Stadol®). Research suggests that kappa-opioids provide better pain relief in women.

Though not prescribed widely, kappa-opioids are currently used for relief of labor pain and in general work best for short-term pain. Investigators are not certain why kappa-opioids work better in women than men. Is it because a woman's estrogen makes them work, or because a man's testosterone prevents them from working? Or is there another explanation, such as differences between men and women in their perception of pain? Continued research may result in a better understanding of how pain affects women differently from men, enabling new and better pain medications to be designed with gender in mind.

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Pain in Aging and Pediatric Populations: Special Needs and Concerns


Pain is the number one complaint of older Americans, and one in five older Americans takes a painkiller regularly. In 1998, the American Geriatrics Society (AGS) issued guidelines* for the management of pain in older people. The AGS panel addressed the incorporation of several non-drug approaches in patients' treatment plans, including exercise. AGS panel members recommend that, whenever possible, patients use alternatives to aspirin, ibuprofen, and other NSAIDs because of the drugs' side effects, including stomach irritation and gastrointestinal bleeding. For older adults, acetaminophen is the first-line treatment for mild-to-moderate pain, according to the guidelines. More serious chronic pain conditions may require opioid drugs (narcotics), including codeine or morphine, for relief of pain.

Pain in younger patients also requires special attention, particularly because young children are not always able to describe the degree of pain they are experiencing. Although treating pain in pediatric patients poses a special challenge to physicians and parents alike, pediatric patients should never be undertreated. Recently, special tools for measuring pain in children have been developed that, when combined with cues used by parents, help physicians select the most effective treatments.

Nonsteroidal agents, and especially acetaminophen, are most often prescribed for control of pain in children. In the case of severe pain or pain following surgery, acetaminophen may be combined with codeine.

* Journal of the American Geriatrics Society (1998; 46:635-651).

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A Pain Primer: What Do We Know About Pain?


We may experience pain as a prick, tingle, sting, burn, or ache. Receptors on the skin trigger a series of events, beginning with an electrical impulse that travels from the skin to the spinal cord. The spinal cord acts as a sort of relay center where the pain signal can be blocked, enhanced, or otherwise modified before it is relayed to the brain. One area of the spinal cord in particular, called the dorsal horn (see section on Spine Basics in the Appendix), is important in the reception of pain signals.

The most common destination in the brain for pain signals is the thalamus and from there to the cortex, the headquarters for complex thoughts. The thalamus also serves as the brain's storage area for images of the body and plays a key role in relaying messages between the brain and various parts of the body. In people who undergo an amputation, the representation of the amputated limb is stored in the thalamus. (For a discussion of the thalamus and its role in this phenomenon, called phantom pain, see section on Phantom Pain in the Appendix.)

Pain is a complicated process that involves an intricate interplay between a number of important chemicals found naturally in the brain and spinal cord. In general, these chemicals, called neurotransmitters, transmit nerve impulses from one cell to another.

There are many different neurotransmitters in the human body; some play a role in human disease and, in the case of pain, act in various combinations to produce painful sensations in the body. Some chemicals govern mild pain sensations; others control intense or severe pain.

The body's chemicals act in the transmission of pain messages by stimulating neurotransmitter receptors found on the surface of cells; each receptor has a corresponding neurotransmitter. Receptors function much like gates or ports and enable pain messages to pass through and on to neighboring cells. One brain chemical of special interest to neuroscientists is glutamate. During experiments, mice with blocked glutamate receptors show a reduction in their responses to pain. Other important receptors in pain transmission are opiate-like receptors. Morphine and other opioid drugs work by locking on to these opioid receptors, switching on pain-inhibiting pathways or circuits, and thereby blocking pain.

Another type of receptor that responds to painful stimuli is called a nociceptor. Nociceptors are thin nerve fibers in the skin, muscle, and other body tissues, that, when stimulated, carry pain signals to the spinal cord and brain. Normally, nociceptors only respond to strong stimuli such as a pinch. However, when tissues become injured or inflamed, as with a sunburn or infection, they release chemicals that make nociceptors much more sensitive and cause them to transmit pain signals in response to even gentle stimuli such as breeze or a caress. This condition is called allodynia -a state in which pain is produced by innocuous stimuli.

The body's natural painkillers may yet prove to be the most promising pain relievers, pointing to one of the most important new avenues in drug development. The brain may signal the release of painkillers found in the spinal cord, including serotonin, norepinephrine, and opioid-like chemicals. Many pharmaceutical companies are working to synthesize these substances in laboratories as future medications.

Endorphins and enkephalins are other natural painkillers. Endorphins may be responsible for the "feel good" effects experienced by many people after rigorous exercise; they are also implicated in the pleasurable effects of smoking.

Similarly, peptides, compounds that make up proteins in the body, play a role in pain responses. Mice bred experimentally to lack a gene for two peptides called tachykinins-neurokinin A and substance P-have a reduced response to severe pain. When exposed to mild pain, these mice react in the same way as mice that carry the missing gene. But when exposed to more severe pain, the mice exhibit a reduced pain response. This suggests that the two peptides are involved in the production of pain sensations, especially moderate-to-severe pain. Continued research on tachykinins, conducted with support from the NINDS, may pave the way for drugs tailored to treat different severities of pain.

Scientists are working to develop potent pain-killing drugs that act on receptors for the chemical acetylcholine. For example, a type of frog native to Ecuador has been found to have a chemical in its skin called epibatidine, derived from the frog's scientific name, Epipedobates tricolor. Although highly toxic, epibatidine is a potent analgesic and, surprisingly, resembles the chemical nicotine found in cigarettes. Also under development are other less toxic compounds that act on acetylcholine receptors and may prove to be more potent than morphine but without its addictive properties.

The idea of using receptors as gateways for pain drugs is a novel idea, supported by experiments involving substance P. Investigators have been able to isolate a tiny population of neurons, located in the spinal cord, that together form a major portion of the pathway responsible for carrying persistent pain signals to the brain. When animals were given injections of a lethal cocktail containing substance P linked to the chemical saporin, this group of cells, whose sole function is to communicate pain, were killed. Receptors for substance P served as a portal or point of entry for the compound. Within days of the injections, the targeted neurons, located in the outer layer of the spinal cord along its entire length, absorbed the compound and were neutralized. The animals' behavior was completely normal; they no longer exhibited signs of pain following injury or had an exaggerated pain response. Importantly, the animals still responded to acute, that is, normal, pain. This is a critical finding as it is important to retain the body's ability to detect potentially injurious stimuli. The protective, early warning signal that pain provides is essential for normal functioning. If this work can be translated clinically, humans might be able to benefit from similar compounds introduced, for example, through lumbar (spinal) puncture.

Another promising area of research using the body's natural pain-killing abilities is the transplantation of chromaffin cells into the spinal cords of animals bred experimentally to develop arthritis. Chromaffin cells produce several of the body's pain-killing substances and are part of the adrenal medulla, which sits on top of the kidney. Within a week or so, rats receiving these transplants cease to exhibit telltale signs of pain. Scientists, working with support from the NINDS, believe the transplants help the animals recover from pain-related cellular damage. Extensive animal studies will be required to learn if this technique might be of value to humans with severe pain.

One way to control pain outside of the brain, that is, peripherally, is by inhibiting hormones called prostaglandins. Prostaglandins stimulate nerves at the site of injury and cause inflammation and fever. Certain drugs, including NSAIDs, act against such hormones by blocking the enzyme that is required for their synthesis.

Blood vessel walls stretch or dilate during a migraine attack and it is thought that serotonin plays a complicated role in this process. For example, before a migraine headache, serotonin levels fall. Drugs for migraine include the triptans: sumatriptan (Imitrix®), naratriptan (Amerge®), and zolmitriptan (Zomig®). They are called serotonin agonists because they mimic the action of endogenous (natural) serotonin and bind to specific subtypes of serotonin receptors.

Ongoing pain research, much of it supported by the NINDS, continues to reveal at an unprecedented pace fascinating insights into how genetics, the immune system, and the skin contribute to pain responses.

The explosion of knowledge about human genetics is helping scientists who work in the field of drug development. We know, for example, that the pain-killing properties of codeine rely heavily on a liver enzyme, CYP2D6, which helps convert codeine into morphine. A small number of people genetically lack the enzyme CYP2D6; when given codeine, these individuals do not get pain relief. CYP2D6 also helps break down certain other drugs. People who genetically lack CYP2D6 may not be able to cleanse their systems of these drugs and may be vulnerable to drug toxicity. CYP2D6 is currently under investigation for its role in pain.

In his research, the late John C. Liebeskind, a renowned pain expert and a professor of psychology at UCLA, found that pain can kill by delaying healing and causing cancer to spread. In his pioneering research on the immune system and pain, Dr. Liebeskind studied the effects of stress-such as surgery-on the immune system and in particular on cells called natural killer or NK cells. These cells are thought to help protect the body against tumors. In one study conducted with rats, Dr. Liebeskind found that, following experimental surgery, NK cell activity was suppressed, causing the cancer to spread more rapidly. When the animals were treated with morphine, however, they were able to avoid this reaction to stress.

The link between the nervous and immune systems is an important one. Cytokines, a type of protein found in the nervous system, are also part of the body's immune system, the body's shield for fighting off disease. Cytokines can trigger pain by promoting inflammation, even in the absence of injury or damage. Certain types of cytokines have been linked to nervous system injury. After trauma, cytokine levels rise in the brain and spinal cord and at the site in the peripheral nervous system where the injury occurred. Improvements in our understanding of the precise role of cytokines in producing pain, especially pain resulting from injury, may lead to new classes of drugs that can block the action of these substances.

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What is the Future of Pain Research?


In the forefront of pain research are scientists supported by the National Institutes of Health (NIH), including the NINDS. Other institutes at NIH that support pain research include the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute of Nursing Research, the National Institute on Drug Abuse, and the National Institute of Mental Health. Developing better pain treatments is the primary goal of all pain research being conducted by these institutes.

Some pain medications dull the patient's perception of pain. Morphine is one such drug. It works through the body's natural pain-killing machinery, preventing pain messages from reaching the brain. Scientists are working toward the development of a morphine-like drug that will have the pain-deadening qualities of morphine but without the drug's negative side effects, such as sedation and the potential for addiction. Patients receiving morphine also face the problem of morphine tolerance, meaning that over time they require higher doses of the drug to achieve the same pain relief. Studies have identified factors that contribute to the development of tolerance; continued progress in this line of research should eventually allow patients to take lower doses of morphine.

One objective of investigators working to develop the future generation of pain medications is to take full advantage of the body's pain "switching center" by formulating compounds that will prevent pain signals from being amplified or stop them altogether. Blocking or interrupting pain signals, especially when there is no injury or trauma to tissue, is an important goal in the development of pain medications. An increased understanding of the basic mechanisms of pain will have profound implications for the development of future medicines. The following areas of research are bringing us closer to an ideal pain drug.

Systems and Imaging: The idea of mapping cognitive functions to precise areas of the brain dates back to phrenology, the now archaic practice of studying bumps on the head. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and other imaging technologies offer a vivid picture of what is happening in the brain as it processes pain. Using imaging, investigators can now see that pain activates at least three or four key areas of the brain's cortex-the layer of tissue that covers the brain. Interestingly, when patients undergo hypnosis so that the unpleasantness of a painful stimulus is not experienced, activity in some, but not all, brain areas is reduced. This emphasizes that the experience of pain involves a strong emotional component as well as the sensory experience, namely the intensity of the stimulus.

Channels: The frontier in the search for new drug targets is represented by channels. Channels are gate-like passages found along the membranes of cells that allow electrically charged chemical particles called ions to pass into the cells. Ion channels are important for transmitting signals through the nerve's membrane. The possibility now exists for developing new classes of drugs, including pain cocktails that would act at the site of channel activity.

Trophic Factors: A class of "rescuer" or "restorer" drugs may emerge from our growing knowledge of trophic factors, natural chemical substances found in the human body that affect the survival and function of cells. Trophic factors also promote cell death, but little is known about how something beneficial can become harmful. Investigators have observed that an over-accumulation of certain trophic factors in the nerve cells of animals results in heightened pain sensitivity, and that some receptors found on cells respond to trophic factors and interact with each other. These receptors may provide targets for new pain therapies.

Molecular Genetics: Certain genetic mutations can change pain sensitivity and behavioral responses to pain. People born genetically insensate to pain-that is, individuals who cannot feel pain-have a mutation in part of a gene that plays a role in cell survival. Using "knockout" animal models-animals genetically engineered to lack a certain gene-scientists are able to visualize how mutations in genes cause animals to become anxious, make noise, rear, freeze, or become hypervigilant. These genetic mutations cause a disruption or alteration in the processing of pain information as it leaves the spinal cord and travels to the brain. Knockout animals can be used to complement efforts aimed at developing new drugs.

Plasticity: Following injury, the nervous system undergoes a tremendous reorganization. This phenomenon is known as plasticity. For example, the spinal cord is "rewired" following trauma as nerve cell axons make new contacts, a phenomenon known as "sprouting." This in turn disrupts the cells' supply of trophic factors. Scientists can now identify and study the changes that occur during the processing of pain. For example, using a technique called polymerase chain reaction, abbreviated PCR, scientists can study the genes that are induced by injury and persistent pain. There is evidence that the proteins that are ultimately synthesized by these genes may be targets for new therapies. The dramatic changes that occur with injury and persistent pain underscore that chronic pain should be considered a disease of the nervous system, not just prolonged acute pain or a symptom of an injury. Thus, scientists hope that therapies directed at preventing the long-term changes that occur in the nervous system will prevent the development of chronic pain conditions.

Neurotransmitters: Just as mutations in genes may affect behavior, they may also affect a number of neurotransmitters involved in the control of pain. Using sophisticated imaging technologies, investigators can now visualize what is happening chemically in the spinal cord. From this work, new therapies may emerge, therapies that can help reduce or obliterate severe or chronic pain.

Hope for the Future

Thousands of years ago, ancient peoples attributed pain to spirits and treated it with mysticism and incantations. Over the centuries, science has provided us with a remarkable ability to understand and control pain with medications, surgery, and other treatments. Today, scientists understand a great deal about the causes and mechanisms of pain, and research has produced dramatic improvements in the diagnosis and treatment of a number of painful disorders. For people who fight every day against the limitations imposed by pain, the work of NINDS-supported scientists holds the promise of an even greater understanding of pain in the coming years. Their research offers a powerful weapon in the battle to prolong and improve the lives of people with pain: hope.

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

National Institute of Dental and Craniofacial Research (NIDCR)
National Institutes of Health, DHHS
31 Center Drive, Room 5B-55
Bethesda, MD   20892
nidcrinfo@mail.nih.gov
http://www.nidcr.nih.gov
Tel: 301-496-4261

American Chronic Pain Association (ACPA)
P.O. Box 850
Rocklin, CA   95677-0850
ACPA@pacbell.net
http://www.theacpa.org
Tel: 916-632-0922 800-533-3231
Fax: 916-652-8190
Provides self-help coping skills and peer support to people with chronic pain. Sponsors local support groups throughout the U.S. and provides assistance in starting and maintaining support groups.

American Headache Society Committee for Headache Education (ACHE)
19 Mantua Road
Mt. Royal, NJ   08061
achehq@talley.com
http://www.achenet.org
Tel: 856-423-0043
Fax: 856-423-0082
The American Headache Society Committee on Headache Education (ACHE) is a nonprofit patient-health professional partnership dedicated to advancing the treatment and management of patients with headache.

National Headache Foundation
820 N. Orleans
Suite 217
Chicago, IL   60610-3132
info@headaches.org
http://www.headaches.org
Tel: 312-274-2650 888-NHF-5552 (643-5552)
Fax: 312-640-9049
Non-profit organization dedicated to service headache sufferers, their families, and the healthcare practitioners who treat them. Promotes research into headache causes and treatments and educates the public.

National Foundation for the Treatment of Pain
P.O. Box 70045
Houston, TX   77270
NFTPain@cwo.com
http://www.paincare.org
Tel: 713-862-9332
Fax: 713-862-9346
Not-for-profit organization dedicated to providing support for patients who are suffering from intractable pain, their families, friends and the physicians who treat them. Offers a patient forum, advocacy programs, information, support resources, and direct medical intervention.

Mayday Fund [For Pain Research]
c/o SPG
136 West 21st Street, 6th Floor
New York, NY   10011
mayday@maydayfund.org
http://www.painandhealth.org
Tel: 212-366-6970
Fax: 212-366-6979
The Mayday Pain Project works to increase awareness and to provide objective information concerning the treatment of pain.

American Pain Foundation
201 North Charles Street
Suite 710
Baltimore, MD   21201-4111
info@painfoundation.org
http://www.painfoundation.org
Tel: 888-615-PAIN (7246)
Fax: 410-385-1832
Independent non-profit information, education, and advocacy organization serving people with pain. Works to improve the quality of life for people with pain by raising public awareness, providing practical information, promoting research, and advocating the removal of barriers and increased access to effective pain management.

Arthritis Foundation
1330 West Peachtree Street
Suite 100
Atlanta, GA   30309
help@arthritis.org
http://www.arthritis.org
Tel: 800-283-7800 404-872-7100 404-965-7888
Fax: 404-872-0457
Volunteer-driven organization that works to improve lives through leadership in the prevention, control, and cure of arthritis and related diseases. Offers free brochures on various types of arthritis, treatment options, and management of daily activities when affected.

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Appendix

Spine Basics: The Vertebrae, Discs, and Spinal Cord

Stacked on top of one another in the spine are more than 30 bones, the vertebrae, which together form the spine. They are divided into four regions:

  • the seven cervical or neck vertebrae (labeled C1-C7),
  • the 12 thoracic or upper back vertebrae (labeled T1-T12),
  • the five lumbar vertebrae (labeled L1-L5), which we know as the lower back, and
  • the sacrum and coccyx, a group of bones fused together at the base of the spine.

The vertebrae are linked by ligaments, tendons, and muscles. Back pain can occur when, for example, someone lifts something too heavy, causing a sprain, pull, strain, or spasm in one of these muscles or ligaments in the back.

Between the vertebrae are round, spongy pads of cartilage called discs that act much like shock absorbers. In many cases, degeneration or pressure from overexertion can cause a disc to shift or protrude and bulge, causing pressure on a nerve and resultant pain. When this happens, the condition is called a slipped, bulging, herniated, or ruptured disc, and it sometimes results in permanent nerve damage.

The column-like spinal cord is divided into segments similar to the corresponding vertebrae: cervical, thoracic, lumbar, sacral, and coccygeal. The cord also has nerve roots and rootlets which form branch-like appendages leading from its ventral side (that is, the front of the body) and from its dorsal side (that is, the back of the body). Along the dorsal root are the cells of the dorsal root ganglia, which are critical in the transmission of "pain" messages from the cord to the brain. It is here where injury, damage, and trauma become pain.

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The Nervous Systems

The central nervous system (CNS) refers to the brain and spinal cord together. The peripheral nervous system refers to the cervical, thoracic, lumbar, and sacral nerve trunks leading away from the spine to the limbs. Messages related to function (such as movement) or dysfunction (such as pain) travel from the brain to the spinal cord and from there to other regions in the body and back to the brain again. The autonomic nervous system controls involuntary functions in the body, like perspiration, blood pressure, heart rate, or heart beat. It is divided into the sympathetic and parasympathetic nervous systems. The sympathetic and parasympathetic nervous systems have links to important organs and systems in the body; for example, the sympathetic nervous system controls the heart, blood vessels, and respiratory system, while the parasympathetic nervous system controls our ability to sleep, eat, and digest food.

The peripheral nervous system also includes 12 pairs of cranial nerves located on the underside of the brain. Most relay messages of a sensory nature. They include the olfactory (I), optic (II), oculomotor (III), trochlear (IV), trigeminal (V), abducens (VI), facial (VII), vestibulocochlear (VIII), glossopharyngeal (IX), vagus (X), accessory (XI), and hypoglossal (XII) nerves. Neuralgia, as in trigeminal neuralgia, is a term that refers to pain that arises from abnormal activity of a nerve trunk or its branches. The type and severity of pain associated with neuralgia vary widely.

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Phantom Pain: How Does the Brain Feel?

Sometimes, when a limb is removed during an amputation, an individual will continue to have an internal sense of the lost limb. This phenomenon is known as phantom limb and accounts describing it date back to the 1800s. Similarly, many amputees are frequently aware of severe pain in the absent limb. Their pain is real and is often accompanied by other health problems, such as depression.

What causes this phenomenon? Scientists believe that following amputation, nerve cells "rewire" themselves and continue to receive messages, resulting in a remapping of the brain's circuitry. The brain's ability to restructure itself, to change and adapt following injury, is called plasticity (see section on Plasticity).

Our understanding of phantom pain has improved tremendously in recent years. Investigators previously believed that brain cells affected by amputation simply died off. They attributed sensations of pain at the site of the amputation to irritation of nerves located near the limb stump. Now, using imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI), scientists can actually visualize increased activity in the brain's cortex when an individual feels phantom pain. When study participants move the stump of an amputated limb, neurons in the brain remain dynamic and excitable. Surprisingly, the brain's cells can be stimulated by other body parts, often those located closest to the missing limb.

Treatments for phantom pain may include analgesics, anticonvulsants, and other types of drugs; nerve blocks; electrical stimulation; psychological counseling, biofeedback, hypnosis, and acupuncture; and, in rare instances, surgery.

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Chili Peppers, Capsaicin, and Pain

The hot feeling, red face, and watery eyes you experience when you bite into a red chili pepper may make you reach for a cold drink, but that reaction has also given scientists important information about pain. The chemical found in chili peppers that causes those feelings is capsaicin (pronounced cap-SAY-sin), and it works its unique magic by grabbing onto receptors scattered along the surface of sensitive nerve cells in the mouth.

In 1997, scientists at the University of California at San Francisco discovered a gene for a capsaicin receptor, called the vanilloid receptor. Once in contact with capsaicin, vanilloid receptors open and pain signals are sent from the peripheral nociceptor and through central nervous system circuits to the brain. Investigators have also learned that this receptor plays a role in the burning type of pain commonly associated with heat, such as the kind you experience when you touch your finger to a hot stove. The vanilloid receptor functions as a sort of "ouch gateway," enabling us to detect burning hot pain, whether it originates from a 3-alarm habanera chili or from a stove burner.

Capsaicin is currently available as a prescription or over-the-counter cream for the treatment of a number of pain conditions, such as shingles. It works by reducing the amount of substance P found in nerve endings and interferes with the transmission of pain signals to the brain. Individuals can become desensitized to the compound, however, perhaps because of long-term damage to nerve tissue. Some individuals find the burning sensation they experience when using capsaicin cream to be intolerable, especially when they are already suffering from a painful condition, such as postherpetic neuralgia. Soon, however, better treatments that relieve pain by blocking vanilloid receptors may arrive in drugstores.

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Marijuana

As a painkiller, marijuana or, by its Latin name, cannabis, continues to remain highly controversial. In the eyes of many individuals campaigning on its behalf, marijuana rightfully belongs with other pain remedies. In fact, for many years, it was sold under highly controlled conditions in cigarette form by the Federal government for just that purpose.

In 1997, the National Institutes of Health held a workshop to discuss research on the possible therapeutic uses for smoked marijuana. Panel members from a number of fields reviewed published research and heard presentations from pain experts. The panel members concluded that, because there are too few scientific studies to prove marijuana's therapeutic utility for certain conditions, additional research is needed. There is evidence, however, that receptors to which marijuana binds are found in many brain regions that process information that can produce pain.

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Nerve Blocks

Nerve blocks may involve local anesthesia, regional anesthesia or analgesia, or surgery; dentists routinely use them for traditional dental procedures. Nerve blocks can also be used to prevent or even diagnose pain.

In the case of a local nerve block, any one of a number of local anesthetics may be used; the names of these compounds, such as lidocaine or novocaine, usually have an aine ending. Regional blocks affect a larger area of the body. Nerve blocks may also take the form of what is commonly called an epidural, in which a drug is administered into the space between the spine's protective covering (the dura) and the spinal column. This procedure is most well known for its use during childbirth. Morphine and methadone are opioid narcotics (such drugs end in ine or one) that are sometimes used for regional analgesia and are administered as an injection.

Neurolytic blocks employ injection of chemical agents such as alcohol, phenol, or glycerol to block pain messages and are most often used to treat cancer pain or to block pain in the cranial nerves (see The Nervous Systems). In some cases, a drug called guanethidine is administered intravenously in order to accomplish the block.

Surgical blocks are performed on cranial, peripheral, or sympathetic nerves. They are most often done to relieve the pain of cancer and extreme facial pain, such as that experienced with trigeminal neuralgia. There are several different types of surgical nerve blocks and they are not without problems and complications. Nerve blocks can cause muscle paralysis and, in many cases, result in at least partial numbness. For that reason, the procedure should be reserved for a select group of patients and should only be performed by skilled surgeons. Types of surgical nerve blocks include:

  • Neurectomy (including peripheral neurectomy) in which a damaged peripheral nerve is destroyed.
  • Spinal dorsal rhizotomy in which the surgeon cuts the root or rootlets of one or more of the nerves radiating from the spine. Other rhizotomy procedures include cranial rhizotomy and trigeminal rhizotomy, performed as a treatment for extreme facial pain or for the pain of cancer.
  • Sympathectomy, also called sympathetic blockade, in which a drug or an agent such as guanethidine is used to eliminate pain in a specific area (a limb, for example). The procedure is also done for cardiac pain, vascular disease pain, the pain of reflex sympathetic dystrophy syndrome, and other conditions. The term takes its name from the sympathetic nervous system (see The Nervous Systems) and may involve, for example, cutting a nerve that controls contraction of one or more arteries.
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"Pain: Hope Through Research," NINDS. Publication date December 2001.

NIH Publication No. 01-2406


 

Dementia

 


Introduction


A woman in her early 50s was admitted to a hospital because of increasingly odd behavior. Her family reported that she had been showing memory problems and strong feelings of jealousy. She also had become disoriented at home and was hiding objects. During a doctor's examination, the woman was unable to remember her husband's name, the year, or how long she had been at the hospital. She could read but did not seem to understand what she read, and she stressed the words in an unusual way. She sometimes became agitated and seemed to have hallucinations and irrational fears.

This woman, known as Auguste D., was the first person reported to have the disease now known as Alzheimer's disease * (AD) after Alois Alzheimer, the German doctor who first described it. After Auguste D. died in 1906, doctors examined her brain and found that it appeared shrunken and contained several unusual features, including strange clumps of protein called plaques and tangled fibers inside the nerve cells. Memory impairments and other symptoms of dementia, which means "deprived of mind," had been described in older adults since ancient times. However, because Auguste D. began to show symptoms at a relatively early age, doctors did not think her disease could be related to what was then called "senile dementia. "The word senile is derived from a Latin term that means, roughly, "old age."

It is now clear that AD is a major cause of dementia in elderly people as well as in relatively young adults. Furthermore, we know that it is only one of many disorders that can lead to dementia. The U. S. Congress Office of Technology Assessment estimates that as many as 6.8 million people in the United States have dementia, and at least 1.8 million of those are severely affected. Studies in some communities have found that almost half of all people age 85 and older have some form of dementia. Although it is common in very elderly individuals, dementia is not a normal part of the aging process. Many people live into their 90s and even 100s without any symptoms of dementia.

Besides senile dementia, other terms often used to describe dementia include senility and organic brain syndrome. Senility and senile dementia are outdated terms that reflect the formerly widespread belief that dementia was a normal part of aging. Organic brain syndrome is a general term that refers to physical disorders (not psychiatric in origin) that impair mental functions.

Research in the last 30 years has led to a greatly improved understanding of what dementia is, who gets it, and how it develops and affects the brain. This work is beginning to pay off with better diagnostic techniques, improved treatments, and even potential ways of preventing these diseases.

*Terms in Italics are defined in the glossary.

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What Is Dementia?


Dementia is not a specific disease. It is a descriptive term for a collection of symptoms that can be caused by a number of disorders that affect the brain. People with dementia have significantly impaired intellectual functioning that interferes with normal activities and relationships. They also lose their ability to solve problems and maintain emotional control, and they may experience personality changes and behavioral problems such as agitation, delusions, and hallucinations. While memory loss is a common symptom of dementia, memory loss by itself does not mean that a person has dementia. Doctors diagnose dementia only if two or more brain functions - such as memory, language skills, perception, or cognitive skills including reasoning and judgment - are significantly impaired without loss of consciousness.

There are many disorders that can cause dementia. Some, such as AD, lead to a progressive loss of mental functions. But other types of dementia can be halted or reversed with appropriate treatment.

With AD and many other types of dementia, disease processes cause many nerve cells to stop functioning, lose connections with other neurons, and die. In contrast, normal aging does not result in the loss of large numbers of neurons in the brain.

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What Are the Different Kinds of Dementia?


Dementing disorders can be classified many different ways. These classification schemes attempt to group disorders that have particular features in common, such as whether they are progressive or what parts of the brain are affected. Some frequently used classifications include the following:

·        Cortical dementia - dementia where the brain damage primarily affects the brain's cortex, or outer layer. Cortical dementias tend to cause problems with memory, language, thinking, and social behavior.

·        Subcortical dementia - dementia that affects parts of the brain below the cortex. Subcortical dementia tends to cause changes in emotions and movement in addition to problems with memory.

·        Progressive dementia - dementia that gets worse over time, gradually interfering with more and more cognitive abilities.

·        Primary dementia - dementia such as AD that does not result from any other disease.

·        Secondary dementia - dementia that occurs as a result of a physical disease or injury.

Some types of dementia fit into more than one of these classifications. For example, AD is considered both a progressive and a cortical dementia.

Alzheimer's disease is the most common cause of dementia in people aged 65 and older. Experts believe that up to 4 million people in the United States are currently living with the disease: one in ten people over the age of 65 and nearly half of those over 85 have AD. At least 360,000 Americans are diagnosed with AD each year and about 50,000 are reported to die from it.

In most people, symptoms of AD appear after age 60. However, there are some early-onset forms of the disease, usually linked to a specific gene defect, which may appear as early as age 30. AD usually causes a gradual decline in cognitive abilities, usually during a span of 7 to 10 years. Nearly all brain functions, including memory, movement, language, judgment, behavior, and abstract thinking, are eventually affected.

AD is characterized by two abnormalities in the brain: amyloid plaques and neurofibrillary tangles. Amyloid plaques, which are found in the tissue between the nerve cells, are unusual clumps of a protein called beta amyloid along with degenerating bits of neurons and other cells.

Neurofibrillary tangles are bundles of twisted filaments found within neurons. These tangles are largely made up of a protein called tau. In healthy neurons, the tau protein helps the functioning of microtubules, which are part of the cell's structural support and deliver substances throughout the nerve cell. However, in AD, tau is changed in a way that causes it to twist into pairs of helical filaments that collect into tangles. When this happens, the microtubules cannot function correctly and they disintegrate. This collapse of the neuron's transport system may impair communication between nerve cells and cause them to die.

Researchers do not know if amyloid plaques and neurofibrillary tangles are harmful or if they are merely side effects of the disease process that damages neurons and leads to the symptoms of AD. They do know that plaques and tangles usually increase in the brain as AD progresses.

In the early stages of AD, patients may experience memory impairment, lapses of judgment, and subtle changes in personality. As the disorder progresses, memory and language problems worsen and patients begin to have difficulty performing activities of daily living, such as balancing a checkbook or remembering to take medications. They also may have visuospatial problems, such as difficulty navigating an unfamiliar route. They may become disoriented about places and times, may suffer delusions (such as the idea that someone is stealing from them or that their spouse is being unfaithful), and may become short-tempered and hostile. During the late stages of the disease, patients begin to lose the ability to control motor functions. They may have difficulty swallowing and lose bowel and bladder control. They eventually lose the ability to recognize family members and to speak. As AD progresses, it begins to affect the person's emotions and behavior. Most people with AD eventually develop symptoms such as aggression, agitation, depression, sleeplessness, or delusions.

On average, patients with AD live for 8 to 10 years after they are diagnosed. However, some people live as long as 20 years. Patients with AD often die of aspiration pneumonia because they lose the ability to swallow late in the course of the disease.

Vascular dementia is the second most common cause of dementia, after AD. It accounts for up to 20 percent of all dementias and is caused by brain damage from cerebrovascular or cardiovascular problems - usually strokes. It also may result from genetic diseases, endocarditis (infection of a heart valve), or amyloid angiopathy (a process in which amyloid protein builds up in the brain's blood vessels, sometimes causing hemorrhagic or "bleeding" strokes). In many cases, it may coexist with AD. The incidence of vascular dementia increases with advancing age and is similar in men and women.

Symptoms of vascular dementia often begin suddenly, frequently after a stroke. Patients may have a history of high blood pressure, vascular disease, or previous strokes or heart attacks. Vascular dementia may or may not get worse with time, depending on whether the person has additional strokes. In some cases, symptoms may get better with time. When the disease does get worse, it often progresses in a stepwise manner, with sudden changes in ability. Vascular dementia with brain damage to the mid-brain regions, however, may cause a gradual, progressive cognitive impairment that may look much like AD. Unlike people with AD, people with vascular dementia often maintain their personality and normal levels of emotional responsiveness until the later stages of the disease.

People with vascular dementia frequently wander at night and often have other problems commonly found in people who have had a stroke, including depression and incontinence.

There are several types of vascular dementia, which vary slightly in their causes and symptoms. One type, called multi-infarct dementia (MID), is caused by numerous small strokes in the brain. MID typically includes multiple damaged areas, called infarcts, along with extensive lesions in the white matter, or nerve fibers, of the brain.

Because the infarcts in MID affect isolated areas of the brain, the symptoms are often limited to one side of the body or they may affect just one or a few specific functions, such as language. Neurologists call these "local" or "focal" symptoms, as opposed to the "global" symptoms seen in AD, which affect many functions and are not restricted to one side of the body.

Although not all strokes cause dementia, in some cases a single stroke can damage the brain enough to cause dementia. This condition is called single-infarct dementia. Dementia is more common when the stroke takes place on the left side (hemisphere) of the brain and/or when it involves the hippocampus, a brain structure important for memory.

Another type of vascular dementia is called Binswanger's disease. This rare form of dementia is characterized by damage to small blood vessels in the white matter of the brain (white matter is found in the inner layers of the brain and contains many nerve fibers coated with a whitish, fatty substance called myelin). Binswanger's disease leads to brain lesions, loss of memory, disordered cognition, and mood changes. Patients with this disease often show signs of abnormal blood pressure, stroke, blood abnormalities, disease of the large blood vessels in the neck, and/or disease of the heart valves. Other prominent features include urinary incontinence, difficulty walking, clumsiness, slowness, lack of facial expression, and speech difficulty. These symptoms, which usually begin after the age of 60, are not always present in all patients and may sometimes appear only temporarily. Treatment of Binswanger's disease is symptomatic, and may include the use of medications to control high blood pressure, depression, heart arrhythmias, and low blood pressure. The disorder often includes episodes of partial recovery.

Another type of vascular dementia is linked to a rare hereditary disorder called CADASIL, which stands for cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy. CADASIL is linked to abnormalities of a specific gene, Notch3, which is located on chromosome 19. This condition causes multi-infarct dementia as well as stroke, migraine with aura, and mood disorders. The first symptoms usually appear in people who are in their twenties, thirties, or forties and affected individuals often die by age 65. Researchers believe most people with CADASIL go undiagnosed, and the actual prevalence of the disease is not yet known.

Other causes of vascular dementia include vasculitis, an inflammation of the blood vessel system; profound hypotension (low blood pressure); and lesions caused by brain hemorrhage. The autoimmune disease lupus erythematosus and the inflammatory disease temporal arteritis can also damage blood vessels in a way that leads to vascular dementia.

Lewy body dementia (LBD) is one of the most common types of progressive dementia. LBD usually occurs sporadically, in people with no known family history of the disease. However, rare familial cases have occasionally been reported.

In LBD, cells die in the brain's cortex, or outer layer, and in a part of the mid-brain called the substantia nigra. Many of the remaining nerve cells in the substantia nigra contain abnormal structures called Lewy bodies that are the hallmark of the disease. Lewy bodies may also appear in the brain's cortex, or outer layer. Lewy bodies contain a protein called alpha-synuclein that has been linked to Parkinson's disease and several other disorders. Researchers, who sometimes refer to these disorders collectively as "synucleinopathies," do not yet know why this protein accumulates inside nerve cells in LBD.

The symptoms of LBD overlap with AD in many ways, and may include memory impairment, poor judgment, and confusion. However, LBD typically also includes visual hallucinations, parkinsonian symptoms such as a shuffling gait and flexed posture, and day-to-day fluctuations in the severity of symptoms. Patients with LBD live an average of 7 years after symptoms begin.

There is no cure for LBD, and treatments are aimed at controlling the parkinsonian and psychiatric symptoms of the disorder. Patients sometimes respond dramatically to treatment with antiparkinsonian drugs and/or cholinesterase inhibitors, such as those used for AD. Some studies indicate that neuroleptic drugs, such as clozapine and olanzapine, also can reduce the psychiatric symptoms of this disease. But neuroleptic drugs may cause severe adverse reactions, so other therapies should be tried first and patients using these drugs should be closely monitored.

Lewy bodies are often found in the brains of people with Parkinson's and AD. These findings suggest that either LBD is related to these other causes of dementia or that the diseases sometimes coexist in the same person.

Frontotemporal dementia (FTD), sometimes called frontal lobe dementia, describes a group of diseases characterized by degeneration of nerve cells - especially those in the frontal and temporal lobes of the brain. Unlike AD, FTD usually does not include formation of amyloid plaques. In many people with FTD, there is an abnormal form of tau protein in the brain, which accumulates into neurofibrillary tangles. This disrupts normal cell activities and may cause the cells to die.

Experts believe FTD accounts for 2 to 10 percent of all cases of dementia. Symptoms of FTD usually appear between the ages of 40 and 65. In many cases, people with FTD have a family history of dementia, suggesting that there is a strong genetic factor in the disease. The duration of FTD varies, with some patients declining rapidly over 2 to 3 years and others showing only minimal changes for many years. People with FTD live with the disease for an average of 5 to 10 years after diagnosis.

Because structures found in the frontal and temporal lobes of the brain control judgment and social behavior, people with FTD often have problems maintaining normal interactions and following social conventions. They may steal or exhibit impolite and socially inappropriate behavior, and they may neglect their normal responsibilities. Other common symptoms include loss of speech and language, compulsive or repetitive behavior, increased appetite, and motor problems such as stiffness and balance problems. Memory loss also may occur, although it typically appears late in the disease.

In one type of FTD called Pick's disease, certain nerve cells become abnormal and swollen before they die. These swollen, or ballooned, neurons are one hallmark of the disease. The brains of people with Pick's disease also have abnormal structures called Pick bodies, composed largely of the protein tau, inside the neurons. The cause of Pick's disease is unknown, but it runs in some families and thus it is probably due at least in part to a faulty gene or genes. The disease usually begins after age 50 and causes changes in personality and behavior that gradually worsen over time. The symptoms of Pick's disease are very similar to those of AD, and may include inappropriate social behavior, loss of mental flexibility, language problems, and difficulty with thinking and concentration. There is currently no way to slow the progressive degeneration found in Pick's disease. However, medication may be helpful in reducing aggression and other behavioral problems, and in treating depression.

In some cases, familial FTD is linked to a mutation in the tau gene. This disorder, called frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), is much like other types of FTD but often includes psychiatric symptoms such as delusions and hallucinations.

Primary progressive aphasia (PPA) is a type of FTD that may begin in people as early as their forties. "Aphasia" is a general term used to refer to deficits in language functions, such as speaking, understanding what others are saying, and naming common objects. In PPA one or more of these functions can become impaired. Symptoms often begin gradually and progress slowly over a period of years. As the disease progresses, memory and attention may also be impaired and patients may show personality and behavior changes. Many, but not all, people with PPA eventually develop symptoms of dementia.

HIV-associated dementia (HAD) results from infection with the human immunodeficiency virus (HIV) that causes AIDS. HAD can cause widespread destruction of the brain's white matter. This leads to a type of dementia that generally includes impaired memory, apathy, social withdrawal, and difficulty concentrating. People with HAD often develop movement problems as well. There is no specific treatment for HAD, but AIDS drugs can delay onset of the disease and may help to reduce symptoms.

Huntington's disease (HD) is a hereditary disorder caused by a faulty gene for a protein called huntingtin. The children of people with the disorder have a 50 percent chance of inheriting it. The disease causes degeneration in many regions of the brain and spinal cord. Symptoms of HD usually begin when patients are in their thirties or forties, and the average life expectancy after diagnosis is about 15 years.

Cognitive symptoms of HD typically begin with mild personality changes, such as irritability, anxiety, and depression, and progress to severe dementia. Many patients also show psychotic behavior. HD causes chorea - involuntary jerky, arrhythmic movements of the body - as well as muscle weakness, clumsiness, and gait disturbances.

Dementia pugilistica, also called chronic traumatic encephalopathy or Boxer's syndrome, is caused by head trauma, such as that experienced by people who have been punched many times in the head during boxing. The most common symptoms of the condition are dementia and parkinsonism, which can appear many years after the trauma ends. Affected individuals may also develop poor coordination and slurred speech. A single traumatic brain injury may also lead to a disorder called post-traumatic dementia (PTD). PTD is much like dementia pugilistica but usually also includes long-term memory problems. Other symptoms vary depending on which part of the brain was damaged by the injury.

Corticobasal degeneration (CBD) is a progressive disorder characterized by nerve cell loss and atrophy of multiple areas of the brain. Brain cells from people with CBD often have abnormal accumulations of the protein tau. CBD usually progresses gradually over the course of 6 to 8 years. Initial symptoms, which typically begin at or around age 60, may first appear on one side of the body but eventually will affect both sides. Some of the symptoms, such as poor coordination and rigidity, are similar to those found in Parkinson's disease. Other symptoms may include memory loss, dementia, visual-spatial problems, apraxia (loss of the ability to make familiar, purposeful movements), hesitant and halting speech, myoclonus (involuntary muscular jerks), and dysphagia (difficulty swallowing). Death is often caused by pneumonia or other secondary problems such as sepsis (severe infection of the blood) or pulmonary embolism (a blood clot in the lungs).

There are no specific treatments available for CBD. Drugs such as clonazepam may help with myoclonus, however, and occupational, physical, and speech therapy can help in managing the disabilities associated with this disease. The symptoms of the disease often do not respond to Parkinson's medications or other drugs.

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, fatal brain disorder that affects about one in every million people per year worldwide. Symptoms usually begin after age 60 and most patients die within 1 year. Many researchers believe CJD results from an abnormal form of a protein called a prion. Most cases of CJD occur sporadically - that is, in people who have no known risk factors for the disease. However, about 5 to 10 percent of cases of CJD in the United States are hereditary, caused by a mutation in the gene for the prion protein. In rare cases, CJD can also be acquired through exposure to diseased brain or nervous system tissue, usually through certain medical procedures. There is no evidence that CJD is contagious through the air or through casual contact with a CJD patient.

Patients with CJD may initially experience problems with muscular coordination; personality changes, including impaired memory, judgment, and thinking; and impaired vision. Other symptoms may include insomnia and depression. As the illness progresses, mental impairment becomes severe. Patients often develop myoclonus and they may go blind. They eventually lose the ability to move and speak, and go into a coma. Pneumonia and other infections often occur in these patients and can lead to death.

CJD belongs to a family of human and animal diseases known as the transmissible spongiform encephalopathies (TSEs). Spongiform refers to the characteristic appearance of infected brains, which become filled with holes until they resemble sponges when viewed under a microscope. CJD is the most common of the known human TSEs. Others include fatal familial insomnia and Gerstmann-Straussler-Scheinker disease (see below).

In recent years, a new type of CJD, called variant CJD (vCJD), has been found in Great Britain and several other European countries. The initial symptoms of vCJD are different from those of classic CJD and the disorder typically occurs in younger patients. Research suggests that vCJD may have resulted from human consumption of beef from cattle with a TSE disease called bovine spongiform encephalopathy (BSE), also known as "mad cow disease."

Other rare hereditary dementias include Gerstmann-Straussler-Scheinker (GSS) disease, fatal familial insomnia, familial British dementia, and familial Danish dementia. Symptoms of GSS typically include ataxia and progressive dementia that begins when people are between 50 and 60 years old. The disease may last for several years before patients eventually die. Fatal familial insomnia causes degeneration of a brain region called the thalamus, which is partially responsible for controlling sleep. It causes a progressive insomnia that eventually leads to a complete inability to sleep. Other symptoms may include poor reflexes, dementia, hallucinations, and eventually coma. It can be fatal within 7 to 13 months after symptoms begin but may last longer. Familial British dementia and familial Danish dementia have been linked to two different defects in a gene found on chromosome 13. The symptoms of both diseases include progressive dementia, paralysis, and loss of balance.

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Secondary Dementias


Dementia may occur in patients who have other disorders that primarily affect movement or other functions. These cases are often referred to as secondary dementias. The relationship between these disorders and the primary dementias is not always clear. For instance, people with advanced Parkinson's disease, which is primarily a movement disorder, sometimes develop symptoms of dementia. Many Parkinson's patients also have amyloid plaques and neurofibrillary tangles like those found in AD. The two diseases may be linked in a yet-unknown way, or they may simply coexist in some people. People with Parkinson's and associated dementia sometimes show signs of Lewy body dementia or progressive supranuclear palsy at autopsy, suggesting that these diseases may also overlap with Parkinson's or that Parkinson's is sometimes misdiagnosed.

Other disorders that may include symptoms of dementia include multiple sclerosis; presenile dementia with motor neuron disease, also called ALS dementia; olivopontocerebellar atrophy (OPCA); Wilson's disease; and normal pressure hydrocephalus (NPH).

More information about these disorders is available from the NINDS (see Where can I get more information?).

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Dementias in Children


While it is usually found in adults, dementia can also occur in children. For example, infections and poisoning can lead to dementia in people of any age. In addition, some disorders unique to children can cause dementia.

Niemann-Pick disease is a group of inherited disorders that affect metabolism and are caused by specific genetic mutations. Patients with Niemann-Pick disease cannot properly metabolize cholesterol and other lipids. Consequently, excessive amounts of cholesterol accumulate in the liver and spleen and excessive amounts of other lipids accumulate in the brain. Symptoms may include dementia, confusion, and problems with learning and memory. These diseases usually begin in young school-age children but may also appear during the teen years or early adulthood.

Batten disease is a fatal, hereditary disorder of the nervous system that begins in childhood. Symptoms are linked to a buildup of substances called lipopigments in the body's tissues. The early symptoms include personality and behavior changes, slow learning, clumsiness, or stumbling. Over time, affected children suffer mental impairment, seizures, and progressive loss of sight and motor skills. Eventually, children with Batten disease develop dementia and become blind and bedridden. The disease is often fatal by the late teens or twenties.

Lafora body disease is a rare genetic disease that causes seizures, rapidly progressive dementia, and movement problems. These problems usually begin in late childhood or the early teens. Children with Lafora body disease have microscopic structures called Lafora bodies in the brain, skin, liver, and muscles. Most affected children die within 2 to 10 years after the onset of symptoms.

A number of other childhood-onset disorders can include symptoms of dementia. Among these are mitochondrial myopathies, Rasmussen's encephalitis, mucopolysaccharidosis III (Sanfilippo syndrome), neurodegeneration with brain iron accumulation, and leukodystrophies such as Alexander disease, Schilder's disease, and metachromatic leukodystrophy.

More information about these disorders is available from the NINDS (see Where can I get more information?).

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What Other Conditions Can Cause Dementia?


Doctors have identified many other conditions that can cause dementia or dementia-like symptoms. Many of these conditions are reversible with appropriate treatment.

Reactions to medications. Medications can sometimes lead to reactions or side effects that mimic dementia. These dementia-like effects can occur in reaction to just one drug or they can result from drug interactions. They may have a rapid onset or they may develop slowly over time.

Metabolic problems and endocrine abnormalities. Thyroid problems can lead to apathy, depression, or dementia. Hypoglycemia, a condition in which there is not enough sugar in the bloodstream, can cause confusion or personality changes. Too little or too much sodium or calcium can also trigger mental changes. Some people have an impaired ability to absorb vitamin B12, which creates a condition called pernicious anemia that can cause personality changes, irritability, or depression. Tests can determine if any of these problems are present.

Nutritional deficiencies. Deficiencies of thiamine (vitamin B1) frequently result from chronic alcoholism and can seriously impair mental abilities, in particular memories of recent events. Severe deficiency of vitamin B6 can cause a neurological illness called pellagra that may include dementia. Deficiencies of vitamin B12 also have been linked to dementia in some cases. Dehydration can also cause mental impairment that can resemble dementia.

Infections. Many infections can cause neurological symptoms, including confusion or delirium, due to fever or other side effects of the body's fight to overcome the infection. Meningitis and encephalitis, which are infections of the brain or the membrane that covers it, can cause confusion, sudden severe dementia, withdrawal from social interaction, impaired judgment, or memory loss. Untreated syphilis also can damage the nervous system and cause dementia. In rare cases, Lyme disease can cause memory or thinking difficulties. People in the advanced stages of AIDS also may develop a form of dementia (see HIV-associated dementia, page 14). People with compromised immune systems, such as those with leukemia and AIDS, may also develop an infection called progressive multifocal leukoencephalopathy (PML). PML is caused by a common human polyomavirus, JC virus, and leads to damage or destruction of the myelin sheath that covers nerve cells. PML can lead to confusion, difficulty with thinking or speaking, and other mental problems.

Subdural hematomas. Subdural hematomas, or bleeding between the brain's surface and its outer covering (the dura), can cause dementia-like symptoms and changes in mental function.

Poisoning. Exposure to lead, other heavy metals, or other poisonous substances can lead to symptoms of dementia. These symptoms may or may not resolve after treatment, depending on how badly the brain is damaged. People who have abused substances such as alcohol and recreational drugs sometimes display signs of dementia even after the substance abuse has ended. This condition is known as substance-induced persisting dementia.

Brain tumors. In rare cases, people with brain tumors may develop dementia because of damage to their brains. Symptoms may include changes in personality, psychotic episodes, or problems with speech, language, thinking, and memory.

Anoxia. Anoxia and a related term, hypoxia, are often used interchangeably to describe a state in which there is a diminished supply of oxygen to an organ's tissues. Anoxia may be caused by many different problems, including heart attack, heart surgery, severe asthma, smoke or carbon monoxide inhalation, high-altitude exposure, strangulation, or an overdose of anesthesia. In severe cases of anoxia the patient may be in a stupor or a coma for periods ranging from hours to days, weeks, or months. Recovery depends on the severity of the oxygen deprivation. As recovery proceeds, a variety of psychological and neurological abnormalities, such as dementia or psychosis, may occur. The person also may experience confusion, personality changes, hallucinations, or memory loss.

Heart and lung problems. The brain requires a high level of oxygen in order to carry out its normal functions. Therefore, problems such as chronic lung disease or heart problems that prevent the brain from receiving adequate oxygen can starve brain cells and lead to the symptoms of dementia.

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What Conditions Are Not Dementia?


Age-related cognitive decline. As people age, they usually experience slower information processing and mild memory impairment. In addition, their brains frequently decrease in volume and some nerve cells, or neurons, are lost. These changes, called age-related cognitive decline, are normal and are not considered signs of dementia.

Mild cognitive impairment. Some people develop cognitive and memory problems that are not severe enough to be diagnosed as dementia but are more pronounced than the cognitive changes associated with normal aging. This condition is called mild cognitive impairment. Although many patients with this condition later develop dementia, some do not. Many researchers are studying mild cognitive impairment to find ways to treat it or prevent it from progressing to dementia.

Depression. People with depression are frequently passive or unresponsive, and they may appear slow, confused, or forgetful. Other emotional problems can also cause symptoms that sometimes mimic dementia.

Delirium. Delirium is characterized by confusion and rapidly altering mental states. The person may also be disoriented, drowsy, or incoherent, and may exhibit personality changes. Delirium is usually caused by a treatable physical or psychiatric illness, such as poisoning or infections. Patients with delirium often, though not always, make a full recovery after their underlying illness is treated.

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What Causes Dementia?


All forms of dementia result from the death of nerve cells and/or the loss of communication among these cells. The human brain is a very complex and intricate machine and many factors can interfere with its functioning. Researchers have uncovered many of these factors, but they have not yet been able to fit these puzzle pieces together in order to form a complete picture of how dementias develop.

Many types of dementia, including AD, Lewy body dementia, Parkinson's dementia, and Pick's disease, are characterized by abnormal structures called inclusions in the brain. Because these inclusions, which contain abnormal proteins, are so common in people with dementia, researchers suspect that they play a role in the development of symptoms. However, that role is unknown, and in some cases the inclusions may simply be a side effect of the disease process that leads to the dementia.

Genes clearly play a role in the development of some kinds of dementia. However, in AD and many other disorders, the dementia usually cannot be tied to a single abnormal gene. Instead, these forms of dementia appear to result from a complex interaction of genes, lifestyle factors, and other environmental influences.

Researchers have identified several genes that influence susceptibility to AD. Mutations in three of the known genes for AD - genes that control the production of proteins such as amyloid precursor protein (APP), presenilin 1, and presenilin 2 - are linked to early-onset forms of the disease.

Variations in another gene, called apolipoprotein E (apoE), have been linked to an increased risk of late-onset AD. The apoE gene does not cause the disease by itself, but one version of the gene, called apoE epsilon4 (apoE E4), appears to increase the risk of AD. People with two copies of the apoE E4 gene have about ten times the risk of developing AD compared to people without apoE E4. This gene variant seems to encourage amyloid deposition in the brain. One study also found that this gene is associated with shorter survival in men with AD. In contrast, another version of the apoE gene, called apoE E2, appears to protect against AD.

Studies have suggested that mutations in another gene, called CYP46, may contribute to an increased risk of developing late-onset sporadic AD. This gene normally produces a protein that helps the brain metabolize cholesterol.

Scientists are trying to determine how beta amyloid influences the development of AD. A number of studies indicate that the buildup of this protein initiates a complex chain of events that culminates in dementia. One study found that beta amyloid buildup in the brain triggers cells called microglia, which act like janitors that mop up potentially harmful substances in the brain, to release a potent neurotoxin called peroxynitrite. This may contribute to nerve cell death in AD. Another study found that beta amyloid causes a protein called p35 to be split into two proteins. One of the resulting proteins triggers changes in the tau protein that lead to formation of neurofibrillary tangles. A third study found that beta amyloid activates cell-death enzymes called caspases that alter the tau protein in a way that causes it to form tangles. Researchers believe these tangles may contribute to the neuron death in AD.

Vascular dementia can be caused by cerebrovascular disease or any other condition that prevents normal blood flow to the brain. Without a normal supply of blood, brain cells cannot obtain the oxygen they need to work correctly, and they often become so deprived that they die.

The causes of other types of dementias vary. Some, such as CJD and GSS, have been tied to abnormal forms of specific proteins. Others, including Huntington's disease and FTDP-17, have been linked to defects in a single gene. Post-traumatic dementia is directly related to brain cell death after injury. HIV-associated dementia is clearly tied to infection by the HIV virus, although the exact way the virus causes damage is not yet certain. For other dementias, such as corticobasal degeneration and most types of frontotemporal dementia, the underlying causes have not yet been identified.

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What Are the Risk Factors for Dementia?


Researchers have identified several risk factors that affect the likelihood of developing one or more kinds of dementia. Some of these factors are modifiable, while others are not.

Age. The risk of AD, vascular dementia, and several other dementias goes up significantly with advancing age.

Genetics/family history. As described in the section "What Causes Dementia?" researchers have discovered a number of genes that increase the risk of developing AD. Although people with a family history of AD are generally considered to be at heightened risk of developing the disease themselves, many people with a family history never develop the disease, and many without a family history of the disease do get it. In most cases, it is still impossible to predict a specific person's risk of the disorder based on family history alone. Some families with CJD, GSS, or fatal familial insomnia have mutations in the prion protein gene, although these disorders can also occur in people without the gene mutation. Individuals with these mutations are at significantly higher risk of developing these forms of dementia. Abnormal genes are also clearly implicated as risk factors in Huntington's disease, FTDP-17, and several other kinds of dementia. These dementias are described in the section "What are the different kinds of dementia?"

Smoking and alcohol use. Several recent studies have found that smoking significantly increases the risk of mental decline and dementia. People who smoke have a higher risk of atherosclerosis and other types of vascular disease, which may be the underlying causes for the increased dementia risk. Studies also have found that drinking large amounts of alcohol appears to increase the risk of dementia. However, other studies have suggested that people who drink moderately have a lower risk of dementia than either those who drink heavily or those who completely abstain from drinking.

Atherosclerosis. Atherosclerosis is the buildup of plaque - deposits of fatty substances, cholesterol, and other matter - in the inner lining of an artery. Atherosclerosis is a significant risk factor for vascular dementia, because it interferes with the delivery of blood to the brain and can lead to stroke. Studies have also found a possible link between atherosclerosis and AD.

Cholesterol. High levels of low-density lipoprotein (LDL), the so-called bad form of cholesterol, appear to significantly increase a person's risk of developing vascular dementia. Some research has also linked high cholesterol to an increased risk of AD.

Plasma homocysteine. Research has shown that a higher-than-average blood level of homocysteine - a type of amino acid - is a strong risk factor for the development of AD and vascular dementia.

Diabetes. Diabetes is a risk factor for both AD and vascular dementia. It is also a known risk factor for atherosclerosis and stroke, both of which contribute to vascular dementia.

Mild cognitive impairment. While not all people with mild cognitive impairment develop dementia, people with this condition do have a significantly increased risk of dementia compared to the rest of the population. One study found that approximately 40 percent of people over age 65 who were diagnosed with mild cognitive impairment developed dementia within 3 years.

Down syndrome. Studies have found that most people with Down syndrome develop characteristic AD plaques and neurofibrillary tangles by the time they reach middle age. Many, but not all, of these individuals also develop symptoms of dementia.

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How Is Dementia Diagnosed?


Doctors employ a number of strategies to diagnose dementia. It is important that they rule out any treatable conditions, such as depression, normal pressure hydrocephalus, or vitamin B12 deficiency, which can cause similar symptoms.

Early, accurate diagnosis of dementia is important for patients and their families because it allows early treatment of symptoms. For people with AD or other progressive dementias, early diagnosis may allow them to plan for the future while they can still help to make decisions. These people also may benefit from drug treatment.

The "gold standard" for diagnosing dementia, autopsy, does not help the patient or caregivers. Therefore, doctors have devised a number of techniques to help identify dementia with reasonable accuracy while the patient is still alive.

Patient history
Doctors often begin their examination of a patient suspected of having dementia by asking questions about the patient's history. For example, they may ask how and when symptoms developed and about the patient's overall medical condition. They also may try to evaluate the patient's emotional state, although patients with dementia often may be unaware of or in denial about how their disease is affecting them. Family members also may deny the existence of the disease because they do not want to accept the diagnosis and because, at least in the beginning, AD and other forms of dementia can resemble normal aging. Therefore additional steps are necessary to confirm or rule out a diagnosis of dementia.

Physical examination
A physical examination can help rule out treatable causes of dementia and identify signs of stroke or other disorders that can contribute to dementia. It can also identify signs of other illnesses, such as heart disease or kidney failure, that can overlap with dementia. If a patient is taking medications that may be causing or contributing to his or her symptoms, the doctor may suggest stopping or replacing some medications to see if the symptoms go away.

Neurological evaluations
Doctors will perform a neurological examination, looking at balance, sensory function, reflexes, and other functions, to identify signs of conditions - for example movement disorders or stroke - that may affect the patient's diagnosis or are treatable with drugs.

Cognitive and neuropsychological tests
Doctors use tests that measure memory, language skills, math skills, and other abilities related to mental functioning to help them diagnose a patient's condition accurately. For example, people with AD often show changes in so-called executive functions (such as problem-solving), memory, and the ability to perform once-automatic tasks.

Doctors often use a test called the Mini-Mental State Examination (MMSE) to assess cognitive skills in people with suspected dementia. This test examines orientation, memory, and attention, as well as the ability to name objects, follow verbal and written commands, write a sentence spontaneously, and copy a complex shape. Doctors also use a variety of other tests and rating scales to identify specific types of cognitive problems and abilities.

Brain scans
Doctors may use brain scans to identify strokes, tumors, or other problems that can cause dementia. Also, cortical atrophy -degeneration of the brain's cortex (outer layer) - is common in many forms of dementia and may be visible on a brain scan. The brain's cortex normally appears very wrinkled, with ridges of tissue (called gyri) separated by "valleys" called sulci. In individuals with cortical atrophy, the progressive loss of neurons causes the ridges to become thinner and the sulci to grow wider. As brain cells die, the ventricles (or fluid-filled cavities in the middle of the brain) expand to fill the available space, becoming much larger than normal. Brain scans also can identify changes in the brain's structure and function that suggest AD.

The most common types of brain scans are computed tomographic (CT) scans and magnetic resonance imaging (MRI). Doctors frequently request a CT scan of the brain when they are examining a patient with suspected dementia. These scans, which use X-rays to detect brain structures, can show evidence of brain atrophy, strokes and transient ischemic attacks (TIAs), changes to the blood vessels, and other problems such as hydrocephalus and subdural hematomas. MRI scans use magnetic fields and focused radio waves to detect hydrogen atoms in tissues within the body. They can detect the same problems as CT scans but they are better for identifying certain conditions, such as brain atrophy and damage from small TIAs.

Doctors also may use electroencephalograms (EEGs) in people with suspected dementia. In an EEG, electrodes are placed on the scalp over several parts of the brain in order to detect and record patterns of electrical activity and check for abnormalities. This electrical activity can indicate cognitive dysfunction in part or all of the brain. Many patients with moderately severe to severe AD have abnormal EEGs. An EEG may also be used to detect seizures, which occur in about 10 percent of AD patients as well as in many other disorders. EEGs also can help diagnose CJD.

Several other types of brain scans allow researchers to watch the brain as it functions. These scans, called functional brain imaging, are not often used as diagnostic tools, but they are important in research and they may ultimately help identify people with dementia earlier than is currently possible. Functional brain scans include functional MRI (fMRI), single photon-emission computed tomography (SPECT), positron emission tomography (PET), and magnetoencephalography (MEG). fMRI uses radio waves and a strong magnetic field to measure the metabolic changes that take place in active parts of the brain. SPECT shows the distribution of blood in the brain, which generally increases with brain activity. PET scans can detect changes in glucose metabolism, oxygen metabolism, and blood flow, all of which can reveal abnormalities of brain function. MEG shows the electromagnetic fields produced by the brain's neuronal activity.

Laboratory tests
Doctors may use a variety of laboratory tests to help diagnose dementia and/or rule out other conditions, such as kidney failure, that can contribute to symptoms. A partial list of these tests includes a complete blood count, blood glucose test, urinalysis, drug and alcohol tests (toxicology screen), cerebrospinal fluid analysis (to rule out specific infections that can affect the brain), and analysis of thyroid and thyroid-stimulating hormone levels. A doctor will order only the tests that he or she feels are necessary and/or likely to improve the accuracy of a diagnosis.

Psychiatric evaluation
A psychiatric evaluation may be obtained to determine if depression or another psychiatric disorder may be causing or contributing to a person's symptoms.

Presymptomatic testing
Testing people before symptoms begin to determine if they will develop dementia is not possible in most cases. However, in disorders such as Huntington's where a known gene defect is clearly linked to the risk of the disease, a genetic test can help identify people who are likely to develop the disease. Since this type of genetic information can be devastating, people should carefully consider whether they want to undergo such testing.

Researchers are examining whether a series of simple cognitive tests, such as matching words with pictures, can predict who will develop dementia. One study suggested that a combination of a verbal learning test and an odor-identification test can help identify AD before symptoms become obvious. Other studies are looking at whether memory tests and brain scans can be useful indicators of future dementia.

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Is There Any Treatment?


While treatments to reverse or halt disease progression are not available for most of the dementias, patients can benefit to some extent from treatment with available medications and other measures, such as cognitive training.

Drugs to specifically treat AD and some other progressive dementias are now available and are prescribed for many patients. Although these drugs do not halt the disease or reverse existing brain damage, they can improve symptoms and slow the progression of the disease. This may improve the patient's quality of life, ease the burden on caregivers, and/or delay admission to a nursing home. Many researchers are also examining whether these drugs may be useful for treating other types of dementia.

Many people with dementia, particularly those in the early stages, may benefit from practicing tasks designed to improve performance in specific aspects of cognitive functioning. For example, people can sometimes be taught to use memory aids, such as mnemonics, computerized recall devices, or note taking.

Behavior modification - rewarding appropriate or positive behavior and ignoring inappropriate behavior - also may help control unacceptable or dangerous behaviors.

Alzheimer's disease
Most of the drugs currently approved by the U. S. Food and Drug Administration (FDA) for AD fall into a category called cholinesterase inhibitors. These drugs slow the breakdown of the neurotransmitter acetylcholine, which is reduced in the brains of people with AD. Acetylcholine is important for the formation of memories and it is used in the hippocampus and the cerebral cortex, two brain regions that are affected by AD. There are currently four cholinesterase inhibitors approved for use in the United States:tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl). These drugs temporarily improve or stabilize memory and thinking skills in some individuals. Many studies have shown that cholinesterase inhibitors help to slow the decline in mental functions associated with AD, and that they can help reduce behavioral problems and improve the ability to perform everyday tasks. However, none of these drugs can stop or reverse the course of AD.

A fifth drug, memantine (Namenda), is also approved for use in the United States. Unlike other drugs for AD, which affect acetylcholine levels, memantine works by regulating the activity of a neurotransmitter called glutamate that plays a role in learning and memory. Glutamate activity is often disrupted in AD. Because this drug works differently from cholinesterase inhibitors, combining memantine with other AD drugs may be more effective than any single therapy. One controlled clinical trial found that patients receiving donepezil plus memantine had better cognition and other functions than patients receiving donepezil alone.

Doctors may also prescribe other drugs, such as anticonvulsants, sedatives, and antidepressants, to treat seizures, depression, agitation, sleep disorders, and other specific problems that can be associated with dementia.  In 2005, research showed that use of "atypical" antipsychotic drugs such as olanzapine and risperdone to treat behavioral problems in elderly people with dementia was associated with an elevated risk of death in these patients.  Most of the deaths were caused by heart problems or infections.  The FDA has issued a public health advisory to alert patients and their caregivers to this safety issue.

Vascular dementia
There is no standard drug treatment for vascular dementia, although some of the symptoms, such as depression, can be treated. Most other treatments aim to reduce the risk factors for further brain damage. However, some studies have found that cholinesterase inhibitors, such as galantamine and other AD drugs, can improve cognitive function and behavioral symptoms in patients with early vascular dementia.

The progression of vascular dementia can often be slowed significantly or halted if the underlying vascular risk factors for the disease are treated. To prevent strokes and TIAs, doctors may prescribe medicines to control high blood pressure, high cholesterol, heart disease, and diabetes. Doctors also sometimes prescribe aspirin, warfarin, or other drugs to prevent clots from forming in small blood vessels. When patients have blockages in blood vessels, doctors may recommend surgical procedures, such as carotid endarterectomy, stenting, or angioplasty, to restore the normal blood supply. Medications to relieve restlessness or depression or to help patients sleep better may also be prescribed.

Other dementias
Some studies have suggested that cholinesterase inhibitors, such as donepezil (Aricept), can reduce behavioral symptoms in some patients with Parkinson's dementia.

At present, no medications are approved specifically to treat or prevent FTD and most other types of progressive dementia. However, sedatives, antidepressants, and other medications may be useful in treating specific symptoms and behavioral problems associated with these diseases.

Scientists continue to search for specific treatments to help people with Lewy body dementia. Current treatment is symptomatic, often involving the use of medication to control the parkinsonian and psychiatric symptoms. Although antiparkinsonian medication may help reduce tremor and loss of muscle movement, it may worsen symptoms such as hallucinations and delusions. Also, drugs prescribed for psychiatric symptoms may make the movement problems worse.  Several studies have suggested that cholinesterase inhibitors may be able to improve cognitive function and behavioral symptoms in patients with Lewy body disease.

There is no known treatment that can cure or control CJD. Current treatment is aimed at alleviating symptoms and making the patient as comfortable as possible. Opiate drugs can help relieve pain, and the drugs clonazepam and sodium valproate may help relieve myoclonus. During later stages of the disease, treatment focuses on supportive care, such as administering intravenous fluids and changing the person's position frequently to prevent bedsores.

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Can Dementia be Prevented?


Research has revealed a number of factors that may be able to prevent or delay the onset of dementia in some people. For example, studies have shown that people who maintain tight control over their glucose levels tend to score better on tests of cognitive function than those with poorly controlled diabetes. Several studies also have suggested that people who engage in intellectually stimulating activities, such as social interactions, chess, crossword puzzles, and playing a musical instrument, significantly lower their risk of developing AD and other forms of dementia. Scientists believe mental activities may stimulate the brain in a way that increases the person's "cognitive reserve" - the ability to cope with or compensate for the pathologic changes associated with dementia.

Researchers are studying other steps people can take that may help prevent AD in some cases. So far, none of these factors has been definitively proven to make a difference in the risk of developing the disease. Moreover, most of the studies addressed only AD, and the results may or may not apply to other forms of dementia. Nevertheless, scientists are encouraged by the results of these early studies and many believe it will eventually become possible to prevent some forms of dementia. Possible preventive actions include:

  • Lowering homocysteine. In one study, elevated blood levels of the amino acid homocysteine were associated with a 2.9 times greater risk of AD and a 4.9 times greater risk of vascular dementia. A preliminary study has shown that high doses of three B vitamins that help lower homocysteine levels - folic acid, B12, and B6 - appear to slow the progression of AD. Researchers are conducting a multi-center clinical trial to test this effect in a larger group of patients.
  • Lowering cholesterol levels. Research has suggested that people with high cholesterol levels have an increased risk of developing AD. Cholesterol is involved in formation of amyloid plaques in the brain. Mutations in a gene called CYP46 and the apoE E4 gene variant, both of which have been linked to an increased risk of AD, are also involved in cholesterol metabolism. Several studies have also found that the use of drugs called statins, which lower cholesterol levels, is associated with a lower likelihood of cognitive impairment.
  • Lowering blood pressure. Several studies have shown that antihypertensive medicine reduces the odds of cognitive impairment in elderly people with high blood pressure. One large European study found a 55 percent lower risk of dementia in people over 60 who received drug treatment for hypertension. These people had a reduced risk of both AD and vascular dementia.
  • Exercise. Regular exercise stimulates production of chemicals called growth factors that help neurons survive and adapt to new situations. These gains may help to delay the onset of dementia symptoms. Exercise also may reduce the risk of brain damage from atherosclerosis.
  • Education. Researchers have found evidence that formal education may help protect people against the effects of AD. In one study, researchers found that people with more years of formal education had relatively less mental decline than people with less schooling, regardless of the number of amyloid plaques and neurofibrillary tangles each person had in his or her brain. The researchers think education may cause the brain to develop robust nerve cell networks that can help compensate for the cell damage caused by AD.
  • Controlling inflammation. Many studies have suggested that inflammation may contribute to AD. Moreover, autopsies of people who died with AD have shown widespread inflammation in the brain that appeared to be caused by the accumulation of beta amyloid. Another study found that men with high levels of C-reactive protein, a general marker of inflammation, had a significantly increased risk of AD and other kinds of dementia.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs). Research indicates that long-term use of NSAIDs - ibuprofen, naproxen, and similar drugs - may prevent or delay the onset of AD. Researchers are not sure how these drugs may protect against the disease, but some or all of the effect may be due to reduced inflammation. A 2003 study showed that these drugs also bind to amyloid plaques and may help to dissolve them and prevent formation of new plaques.

The risk of vascular dementia is strongly correlated with risk factors for stroke, including high blood pressure, diabetes, elevated cholesterol levels, and smoking. This type of dementia may be prevented in many cases by changing lifestyle factors, such as excessive weight and high blood pressure, which are associated with an increased risk of cerebrovascular disease. One European study found that treating isolated systolic hypertension (high blood pressure in which only the systolic or top number is high) in people age 60 and older reduced the risk of dementia by 50 percent. These studies strongly suggest that effective use of current treatments can prevent many future cases of vascular dementia.

A study published in 2005 found that people with mild cognitive impairment who took 10 mg/day of the drug donepezil had a significantly reduced risk of developing AD during the first two years of treatment, compared to people who received vitamin E or a placebo.  By the end of the third year, however, the rate of AD was just as high in the people treated with donepezil as it was in the other two groups.

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What Kind of Care Does a Person with Dementia Need?


People with moderate and advanced dementia typically need round-the-clock care and supervision to prevent them from harming themselves or others. They also may need assistance with daily activities such as eating, bathing, and dressing. Meeting these needs takes patience, understanding, and careful thought by the person's caregivers.

A typical home environment can present many dangers and obstacles to a person with dementia, but simple changes can overcome many of these problems. For example, sharp knives, dangerous chemicals, tools, and other hazards should be removed or locked away. Other safety measures include installing bed and bathroom safety rails, removing locks from bedroom and bathroom doors, and lowering the hot water temperature to 120°F (48. 9°C) or less to reduce the risk of accidental scalding. People with dementia also should wear some form of identification at all times in case they wander away or become lost. Caregivers can help prevent unsupervised wandering by adding locks or alarms to outside doors.

People with dementia often develop behavior problems because of frustration with specific situations. Understanding and modifying or preventing the situations that trigger these behaviors may help to make life more pleasant for the person with dementia as well as his or her caregivers. For instance, the person may be confused or frustrated by the level of activity or noise in the surrounding environment. Reducing unnecessary activity and noise (such as limiting the number of visitors and turning off the television when it's not in use) may make it easier for the person to understand requests and perform simple tasks. Confusion also may be reduced by simplifying home decorations, removing clutter, keeping familiar objects nearby, and following a predictable routine throughout the day. Calendars and clocks also may help patients orient themselves.

People with dementia should be encouraged to continue their normal leisure activities as long as they are safe and do not cause frustration. Activities such as crafts, games, and music can provide important mental stimulation and improve mood. Some studies have suggested that participating in exercise and intellectually stimulating activities may slow the decline of cognitive function in some people.

Many studies have found that driving is unsafe for people with dementia. They often get lost and they may have problems remembering or following rules of the road. They also may have difficulty processing information quickly and dealing with unexpected circumstances. Even a second of confusion while driving can lead to an accident. Driving with impaired cognitive functions can also endanger others. Some experts have suggested that regular screening for changes in cognition might help to reduce the number of driving accidents among elderly people, and some states now require that doctors report people with AD to their state motor vehicle department. However, in many cases, it is up to the person's family and friends to ensure that the person does not drive.

The emotional and physical burden of caring for someone with dementia can be overwhelming. Support groups can often help caregivers deal with these demands and they can also offer helpful information about the disease and its treatment. It is important that caregivers occasionally have time off from round-the-clock nursing demands. Some communities provide respite facilities or adult day care centers that will care for dementia patients for a period of time, giving the primary caregivers a break. Eventually, many patients with dementia require the services of a full-time nursing home.

A list of caregiver organizations and support groups is included at the end of this booklet.

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What Research Is Being Done?


Current research focuses on many different aspects of dementia. This research promises to improve the lives of people affected by the dementias and may eventually lead to ways of preventing or curing these disorders.

Causes and prevention
Research on the causes of AD and other dementias includes studies of genetic factors, neurotransmitters, inflammation, factors that influence programmed cell death in the brain, and the roles of tau, beta amyloid, and the associated neurofibrillary tangles and plaques in AD. Some other researchers are trying to determine the possible roles of cholesterol metabolism, oxidative stress (chemical reactions that can damage proteins, DNA, and lipids inside cells), and microglia in the development of AD. Scientists also are investigating the role of aging-related proteins such as the enzyme telomerase.

Since many dementias and other neurodegenerative diseases have been linked to abnormal clumps of proteins in cells, researchers are trying to learn how these clumps develop, how they affect cells, and how the clumping can be prevented.

Some studies are examining whether changes in white matter - nerve fibers lined with myelin - may play a role in the onset of AD. Myelin may erode in AD patients before other changes occur. This may be due to a problem with oligodendrocytes, the cells that produce myelin.

Researchers are searching for additional genes that may contribute to AD, and they have identified a number of gene regions that may be involved. Some researchers suggest that people will eventually be screened for a number of genes that contribute to AD and that they will be able to receive treatments that specifically address their individual genetic risks. However, such individualized screening and treatment is still years away.

Insulin resistance is common in people with AD, but it is not clear whether the insulin resistance contributes to the development of the disease or if it is merely a side effect.

Several studies have found a reduced risk of dementia in people who take cholesterol-lowering drugs called statins. However, it is not yet clear if the apparent effect is due to the drugs or to other factors.

Early studies of estrogen suggested that it might help prevent AD in older women.  However, a clinical study of several thousand postmenopausal women aged 65 or older found that combination therapy with estrogen and progestin substantially increased the risk of AD.  Estrogen alone also appeared to slightly increase the risk of dementia in this study.

A 2003 study found that people with HIV-associated dementia have different levels of activity for more than 30 different proteins, compared to people who have HIV but no signs of dementia. The study suggests a possible way to screen HIV patients for the first signs of cognitive impairment, and it may lead to ways of intervening to prevent this form of dementia.

Diagnosis
Improving early diagnosis of AD and other types of dementia is important not only for patients and families, but also for researchers who seek to better understand the causes of dementing diseases and find ways to reverse or halt them at early stages. Improved diagnosis can also reduce the risk that people will receive inappropriate treatments.

Some researchers are investigating whether three-dimensional computer models of PET and MRI images can identify brain changes typical of early AD, before any symptoms appear. This research may lead to ways of preventing the symptoms of the disease.

One study found that levels of beta amyloid and tau in spinal fluid can be used to diagnose AD with a sensitivity of 92 percent. If other studies confirm the validity of this test, it may allow doctors to identify people who are beginning to develop the disorder before they start to show symptoms. This would allow treatment at very early stages of the disorder, and may help in testing new treatments to prevent or delay symptoms of the disease. Other researchers have identified factors in the skin and blood of AD patients that are different from those in healthy people. They are trying to determine if these factors can be used to diagnose the disease.

Treatment
Researchers are continually working to develop new drugs for AD and other types of dementia. Many researchers believe a vaccine that reduces the number of amyloid plaques in the brain might ultimately prove to be the most effective treatment for AD. In 2001, researchers began one clinical trial of a vaccine called AN-1792. The study was halted after a number of people developed inflammation of the brain and spinal cord. Despite these problems, one patient appeared to have reduced numbers of amyloid plaques in the brain. Other patients showed little or no cognitive decline during the course of the study, suggesting that the vaccine may slow or halt the disease. Researchers are now trying to find safer and more effective vaccines for AD.

Researchers are also investigating possible methods of gene therapy for AD. In one case, researchers used cells genetically engineered to produce nerve growth factor and transplanted them into monkeys' forebrains. The transplanted cells boosted the amount of nerve growth factors in the brain and seemed to prevent degeneration of acetylcholine-producing neurons in the animals. This suggests that gene therapy might help to reduce or delay symptoms of the disease. Researchers are now testing a similar therapy in a small number of patients. Other researchers have experimented with gene therapy that adds a gene called neprilysin in a mouse model that produces human beta amyloid. They found that increasing the level of neprilysin greatly reduced the amount of beta amyloid in the mice and halted the amyloid-related brain degeneration. They are now trying to determine whether neprilysin gene therapy can improve cognition in mice.

A clinical trial called the Vitamins to Slow Alzheimer's Disease (VITAL) study is testing whether high doses of three common B vitamins - folic acid, B12, and B6 - can reduce homocysteine levels and slow the rate of cognitive decline in AD.

Since many studies have found evidence of brain inflammation in AD, some researchers have proposed that drugs that control inflammation, such as NSAIDs, might prevent the disease or slow its progression. Studies in mice have suggested that these drugs can limit production of amyloid plaques in the brain.  Early studies of these drugs in humans have shown promising results.  However, a large NIH-funded clinical trial of two NSAIDS (naproxen and celecoxib) to prevent AD was stopped in late 2004 because of an increase in stroke and heart attack in people taking naproxen, and an unrelated study that linked celecoxib to an increased risk of heart attack.

Some studies have suggested that two drugs, pentoxifylline and propentofylline, may be useful in treating vascular dementia. Pentoxifylline improves blood flow, while propentofylline appears to interfere with some of the processes that cause cell death in the brain.

One study is testing the safety and effectiveness of donepezil (Aricept) for treating mild dementia in patients with Parkinson's dementia, while another is investigating whether skin patches with the drug selegiline can improve mental function in patients with cognitive problems related to HIV.

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How Can I Help Research?


People with dementia and others who wish to help research on dementing disorders may be able to do so by participating in clinical studies designed to learn more about the disorders or to test potential new therapies. Information about many such studies is available free of charge from the Federal government's database of clinical trials, clinicaltrials.gov (http://clinicaltrials.gov).

Information about clinical trials specific to AD is available from the Alzheimer's Disease Clinical Trials Database (www.alzheimers.org/trials), a joint project of the U. S. Food and Drug Administration and the National Institute on Aging (NIA) that is maintained by the NIA's Alzheimer's Disease Education and Referral Center.

For clinical trials taking place at the National Institutes of Health, additional information is available from the following office:

Patient Recruitment and Public Liaison Office
Clinical Center
National Institutes of Health
Building 61, 10 Cloister Court
Bethesda, Maryland 20892-4754
800-411-1222
TTY: 301-594-9774 (local), 866-411-1010 (toll free)
www.cc.nih.gov/ccc/prpl/

Voluntary health organizations, such as those listed in Information Resources, may be able to provide information about additional clinical studies.

Another important way that people can help dementia research is by arranging to donate their brains to brain and tissue banks after they die. Tissue from these banks is made available to qualified researchers so that they can continue their studies of how these diseases develop and how they affect the brain. Brain banks accepting donations include the following:

National Disease Research Interchange
1628 JFK Blvd.
8 Penn Cntr. 8th floor
Philadelphia,  PA  19103
Tel: 215-557-7361 800-222-NDRI (6374)
Fax: 215-557-7154
EMail: info@ndriresource.org
http://www.ndriresource.org

Human Brain and Spinal Fluid Resource Center
Neurology Research (127A) W. Los Angeles Healthcare Center
11301 Wilshire Blvd. Bldg. 212
Los Angeles,  CA  90073
Tel: 310-268-3536 Page: 310-636-5199
Fax: 310-268-4768
EMail: RMNbbank@ucla.edu
http://www.loni.ucla.edu/~nnrsb/NNRSB

UM/NPF Brain Endowment Bank
University of Miami Dept. of Neurology
1501 N.W. 9th Ave., Rm. 4013 (D 4-5)
Miami,  FL  33136
Tel: 305-243-6219 800-UM-BRAIN (862-7246)
Fax: 305-243-3649

Harvard Brain Tissue Resource Center
McLean Hospital
115 Mill Street
Belmont,  MA  02478
Tel: 800-BRAIN BANK (272-4622) 617-855-2400
Fax: 617-855-3199
EMail: btrc@mclean.harvard.org
http://www.brainbank.mclean.org

People who have more than one family member affected by AD also may be able to help research by contributing blood samples to a gene bank. A large initiative to collect such samples was announced in 2003. This large gene bank should accelerate research efforts to identify genes that play a role in AD. People interested in participating in this gene bank can learn more about it at the address and telephone numbers below:

Alzheimer's Disease Genetics Initiative
National Cell Repository for Alzheimer's Disease (NCRAD)
Indiana University
Indianapolis, Indiana 46202-5251
800-526-2839
317-274-7360
EMail:  alzstudy@iupui.edu
http://ncrad.iu.edu

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

Alzheimer's Disease Education and Referral Center (ADEAR)
P.O. Box 8250
Silver Spring, MD   20907-8250
adear@nia.nih.gov
http://www.alzheimers.nia.nih.gov
Tel: 301-495-3311 800-438-4380
Fax: 301-495-3334

Alzheimer's Association
225 North Michigan Avenue
17th Floor
Chicago, IL   60601-7633
info@alz.org
http://www.alz.org
Tel: 312-335-8700 1-800-272-3900 (24-hour helpline) TDD: 312-335-5886
Fax: 866.699.1246
National voluntary health organization committed to finding a cure for Alzheimer’s and helping those affected by the disease.

Alzheimer's Foundation of America
322 Eighth Avenue
7th Floor
New York, NY   10001
info@alzfdn.org
http://www.alzfdn.org
Tel: 866-AFA-8484 (232-8484)
Fax: 646-638-1546
Works to provide optimal care and services to individuals confronting dementia and to their caregivers and families thruogh member organizations dedicated to improving quality of life.

John Douglas French Alzheimer's Foundation
11620 Wilshire Blvd.
Suite 270
Los Angeles, CA   90025
jdfaf@earthlink.net
http://www.jdfaf.org
Tel: 310-445-4650 800-477-2243
Fax: 310-479-0516
Generates funds for Alzheimer’s research targeted at areas of research typically not supported by Federal agencies.

Association for Frontotemporal Dementias (AFTD)
1616 Walnut Street
Suite 1100
Philadelphia, PA   19103
info@FTD-Picks.org
http://www.FTD-Picks.org
Tel: 267-514-7221 866-507-7222
Non-profit organization that promotes and funds research into finding the cause and cure for frontotemporal dementias (FTD); provides information, education, and support to those affected by FTD and their caregivers; and sponsors professional health education programs related to FTD.

National Organization for Rare Disorders (NORD)
P.O. Box 1968
(55 Kenosia Avenue)
Danbury, CT   06813-1968
orphan@rarediseases.org
http://www.rarediseases.org
Tel: 203-744-0100 Voice Mail 800-999-NORD (6673)
Fax: 203-798-2291
Federation of voluntary health organizations dedicated to helping people with rare "orphan" diseases and assisting the organizations that serve them. Committed to the identification, treatment, and cure of rare disorders through programs of education, advocacy, research, and service.

Family Caregiver Alliance/ National Center on Caregiving
180 Montgomery Street
Suite 1100
San Francisco, CA   94104
info@caregiver.org
http://www.caregiver.org
Tel: 415-434-3388 800-445-8106
Fax: 415-434-3508
Supports and assists families and caregivers of adults with debilitating health conditions. Offers programs and consultation on caregiving issues at local, state, and national levels. Offers free publications and support online, including a national directory of publicly funded caregiver support programs.

C-Mac Informational Services/Caregiver News [For Alzheimer's-Type Dementia Caregivers]
120 Clinton Lane
Cookeville, TN   38501-8946
caregiver_cmi@hotmail.com
http://www.caregivernews.org
Nonprofit, tax-exempt, charitable organization that offers information about care for patients with Alzheimer’s-type dementia. Publishes and distributes a newsletter, cookbook, and the Caregiver’s Information Pack.

National Institute of Mental Health (NIMH)
National Institutes of Health, DHHS
6001 Executive Blvd. Rm. 8184, MSC 9663
Bethesda, MD   20892-9663
nimhinfo@nih.gov
http://www.nimh.nih.gov
Tel: 301-443-4513/866-415-8051 301-443-8431 (TTY)
Fax: 301-443-4279

National Family Caregivers Association
10400 Connecticut Avenue
Suite 500
Kensington, MD   20895-3944
info@thefamilycaregiver.org
http://www.thefamilycaregiver.org
Tel: 800-896-3650
Fax: 301-942-2302
Grassroots organization dedicated to supporting and improving the lives of America's family caregivers. Created to educate, support, empower, and advocate for the millions of Americans who care for their ill, aged, or disabled loved ones.

Lewy Body Dementia Association
P.O. Box 451429
Atlanta, GA   31145-9429
lbda@lbda.org
http://www.lewybodydementia.org
Tel: Telephone: 404-935-6444 Helpline: 800-LEWYSOS (539-9767)
Fax: 480-422-5434
Supports those affected by Lewy body dementias and promotes research for a cure. Sponsors education and outreach programs.

Alzheimer’s Drug Discovery Foundation (formerly, Institute for the Study of Aging)
1414 Avenue of the Americas
Suite 1502
New York, NY   10019
ahorton@alzdiscovery.org
http://www.alzdiscovery.org
Tel: 212-935-2402
Fax: 212-935-2408
Public charity whose mission is to accelerate the discovery and development of drugs to prevent, treat, and cure Alzheimer's disease, related dementias, and cognitive aging.

Creutzfeldt-Jakob Disease (CJD) Foundation Inc.
P.O. Box 5312
Akron, OH   44334
help@cjdfoundation.org
http://www.cjdfoundation.org
Tel: 800-659-1991
Fax: 330-668-2474
Non-profit, volunteer foundation that promotes research, education, and awareness of CJD and reaches out to people affected by CJD.

CJD Aware!
2527 South Carrollton Ave.
New Orleans, LA   70118-3013
cjdaware@iwon.com; info@cjdaware.com
http://www.cjdaware.com
Tel: 504-861-4627
Non-profit organization established for support, information sharing, and advocacy.

Well Spouse Association
63 West Main Street
Suite H
Freehold, NJ   07728
info@wellspouse.org
http://www.wellspouse.org
Tel: 800-838-0879 732-577-8899
Fax: 732-577-8644
International non-profit, volunteer-based organization whose mission is to provide emotional support to, raise consciousness about, and advocate for the spouses/partners of the chronically ill and/or disabled.

National Respite Network and Resource Center
800 Eastowne Drive
Suite 105
Chapel Hill, NC   27514
http://www.archrespite.org
Tel: 919-490-5577 x222
Fax: 919-490-4905
Information and referral service that assists and promotes the development of quality respite and crisis care programs; helps families locate respite and crisis care services in their communities; and sponsors advocacy and awareness efforts concerning respite care.

American Health Assistance Foundation
22512 Gateway Center Drive
Clarksburg, MD   20871
info@ahaf.org
www.ahaf.org/alzheimers/
Tel: 301-948-3244 800-437-AHAF (2423)
Fax: 301-258-9454
Non-profit charitable organization dedicated to funding research and educating the public on Alzheimer's disease, glaucoma, and macular degeneration.

National Hospice and Palliative Care Organization /Natl. Hospice Foundation
1700 Diagonal Road
Suite 625
Alexandria, VA   22314
nhpco_info@nhpco.org
http://www.nhpco.org
Tel: 703-837-1500 Helpline: 800-658-8898
Fax: 703-837-1233
Non-profit membership organization representing hospice and palliative care programs and professionals. Provides free referrals to the public for hospice listings across the United States and internationally. Distributes free packets of general information describing hospice services and the Medicare Hospice Benefit.

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Glossary

acetylcholine - a neurotransmitter that is important for the formation of memories. Studies have shown that levels of acetylcholine are reduced in the brains of people with Alzheimer's disease.

Alzheimer's disease - the most common cause of dementia in people aged 65 and older. Nearly all brain functions, including memory, movement, language, judgment, behavior, and abstract thinking, are eventually affected.

amyloid plaques - unusual clumps of material found in the tissue between nerve cells. Amyloid plaques, which consist of a protein called beta amyloid along with degenerating bits of neurons and other cells, are a hallmark of Alzheimer's disease.

amyloid precursor protein - a normal brain protein that is a precursor for beta amyloid, the abnormal substance found in the characteristic amyloid plaques of Alzheimer's disease patients.

apolipoprotein E - a gene that has been linked to an increased risk of Alzheimer's disease. People with a variant form of the gene, called apoE epsilon 4, have about ten times the risk of developing Alzheimer's disease.

ataxia - a loss of muscle control.

atherosclerosis - a blood vessel disease characterized by the buildup of plaque, or deposits of fatty substances and other matter in the inner lining of an artery.

beta amyloid - a protein found in the characteristic clumps of tissue (called plaques) that appear in the brains of Alzheimer's patients.

Binswanger's disease - a rare form of dementia characterized by damage to small blood vessels in the white matter of the brain. This damage leads to brain lesions, loss of memory, disordered cognition, and mood changes.

CADASIL - a rare hereditary disorder which is linked to a type of vascular dementia. It stands for cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy.

cholinesterase inhibitors - drugs that slow the breakdown of the neurotransmitter acetylcholine.

cognitive training - a type of training in which patients practice tasks designed to improve mental performance. Examples include memory aids, such as mnemonics, and computerized recall devices.

computed tomographic (CT) scans - a type of brain scan that uses X-rays to detect brain structures.

cortical atrophy - degeneration of the brain's cortex (outer layer). Cortical atrophy is common in many forms of dementia and may be visible on a brain scan.

cortical dementia - a type of dementia in which the damage primarily occurs in the brain's cortex, or outer layer.

corticobasal degeneration - a progressive disorder characterized by nerve cell loss and atrophy in multiple areas of the brain.

Creutzfeldt-Jakob disease - a rare, degenerative, fatal brain disorder believed to be linked to an abnormal form of a protein called a prion.

dementia -a term for a collection of symptoms that significantly impair thinking and normal activities and relationships.

dementia pugilistica - a form of dementia caused by head trauma such as that experienced by boxers. It is also called chronic traumatic encephalopathy or Boxer's syndrome.

electroencephalogram (EEG) - a medical procedure that records patterns of electrical activity in the brain.

fatal familial insomnia - an inherited disease that affects a brain region called the thalamus, which is partially responsible for controlling sleep. The disease causes dementia and a progressive insomnia that eventually leads to a complete lack of sleep.

frontotemporal dementias - a group of dementias characterized by degeneration of nerve cells, especially those in the frontal and temporal lobes of the brain.

FTDP-17 - one of the frontotemporal dementias, linked to a mutation in the tau gene. It is much like other types of the frontotemporal dementias but often includes psychiatric symptoms such as delusions and hallucinations.

Gerstmann-Straussler-Scheinker disease - a rare, fatal hereditary disease that causes ataxia and progressive dementia.

HIV-associated dementia - a dementia that results from infection with the human immunodeficiency virus (HIV) that causes AIDS. It can cause widespread destruction of the brain's white matter.

Huntington's disease - a degenerative hereditary disorder caused by a faulty gene for a protein called huntington. The disease causes degeneration in many regions of the brain and spinal cord and patients eventually develop severe dementia.

Lewy body dementia - one of the most common types of progressive dementia, characterized by the presence of abnormal structures called Lewy bodies in the brain. In many ways the symptoms of this disease overlap with those of Alzheimer's disease.

magnetic resonance imaging (MRI) - a diagnostic imaging technique that uses magnetic fields and radio waves to produce detailed images of body structures.

mild cognitive impairment - a condition associated with impairments in understanding and memory not severe enough to be diagnosed as dementia, but more pronounced than those associated with normal aging.

Mini-Mental State Examination - a test used to assess cognitive skills in people with suspected dementia. The test examines orientation, memory, and attention, as well as the ability to name objects, follow verbal and written commands, write a sentence spontaneously, and copy a complex shape.

multi-infarct dementia - a type of vascular dementia caused by numerous small strokes in the brain.

myelin - a fatty substance that coats and insulates nerve cells.

neurofibrillary tangles - bundles of twisted filaments found within neurons, and a characteristic feature found in the brains of Alzheimer's patients. These tangles are largely made up of a protein called tau.

neurotransmitter - a type of chemical, such as acetylcholine, that transmits signals from one neuron to another. People with Alzheimer's disease have reduced supplies of acetylcholine.

organic brain syndrome - a term that refers to physical disorders (not psychiatric in origin) that impair mental functions.

Parkinson's dementia - a secondary dementia that sometimes occurs in people with advanced Parkinson's disease, which is primarily a movement disorder. Many Parkinson's patients have the characteristic amyloid plaques and neurofibrillary tangles found in Alzheimer's disease, but it is not yet clear if the diseases are linked.

Pick's disease - a type of frontotemporal dementia where certain nerve cells become abnormal and swollen before they die. The brains of people with Pick's disease have abnormal structures, called Pick bodies, inside the neurons. The symptoms are very similar to those of Alzheimer's diease.

plaques - unusual clumps of material found between the tissues of the brain in Alzheimer's disease. See also amyloid plaques.

post-traumatic dementia - a dementia brought on by a single traumatic brain injury. It is much like dementia pugilistica, but usually also includes long-term memory problems.

presenilin 1 and 2 - proteins produced by genes that influence susceptibility to early-onset Alzheimer's disease.

primary dementia - a dementia, such as Alzheimer's disease, that is not the result of another disease.

primary progressive aphasia - a type of frontotemporal dementia resulting in deficits in language functions. Many, but not all, people with this type of aphasia eventually develop symptoms of dementia.

progressive dementia - a dementia that gets worse over time, gradually interfering with more and more cognitive abilities.

secondary dementia - a dementia that occurs as a consequence of another disease or an injury.

senile dementia - an outdated term that reflects the formerly widespread belief that dementia was a normal part of aging. The word senile is derived from a Latin term that means, roughly, "old age. "

subcortical dementia - dementia that affects parts of the brain below the outer brain layer, or cortex.

substance-induced persisting dementia - dementia caused by abuse of substances such as alcohol and recreational drugs that persists even after the substance abuse has ended.

tau protein - a protein that helps the functioning of microtubules, which are part of the cell's structural support and help to deliver substances throughout the cell. In Alzheimer's disease, tau is changed in a way that causes it to twist into pairs of helical filaments that collect into tangles.

transmissible spongiform encephalopathies - part of a family of human and animal diseases in which brains become filled with holes resembling sponges when examined under a microscope. CJD is the most common of the known transmissible spongiform encephalopathies.

vascular dementia - a type of dementia caused by brain damage from cerebrovascular or cardiovascular problems - usually strokes. It accounts for up to 20 percent of all dementias.

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"Dementia: Hope Through Research," NINDS.

 

Huntington's Disease

Introduction
What Causes Huntington's Disease?
How is HD Inherited?
What are the Major Effects of the Disease?
At What Age Does HD Appear?
How is HD Diagnosed?
What is Presymptomatic Testing?
How is the Presymptomatic Test Conducted?
How Does a Person Decide Whether to be Tested?
Is There a Treatment for HD?
What Kind of Care Does the Individual with HD Need?
What Community Resources are Available?
What Research is Being Done?
Molecular Genetics
The HD Gene and Its Product
Cell Death in HD
Animal Models of HD
Fetal Tissue Research
Clinical Studies
Imaging
How Can I Help?
What is the Role of Voluntary Organizations?
Where can I get more information?
Glossary

Introduction


In 1872, the American physician George Huntington wrote about an illness that he called "an heirloom from generations away back in the dim past." He was not the first to describe the disorder, which has been traced back to the Middle Ages at least. One of its earliest names was chorea,* which, as in "choreography," is the Greek word for dance. The term chorea describes how people affected with the disorder writhe, twist, and turn in a constant, uncontrollable dance-like motion. Later, other descriptive names evolved. "Hereditary chorea" emphasizes how the disease is passed from parent to child. "Chronic progressive chorea" stresses how symptoms of the disease worsen over time. Today, physicians commonly use the simple term Huntington's disease (HD) to describe this highly complex disorder that causes untold suffering for thousands of families.

More than 15,000 Americans have HD. At least 150,000 others have a 50 percent risk of developing the disease and thousands more of their relatives live with the possibility that they, too, might develop HD.

Until recently, scientists understood very little about HD and could only watch as the disease continued to pass from generation to generation. Families saw the disease destroy their loved ones' ability to feel, think, and move. In the last several years, scientists working with support from the National Institute of Neurological Disorders and Stroke (NINDS) have made several breakthroughs in the area of HD research. With these advances, our understanding of the disease continues to improve.

This brochure presents information about HD, and about current research progress, to health professionals, scientists, caregivers, and, most important, to those already too familiar with the disorder: the many families who are affected by HD.

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What Causes Huntington's Disease?


HD results from genetically programmed degeneration of nerve cells, called neurons,* in certain areas of the brain. This degeneration causes uncontrolled movements, loss of intellectual faculties, and emotional disturbance. Specifically affected are cells of the basal ganglia, structures deep within the brain that have many important functions, including coordinating movement. Within the basal ganglia, HD especially targets neurons of the striatum, particularly those in the caudate nuclei and the pallidum. Also affected is the brain's outer surface, or cortex, which controls thought, perception, and memory.

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How is HD Inherited?


HD is found in every country of the world. It is a familial disease, passed from parent to child through a mutation or misspelling in the normal gene.

A single abnormal gene, the basic biological unit of heredity, produces HD. Genes are composed of deoxyribonucleic acid (DNA), a molecule shaped like a spiral ladder. Each rung of this ladder is composed of two paired chemicals called bases. There are four types of bases—adenine, thymine, cytosine, and guanine—each abbreviated by the first letter of its name: A, T, C, and G. Certain bases always "pair" together, and different combinations of base pairs join to form coded messages. A gene is a long string of this DNA in various combinations of A, T, C, and G. These unique combinations determine the gene's function, much like letters join together to form words. Each person has about 30,000 genes—a billion base pairs of DNA or bits of information repeated in the nuclei of human cells—which determine individual characteristics or traits.

Genes are arranged in precise locations along 23 rod-like pairs of chromosomes. One chromosome from each pair comes from an individual's mother, the other from the father. Each half of a chromosome pair is similar to the other, except for one pair, which determines the sex of the individual. This pair has two X chromosomes in females and one X and one Y chromosome in males. The gene that produces HD lies on chromosome 4, one of the 22 non-sex-linked, or "autosomal," pairs of chromosomes, placing men and women at equal risk of acquiring the disease.

The impact of a gene depends partly on whether it is dominant or recessive. If a gene is dominant, then only one of the paired chromosomes is required to produce its called-for effect. If the gene is recessive, both parents must provide chromosomal copies for the trait to be present. HD is called an autosomal dominant disorder because only one copy of the defective gene, inherited from one parent, is necessary to produce the disease.

The genetic defect responsible for HD is a small sequence of DNA on chromosome 4 in which several base pairs are repeated many, many times. The normal gene has three DNA bases, composed of the sequence CAG. In people with HD, the sequence abnormally repeats itself dozens of times. Over time—and with each successive generation—the number of CAG repeats may expand further.

Each parent has two copies of every chromosome but gives only one copy to each child. Each child of an HD parent has a 50-50 chance of inheriting the HD gene. If a child does not inherit the HD gene, he or she will not develop the disease and cannot pass it to subsequent generations. A person who inherits the HD gene, and survives long enough, will sooner or later develop the disease. In some families, all the children may inherit the HD gene; in others, none do. Whether one child inherits the gene has no bearing on whether others will or will not share the same fate.

A small number of cases of HD are sporadic, that is, they occur even though there is no family history of the disorder. These cases are thought to be caused by a new genetic mutation-an alteration in the gene that occurs during sperm development and that brings the number of CAG repeats into the range that causes disease.

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What are the Major Effects of the Disease?


Early signs of the disease vary greatly from person to person. A common observation is that the earlier the symptoms appear, the faster the disease progresses.

Family members may first notice that the individual experiences mood swings or becomes uncharacteristically irritable, apathetic, passive, depressed, or angry. These symptoms may lessen as the disease progresses or, in some individuals, may continue and include hostile outbursts or deep bouts of depression.

HD may affect the individual's judgment, memory, and other cognitive functions. Early signs might include having trouble driving, learning new things, remembering a fact, answering a question, or making a decision. Some may even display changes in handwriting. As the disease progresses, concentration on intellectual tasks becomes increasingly difficult.

In some individuals, the disease may begin with uncontrolled movements in the fingers, feet, face, or trunk. These movements—which are signs of chorea—often intensify when the person is anxious. HD can also begin with mild clumsiness or problems with balance. Some people develop choreic movements later, after the disease has progressed. They may stumble or appear uncoordinated. Chorea often creates serious problems with walking, increasing the likelihood of falls.

The disease can reach the point where speech is slurred and vital functions, such as swallowing, eating, speaking, and especially walking, continue to decline. Some individuals cannot recognize other family members. Many, however, remain aware of their environment and are able to express emotions.

Some physicians have employed a recently developed Unified HD Rating Scale, or UHDRS, to assess the clinical features, stages, and course of HD. In general, the duration of the illness ranges from 10 to 30 years. The most common causes of death are infection (most often pneumonia), injuries related to a fall, or other complications.

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At What Age Does HD Appear?


The rate of disease progression and the age at onset vary from person to person. Adult-onset HD, with its disabling, uncontrolled movements, most often begins in middle age. There are, however, other variations of HD distinguished not just by age at onset but by a distinct array of symptoms. For example, some persons develop the disease as adults, but without chorea. They may appear rigid and move very little, or not at all, a condition called akinesia.

Some individuals develop symptoms of HD when they are very young—before age 20. The terms "early-onset" or "juvenile" HD are often used to describe HD that appears in a young person. A common sign of HD in a younger individual is a rapid decline in school performance. Symptoms can also include subtle changes in handwriting and slight problems with movement, such as slowness, rigidity, tremor, and rapid muscular twitching, called myoclonus. Several of these symptoms are similar to those seen in Parkinson's disease, and they differ from the chorea seen in individuals who develop the disease as adults. These young individuals are said to have "akinetic-rigid" HD or the Westphal variant of HD. People with juvenile HD may also have seizures and mental disabilities. The earlier the onset, the faster the disease seems to progress. The disease progresses most rapidly in individuals with juvenile or early-onset HD, and death often follows within 10 years.

Individuals with juvenile HD usually inherit the disease from their fathers. These individuals also tend to have the largest number of CAG repeats. The reason for this may be found in the process of sperm production. Unlike eggs, sperm are produced in the millions. Because DNA is copied millions of times during this process, there is an increased possibility for genetic mistakes to occur. To verify the link between the number of CAG repeats in the HD gene and the age at onset of symptoms, scientists studied a boy who developed HD symptoms at the age of two, one of the youngest and most severe cases ever recorded. They found that he had the largest number of CAG repeats of anyone studied so far—nearly 100. The boy's case was central to the identification of the HD gene and at the same time helped confirm that juveniles with HD have the longest segments of CAG repeats, the only proven correlation between repeat length and age at onset.

A few individuals develop HD after age 55. Diagnosis in these people can be very difficult. The symptoms of HD may be masked by other health problems, or the person may not display the severity of symptoms seen in individuals with HD of earlier onset. These individuals may also show symptoms of depression rather than anger or irritability, or they may retain sharp control over their intellectual functions, such as memory, reasoning, and problem-solving.

There is also a related disorder called senile chorea. Some elderly individuals display the symptoms of HD, especially choreic movements, but do not become demented, have a normal gene, and lack a family history of the disorder. Some scientists believe that a different gene mutation may account for this small number of cases, bu this has not been proven.

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How is HD Diagnosed?


The great American folk singer and composer Woody Guthrie died on October 3, 1967, after suffering from HD for 13 years. He had been misdiagnosed, considered an alcoholic, and shuttled in and out of mental institutions and hospitals for years before being properly diagnosed. His case, sadly, is not extraordinary, although the diagnosis can be made easily by experienced neurologists.

A neurologist will interview the individual intensively to obtain the medical history and rule out other conditions. A tool used by physicians to diagnose HD is to take the family history, sometimes called a pedigree or genealogy. It is extremely important for family members to be candid and truthful with a doctor who is taking a family history.

The doctor will also ask about recent intellectual or emotional problems, which may be indications of HD, and will test the person's hearing, eye movements, strength, coordination, involuntary movements (chorea), sensation, reflexes, balance, movement, and mental status, and will probably order a number of laboratory tests as well.

People with HD commonly have impairments in the way the eye follows or fixes on a moving target. Abnormalities of eye movements vary from person to person and differ, depending on the stage and duration of the illness.

The discovery of the HD gene in 1993 resulted in a direct genetic test to make or confirm a diagnosis of HD in an individual who is exhibiting HD-like symptoms. Using a blood sample, the genetic test analyzes DNA for the HD mutation by counting the number of repeats in the HD gene region. Individuals who do not have HD usually have 28 or fewer CAG repeats. Individuals with HD usually have 40 or more repeats. A small percentage of individuals, however, have a number of repeats that fall within a borderline region (see table 1).

Table 1

No. of CAG repeats

Outcome

<

28

Normal range; individual will not develop HD

29-34

Individual will not develop HD but the next generation is at risk

35-39

Some, but not all, individuals in this range will develop HD; next generation is also at risk

>

40

Individual will develop HD

The physician may ask the individual to undergo a brain imaging test. Computed tomography (CT) and magnetic resonance imaging (MRI) provide excellent images of brain structures with little if any discomfort. Those with HD may show shrinkage of some parts of the brain—particularly two areas known as the caudate nuclei and putamen—and enlargement of fluid-filled cavities within the brain called ventricles. These changes do not definitely indicate HD, however, because they can also occur in other disorders. In addition, a person can have early symptoms of HD and still have a normal CT scan. When used in conjunction with a family history and record of clinical symptoms, however, CT can be an important diagnostic tool.

Another technology for brain imaging includes positron emission tomography (PET,) which is important in HD research efforts but is not often needed for diagnosis.

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What is Presymptomatic Testing?


Presymptomatic testing is used for people who have a family history of HD but have no symptoms themselves. If either parent had HD, the person's chance would be 50-50. In the past, no laboratory test could positively identify people carrying the HD gene—or those fated to develop HD—before the onset of symptoms. That situation changed in 1983, when a team of scientists supported by the NINDS located the first genetic marker for HD—the initial step in developing a laboratory test for the disease.

A marker is a piece of DNA that lies near a gene and is usually inherited with it. Discovery of the first HD marker allowed scientists to locate the HD gene on chromosome 4. The marker discovery quickly led to the development of a presymptomatic test for some individuals, but this test required blood or tissue samples from both affected and unaffected family members in order to identify markers unique to that particular family. For this reason, adopted individuals, orphans, and people who had few living family members were unable to use the test.

Discovery of the HD gene has led to a less expensive, scientifically simpler, and far more accurate presymptomatic test that is applicable to the majority of at-risk people. The new test uses CAG repeat length to detect the presence of the HD mutation in blood. This is discussed further in the next section.

There are many complicating factors that reflect the complexity of diagnosing HD. In a small number of individuals with HD—1 to 3 percent—no family history of HD can be found. Some individuals may not be aware of their genetic legacy, or a family member may conceal a genetic disorder from fear of social stigma. A parent may not want to worry children, scare them, or deter them from marrying. In other cases, a family member may die of another cause before he or she begins to show signs of HD. Sometimes, the cause of death for a relative may not be known, or the family is not aware of a relative's death. Adopted children may not know their genetic heritage, or early symptoms in an individual may be too slight to attract attention.

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How is the Presymptomatic Test Conducted?


An individual who wishes to be tested should contact the nearest testing center. (A list of such centers can be obtained from the Huntington Disease Society of America at 1-800-345-HDSA.) The testing process should include several components. Most testing programs include a neurological examination, pretest counseling, and follow up. The purpose of the neurological examination is to determine whether or not the person requesting testing is showing any clinical symptoms of HD. It is important to remember that if an individual is showing even slight symptoms of HD, he or she risks being diagnosed with the disease during the neurological examination, even before the genetic test. During pretest counseling, the individual will learn about HD, and about his or her own level of risk, about the testing procedure. The person will be told about the test's limitations, the accuracy of the test, and possible outcomes. He or she can then weigh the risks and benefits of testing and may even decide at that time against pursuing further testing.

If a person decides to be tested, a team of highly trained specialists will be involved, which may include neurologists, genetic counselors, social workers, psychiatrists, and psychologists. This team of professionals helps the at-risk person decide if testing is the right thing to do and carefully prepares the person for a negative, positive, or inconclusive test result.

Individuals who decide to continue the testing process should be accompanied to counseling sessions by a spouse, a friend, or a relative who is not at risk. Other interested family members may participate in the counseling sessions if the individual being tested so desires.

The genetic testing itself involves donating a small sample of blood that is screened in the laboratory for the presence or absence of the HD mutation. Testing may require a sample of DNA from a closely related affected relative, preferably a parent, for the purpose of confirming the diagnosis of HD in the family. This is especially important if the family history for HD is unclear or unusual in some way.

Results of the test should be given only in person and only to the individual being tested. Test results are confidential. Regardless of test results, follow up is recommended.

In order to protect the interests of minors, including confidentiality, testing is not recommended for those under the age of 18 unless there is a compelling medical reason (for example, the child is exhibiting symptoms).

Testing of a fetus (prenatal testing) presents special challenges and risks; in fact some centers do not perform genetic testing on fetuses. Because a positive test result using direct genetic testing means the at-risk parent is also a gene carrier, at-risk individuals who are considering a pregnancy are advised to seek genetic counseling prior to conception.

Some at-risk parents may wish to know the risk to their fetus but not their own. In this situation, parents may opt for prenatal testing using linked DNA markers rather than direct gene testing. In this case, testing does not look for the HD gene itself but instead indicates whether or not the fetus has inherited a chromosome 4 from the affected grandparent or from the unaffected grandparent on the side of the family with HD. If the test shows that the fetus has inherited a chromosome 4 from the affected grandparent, the parents then learn that the fetus's risk is the same as the parent (50-50), but they learn nothing new about the parent's risk. If the test shows that the fetus has inherited a chromosome 4 from the unaffected grandparent, the risk to the fetus is very low (less than 1%) in most cases.

Another option open to parents is in vitro fertilization with preimplantation screening. In this procedure, embryos are screened to determine which ones carry the HD mutation. Embryos determined not to have the HD gene mutation are then implanted in the woman's uterus.

In terms of emotional and practical consequences, not only for the individual taking the test but for his or her entire family, testing is enormously complex and has been surrounded by considerable controversy. For example, people with a positive test result may risk losing health and life insurance, suffer loss of employment, and other liabilities. People undergoing testing may wish to cover the cost themselves, since coverage by an insurer may lead to loss of health insurance in the event of a positive result, although this may change in the future.

With the participation of health professionals and people from families with HD, scientists have developed testing guidelines. All individuals seeking a genetic test should obtain a copy of these guidelines, either from their testing center or from the organizations listed on the card in the back of this brochure. These organizations have information on sites that perform testing using the established procedures and they strongly recommend that individuals avoid testing that does not adhere to these guidelines.

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How Does a Person Decide Whether to be Tested?


The anxiety that comes from living with a 50 percent risk for HD can be overwhelming. How does a young person make important choices about long-term education, marriage, and children? How do older parents of adult children cope with their fears about children and grandchildren? How do people come to terms with the ambiguity and uncertainty of living at risk?

Some individuals choose to undergo the test out of a desire for greater certainty about their genetic status. They believe the test will enable them to make more informed decisions about the future. Others choose not to take the test. They are able to make peace with the uncertainty of being at risk, preferring to forego the emotional consequences of a positive result, as well as possible losses of insurance and employment. There is no right or wrong decision, as each choice is highly individual. The guidelines for genetic testing for HD, discussed in the previous section, were developed to help people with this life-changing choice.

Whatever the results of genetic testing, the at-risk individual and family members can expect powerful and complex emotional responses. The health and happiness of spouses, brothers and sisters, children, parents, and grandparents are affected by a positive test result, as are an individual's friends, work associates, neighbors, and others. Because receiving test results may prove to be devastating, testing guidelines call for continued counseling even after the test is complete and the results are known.

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Is There a Treatment for HD?


Physicians may prescribe a number of medications to help control emotional and movement problems associated with HD. It is important to remember however, that while medicines may help keep these clinical symptoms under control, there is no treatment to stop or reverse the course of the disease.

In August 2008 the U.S. Food and Drug Administration approved tetrabenazine to treat Huntington's chorea, making it the first drug approved for use in the United States to treat the disease. Antipsychotic drugs, such as haloperidol, or other drugs, such as clonazepam, may help to alleviate choreic movements and may also be used to help control hallucinations, delusions, and violent outbursts. Antipsychotic drugs, however, are not prescribed for another form of muscle contraction associated with HD, called dystonia, and may in fact worsen the condition, causing stiffness and rigidity. These medications may also have severe side effects, including sedation, and for that reason should be used in the lowest possible doses.

For depression, physicians may prescribe fluoxetine, sertraline, nortriptyline, or other compounds. Tranquilizers can help control anxiety and lithium may be prescribed to combat pathological excitement and severe mood swings. Medications may also be needed to treat the severe obsessive-compulsive rituals of some individuals with HD.

Most drugs used to treat the symptoms of HD have side effects such as fatigue, restlessness, or hyperexcitability. Sometimes it may be difficult to tell if a particular symptom, such as apathy or incontinence, is a sign of the disease or a reaction to medication.

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What Kind of Care Does the Individual with HD Need?


Although a psychologist or psychiatrist, a genetic counselor, and other specialists may be needed at different stages of the illness, usually the first step in diagnosis and in finding treatment is to see a neurologist. While the family doctor may be able to diagnose HD, and may continue to monitor the individual's status, it is better to consult with a neurologist about management of the varied symptoms.

Problems may arise when individuals try to express complex thoughts in words they can no longer pronounce intelligibly. It can be helpful to repeat words back to the person with HD so that he or she knows that some thoughts are understood. Sometimes people mistakenly assume that if individuals do not talk, they also do not understand. Never isolate individuals by not talking, and try to keep their environment as normal as possible. Speech therapy may improve the individual's ability to communicate.

It is extremely important for the person with HD to maintain physical fitness as much as his or her condition and the course of the disease allows. Individuals who exercise and keep active tend to do better than those who do not. A daily regimen of exercise can help the person feel better physically and mentally. Although their coordination may be poor, individuals should continue walking, with assistance if necessary. Those who want to walk independently should be allowed to do so as long as possible, and careful attention should be given to keeping their environment free of hard, sharp objects. This will help ensure maximal independence while minimizing the risk of injury from a fall. Individuals can also wear special padding during walks to help protect against injury from falls. Some people have found that small weights around the ankles can help stability. Wearing sturdy shoes that fit well can help too, especially shoes without laces that can be slipped on or off easily.

Impaired coordination may make it difficult for people with HD to feed themselves and to swallow. As the disease progresses, persons with HD may even choke. In helping individuals to eat, caregivers should allow plenty of time for meals. Food can be cut into small pieces, softened, or pureed to ease swallowing and prevent choking. While some foods may require the addition of thickeners, other foods may need to be thinned. Dairy products, in particular, tend to increase the secretion of mucus, which in turn increases the risk of choking. Some individuals may benefit from swallowing therapy, which is especially helpful if started before serious problems arise. Suction cups for plates, special tableware designed for people with disabilities, and plastic cups with tops can help prevent spilling. The individual's physician can offer additional advice about diet and about how to handle swallowing difficulties or gastrointestinal problems that might arise, such as incontinence or constipation.

Caregivers should pay attention to proper nutrition so that the individual with HD takes in enough calories to maintain his or her body weight. Sometimes people with HD, who may burn as many as 5,000 calories a day without gaining weight, require five meals a day to take in the necessary number of calories. Physicians may recommend vitamins or other nutritional supplements. In a long-term care institution, staff will need to assist with meals in order to ensure that the individual's special caloric and nutritional requirements are met. Some individuals and their families choose to use a feeding tube; others choose not to.

Individuals with HD are at special risk for dehydration and therefore require large quantities of fluids, especially during hot weather. Bendable straws can make drinking easier for the person. In some cases, water may have to be thickened with commercial additives to give it the consistency of syrup or honey.

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What Community Resources are Available?


Individuals and families affected by HD can take steps to ensure that they receive the best advice and care possible. Physicians and state and local health service agencies can provide information on community resources and family support groups that may exist. Possible types of help include:

Legal and social aid. HD affects a person's capacity to reason, make judgments, and handle responsibilities. Individuals may need help with legal affairs. Wills and other important documents should be drawn up early to avoid legal problems when the person with HD may no longer be able to represent his or her own interests. Family members should also seek out assistance if they face discrimination regarding insurance, employment, or other matters.

Home care services. Caring for a person with HD at home can be exhausting, but part-time assistance with household chores or physical care of the individual can ease this burden. Domestic help, meal programs, nursing assistance, occupational therapy, or other home services may be available from federal, state, or local health service agencies.

Recreation and work centers. Many people with HD are eager and able to participate in activities outside the home. Therapeutic work and recreation centers give individuals an opportunity to pursue hobbies and interests and to meet new people. Participation in these programs, including occupational, music, and recreational therapy, can reduce the person's dependence on family members and provides home caregivers with a temporary, much needed break.

Group housing. A few communities have group housing facilities that are supervised by a resident attendant and that provide meals, housekeeping services, social activities, and local transportation services for residents. These living arrangements are particularly suited to the needs of individuals who are alone and who, although still independent and capable, risk injury when they undertake routine chores like cooking and cleaning.

Institutional care. The individual's physical and emotional demands on the family may eventually become overwhelming. While many families may prefer to keep relatives with HD at home whenever possible, a long-term care facility may prove to be best. To hospitalize or place a family member in a care facility is a difficult decision; professional counseling can help families with this.

Finding the proper facility can itself prove difficult. Organizations such as the Huntington's Disease Society of America (see listing on the Information Resources card in the back pocket of this brochure) may be able to refer the family to facilities that have met standards set for the care of individuals with HD. Very few of these exist however, and even fewer have experience with individuals with juvenile or early-onset HD who require special care because of their age and symptoms.

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What Research is Being Done?


Although HD attracted considerable attention from scientists in the early 20th century, there was little sustained research on the disease until the late 1960s when the Committee to Combat Huntington's Disease and the Huntington's Chorea Foundation, later called the Hereditary Disease Foundation, first began to fund research and to campaign for federal funding. In 1977, Congress established the Commission for the Control of Huntington's Disease and Its Consequences, which made a series of important recommendations. Since then, Congress has provided consistent support for federal research, primarily through the National Institute of Neurological Disorders and Stroke, the government's lead agency for biomedical research on disorders of the brain and nervous system. The effort to combat HD proceeds along the following lines of inquiry, each providing important information about the disease:

Basic neurobiology. Now that the HD gene has been located, investigators in the field of neurobiology-which encompasses the anatomy, physiology, and biochemistry of the nervous system-are continuing to study the HD gene with an eye toward understanding how it causes disease in the human body.

Clinical research. Neurologists, psychologists, psychiatrists, and other investigators are improving our understanding of the symptoms and progression of the disease in patients while attempting to develop new therapeutics.

Imaging. Scientific investigations using PET and other technologies are enabling scientists to see what the defective gene does to various structures in the brain and how it affects the body's chemistry and metabolism.

Animal models. Laboratory animals, such as mice, are being bred in the hope of duplicating the clinical features of HD and can soon be expected to help scientists learn more about the symptoms and progression of the disease.

Fetal tissue research. Investigators are implanting fetal tissue in rodents and nonhuman primates with the hope that success in this area will lead to understanding, restoring, or replacing functions typically lost by neuronal degeneration in individuals with HD.

These areas of research are slowly converging and, in the process, are yielding important clues about the gene's relentless destruction of mind and body. The NINDS supports much of this exciting work.

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Molecular Genetics


For 10 years, scientists focused on a segment of chromosome 4 and, in 1993, finally isolated the HD gene. The process of isolating the responsible gene—motivated by the desire to find a cure—was more difficult than anticipated. Scientists now believe that identifying the location of the HD gene is the first step on the road to a cure.

Finding the HD gene involved an intense molecular genetics research effort with cooperating investigators from around the globe. In early 1993, the collaborating scientists announced they had isolated the unstable triplet repeat DNA sequence that has the HD gene. Investigators relied on the NINDS-supported Research Roster for Huntington's Disease, based at Indiana University in Indianapolis, to accomplish this work. First started in 1979, the roster contains data on many American families with HD, provides statistical and demographic data to scientists, and serves as a liaison between investigators and specific families. It provided the DNA from many families affected by HD to investigators involved in the search for the gene and was an important component in the identification of HD markers.

For several years, NINDS-supported investigators involved in the search for the HD gene made yearly visits to the largest known kindred with HD—14,000 individuals—who live on Lake Maracaibo in Venezuela. The continuing trips enable scientists to study inheritance patterns of several interrelated families.

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The HD Gene and Its Product


Although scientists know that certain brain cells die in HD, the cause of their death is still unknown. Recessive diseases are usually thought to result from a gene that fails to produce adequate amounts of a substance essential to normal function. This is known as a loss-of-function gene. Some dominantly inherited disorders, such as HD, are thought to involve a gene that actively interferes with the normal function of the cell. This is known as a gain-of-function gene.

How does the defective HD gene cause harm? The HD gene encodes a protein—which has been named huntingtin—the function of which is as yet unknown. The repeated CAG sequence in the gene causes an abnormal form of huntingtin to be made, in which the amino acid glutamine is repeated. It is the presence of this abnormal form, and not the absence of the normal form, that causes harm in HD. This explains why the disease is dominant and why two copies of the defective gene—one from both the mother and the father—do not cause a more serious case than inheritance from only one parent. With the HD gene isolated, NINDS-supported investigators are now turning their attention toward discovering the normal function of huntingtin and how the altered form causes harm. Scientists hope to reproduce, study, and correct these changes in animal models of the disease.

Huntingtin is found everywhere in the body but only outside the cell's nucleus. Mice called "knockout mice" are bred in the laboratory to produce no huntingtin; they fail to develop past a very early embryo stage and quickly die. Huntingtin, scientists now know, is necessary for life. Investigators hope to learn why the abnormal version of the protein damages only certain parts of the brain. One theory is that cells in these parts of the brain may be supersensitive to this abnormal protein.

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Cell Death in HD


Although the precise cause of cell death in HD is not yet known, scientists are paying close attention to the process of genetically programmed cell death that occurs deep within the brains of individuals with HD. This process involves a complex series of interlinked events leading to cellular suicide. Related areas of investigation include:

  • Excitotoxicity. Overstimulation of cells by natural chemicals found in the brain.
  • Defective energy metabolism. A defect in the power plant of the cell, called mitochondria, where energy is produced.
  • Oxidative stress. Normal metabolic activity in the brain that produces toxic compounds called free radicals.
  • Trophic factors. Natural chemical substances found in the human body that may protect against cell death.

Several HD studies are aimed at understanding losses of nerve cells and receptors in HD. Neurons in the striatum are classified both by their size (large, medium, or small) and appearance (spiny or aspiny). Each type of neuron contains combinations of neurotransmitters. Scientists know that the destructive process of HD affects different subsets of neurons to varying degrees. The hallmark of HD, they are learning, is selective degeneration of medium-sized spiny neurons in the striatum. NINDS-supported studies also suggest that losses of certain types of neurons and receptors are responsible for different symptoms and stages of HD.

What do these changes look like? In spiny neurons, investigators have observed two types of changes, each affecting the nerve cells' dendrites. Dendrites, found on every nerve cell, extend out from the cell body and are responsible for receiving messages from other nerve cells. In the intermediate stages of HD, dendrites grow out of control. New, incomplete branches form and other branches become contorted. In advanced, severe stages of HD, degenerative changes cause sections of dendrites to swell, break off, or disappear altogether. Investigators believe that these alterations may be an attempt by the cell to rebuild nerve cell contacts lost early in the disease. As the new dendrites establish connections, however, they may in fact contribute to nerve cell death. Such studies give compelling, visible evidence of the progressive nature of HD and suggest that new experimental therapies must consider the state of cellular degeneration. Scientists do not yet know exactly how these changes affect subsets of nerve cells outside the striatum.

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Animal Models of HD


As more is learned about cellular degeneration in HD, investigators hope to reproduce these changes in animal models and to find a way to correct or halt the process of nerve cell death. Such models serve the scientific community in general by providing a means to test the safety of new classes of drugs in nonhuman primates. NINDS-supported scientists are currently working to develop both nonhuman primate and mouse models to investigate nerve degeneration in HD and to study the effects of excitotoxicity on nerve cells in the brain.

Investigators are working to build genetic models of HD using transgenic mice. To do this, scientists transfer the altered human HD gene into mouse embryos so that the animals will develop the anatomical and biological characteristics of HD. This genetic model of mouse HD will enable in-depth study of the disease and testing of new therapeutic compounds.

Another idea is to insert into mice a section of DNA containing CAG repeats in the abnormal, disease gene range. This mouse equivalent of HD could allow scientists to explore the basis of CAG instability and its role in the disease process.

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Fetal Tissue Research


A relatively new field in biomedical research involves the use of brain tissue grafts to study, and potentially treat, neurodegenerative disorders. In this technique, tissue that has degenerated is replaced with implants of fresh, fetal tissue, taken at the very early stages of development. Investigators are interested in applying brain tissue implants to HD research. Extensive animal studies will be required to learn if this technique could be of value in patients with HD.

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Clinical Studies


Scientists are pursuing clinical studies that may one day lead to the development of new drugs or other treatments to halt the disease's progression. Examples of NINDS-supported investigations, using both asymptomatic and symptomatic individuals, include:

Genetic studies on age of onset, inheritance patterns, and markers found within families. These studies may shed additional light on how HD is passed from generation to generation.

Studies of cognition, intelligence, and movement. Studies of abnormal eye movements, both horizontal and vertical, and tests of patients' skills in a number of learning, memory, neuropsychological, and motor tasks may serve to identify when the various symptoms of HD appear and to characterize their range and severity.

Clinical trials of drugs. Testing of various drugs may lead to new treatments and at the same time improve our understanding of the disease process in HD. Classes of drugs being tested include those that control symptoms, slow the rate of progression of HD, and block effects of excitotoxins, and those that might correct or replace other metabolic defects contributing to the development and progression of HD.

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Imaging


NINDS-supported scientists are using positron emission tomography (PET) to learn how the gene affects the chemical systems of the body. PET visualizes metabolic or chemical abnormalities in the body, and investigators hope to ascertain if PET scans can reveal any abnormalities that signal HD. Investigators conducting HD research are also using PET to characterize neurons that have died and chemicals that are depleted in parts of the brain affected by HD.

Like PET, a form of magnetic resonance imaging (MRI) called functional MRI can measure increases or decreases in certain brain chemicals thought to play a key role in HD. Functional MRI studies are also helping investigators understand how HD kills neurons in different regions of the brain.

Imaging technologies allow investigators to view changes in the volume and structures of the brain and to pinpoint when these changes occur in HD. Scientists know that in brains affected by HD, the basal ganglia, cortex, and ventricles all show atrophy or other alterations.

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How Can I Help?


In order to conduct HD research, investigators require samples of tissue or blood from families with HD. Access to individuals with HD and their families may be difficult however, because families with HD are often scattered across the country or around the world. A research project may need individuals of a particular age or gender or from a certain geographic area. Some scientists need only statistical data while others may require a sample of blood, urine, or skin from family members. All of these factors complicate the task of finding volunteers. The following NINDS-supported efforts bring together families with HD, voluntary health agencies, and scientists in an effort to advance science and speed a cure.

The NINDS-sponsored HD Research Roster at the Indiana University Medical Center in Indianapolis, which was discussed earlier, makes research possible by matching scientists with patient and family volunteers. The first DNA bank was established through the roster. Although the gene has already been located, DNA from individuals who have HD is still of great interest to investigators. Of continuing interest are twins, unaffected individuals who have affected offspring, and individuals with two defective HD genes, one from each parent-a very rare occurrence. Participation in the roster and in specific research projects is voluntary and confidential. For more information about the roster and DNA bank, contact:

Indiana University Medical Center
Department of Medical and Molecular Genetics
Medical Research and Library Building
975 W. Walnut Street
Indianapolis, IN 46202-5251
(317) 274-5744 (call collect)

The NINDS supports two national brain specimen banks. These banks supply research scientists around the world with nervous system tissue from patients with neurological and psychiatric disorders. They need tissue from patients with HD so that scientists can study and understand the disorder. Those who may be interested in donating should write to:

Human Brain and Spinal Fluid Resource Center
Neurology Research (127A)
W. Los Angeles Healthcare Center
11301 Wilshire Blvd. Bldg. 212
Los Angeles, CA 90073
310-268-3536
24-hour pager: 310-636-5199
Email: RMNbbank@ucla.edu
http://www.loni.ucla.edu/~nnrsb/NNRSB

Francine M. Benes, M.D., Ph.D., Director
Harvard Brain Tissue Resource Center
McLean Hospital
115 Mill Street
Belmont, Massachusetts 02478
800-BRAIN-BANK (800-272-4622)
(617) 855-2400
www.brainbank.mclean.org

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What is the Role of Voluntary Organizations?


Private organizations have been a mainstay of support and guidance for at-risk individuals, people with HD, and their families. These organizations vary in size and emphasis, but all are concerned with helping individuals and their families, educating lay and professional audiences about HD, and promoting medical research on the disorder. Some voluntary health agencies support scientific workshops and research and some have newsletters and local chapters throughout the country. These agencies enable families, health professionals, and investigators to exchange information, learn of available services and benefits, and work toward common goals. The organizations listed on the Information Resources card in the back pocket of this brochure welcome inquiries from the public.

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

Hereditary Disease Foundation
3960 Broadway
6th Floor
New York, NY   10032
cures@hdfoundation.org
http://www.hdfoundation.org
Tel: 212-928-2121
Fax: 212-928-2172
Non-profit basic science organization dedicated to the cure of genetic disease. All publicly donated funds are directed toward the support of biomedical research.

Huntington's Disease Society of America
505 Eighth Avenue
Suite 902
New York, NY   10018
hdsainfo@hdsa.org
http://www.hdsa.org
Tel: 212-242-1968 800-345-HDSA (4372)
Fax: 212-239-3430
Dedicated to finding a cure for Huntington’s Disease while providing support and services for those with HD and their families.

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Glossary

akinesia-decreased body movements.

at-risk -a description of a person whose mother or father has HD or has inherited the HD gene and who therefore has a 50-50 chance of inheriting the disorder.

autosomal dominant disorder -a non-sex-linked disorder that can be inherited even if only one parent passes on the defective gene.

basal ganglia -a region located at the base of the brain composed of four clusters of neurons, or nerve cells. This area is responsible for body movement and coordination. The neuron groups most prominently and consistently affected by HD—the pallidum and striatum—are located here. See neuron, pallidum, striatum.

caudate nuclei -part of the striatum in the basal ganglia. See basal ganglia, striatum.

chorea -uncontrolled body movements. Chorea is derived from the Greek word for dance.

chromosomes -the structures in cells that contain genes. They are composed of deoxyribonucleic acid (DNA) and proteins and, under a microscope, appear as rod-like structures. See deoxyribonucleic acid (DNA), gene.

computed tomography (CT)- a technique used for diagnosing brain disorders. CT uses a computer to produce a high-quality image of brain structures. These images are called CT scans.

cortex -part of the brain responsible for thought, perception, and memory. HD affects the basal ganglia and cortex. See basal ganglia.

deoxyribonucleic acid (DNA)- the substance of heredity containing the genetic information necessary for cells to divide and produce proteins. DNA carries the code for every inherited characteristic of an organism. See gene.

dominant -a trait that is apparent even when the gene for that disorder is inherited from only one parent. See autosomal dominant disorder, recessive, gene.

gene -the basic unit of heredity, composed of a segment of DNA containing the code for a specific trait. See deoxyribonucleic acid (DNA).

huntingtin -the protein encoded by the gene that carries the HD defect. The repeated CAG sequence in the gene causes an abnormal form of huntingtin to be formed. The function of the normal form of huntingtin is not yet known.

kindred -a group of related persons, such as a family or clan.

magnetic resonance imaging (MRI) -an imaging technique that uses radiowaves, magnetic fields, and computer analysis to create a picture of body tissues and structures.

marker -a piece of DNA that lies on the chromosome so close to a gene that the two are inherited together. Like a signpost, markers are used during genetic testing and research to locate the nearby presence of a gene. See chromosome, deoxyribonucleic acid (DNA).

mitochondria -microscopic, energy-producing bodies within cells that are the cells' "power plants."

mutation -in genetics, any defect in a gene. See gene.

myoclonus -a condition in which muscles or portions of muscles contract involuntarily in a jerky fashion.

neuron -Greek word for a nerve cell, the basic impulse-conducting unit of the nervous system. Nerve cells communicate with other cells through an electrochemical process called neurotransmission.

neurotransmitters -special chemicals that transmit nerve impulses from one cell to another.

pallidum -part of the basal ganglia of the brain. The pallidum is composed of the globus pallidus and the ventral pallidum. See basal ganglia.

positron emission tomography (PET)- a tool used to diagnose brain functions and disorders. PET produces three-dimensional, colored images of chemicals or substances functioning within the body. These images are called PET scans. PET shows brain function, in contrast to CT or MRI, which show brain structure.

prevalence -the number of cases of a disease that are present in a particular population at a given time.

putamen -an area of the brain that decreases in size as a result of the damage produced by HD.

receptor -proteins that serve as recognition sites on cells and cause a response in the body when stimulated by chemicals called neurotransmitters. They act as on-and-off switches for the next nerve cell. See neuron, neurotransmitters.

recessive -a trait that is apparent only when the gene or genes for it are inherited from both parents. See dominant, gene.

senile chorea -a relatively mild and rare disorder found in elderly adults and characterized by choreic movements. It is believed by some scientists to be caused by a different gene mutation than that causing HD.

striatum -part of the basal ganglia of the brain. The striatum is composed of the caudate nucleus, putamen, and ventral striatum. See basal ganglia, caudate nuclei.

trait -any genetically determined characteristic. See dominant, gene, recessive.

transgenic mice-mice that receive injections of foreign genes during the embryonic stage of development. Their cells then follow the "instructions" of the foreign genes, resulting in the development of a certain trait or characteristic. Transgenic mice can serve as an animal model of a certain disease, telling researchers how genes work in specific cells.

ventricles -cavities within the brain that are filled with cerebrospinal fluid. In HD, tissue loss causes enlargement of the ventricles.

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"Huntington's Disease: Hope Through Research," NINDS.

NIH Publication No. 98-49



 

Migraines & Headaches

Introduction
Why Does it Hurt?
When Should You See a Physician?
What Tests Are Used to Diagnose Headache?
What Are Migraine Headaches?
How is Migraine Headache Treated?
Besides Migraine, What Are Other Types of Vascular Headaches?
What Are Muscle-Contraction Headaches?
When is Headache a Warning of a More Serious Condition?
What Causes Headache in Children?
Conclusion
Where can I get more information?
Glossary

Introduction


For 2 years, Jim suffered the excruciating pain of cluster headaches. Night after night he paced the floor, the pain driving him to constant motion. He was only 48 years old when the clusters forced him to quit his job as a systems analyst. One year later, his headaches are controlled. The credit for Jim's recovery belongs to the medical staff of a headache clinic. Physicians there applied the latest research findings on headache, and prescribed for Jim a combination of new drugs.

Joan was a victim of frequent migraine. Her headaches lasted 2 days. Nauseous and weak, she stayed in the dark until each attack was over. Today, although migraine still interferes with her life, she has fewer attacks and less severe headaches than before. A specialist prescribed an antimigraine program for Joan that included improved drug therapy, a new diet and relaxation training.

An avid reader, Peggy couldn't put down the new mystery thriller. After 4 hours of reading slumped in bed, she knew she had overdone it. Her tensed head and neck muscles felt as if they were being squeezed between two giant hands. But for Peggy, the muscle-contraction headache and neck pain were soon relieved by a hot shower and aspirin.

Understanding why headaches occur and improving headache treatment are among the research goals of the National Institute of Neurological Disorders and Stroke (NINDS). As the leading supporter of brain research in the Federal Government, the NINDS also supports and conducts studies to improve the diagnosis of headaches and to find ways to prevent them.

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Why Does it Hurt?


What hurts when you have a headache? The bones of the skull and tissues of the brain itself never hurt, because they lack pain-sensitive nerve fibers. Several areas of the head can hurt, including a network of nerves which extends over the scalp and certain nerves in the face, mouth, and throat. Also sensitive to pain, because they contain delicate nerve fibers, are the muscles of the head and blood vessels found along the surface and at the base of the brain.

The ends of these pain-sensitive nerves, called nociceptors, can be stimulated by stress, muscular tension, dilated blood vessels, and other triggers of headache. Once stimulated, a nociceptor sends a message up the length of the nerve fiber to the nerve cells in the brain, signaling that a part of the body hurts. The message is determined by the location of the nociceptor. A person who suddenly realizes "My toe hurts," is responding to nociceptors in the foot that have been stimulated by the stubbing of a toe.

A number of chemicals help transmit pain-related information to the brain. Some of these chemicals are natural painkilling proteins called endorphins, Greek for "the morphine within." One theory suggests that people who suffer from severe headache and other types of chronic pain have lower levels of endorphins than people who are generally pain free.

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When Should You See a Physician?


Not all headaches require medical attention. Some result from missed meals or occasional muscle tension and are easily remedied. But some types of headache are signals of more serious disorders, and call for prompt medical care. These include:

  • Sudden, severe headache
  • Sudden, severe headache associated with a stiff neck
  • Headache associated with fever
  • Headache associated with convulsions
  • Headache accompanied by confusion or loss of consciousness
  • Headache following a blow on the head
  • Headache associated with pain in the eye or ear
  • Persistent headache in a person who was previously headache free
  • Recurring headache in children
  • Headache which interferes with normal life

A headache sufferer usually seeks help from a family practitioner. If the problem is not relieved by standard treatments, the patient may then be referred to a specialist - perhaps an internist or neurologist. Additional referrals may be made to psychologists.

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What Tests Are Used to Diagnose Headache?


Diagnosing a headache is like playing Twenty Questions. Experts agree that a detailed question-and-answer session with a patient can often produce enough information for a diagnosis. Many types of headaches have clear-cut symptoms which fall into an easily recognizable pattern.

Patients may be asked: How often do you have headaches? Where is the pain? How long do the headaches last? When did you first develop headaches? The patient's sleep habits and family and work situations may also be probed.

Most physicians will also obtain a full medical history from the patient, inquiring about past head trauma or surgery, eye strain, sinus problems, dental problems, difficulties with opening and closing of the jaw, and the use of medications. This may be enough to suggest strongly that the patient has migraine or cluster headaches. A complete and careful physical and neurological examination will exclude many possibilities and the suspicion of aneurysm, meningitis, or certain brain tumors. A blood test may be ordered to screen for thyroid disease, anemia, or infections which might cause a headache.

A test called an electroencephalogram (EEG) may be given to measure brain activity. EEG's can indicate a malfunction in the brain, but they cannot usually pinpoint a problem that might be causing a headache. A physician may suggest that a patient with unusual headaches undergo a computed tomographic (CT) scan and/or a magnetic resonance imaging (MRI) scan. The scans enable the physician to distinguish, for example, between a bleeding blood vessel in the brain and a brain tumor, and are important diagnostic tools in cases of headache associated with brain lesions or other serious disease. CT scans produce X-ray images of the brain that show structures or variations in the density of different types of tissue. MRI scans use magnetic fields and radio waves to produce an image that provides information about the structure and biochemistry of the brain.

If an aneurysm-an abnormal ballooning of a blood vessel-is suspected, a physician may order a CT scan to examine for blood and then an angiogram. In this test, a special fluid which can be seen on an X-ray is injected into the patient and carried in the bloodstream to the brain to reveal any abnormalities in the blood vessels there.

A physician analyzes the results of all these diagnostic tests along with a patient's medical history and examination in order to arrive at a diagnosis.

Headaches are diagnosed as

  • Vascular
  • Muscle contraction (tension)
  • Traction
  • Inflammatory

Vascular headaches - a group that includes the well-known migraine - are so named because they are thought to involve abnormal function of the brain's blood vessels or vascular system. Muscle contraction headaches appear to involve the tightening or tensing of facial and neck muscles. Traction and inflammatory headaches are symptoms of other disorders, ranging from stroke to sinus infection. Some people have more than one type of headache.

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What Are Migraine Headaches?


The most common type of vascular headache is migraine. Migraine headaches are usually characterized by severe pain on one or both sides of the head, an upset stomach, and at times disturbed vision.

Former basketball star Kareem Abdul-Jabbar remembers experiencing his first migraine at age 14. The pain was unlike the discomfort of his previous mild headaches.

"When I got this one I thought, 'This is a headache'," he says. "The pain was intense and I felt nausea and a great sensitivity to light. All I could think about was when it would stop. I sat in a dark room for an hour and it passed."

Symptoms of migraine. Abdul-Jabbar's sensitivity to light is a standard symptom of the two most prevalent types of migraine-caused headache: classic and common.

The major difference between the two types is the appearance of neurological symptoms 10 to 30 minutes before a classic migraine attack. These symptoms are called an aura. The person may see flashing lights or zigzag lines, or may temporarily lose vision. Other classic symptoms include speech difficulty, weakness of an arm or leg, tingling of the face or hands, and confusion.

The pain of a classic migraine headache may be described as intense, throbbing, or pounding and is felt in the forehead, temple, ear, jaw, or around the eye. Classic migraine starts on one side of the head but may eventually spread to the other side. An attack lasts 1 to 2 pain-wracked days.

Common migraine - a term that reflects the disorder's greater occurrence in the general population - is not preceded by an aura. But some people experience a variety of vague symptoms beforehand, including mental fuzziness, mood changes, fatigue, and unusual retention of fluids. During the headache phase of a common migraine, a person may have diarrhea and increased urination, as well as nausea and vomiting. Common migraine pain can last 3 or 4 days.

Both classic and common migraine can strike as often as several times a week, or as rarely as once every few years. Both types can occur at any time. Some people, however, experience migraines at predictable times - for example, near the days of menstruation or every Saturday morning after a stressful week of work.

The migraine process. Research scientists are unclear about the precise cause of migraine headaches. There seems to be general agreement, however, that a key element is blood flow changes in the brain. People who get migraine headaches appear to have blood vessels that overreact to various triggers.

Scientists have devised one theory of migraine which explains these blood flow changes and also certain biochemical changes that may be involved in the headache process. According to this theory, the nervous system responds to a trigger such as stress by causing a spasm of the nerve-rich arteries at the base of the brain. The spasm closes down or constricts several arteries supplying blood to the brain, including the scalp artery and the carotid or neck arteries.

As these arteries constrict, the flow of blood to the brain is reduced. At the same time, blood-clotting particles called platelets clump together-a process which is believed to release a chemical called serotonin. Serotonin acts as a powerful constrictor of arteries, further reducing the blood supply to the brain.

Reduced blood flow decreases the brain's supply of oxygen. Symptoms signaling a headache, such as distorted vision or speech, may then result, similar to symptoms of stroke.

Reacting to the reduced oxygen supply, certain arteries within the brain open wider to meet the brain's energy needs. This widening or dilation spreads, finally affecting the neck and scalp arteries. The dilation of these arteries triggers the release of pain-producing substances called prostaglandins from various tissues and blood cells. Chemicals which cause inflammation and swelling, and substances which increase sensitivity to pain, are also released. The circulation of these chemicals and the dilation of the scalp arteries stimulate the pain-sensitive nociceptors. The result, according to this theory: a throbbing pain in the head.

Women and migraine. Although both males and females seem to be equally affected by migraine, the condition is more common in adult women. Both sexes may develop migraine in infancy, but most often the disorder begins between the ages of 5 and 35.

The relationship between female hormones and migraine is still unclear. Women may have "menstrual migraine" - headaches around the time of their menstrual period - which may disappear during pregnancy. Other women develop migraine for the first time when they are pregnant. Some are first affected after menopause.

The effect of oral contraceptives on headaches is perplexing. Scientists report that some women with migraine who take birth control pills experience more frequent and severe attacks. However, a small percentage of women have fewer and less severe migraine headaches when they take birth control pills. And normal women who do not suffer from headaches may develop migraines as a side effect when they use oral contraceptives. Investigators around the world are studying hormonal changes in women with migraine in the hope of identifying the specific ways these naturally occurring chemicals cause headaches.

Triggers of headache. Although many sufferers have a family history of migraine, the exact hereditary nature of this condition is still unknown. People who get migraines are thought to have an inherited abnormality in the regulation of blood vessels.

"It's like a cocked gun with a hair trigger," explains one specialist. "A person is born with a potential for migraine and the headache is triggered by things that are really not so terrible."

These triggers include stress and other normal emotions, as well as biological and environmental conditions. Fatigue, glaring or flickering lights, changes in the weather, and certain foods can set off migraine. It may seem hard to believe that eating such seemingly harmless foods as yogurt, nuts, and lima beans can result in a painful migraine headache. However, some scientists believe that these foods and several others contain chemical substances, such as tyramine, which constrict arteries - the first step of the migraine process. Other scientists believe that foods cause headaches by setting off an allergic reaction in susceptible people.

While a food-triggered migraine usually occurs soon after eating, other triggers may not cause immediate pain. Scientists report that people can develop migraine not only during a period of stress but also afterwards when their vascular systems are still reacting. For example, migraines that wake people up in the middle of the night are believed to result from a delayed reaction to stress.

Other forms of migraine. In addition to classic and common, migraine headache can take several other forms:

Patients with hemiplegic migraine have temporary paralysis on one side of the body, a condition known as hemiplegia. Some people may experience vision problems and vertigo - a feeling that the world is spinning. These symptoms begin 10 to 90 minutes before the onset of headache pain.

In ophthalmoplegic migraine, the pain is around the eye and is associated with a droopy eyelid, double vision, and other problems with vision.

Basilar artery migraine involves a disturbance of a major brain artery at the base of the brain. Preheadache symptoms include vertigo, double vision, and poor muscular coordination. This type of migraine occurs primarily in adolescent and young adult women and is often associated with the menstrual cycle.

Benign exertional headache is brought on by running, lifting, coughing, sneezing, or bending. The headache begins at the onset of activity, and pain rarely lasts more than several minutes.

Status migrainosus is a rare and severe type of migraine that can last 72 hours or longer. The pain and nausea are so intense that people who have this type of headache must be hospitalized. The use of certain drugs can trigger status migrainosus. Neurologists report that many of their status migrainosus patients were depressed and anxious before they experienced headache attacks.

Headache-free migraine is characterized by such migraine symptoms as visual problems, nausea, vomiting, constipation, or diarrhea. Patients, however, do not experience head pain. Headache specialists have suggested that unexplained pain in a particular part of the body, fever, and dizziness could also be possible types of headache-free migraine.

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How is Migraine Headache Treated?


During the Stone Age, pieces of a headache sufferer's skull were cut away with flint instruments to relieve pain. Another unpleasant remedy used in the British Isles around the ninth Century involved drinking "the juice of elderseed, cow's brain, and goat's dung dissolved in vinegar." Fortunately, today's headache patients are spared such drastic measures.

Drug therapy, biofeedback training, stress reduction, and elimination of certain foods from the diet are the most common methods of preventing and controlling migraine and other vascular headaches. Joan, the migraine sufferer, was helped by treatment with a combination of an antimigraine drug and diet control.

Regular exercise, such as swimming or vigorous walking, can also reduce the frequency and severity of migraine headaches. Joan found that whirlpool and yoga baths helped her relax.

During a migraine headache, temporary relief can sometimes be obtained by applying cold packs to the head or by pressing on the bulging artery found in front of the ear on the painful side of the head.

Drug therapy. There are two ways to approach the treatment of migraine headache with drugs: prevent the attacks, or relieve symptoms after the headache occurs.

For infrequent migraine, drugs can be taken at the first sign of a headache in order to stop it or to at least ease the pain. People who get occasional mild migraine may benefit by taking aspirin or acetaminophen at the start of an attack. Aspirin raises a person's tolerance to pain and also discourages clumping of blood platelets. Small amounts of caffeine may be useful if taken in the early stages of migraine. But for most migraine sufferers who get moderate to severe headaches, and for all cluster headache patients (see section "Besides Migraine, What Are Other Types of Vascular Headaches?"), stronger drugs may be necessary to control the pain.

Several drugs for the prevention of migraine have been developed in recent years, including serotonin agonists which mimic the action of this key brain chemical. One of the most commonly used drugs for the relief of classic and common migraine symptoms is sumatriptan, which binds to serotonin receptors. For optimal benefit, the drug is taken during the early stages of an attack. If a migraine has been in progress for about an hour after the drug is taken, a repeat dose can be given.

Physicians caution that sumatriptan should not be taken by people who have angina pectoris, basilar migraine, severe hypertension, or vascular, or liver disease.

Another migraine drug is ergotamine tartrate, a vasoconstrictor which helps counteract the painful dilation stage of the headache. Other drugs that constrict dilated blood vessels or help reduce blood vessel inflammation also are available.

For headaches that occur three or more times a month, preventive treatment is usually recommended. Drugs used to prevent classic and common migraine include methysergide maleate, which counteracts blood vessel constriction; propranolol hydrochloride, which stops blood vessel dilation; amitriptyline, an antidepressant; valproic acid, an anticonvulsant; and verapamil, a calcium channel blocker.

Antidepressants called MAO inhibitors also prevent migraine. These drugs block an enzyme called monoamine oxidase which normally helps nerve cells absorb the artery-constricting brain chemical, serotonin. MAO inhibitors can have potentially serious side effects - particularly if taken while ingesting foods or beverages that contain tyramine, a substance that constricts arteries.

Many antimigraine drugs can have adverse side effects. But like most medicines they are relatively safe when used carefully and under a physician's supervision. To avoid long-term side effects of preventive medications, headache specialists advise patients to reduce the dosage of these drugs and then stop taking them as soon as possible.

Biofeedback and relaxation training. Drug therapy for migraine is often combined with biofeedback and relaxation training. Biofeedback refers to a technique that can give people better control over such body function indicators as blood pressure, heart rate, temperature, muscle tension, and brain waves. Thermal biofeedback allows a patient to consciously raise hand temperature. Some patients who are able to increase hand temperature can reduce the number and intensity of migraines. The mechanisms underlying these self-regulation treatments are being studied by research scientists.

"To succeed in biofeedback," says a headache specialist, "you must be able to concentrate and you must be motivated to get well."

A patient learning thermal biofeedback wears a device which transmits the temperature of an index finger or hand to a monitor. While the patient tries to warm his hands, the monitor provides feedback either on a gauge that shows the temperature reading or by emitting a sound or beep that increases in intensity as the temperature increases. The patient is not told how to raise hand temperature, but is given suggestions such as "Imagine your hands feel very warm and heavy."

"I have a good imagination," says one headache sufferer who traded in her medication for thermal biofeedback. The technique decreased the number and severity of headaches she experienced.

In another type of biofeedback called electromyographic or EMG training, the patient learns to control muscle tension in the face, neck, and shoulders.

Either kind of biofeedback may be combined with relaxation training, during which patients learn to relax the mind and body.

Biofeedback can be practiced at home with a portable monitor. But the ultimate goal of treatment is to wean the patient from the machine. The patient can then use biofeedback anywhere at the first sign of a headache.

The antimigraine diet. Scientists estimate that a small percentage of migraine sufferers will benefit from a treatment program focused solely on eliminating headache-provoking foods and beverages.

Other migraine patients may be helped by a diet to prevent low blood sugar. Low blood sugar, or hypoglycemia, can cause headache. This condition can occur after a period without food: overnight, for example, or when a meal is skipped. People who wake up in the morning with a headache may be reacting to the low blood sugar caused by the lack of food overnight.

Treatment for headaches caused by low blood sugar consists of scheduling smaller, more frequent meals for the patient. A special diet designed to stabilize the body's sugar-regulating system is sometimes recommended.

For the same reason, many specialists also recommend that migraine patients avoid oversleeping on weekends. Sleeping late can change the body's normal blood sugar level and lead to a headache.

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Besides Migraine, What Are Other Types of Vascular Headaches?


After migraine, the most common type of vascular headache is the toxic headache produced by fever. Pneumonia, measles, mumps, and tonsillitis are among the diseases that can cause severe toxic vascular headaches. Toxic headaches can also result from the presence of foreign chemicals in the body. Other kinds of vascular headaches include "clusters," which cause repeated episodes of intense pain, and headaches resulting from a rise in blood pressure.

Chemical culprits. Repeated exposure to nitrite compounds can result in a dull, pounding headache that may be accompanied by a flushed face. Nitrite, which dilates blood vessels, is found in such products as heart medicine and dynamite, but is also used as a chemical to preserve meat. Hot dogs and other processed meats containing sodium nitrite can cause headaches.

Eating foods prepared with monosodium glutamate (MSG) can result in headache. Soy sauce, meat tenderizer, and a variety of packaged foods contain this chemical which is touted as a flavor enhancer.

Headache can also result from exposure to poisons, even common household varieties like insecticides, carbon tetrachloride, and lead. Children who ingest flakes of lead paint may develop headaches. So may anyone who has contact with lead batteries or lead-glazed pottery.

Artists and industrial workers may experience headaches after exposure to materials that contain chemical solvents. These solvents, like benzene, are found in turpentine, spray adhesives, rubber cement, and inks.

Drugs such as amphetamines can cause headaches as a side effect. Another type of drug-related headache occurs during withdrawal from long-term therapy with the antimigraine drug ergotamine tartrate.

Jokes are often made about alcohol hangovers but the headache associated with "the morning after" is no laughing matter. Fortunately, there are several suggested treatments for the pain. The hangover headache may also be reduced by taking honey, which speeds alcohol metabolism, or caffeine, a constrictor of dilated arteries. Caffeine, however, can cause headaches as well as cure them. Heavy coffee drinkers often get headaches when they try to break the caffeine habit.

Cluster headaches. Cluster headaches are a rare form of headache notable for their extreme pain and their pattern of occurring in "clusters", usually at the same time(s) of the day for several weeks.  A cluster headache usually begins suddenly with excruciating pain on one side of the head, often behind or around one eye.  In some individuals, it may be preceded by a migraine-like "aura." The pain usually peaks over the next 5 to 10 minutes, and then continues at that intensity for up to an hour or two before going away.

People with cluster headaches describe the pain as piercing and unbearable. The nose and the eye on the affected side of the face may also get red, swollen, and runny, and some people will experience nausea, restlessness and agitation, or sensitivities to light, sound, or smell. Most affected individuals have one to three cluster headaches a day and two cluster periods a year, separated by periods of freedom from symptoms.

A small group of people develop a chronic form of the disorder, characterized by bouts of cluster headaches that can go on for years with only brief periods (2 weeks or less) of remission.

Cluster headaches generally begin between the ages of 20 and 50, although the syndrome can also start in childhood or late in life. Males are much more likely than females to develop cluster headaches.  Alcohol (especially red wine) provokes attacks in more than half of those with cluster headaches, but has no effect once the cluster period ends. Cluster headaches are also strongly associated with cigarette smoking.

Scientists aren't sure what causes the disorder. The tendency of cluster headaches to occur during the same time(s) from day to day, and more often at night than during the daylight hours, suggests they could be caused by irregularities in the body’s circadian rhythms, which are controlled by the brain and a family of hormones that regulate the sleep-wake cycle.

There are medications available to lessen the pain of a cluster headache and suppress future attacks. Oxygen inhalation and triptan drugs (such as those used to treat migraine) administered as a tablet, nasal spray, or injection can provide quick relief from acute cluster headache pain. Lidocaine nasal spray, which numbs the nose and nostrils, may also be effective.  Ergotamine and corticosteroids such as prednisone and dexamethasone may be prescribed to break the cluster cycle and then tapered off once headaches end.  Verapamil may be used preventively to decrease the frequency and pain level of attacks.  Lithium, valproic acid, and topiramate are sometimes also used preventively. 

Painful pressure . Chronic high blood pressure can cause headache, as can rapid rises in blood pressure like those experienced during anger, vigorous exercise, or sexual excitement.

The severe "orgasmic headache" occurs right before orgasm and is believed to be a vascular headache. Since sudden rupture of a cerebral blood vessel can occur, this type of headache should be evaluated by a doctor.

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What Are Muscle-Contraction Headaches?


It's 5:00 p.m. and your boss has just asked you to prepare a 20-page briefing paper. Due date: tomorrow. You're angry and tired and the more you think about the assignment, the tenser you become. Your teeth clench, your brow wrinkles, and soon you have a splitting tension headache.

Tension headache is named not only for the role of stress in triggering the pain, but also for the contraction of neck, face, and scalp muscles brought on by stressful events. Tension headache is a severe but temporary form of muscle-contraction headache. The pain is mild to moderate and feels like pressure is being applied to the head or neck. The headache usually disappears after the period of stress is over. Ninety percent of all headaches are classified as tension/muscle contraction headaches.

By contrast, chronic muscle-contraction headaches can last for weeks, months, and sometimes years. The pain of these headaches is often described as a tight band around the head or a feeling that the head and neck are in a cast. "It feels like somebody is tightening a giant vise around my head," says one patient. The pain is steady, and is usually felt on both sides of the head. Chronic muscle-contraction headaches can cause sore scalps - even combing one's hair can be painful.

In the past, many scientists believed that the primary cause of the pain of muscle-contraction headache was sustained muscle tension. However, a growing number of authorities now believe that a far more complex mechanism is responsible.

Occasionally, muscle-contraction headaches will be accompanied by nausea, vomiting, and blurred vision, but there is no preheadache syndrome as with migraine. Muscle-contraction headaches have not been linked to hormones or foods, as has migraine, nor is there a strong hereditary connection.

Research has shown that for many people, chronic muscle-contraction headaches are caused by depression and anxiety. These people tend to get their headaches in the early morning or evening when conflicts in the office or home are anticipated.

Emotional factors are not the only triggers of muscle-contraction headaches. Certain physical postures that tense head and neck muscles - such as holding one's chin down while reading - can lead to head and neck pain. So can prolonged writing under poor light, or holding a phone between the shoulder and ear, or even gum-chewing.

More serious problems that can cause muscle-contraction headaches include degenerative arthritis of the neck and temporomandibular joint dysfunction, or TMD. TMD is a disorder of the joint between the temporal bone (above the ear) and the mandible or lower jaw bone. The disorder results from poor bite and jaw clenching.

Treatment for muscle-contraction headache varies. The first consideration is to treat any specific disorder or disease that may be causing the headache. For example, arthritis of the neck is treated with anti-inflammatory medication and TMD may be helped by corrective devices for the mouth and jaw.

Acute tension headaches not associated with a disease are treated with analgesics like aspirin and acetaminophen. Stronger analgesics, such as propoxyphene and codeine, are sometimes prescribed. As prolonged use of these drugs can lead to dependence, patients taking them should have periodic medical checkups and follow their physicians' instructions carefully.

Nondrug therapy for chronic muscle-contraction headaches includes biofeedback, relaxation training, and counseling. A technique called cognitive restructuring teaches people to change their attitudes and responses to stress. Patients might be encouraged, for example, to imagine that they are coping successfully with a stressful situation. In progressive relaxation therapy, patients are taught to first tense and then relax individual muscle groups. Finally, the patient tries to relax his or her whole body. Many people imagine a peaceful scene - such as lying on the beach or by a beautiful lake. Passive relaxation does not involve tensing of muscles. Instead, patients are encouraged to focus on different muscles, suggesting that they relax. Some people might think to themselves, Relax or My muscles feel warm.

People with chronic muscle-contraction headaches my also be helped by taking antidepressants or MAO inhibitors. Mixed muscle-contraction and migraine headaches are sometimes treated with barbiturate compounds, which slow down nerve function in the brain and spinal cord.

People who suffer infrequent muscle-contraction headaches may benefit from a hot shower or moist heat applied to the back of the neck. Cervical collars are sometimes recommended as an aid to good posture. Physical therapy, massage, and gentle exercise of the neck may also be helpful.

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When is Headache a Warning of a More Serious Condition?


Like other types of pain, headaches can serve as warning signals of more serious disorders. This is particularly true for headaches caused by traction or inflammation.

Traction headaches can occur if the pain-sensitive parts of the head are pulled, stretched, or displaced, as, for example, when eye muscles are tensed to compensate for eyestrain. Headaches caused by inflammation include those related to meningitis as well as those resulting from diseases of the sinuses, spine, neck, ears, and teeth. Ear and tooth infections and glaucoma can cause headaches. In oral and dental disorders, headache is experienced as pain in the entire head, including the face. These headaches are treated by curing the underlying problem. This may involve surgery, antibiotics, or other drugs.

Characteristics of the various types of more serious traction and inflammatory headaches vary by disorder:

  • Brain tumor .  As they grow, brain tumors sometimes cause headache by pushing on the outer layer of nerve tissue that covers the brain or by pressing against pain-sensitive blood vessel walls. Headache resulting from a brain tumor may be periodic or continuous. Typically, it feels like a strong pressure is being applied to the head. The pain is relieved when the tumor is treated by surgery, radiation, or chemotherapy.

  • Stroke. Headache may accompany several conditions that can lead to stroke, including hypertension or high blood pressure, arteriosclerosis, and heart disease. Headaches are also associated with completed stroke, when brain cells die from lack of sufficient oxygen.

    Many stroke-related headaches can be prevented by careful management of the patient's condition through diet, exercise, and medication.

    Mild to moderate headaches are associated with transient ischemic attacks (TIA's), sometimes called "mini-strokes,"which result from a temporary lack of blood supply to the brain. The head pain occurs near the clot or lesion that blocks blood flow. The similarity between migraine and symptoms of TIA can cause problems in diagnosis. The rare person under age 40 who suffers a TIA may be misdiagnosed as having migraine; similarly, TIA-prone older patients who suffer migraine may be misdiagnosed as having stroke-related headaches.

  • Spinal tap. About one-fourth of the people who undergo a lumbar puncture or spinal tap develop a headache. Many scientists believe these headaches result from leakage of the cerebrospinal fluid that flows through pain-sensitive membranes around the brain and down to the spinal cord. The fluid, they suggest, drains through the tiny hole created by the spinal tap needle, causing the membranes to rub painfully against the bony skull. Since headache pain occurs only when the patient stands up, the "cure" is to remain lying down until the headache runs its course - anywhere from a few hours to several days.

  • Head trauma. Headaches may develop after a blow to the head, either immediately or months later. There is little relationship between the severity of the trauma and the intensity of headache pain. In most cases, the cause of the headache is not known. Occasionally the cause is ruptured blood vessels which result in an accumulation of blood called a hematoma. This mass of blood can displace brain tissue and cause headaches as well as weakness, confusion, memory loss, and seizures. Hematomas can be drained to produce rapid relief of symptoms.

  • Temporal arteritis. Arteritis, an inflammation of certain arteries in the head, primarily affects people over age 50. Symptoms include throbbing headache, fever, and loss of appetite. Some patients experience blurring or loss of vision. Prompt treatment with corticosteroid drugs helps to relieve symptoms.

  • Meningitis and encephalitis headaches are caused by infections of meninges-the brain's outer covering-and in encephalitis, inflammation of the brain itself.

  • Trigeminal neuralgia. Trigeminal neuralgia, or tic douloureux, results from a disorder of the trigeminal nerve. This nerve supplies the face, teeth, mouth, and nasal cavity with feeling and also enables the mouth muscles to chew. Symptoms are headache and intense facial pain that comes in short, excruciating jabs set off by the slightest touch to or movement of trigger points in the face or mouth. People with trigeminal neuralgia often fear brushing their teeth or chewing on the side of the mouth that is affected. Many trigeminal neuralgia patients are controlled with drugs, including carbamazepine. Patients who do not respond to drugs may be helped by surgery on the trigeminal nerve.

  • Sinus infection. In a condition called acute sinusitis, a viral or bacterial infection of the upper respiratory tract spreads to the membrane which lines the sinus cavities. When one or more of these cavities are filled with fluid from the inflammation, they become painful. Treatment of acute sinusitis includes antibiotics, analgesics, and decongestants. Chronic sinusitis may be caused by an allergy to such irritants as dust, ragweed, animal hair, and smoke. Research scientists disagree about whether chronic sinusitis triggers headache.

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What Causes Headache in Children?


Like adults, children experience the infections, trauma, and stresses that can lead to headaches. In fact, research shows that as young people enter adolescence and encounter the stresses of puberty and secondary school, the frequency of headache increases.

Migraine headaches often begin in childhood or adolescence. According to recent surveys, as many as half of all schoolchildren experience some type of headache.

Children with migraine often have nausea and excessive vomiting. Some children have periodic vomiting, but no headache - the so-called abdominal migraine. Research scientists have found that these children usually develop headaches when they are older.

Physicians have many drugs to treat migraine in children. Different classes that may be tried include analgesics, antiemetics, anticonvulsants, beta-blockers, and sedatives. A diet may also be prescribed to protect the child from foods that trigger headache. Sometimes psychological counseling or even psychiatric treatment for the child and the parents is recommended

Childhood headache can be a sign of depression. Parents should alert the family pediatrician if a child develops headaches along with other symptoms such as a change in mood or sleep habits. Antidepressant medication and psychotherapy are effective treatments for childhood depression and related headache.

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Conclusion


If you suffer from headaches and none of the standard treatments help, do not despair. Some people find that their headaches disappear once they deal with a troubled marriage, pass their certifying board exams, or resolve some other stressful problem. Others find that if they control their psychological reaction to stress, the headaches disappear.

"I had migraines for several years," says one woman, "and then they went away. I think it was because I lowered my personal goals in life. Today, even though I have 100 things to do at night, I don't worry about it. I learned to say no."

For those who cannot say no, or who get headaches anyway, today's headache research offers hope. The work of NINDS-supported scientists around the world promises to improve our understanding of this complex disorder and provide better tools to treat it.

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 Where can I get more information?

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

BRAIN
P.O. Box 5801
Bethesda, MD 20824
(800) 352-9424
http://www.ninds.nih.gov

Information also is available from the following organizations:

American Headache Society Committee for Headache Education (ACHE)
19 Mantua Road
Mt. Royal, NJ   08061
achehq@talley.com
http://www.achenet.org
Tel: 856-423-0043
Fax: 856-423-0082
The American Headache Society Committee on Headache Education (ACHE) is a nonprofit patient-health professional partnership dedicated to advancing the treatment and management of patients with headache.

National Headache Foundation
820 N. Orleans
Suite 217
Chicago, IL   60610-3132
info@headaches.org
http://www.headaches.org
Tel: 312-274-2650 888-NHF-5552 (643-5552)
Fax: 312-640-9049
Non-profit organization dedicated to service headache sufferers, their families, and the healthcare practitioners who treat them. Promotes research into headache causes and treatments and educates the public.

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Glossary

angiography-an imaging technique that provides a picture, called an angiogram, of blood vessels.

aura-a symptom of classic migraine headache in which the patient sees flashing lights or zigzag lines, or may temporarily lose vision

basilar artery migraine-migraine, occurring primarily in young women and often associated with the menstrual cycle, that involves a disturbance of a major brain artery. Symptoms include vertigo, double vision, and poor muscular coordination.

benign exertional headache-headache brought on by running, lifting, coughing, sneezing, or bending.

biofeedback-a technique in which patients are trained to gain some voluntary control over certain physiological conditions, such as blood pressure and muscle tension, to promote relaxation. Thermal biofeedback helps patients consciously raise hand temperature, which can sometimes reduce the number and intensity of migraines.

cluster headaches-intensely painful headaches-occurring suddenly and lasting between 30 and 45 minutes-named for their repeated occurrence in groups or clusters. They begin as minor pain around one eye and eventually spread to that side of the face.

computer tomography (CT)-an imaging technique that uses X-rays and computer analysis to provide a picture of body tissues and structures.

dihydroergotamine-a drug that is given by injection to treat cluster headaches. It is a form of the antimigraine drug ergotamine tartrate.

electroencephalogram (EEG)-a technique for recording electrical activity in the brain.

electromyography (EMG)-a special recording technique that detects electric activity in muscle. Patients are sometimes offered a type of biofeedback called EMG training, in which they learn to control muscle tension in the face, neck, and shoulders.

endorphins-naturally occurring painkilling chemicals. Some scientists theorize that people who suffer from severe headache have lower levels of endorphins than people who are generally pain free.

ergotamine tartrate-a drug that is used to control the painful dilation stage of migraine.

hemiplegic migraine-a type of migraine causing temporary paralysis on one side of the body (hemiplegia)

inflammatory headache-a headache that is a symptom of another disorder, such as sinus infection, and is treated by curing the underlying problem.

magnetic resonance imaging (MRI)-an imaging technique that uses radio waves, magnetic fields, and computer analysis to provide a picture of body tissues and structures.

migraine-a vascular headache believed to be caused by blood flow changes and certain chemical changes in the brain leading to a cascade of events - including constriction of arteries supplying blood to the brain and the release of certain brain chemicals - that result in severe head pain, stomach upset, and visual disturbances.

muscle-contraction headaches-headaches caused primarily by sustained muscle tension or, possibly, by restricted blood flow to the brain. Two forms of muscle-contraction headache are tension headache, induced by stress, and chronic muscle-contraction headache, which can last for extended periods, involves steady pain, and is usually felt on both sides of the head.

nociceptors-the endings of pain-sensitive nerves that, when stimulated by stress, muscular tension, dilated blood vessels, or other triggers, send messages up the nerve fibers to nerve cells in the brain, signaling that a part of the body hurts.

ophthalmoplegic migraine-a form of migraine felt around the eye and associated with a droopy eyelid, double vision, and other sight problems.

prostaglandins-naturally occurring pain-producing substances thought to be implicated in migraine attacks. Their release is triggered by the dilation of arteries. Prostaglandins are extremely potent chemicals involved in a diverse group of physiological processes.

serotonin-a key neurotransmitter that acts as a powerful constrictor of arteries, reducing the blood supply to the brain and contributing to the pain of headache.

sinusitis-an infection, either viral or bacterial, of the sinus cavities. The infection leads to inflammation of these cavities, causing pain and sometimes headache.

sumatriptan-a commonly used migraine drug that binds to receptors for the neurotransmitter serotonin.

status migrainosus-a rare, sustained, and severe type of migraine, characterized by intense pain and nausea and often leading to hospitalization of the patient.

thermography-a technique sometimes used for diagnosing headache in which an infrared camera converts skin temperature into a color picture, called a thermogram, with different degrees of heat appearing as different colors.

temporomandibular joint dysfunction-a disorder of the joint between the temporal bone (above the ear) and the lower jaw bone that can cause muscle-contraction headaches.

tic douloureux-see trigeminal neuralgia

traction headaches-headaches caused by pulling or stretching pain-sensitive parts of the head, as, for example, when eye muscles are tensed to compensate for eyestrain.

trigeminal neuralgia-a condition resulting from a disorder of the trigeminal nerve. Symptoms are headache and intense facial pain that comes in short, excruciating jabs.

vascular headaches- headaches caused by abnormal function of the brain's blood vessels or vascular system. Migraine is a type of vascular headache.

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"Headache: Hope Through Research," NINDS.

NIH Publication No. 02-158



 

Mild Traumatic Brain Injury:

Heads Up
Facts for Physicians About Mild Traumatic Brain Injury
U.S. Department of Health and Human Services

Download the pdf file:
Mild Traumatic Brain Injury

Download the pdf file:
Acute concussion evaluation

 

Mild Traumatic Brain Injury:

Acute Management of Mild Traumatic Brain Injury in Military Operational Settings:
Clinical Practice Guidelines and Recommendations
The Defense and Veterans Brain Injury Center Working Group

Download the pdf file:
Acute Management of Mild Traumatic Brain Injury in Military
Operational Settings: Clinical Practice Guidelines and Recommendations

Download the pdf file:
Military Acute Concussion Evaluation (MACE)

 

 

Multiple Sclerosis

Introduction
What is Multiple Sclerosis?
How Many People Have MS?
Who Gets MS?
How Much Does MS Cost America?
What Causes MS?
The Immune System
Genetics
What is the Course of MS?
Can Life Events Affect the Course of MS?
What are the Symptoms of MS?
How is MS Diagnosed?
Can MS be Treated?
Immunotherapy
Therapy to Improve Nerve Impulse Conduction
Therapies Targeting an Antigen
Cytokines
Remyelination
Diet
Unproven Therapies
Are Any MS Symptoms Treatable?
What Recent Advances Have Been Made in MS Research?
What Research Remains to be Done?
What is the Outlook for People With MS?
How Can I Help Research?
Where can I get more information?
Glossary

Introduction


Although multiple sclerosis (MS) was first diagnosed in 1849, the earliest known description of a person with possible MS dates from fourteenth century Holland. An unpredictable disease of the central nervous system, MS can range from relatively benign to somewhat disabling to devastating as communication between the brain and other parts of the body is disrupted.

The vast majority of patients are mildly affected, but in the worst cases MS can render a person unable to write, speak, or walk. A physician can diagnose MS in some patients soon after the onset of the illness. In others, however, physicians may not be able to readily identify the cause of the symptoms, leading to years of uncertainty and multiple diagnoses punctuated by baffling symptoms that mysteriously wax and wane.

Once a diagnosis is made with confidence, patients must consider a profusion of information-and misinformation-associated with this complex disease. This brochure is designed to convey the latest information on the diagnosis, course, and possible treatment of MS, as well as highlights of current research. Although a pamphlet cannot substitute for the advice and expertise of a physician, it can provide patients and their families with information to understand MS better so that they can actively participate in their care and treatment.

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What is Multiple Sclerosis?


During an MS attack, inflammation occurs in areas of the white matter* of the central nervous system in random patches called plaques. This process is followed by destruction of myelin, the fatty covering that insulates nerve cell fibers in the brain and spinal cord. Myelin facilitates the smooth, high-speed transmission of electrochemical messages between the brain, the spinal cord, and the rest of the body; when it is damaged, neurological transmission of messages may be slowed or blocked completely, leading to diminished or lost function. The name "multiple sclerosis" signifies b