Understanding Pompe Disease

January 2010

What is Pompe disease?

Pompe (POM-pay) disease, also known as glycogen storage disease type II or acid maltase deficiency, is a rare genetic disorder that results in profound muscle weakness. The disease is caused by mutations in the gene that instructs the body to make an enzyme called acid alpha-glucosidase (GAA). Normally, the body uses this enzyme to break down glycogen (stored sugar) into glucose (sugar). But in Pompe disease, GAA is absent or significantly reduced, causing excessive amounts of glycogen to accumulate in the body’s tissues, which results in major damage. The heart and skeletal muscles are most affected.

Pompe disease is an autosomal recessive condition — meaning that each parent of an affected individual must pass on a copy of the mutated gene. This is part of the reason that the disease is relatively rare, affecting one in 40,000 people.

How does the disease progress?

Two forms of Pompe disease have been identified: a severe "infantile" form, and a milder "late-onset" form. The infantile form of the disease usually occurs within the first months of life and progresses rapidly, with severe muscle weakness, heart failure, and often death before the age of one or two. The late-onset form of the disease (also referred to as the juvenile/adult form) presents after infancy and progresses more slowly. Muscle weakness is the primary symptom, and the heart is typically spared. Life expectancy is usually shortened due to weakness of the respiratory (breathing) muscles in people with this form of the disease.

How is the disease diagnosed?

Pompe disease is diagnosed by screening for the common mutations in the GAA gene, by measuring the level of the GAA enzyme in a blood sample, or by a muscle biopsy. Once a diagnosis is obtained, consultation with a geneticist and screening of other family members is recommended.

Is there any treatment?

The U.S. Food and Drug Administration has approved alglucosidase alfa (Myozyme) for use in patients with Pompe disease. A type of enzyme replacement therapy, Myozyme is a form of GAA — the enzyme that is absent or reduced in the disorder. The drug is usually administered via intravenous infusion every other week. Myozyme has been remarkably successful in reversing cardiac muscle damage and in enhancing life expectancy in those with the infantile form of the disease. The therapy, however, is less effective in skeletal muscle.

People with Pompe disease need highly specialized care from a variety of specialists, especially as the disease progresses.

What are some key areas of Pompe research at NIAMS?

For the past two decades, researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) – Dr. Paul Plotz, Chief of the NIAMS Arthritis and Rheumatism Branch, and a group of scientists in his lab led by Dr. Nina Raben – have made significant strides toward our understanding of Pompe disease. While it was originally hoped that enzyme replacement therapy could cure Pompe disease, the NIAMS group discovered that skeletal muscle is resistant to the treatment. This finding was made in mouse models of the disease that were generated in the lab; these models are now used throughout the world by scientists involved in the research and development of Pompe therapies.

The group is focusing its current efforts on using the new information to improve treatment of the resistant muscle fibers. These studies are partially funded by a cooperative research and development agreement (CRADA) with Genzyme, the company that produces Myozyme.

The NIAMS group recently uncovered new clues related to the cellular defects in Pompe disease. They identified structures in many skeletal muscle cells in Pompe patients and mice that appeared to be large collections of cellular debris that should have been delivered to, and processed in, the lysosomes, the "recycling centers" of the cell. This debris would normally have been digested in the lysosomes into the building blocks that the cell uses to keep itself in shape — amino acids to build proteins, sugars like glucose to provide energy, and fatty acids to build membranes and to provide energy. So, not only were the lysosomes filled with glycogen which could not be digested, but other materials were building up outside — unable to reach the recycling place. This buildup looked like the kind of material that is normally carried to the lysosomes by a remarkable system, called "autophagy" — literally meaning self-eating. This system picks up worn out cell parts for delivery to the lysosomes for recycling. Dr. Raben recognized that this pick-up and recycling system does not function properly in Pompe skeletal muscle, and the stressed recycling centers appear to be overwhelmed. The NIAMS group is currently testing new strategies to intervene in Pompe disease by exploring ways to modulate the autophagic machinery.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases.

NIAMS

What is alpha thalassemia X-linked mental retardation syndrome?

What is alpha thalassemia X-linked mental retardation syndrome?

Alpha thalassemia X-linked mental retardation syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males.

Males with alpha thalassemia X-linked mental retardation syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently.

Almost everyone with alpha thalassemia X-linked mental retardation syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down "V," and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose.

Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue.

Additional features of alpha thalassemia X-linked mental retardation syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female (ambiguous genitalia).

How common is alpha thalassemia X-linked mental retardation syndrome?

Alpha thalassemia X-linked mental retardation syndrome appears to be a rare condition, although its exact prevalence is unknown. More than 200 affected individuals have been reported.

What genes are related to alpha thalassemia X-linked mental retardation syndrome?

Alpha thalassemia X-linked mental retardation syndrome results from mutations in the ATRX gene. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes. Among these genes are HBA1 and HBA2, which are necessary for normal hemoglobin production.

Mutations in the ATRX gene change the structure of the ATRX protein, which likely prevents it from effectively regulating gene expression. Reduced activity of the HBA1 and HBA2 genes causes alpha thalassemia. Abnormal expression of other genes, which have not been identified, probably causes developmental delay, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked mental retardation syndrome.

How do people inherit alpha thalassemia X-linked mental retardation syndrome?

This condition is inherited in an X-linked recessive pattern. The ATRX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one working copy of the ATRX gene can usually compensate for the mutated copy. Therefore, females who carry a single mutated ATRX gene almost never have signs of alpha thalassemia X-linked mental retardation.

A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

NIH

Brain Injury Awareness

Take Concussions Out of Play: Learn to Prevent, Recognize, and Respond to Concussions

In recognition of Brain Injury Awareness Month, CDC encourages you to take this opportunity to talk with your coaches, parents, athletes, and others about concussion in sports and the steps to take to help prevent, recognize, and respond to this serious injury.

This year, in recognition of Brain Injury Awareness Month, CDC's Injury Center encourages coaches, school professionals, parents, and athletes to learn the risks of concussions in youth sports.

CDC estimates 135,000 sports- and recreation-related traumatic brain injuries (TBI), including concussions, are treated in U.S. emergency departments each year.

A bump, blow, or jolt to the head can cause a concussion, a type of TBI. Concussions can also occur from a blow to the body that causes the head to move rapidly back and forth. Even a "ding," "getting your bell rung," or what seems to be mild bump or blow to the head can be serious.

Concussions can occur in any sport or recreation activity. So, all coaches, parents, and athletes need to learn concussion signs and symptoms and what to do if a concussion occurs.

CDC's "Heads Up: Concussion in High School" and "Heads Up: Concussion in Youth Sports" initiatives include materials and information to help coaches of all sports to help identify concussions and take immediate steps to respond when one is suspected.

Prevention and Preparation

Check with your league or school about concussion policies. Concussion policy statements can be developed to include the league or school's commitment to safety, a brief description about concussion, and information on when athletes can safely return to play. Parents and athletes should sign the concussion policy statement before the first practice.

Insist that safety comes first. No one technique or safety equipment is 100 percent effective in preventing concussion, but there are things you can do to help minimize the risks for concussion and other injuries.

For example, to help prevent injuries:

Enforce no hits to the head or other types of dangerous play.

Practice safe playing techniques and encourage athletes to follow the rules of play.

Make sure players wear approved and properly-fitted protective equipment. Protective equipment should be well-maintained and be worn consistently and correctly.

Learn about concussion. Before the first practice, talk your athlete(s) and others about the dangers of concussion and potential long-term consequences of concussion. Review the signs and symptoms of concussion and keep the four-step action plan with you at games and practices.

CDC

What is neurofibromatosis type 1?

What id neurofibromatosis type 1?

Neurofibromatosis type 1 is a condition characterized by changes in skin coloring (pigmentation) and the growth of tumors along nerves in the skin, brain, and other parts of the body. The signs and symptoms of this condition vary widely among affected people.

Beginning in early childhood, almost all people with neurofibromatosis type 1 have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. These spots increase in size and number as the individual grows older. Freckles in the underarms and groin typically develop later in childhood.

Most adults with neurofibromatosis type 1 develop neurofibromas, which are noncancerous (benign) tumors that are usually located on or just under the skin. These tumors may also occur in nerves near the spinal cord or along nerves elsewhere in the body. Some people with neurofibromatosis type 1 develop cancerous tumors that grow along nerves. These tumors, which usually develop in adolescence or adulthood, are called malignant peripheral nerve sheath tumors. People with neurofibromatosis type 1 also have an increased risk of developing other cancers, including brain tumors and cancer of blood-forming tissue (leukemia).

During childhood, benign growths called Lisch nodules often appear in the colored part of the eye (the iris). Lisch nodules do not interfere with vision. Some affected individuals also develop tumors that grow along the nerve leading from the eye to the brain (the optic nerve). These tumors, which are called optic gliomas, may lead to reduced vision or total vision loss. In some cases, optic gliomas have no effect on vision.

Additional signs and symptoms of neurofibromatosis type 1 include high blood pressure (hypertension), short stature, an unusually large head (macrocephaly), and skeletal abnormalities such as an abnormal curvature of the spine (scoliosis). Although most people with neurofibromatosis type 1 have normal intelligence, learning disabilities and attention deficit hyperactivity disorder (ADHD) occur frequently in affected individuals.

How common is neurofibromatosis type 1?

Neurofibromatosis type 1 occurs in 1 in 3,000 to 4,000 people worldwide.

What genes are related to neurofibromatosis type 1?

Mutations in the NF1 gene cause neurofibromatosis type 1.

The NF1 gene provides instructions for making a protein called neurofibromin. This protein is produced in many cells, including nerve cells and specialized cells surrounding nerves (oligodendrocytes and Schwann cells). Neurofibromin acts as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the NF1 gene lead to the production of a nonfunctional version of neurofibromin that cannot regulate cell growth and division. As a result, tumors such as neurofibromas can form along nerves throughout the body. It is unclear how mutations in the NF1 gene lead to the other features of neurofibromatosis type 1, such as café-au-lait spots and learning disabilities.

How do people inherit neurofibromatosis type 1?

Neurofibromatosis type 1 is considered to have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the NF1 gene in each cell. In about half of cases, the altered gene is inherited from an affected parent. The remaining cases result from new mutations in the NF1 gene and occur in people with no history of the disorder in their family.

Unlike most other autosomal dominant conditions, in which one altered copy of a gene in each cell is sufficient to cause the disorder, two copies of the NF1 gene must be altered to trigger tumor formation in neurofibromatosis type 1. A mutation in the second copy of the NF1 gene occurs during a person's lifetime in specialized cells surrounding nerves. Almost everyone who is born with one NF1 mutation acquires a second mutation in many cells and develops the tumors characteristic of neurofibromatosis type 1.

NIH

What is cystic fibrosis?

What is cystic fibrosis?

Cystic fibrosis is an inherited disease of the mucus glands that affects many body systems. The disorder's most common signs and symptoms include progressive damage to the respiratory system and chronic digestive system problems.

Mucus is a slippery substance that lubricates and protects the linings of the airways, digestive system, reproductive system, and other organs and tissues. In people with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This abnormal mucus can obstruct the airways, leading to severe problems with breathing and bacterial infections in the lungs. These infections cause chronic coughing, wheezing, and inflammation. Over time, mucus buildup and infections result in permanent lung damage, including the formation of scar tissue (fibrosis) and cysts in the lungs.

Most people with cystic fibrosis also have digestive problems because thick, sticky mucus interferes with the function of the pancreas. The pancreas is an organ that produces insulin (a hormone that helps control blood sugar levels). It also makes enzymes that help digest food. In people with cystic fibrosis, mucus blocks the ducts of the pancreas, preventing these enzymes from reaching the intestines to aid digestion. Problems with digestion can lead to diarrhea, malnutrition, poor growth, and weight loss. Some babies with cystic fibrosis have meconium ileus, a blockage of the intestine that occurs shortly after birth.

Cystic fibrosis used to be considered a fatal disease of childhood. With improved treatments and better ways to manage the disease, many people with cystic fibrosis now live well into adulthood. Adults with cystic fibrosis experience medical problems affecting the respiratory, digestive, and reproductive systems. For example, most men with cystic fibrosis are unable to father children (infertile) because the tubes that carry sperm (the vas deferens) are blocked by mucus and do not develop properly. This condition is known as congenital bilateral absence of the vas deferens (CBAVD). Infertility is also possible, though less common, in women with cystic fibrosis.

How common is cystic fibrosis?

Cystic fibrosis is a common genetic disease within the Caucasian (white) population in the United States. The disease occurs in 1 in 2,500 to 3,500 Caucasian newborns. Cystic fibrosis is less common in other ethnic groups, affecting about 1 in 17,000 African Americans and 1 in 31,000 Asian Americans.

What genes are related to cystic fibrosis?

Mutations in the CFTR gene cause cystic fibrosis.

The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells. The flow of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus.

Mutations in the CFTR gene disrupt the function of the chloride channels, preventing them from regulating the flow of chloride ions and water across cell membranes. As a result, cells that line the passageways of the lungs, pancreas, and other organs produce mucus that is unusually thick and sticky. This mucus clogs the airways and glands, causing the characteristic signs and symptoms of cystic fibrosis.

Other genetic and environmental factors likely influence the severity of the condition. For example, mutations in genes other than CFTR might help explain why some people with cystic fibrosis are more severely affected than others. Most of these genetic changes have not been identified, however.

How do people inherit cystic fibrosis?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about treatment for cystic fibrosis?

These resources address the management of cystic fibrosis and may include treatment providers.

NIH

Glycogen storage disease type II (GSD II), or Pompe disease

Glycogen storage disease type II (GSD II), or Pompe disease, is classified by age of onset, organ involvement, severity, and rate of progression. Classic infantile-onset Pompe disease may be apparent in utero but more often presents in the first month of life with hypotonia, generalized muscle weakness, cardiomegaly and hypertrophic cardiomyopathy, feeding difficulties, failure to thrive, respiratory distress, and hearing loss. Without treatment by enzyme replacement therapy (ERT), classic infantile-onset Pompe disease commonly results in death in the first year of life from progressive left ventricular outflow obstruction. The non-classic variant of infantile-onset Pompe disease usually presents within the first year of life with motor delays and/or slowly progressive muscle weakness, typically resulting in death from ventilatory failure in early childhood. Cardiomegaly can be seen, but heart disease is not a major source of morbidity. Late-onset (i.e., childhood, juvenile, and adult-onset) Pompe disease is characterized by proximal muscle weakness and respiratory insufficiency without cardiac involvement.

CDC

How much is my allowance for oils?

Most Americans consume enough oil in the foods they eat, such as:

• nuts
• fish
• cooking oil

How much is my allowance for oils?

Most Americans consume enough oil in the foods they eat, such as:

• nuts
• fish
• cooking oil
• salad dressings

A person’s allowance for oils depends on age, sex, and level of physical activity. Daily allowances are shown in the chart.

Daily allowance*
Children		2-3 years old		3 teaspoons
		4-8 years old		4 teaspoons
Girls		9-13 years old		5 teaspoons
		14-18 years old		5 teaspoons
Boys		9-13 years old		5 teaspoons
		14-18 years old		6 teaspoons
Women		19-30 years old		6 teaspoons
		31-50 years old		5 teaspoons
		51+ years old		5 teaspoons
Men		19-30 years old		7 teaspoons
		31-50 years old		6 teaspoons
		51+ years old		6 teaspoons

*These amounts are appropriate for individuals who get less than 30 minutes per day of moderate physical activity, beyond normal daily activities. Those who are more physically active may be able to consume more while staying within calorie needs.

A person’s allowance for oils depends on age, sex, and level of physical activity. Daily allowances are shown in the chart.

CDC

Balance and Dizziness

Balance, Dizziness, and You

Millions of Americans have disorders of balance they describe as dizziness. What can be difficult for both a patient and his or her doctor is that dizziness is what is called "a subjective term." (That means a word like dizziness can be used by people to describe different sensations they are experiencing, but it is hard for anyone but the person experiencing the symptoms to understand or measure the nature or severity of the sensations.) Another difficulty is that people tend to use different terms to describe the same kind of problem. "Balance problems," "dizziness," "imbalance," and "disorders of balance" are all used interchangeably.

What is dizziness?

For some people, dizziness is a feeling of unsteadiness or a spinning sensation. Others may experience extreme balance disorders that affect many aspects of their lives. Dizziness may be a fleeting sensation or the prolonged and intense symptom of a wide range of health problems that can affect a person's independence, ability to work, and quality of life. Experts believe that more than 40 percent of Americans will experience dizziness that is serious enough to go to a doctor. Even dizziness that seems minor, if undiagnosed, may be a signal of underlying disorders.

Balance problems are among the most common reasons that older adults seek help from a doctor. Many people are surprised to learn that the source of their imbalance may be in their inner ears. Balance (or vestibular) problems are reported in about 9 percent of the population who are 65 years of age or older. Fall-related injuries such as breaking (or fracturing) a hip are a leading cause of death and disability in older individuals. Many of these hip fractures are related to balance disorders. Although this fact sheet is about adults, children who complain about or describe balance problems should be seen by a doctor.

Balance disorders may also lead to other problems including fatigue, difficulty walking, or disinterest in everyday and leisure activities. If you or your child, parent, friend, or co-worker has a balance problem–take it seriously. Talk to the doctor about what happens when you feel dizzy or lose your balance. Be as careful as possible to describe your experience of dizziness specifically.

Describe your symptoms for your doctor

Ask yourself the following questions. If you answer "yes" to any of these questions, you should discuss the symptom with your doctor.

Do I feel unsteady?

Do I feel as if the room is "spinning" around me?

Do I feel as if I'm moving when I know I'm standing or sitting still?

Do I lose my balance and fall?

Do I feel as if I'm falling?

Do I feel as if I might faint? (sometimes people call this "lightheaded")

Does my vision become blurred?

Do I ever feel disoriented? (lose my sense of time, place, identity)

What should I do?

Balance disorders are serious. The most important thing you can do if you think you have a balance disorder is to see a doctor. Your doctor may refer you to an otolaryngologist (oh-toe-lair-in-GAH-luh-jist), the doctor who specializes in the ear, nose, and throat. An otolaryngologist will try to find out why you have balance problems and may discuss treatment options.

NIDCD

What is a Balance Disorder?

What is a balance disorder?

A balance disorder is a disturbance that causes an individual to feel unsteady, giddy, woozy, or have a sensation of movement, spinning, or floating. An organ in our inner ear, the labyrinth, is an important part of our vestibular (balance) system. The labyrinth interacts with other systems in the body, such as the visual (eyes) and skeletal (bones and joints) systems, to maintain the body's position. These systems, along with the brain and the nervous system, can be the source of balance problems.

Three structures of the labyrinth, the semicircular canals, let us know when we are in a rotary (circular) motion. The semicircular canals, the superior, posterior, and horizontal, are fluid-filled. Motion of the fluid tells us if we are moving. The semicircular canals and the visual and skeletal systems have specific functions that determine an individual's orientation. The vestibule is the region of the inner ear where the semicircular canals converge, close to the cochlea (the hearing organ). The vestibular system works with the visual system to keep objects in focus when the head is moving. Joint and muscle receptors also are important in maintaining balance. The brain receives, interprets, and processes the information from these systems that control our balance.

How does the balance system work?

Movement of fluid in the semicircular canals signals the brain about the direction and speed of rotation of the head–for example, whether we are nodding our head up and down or looking from right to left. Each semicircular canal has a bulbed end, or enlarged portion, that contains hair cells. Rotation of the head causes a flow of fluid, which in turn causes displacement of the top portion of the hair cells that are embedded in the jelly-like cupula. Two other organs that are part of the vestibular system are the utricle and saccule. These are called the otolithic organs and are responsible for detecting linear acceleration, or movement in a straight line. The hair cells of the otolithic organs are blanketed with a jelly-like layer studded with tiny calcium stones called otoconia. When the head is tilted or the body position is changed with respect to gravity, the displacement of the stones causes the hair cells to bend.

What are the symptoms of a balance disorder?

When balance is impaired, an individual has difficulty maintaining orientation. For example, an individual may experience the "room spinning" and may not be able to walk without staggering, or may not even be able to arise. Some of the symptoms a person with a balance disorder may experience are:

A sensation of dizziness or vertigo (spinning).

Falling or a feeling of falling.

Lightheadedness or feeling woozy.

Visual blurring.

Disorientation.

Some individuals may also experience nausea and vomiting, diarrhea, faintness, changes in heart rate and blood pressure, fear, anxiety, or panic. Some reactions to the symptoms are fatigue, depression, and decreased concentration. The symptoms may appear and disappear over short time periods or may last for a longer period of time.

What causes a balance disorder?

Infections (viral or bacterial), head injury, disorders of blood circulation affecting the inner ear or brain, certain medications, and aging may change our balance system and result in a balance problem. Individuals who have illnesses, brain disorders, or injuries of the visual or skeletal systems, such as eye muscle imbalance and arthritis, may also experience balance difficulties. A conflict of signals to the brain about the sensation of movement can cause motion sickness (for instance, when an individual tries to read while riding in a car). Some symptoms of motion sickness are dizziness, sweating, nausea, vomiting, and generalized discomfort. Balance disorders can be due to problems in any of four areas:

Peripheral vestibular disorder, a disturbance in the labyrinth.

Central vestibular disorder, a problem in the brain or its connecting nerves.

Systemic disorder, a problem of the body other than the head and brain.

Vascular disorder, or blood flow problems.

What are some types of balance disorders?
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Some of the more common balance disorders are:

Benign Paroxysmal Positional Vertigo (BPPV)–a brief, intense sensation of vertigo that occurs because of a specific positional change of the head. An individual may experience BPPV when rolling over to the left or right upon getting out of bed in the morning, or when looking up for an object on a high shelf. The cause of BPPV is not known, although it may be caused by an inner ear infection, head injury, or aging.

Labyrinthitis–an infection or inflammation of the inner ear causing dizziness and loss of balance.

Ménière's disease–an inner ear fluid balance disorder that causes episodes of vertigo, fluctuating hearing loss, tinnitus (a ringing or roaring in the ears), and the sensation of fullness in the ear. The cause of Ménière's disease is unknown.

Vestibular neuronitis–an infection of the vestibular nerve, generally viral.

Perilymph fistula–a leakage of inner ear fluid to the middle ear. It can occur after head injury, physical exertion or, rarely, without a known cause.

How are balance disorders diagnosed?

Diagnosis of a balance disorder is complicated because there are many kinds of balance disorders and because other medical conditions–including ear infections, blood pressure changes, and some vision problems–and some medications may contribute to a balance disorder. A person experiencing dizziness should see a physician for an evaluation.

The primary physician may request the opinion of an otolaryngologist to help evaluate a balance problem. An otolaryngologist is a physician/surgeon who specializes in diseases and disorders of the ear, nose, throat, head, and neck, with expertise in balance disorders. He or she will usually obtain a detailed medical history and perform a physical examination to start to sort out possible causes of the balance disorder. The physician may require tests to assess the cause and extent of the disruption of balance. The kinds of tests needed will vary based on the patient's symptoms and health status. Because there are so many variables, not all patients will require every test.

Some examples of diagnostic tests the otolaryngologist may request are a hearing examination, blood tests, an electronystagmogram (ENG–a test of the vestibular system), or imaging studies of the head and brain.

The caloric test may be performed as part of the ENG. In this test, each ear is flushed with warm and then cool water, usually one ear at a time; the amount of nystagmus resulting is measured. Weak nystagmus or the absence of nystagmus may indicate an inner ear disorder.

Another test of the vestibular system, posturography, requires the individual to stand on a special platform capable of movement within a controlled visual environment; body sway is recorded in response to movement of the platform and/or the visual environment.

How are balance disorders treated?

There are various options for treating balance disorders. One option includes treatment for a disease or disorder that may be contributing to the balance problem, such as ear infection, stroke, or multiple sclerosis. Individual treatment will vary and will be based upon symptoms, medical history, general health, examination by a physician, and the results of medical tests.

Another treatment option includes balance retraining exercises (vestibular rehabilitation). The exercises include movements of the head and body specifically developed for the patient. This form of therapy is thought to promote compensation for the disorder. Vestibular retraining programs are administered by professionals with knowledge and understanding of the vestibular system and its relationship with other systems in the body.

For people diagnosed with Ménière's disease, dietary changes such as reducing intake of sodium may help. For some people, reducing alcohol, caffeine, and/or avoiding nicotine may be helpful. Some aminoglycoside antibiotics, such as gentamicin and streptomycin, are used to treat Ménière's disease. Systemic streptomycin (given by injection) and topical gentamicin (given directly to the inner ear) are useful for their ability to affect the hair cells of the balance system. Gentamicin also can affect the hair cells of the cochlea, though, and cause hearing loss. In cases that do not respond to medical management, surgery may be indicated.

A program of talk therapy and/or physical rehabilitation may be recommended for people with anxiety.

How can I help my doctor make a diagnosis?

You can take the following steps that may be helpful to your physician in determining a diagnosis and treatment plan.

Bring a written list of symptoms to your doctor.

Bring a list of medications currently being used for balance disorders to your doctor.

Be specific when you describe the nature of your symptoms to your doctor. For example, describe how, when, and where you experience dizziness.

Lastly, remember to write down any instructions or tips your doctor gives you.

What research is being done for balance disorders?

Scientists are working to understand the various balance disorders and the complex interactions between the labyrinth, other balance-sensing organs, and the brain. Scientists are studying eye movement to understand the changes that occur in aging, disease, and injury. Scientists are collecting data about eye movement and posture to improve diagnosis and treatment of balance disorders. Scientists are also studying the effectiveness of certain exercises as a treatment option.

Recent findings from studies supported by the National Institute on Deafness and Other Communication Disorders (NIDCD) suggest that the vestibular system plays an important role in modulating blood pressure. The information from these studies has potential clinical relevance in understanding and managing orthostatic hypotension (lowered blood pressure related to a change in body posture). Other studies of the otolithic organs, the detectors of linear movement, are exploring how these organs differentiate between downward (gravitational) motion from linear (forward-to-aft, side-to-side) motion.

Other projects supported by NIDCD include studies of the genes essential to normal development and function in the vestibular system. Scientists are also studying inherited syndromes of the brain that affect balance and coordination.

The Institute supports research to develop new tests and refine current tests of balance and vestibular function. For example, scientists have developed computer-controlled systems to measure eye movement and body position by stimulating specific parts of the vestibular and nervous systems. Other tests to determine disability, as well as new physical rehabilitation strategies, are under investigation in clinical and research settings.

NIDCD, along with other Institutes at the National Institutes of Health, joined the National Aeronautics and Space Administration (NASA) for Neurolab, a research mission dedicated to the study of life sciences. Neurolab focused on the most complex and least understood part of the human body, the nervous system (including the balance system).

Exposure to the weightlessness of space is known to temporarily disrupt balance on return to Earth and to gravity. A team of NIDCD and NASA investigators had previously studied the effects of microgravity exposure on balance control in astronauts who had returned from short-duration space flight missions, but these studies did not include an aged individual. During the October 29-November 7, 1998, Space Shuttle Discovery mission, NIDCD and NASA collaborated in another study of postflight balance control. For the first time, a previously experienced, but now elderly astronaut, Senator John Glenn, participated. Data collected during this mission, which are still being analyzed, may help to explain the mechanisms of recovery from balance disorders experienced on Earth as well as in the space environment. Scientists also hope that this data will help to develop strategies to prevent injury from falls, a common occurrence among people with balance disorders, particularly as they grow older.

NIDCD

Adult Brain Tumors

An adult brain tumor is a disease in which abnormal cells form in the tissues of the brain.

There are many types of brain and spinal cord tumors. The tumors are formed by the abnormal growth of cells and may begin in different parts of the brain or spinal cord. Together, the brain and spinal cord make up the central nervous system (CNS).

The tumors may be benign (not cancer) or malignant (cancer). Benign brain tumors grow and press on nearby areas of the brain. They rarely spread into other tissues and may recur (come back). Malignant brain tumors are likely to grow quickly and spread into other brain tissue. When a tumor grows into or presses on an area of the brain, it may keep that part of the brain from working the way it should. Both benign and malignant brain tumors can cause symptoms and, sometimes, death.

Brain tumors can occur in both adults and children. However, treatment for children may be different than treatment for adults.

A brain tumor that starts in another part of the body and spreads to the brain is called a metastatic tumor.

Tumors that start in the brain are called primary brain tumors. Often, tumors found in the brain have started somewhere else in the body and spread to one or more parts of the brain. These are called metastatic brain tumors (or brain metastases). Metastatic brain tumors are more common than primary brain tumors.

The types of cancer that commonly spread to the brain are melanoma and cancer of the breast, colon, lung, and unknown primary site. The types of cancer that commonly spread to the spinal cord are lymphoma and cancer of the lung, breast, and prostate. About half of metastatic brain and spinal cord tumors are caused by lung cancer. Leukemia, lymphoma, breast cancer, and gastrointestinal cancer may spread to the leptomeninges (the two innermost membranes covering the brain and spinal cord).

The brain controls many important body functions.

The brain has three major parts:

• The cerebrum is the largest part of the brain. It is at the top of the head. The cerebrum controls thinking, learning, problem solving, emotions, speech, reading, writing, and voluntary movement.
• The cerebellum is in the lower back of the brain (near the middle of the back of the head). It controls movement, balance, and posture.
• The brain stem connects the brain to the spinal cord. It is in the lowest part of the brain (just above the back of the neck). The brain stem controls breathing, heart rate, and the nerves and muscles used in seeing, hearing, walking, talking, and eating.

The spinal cord connects the brain to nerves in most parts of the body.

The spinal cord is a column of nerve tissue that runs from the brain stem down the center of the back. It is covered by three thin layers of tissue called membranes. These membranes are surrounded by the vertebrae (back bones). Spinal cord nerves carry messages between the brain and the rest of the body, such as a signal from the brain to cause muscles to move or from the skin to the brain about the sense of touch.

There are different types of brain and spinal cord tumors.

Brain and spinal cord tumors are named based on the type of cell they formed in and where the tumor first formed in the CNS. The grade of a tumor may be used to tell the difference between slow- and fast-growing types of the tumor. The grade of a tumor is based on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread.

Tumor Grading System

• Grade I (low-grade) — The tumor grows slowly, has cells that look a lot like normal cells, and rarely spreads into nearby tissues. It may be possible to remove the entire tumor by surgery.
• Grade II — The tumor grows slowly, but may spread into nearby tissue and may recur (come back). Some tumors may become a higher-grade tumor.
• Grade III — The tumor grows quickly, is likely to spread into nearby tissue, and the tumor cells look very different from normal cells.
• Grade IV (high-grade) — The tumor grows and spreads very quickly and the cells do not look like normal cells. There may be areas of dead cells in the tumor. Grade IV brain tumors are harder to cure than lower-grade tumors.

Astrocytic Tumors

An astrocytic tumor begins in star-shaped brain cells called astrocytes, which help keep nerve cells healthy. An astrocyte is a type of glial cell and is sometimes called a glioma. Astrocytic tumors include the following:

• Brain stem glioma: A brain stem glioma forms in the brain stem, which is the part of the brain connected to the spinal cord. It is often a high-grade tumor, which spreads widely through the brain stem and is hard to cure. A brain stem glioma rarely occurs in adults.
• Pineal astrocytic tumor: A pineal astrocytic tumor forms in tissue around the pineal gland and may be any grade. The pineal gland is a tiny organ in the brain that makes melatonin, a hormone that helps control the sleeping and waking cycle.
• Pilocytic astrocytoma (grade I): A pilocytic astrocytoma grows slowly in the brain or spinal cord. It may be in the form of a cyst and rarely spreads into nearby tissues. This type of tumor is most common in children and young adults and in people with neurofibromatosis type 1 (NF1). A pilocytic astrocytoma rarely causes death.
• Diffuse astrocytoma (grade II): A diffuse astrocytoma grows slowly, but often spreads into nearby tissues. Sometimes a diffuse astrocytoma progresses to a higher grade and becomes an anaplastic astrocytoma or a glioblastoma. A diffuse astrocytoma can form in any part of the brain but most often forms in the cerebrum. It is most common in young adults and in people with Li-Fraumeni syndrome. It is also called a low-grade diffuse astrocytoma.
• Anaplastic astrocytoma (grade III): An anaplastic astrocytoma grows quickly and spreads into nearby tissues. An anaplastic astrocytoma may progress to a higher grade and become a glioblastoma. An anaplastic astrocytoma forms most often in the cerebrum and is most common in adults. An anaplastic astrocytoma is also called a malignant astrocytoma or high-grade astrocytoma.
• Glioblastoma (grade IV): A glioblastoma grows and spreads very quickly. A glioblastoma forms most often in the cerebrum. This type of tumor is most common in adults. This type of tumor has a poor prognosis. It is also called glioblastoma multiforme.

Oligodendroglial Tumors

An oligodendroglial tumor begins in brain cells called oligodendrocytes, which help keep nerve cells healthy. Oligodendrocytes are a type of glial cell and are sometimes called a glioma. Grades of oligodendroglial tumors include the following:

• Oligodendroglioma (grade II): An oligodendroglioma grows and spreads slowly and the tumor cells look very much like normal cells. This type of tumor most often forms in the cerebrum. An oligodendroglioma is most common in adults.
• Anaplastic oligodendroglioma (grade III): An anaplastic oligodendroglioma grows quickly and the tumor cells look very different from normal cells. It may grow in one place or in many places throughout the brain. This type of cancer most often forms in the cerebrum.

Mixed Gliomas

A mixed glioma is a brain tumor that has two types of tumor cells in it — oligodendrocytes and astrocytes. This type of tumor most often forms in the cerebrum.

• Oligoastrocytoma (grade II): An oligoastrocytoma is a slow-growing tumor and the tumor cells don't look very different from normal cells.
• Anaplastic oligoastrocytoma (grade III): The tumor cells in an anaplastic oligoastrocytoma look very different from normal cells.

Ependymal Tumors

An ependymal tumor usually begins in cells that line the fluid -filled spaces in the brain and around the spinal cord. Ependymal cells are a type of glial cell and are sometimes called a glioma. Grades of ependymal tumors include the following:

• Ependymoma (grade I or II): A grade I or II ependymoma grows slowly and has cells that look very much like normal cells. There are two types of grade I ependymoma — myxopapillary ependymoma and subependymoma. These tumors are most common in adults. A grade II ependymoma grows in the ventricle and its connecting paths or in the spinal cord. It is most common in children and young adults and in people with neurofibromatosis type 2 (NF2).
• Anaplastic ependymoma (grade III): An anaplastic ependymoma grows very quickly and has a poor prognosis.

Embryonal Cell Tumors: Medulloblastoma (Grade IV)

A medulloblastoma is a type of embryonal tumor. The tumor forms in brain cells when the fetus is beginning to develop. This type of brain tumor often begins in the cerebellum. The tumor may spread from the brain to the spine through the cerebrospinal fluid (CSF). A medulloblastoma occurs most often in children or young adults and in people with Turcot syndrome type 2 or nevoid basal cell carcinoma syndrome.

Pineal Parenchymal Tumors

A pineal parenchymal tumor forms in parenchymal cells or pineocytes, which are the cells that make up most of the pineal gland. These tumors are different from pineal astrocytic tumors. Grades of pineal parenchymal tumors include the following:

• Pineocytomas (grade II): A pineocytoma is a slow-growing pineal tumor that occurs most often in adults.
• Pineoblastomas (grade IV): A pineoblastoma is a rare tumor that is very likely to spread. This type of tumor is most common in children.

Meningeal Tumors

A meningeal tumor, also called a meningioma, forms in the meninges (thin layers of tissue that cover the brain and spinal cord). It can form from different types of brain or spinal cord cells. A meningioma is most common in adults. Types of meningeal tumors include the following:

• Meningioma (grade I): A grade I meningioma is the most common type of meningeal tumor. A grade I meningioma is a slow-growing, benign tumor that forms most often in the dura mater (the layer of tissue that covers the brain and is closest to the skull). It is most common in women.
• Meningioma (grade II and III): This is a rare, malignant meningeal tumor. It grows quickly and is likely to spread within the brain and spinal cord. A grade III meningioma is most common in men.

A hemangiopericytoma is not a meningeal tumor but is treated like a grade II or III meningioma. A hemangiopericytoma usually forms in the dura mater. It often recurs (comes back) after treatment and usually spreads to other parts of the body.

Germ Cell Tumors

A germ cell tumor forms in germ cells, which are the cells that develop into sperm in men or ova (eggs) in women. Germ cell tumors usually form in the center of the brain, near the pineal gland. Germ cell tumors can spread to other parts of the brain and spinal cord. There are different types of germ cell tumors. These include germinomas, teratomas, embryonal yolk sac carcinomas, and choriocarcinomas. Germ cell tumors can be either benign or malignant.

Most germ cell tumors occur in children and in people with Klinefelter syndrome.

Tumors of the Sellar Region: Craniopharyngioma (Grade I) and Pituitary Tumor

A tumor of the sellar region begins in the center of the brain, just above the back of the nose. It can form from different types of brain or spinal cord cells.

• Craniopharyngioma (grade I): A craniopharyngioma is a rare tumor that usually forms just above the pituitary gland (a pea-sized organ at the bottom of the brain that controls other glands). The tumor may grow into nearby tissues, including the pituitary gland and optic nerves. This can affect many functions, including hormone-making and vision. These tumors occur in adults and children.

Other Adult Brain Tumors

There are many other types of adult brain tumors that are rare and are not discussed in this summary.

Recurrent Brain Tumors

A recurrent brain tumor is a tumor that has recurred (come back) after it has been treated. Brain tumors often recur, sometimes many years after the first tumor. The tumor may recur at the same place in the brain or in other parts of the central nervous system.

The cause of most adult brain tumors is unknown.

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. There are few known risk factors for brain tumors. The following conditions may increase the risk of developing certain types of brain tumors:

• Being exposed to vinyl chloride may increase the risk of glioma.
• Past treatment with radiation therapy to the scalp or brain may increase the risk of meningioma.
• Infection with the Epstein-Barr virus, having AIDS (acquired immunodeficiency syndrome), or receiving an organ transplant may increase the risk of primary CNS lymphoma.
• Having certain genetic syndromes may increase the risk of developing the following types of brain tumors:

• • Neurofibromatosis type 1 or 2.
  • von Hippel-Lindau disease.
  • Tuberous sclerosis.
  • Li-Fraumeni syndrome.
  • Turcot syndrome type 1 and type 2.
  • Klinefelter syndrome.
  • Nevoid basal cell carcinoma syndrome.

The symptoms of adult brain and spinal cord tumors are not the same in every person.

The symptoms caused by a brain tumor depend on where the tumor formed in the brain, the functions controlled by that part of the brain, and the size of the tumor. Headaches and other symptoms may be caused by adult brain tumors. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

Brain Tumors

• Morning headache or headache that goes away after vomiting.
• Frequent nausea and vomiting.
• Vision, hearing, and speech problems.
• Loss of balance and trouble walking.
• Weakness on one side of the body.
• Unusual sleepiness or change in activity level.
• Unusual changes in personality or behavior.

• Seizures.

Spinal Cord Tumors

• Back pain or pain that spreads from the back towards the arms or legs.
• A change in bowel habits or trouble urinating.
• Weakness in the legs.
• Trouble walking.

Tests that examine the brain and spinal cord are used to detect (find) adult brain tumors.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
• Visual field exam: An exam to check a person’s field of vision (the total area in which objects can be seen). This test measures both central vision (how much a person can see when looking straight ahead) and peripheral vision (how much a person can see in all other directions while staring straight ahead). Any loss of vision may be a sign of a tumor that has damaged or pressed on the parts of the brain that affect eyesight.
• Tumor marker test: A procedure in which a sample of blood, urine, or tissue is checked to measure the amounts of certain substances made by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the body. These are called tumor markers.
• Gene testing: A laboratory test in which a sample of blood or tissue is tested for changes in a chromosome that has been linked with a certain type of brain tumor.
• Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. The cerebrospinal fluid is viewed under a microscope by a pathologist to check for signs of cancer. This procedure is also called an LP or spinal tap.
• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of the brain and spinal cord. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI). Sometimes a procedure called magnetic resonance spectroscopy (MRS) is done during the MRI scan. An MRS is used to diagnose tumors, based on their chemical make-up.
• SPECT scan (single photon emission computed tomography scan): A procedure that uses a special camera linked to a computer to make a 3-dimensional (3-D) picture of the brain. A small amount of a radioactive substance is injected into a vein or inhaled through the nose. As the substance travels through the blood, the camera rotates around the head and takes pictures of the brain. There will be increased blood flow and more chemical reactions (metabolism) in areas where cancer cells are growing. These areas will show up brighter in the picture. This procedure may be done just before or after a CT scan.
• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the brain. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• Angiogram: A procedure to look at blood vessels and the flow of blood in the brain. A contrast dye is injected into the blood vessel. As the contrast dye moves through the blood vessel, x-rays are taken to see if there are any blockages.

Most adult brain tumors are diagnosed and removed in surgery.

If doctors think there may be a brain tumor, a biopsy may be done to remove a sample of tissue. For tumors in the brain, the biopsy is done by removing part of the skull and using a needle to remove the tissue sample. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are found, the doctor may remove as much tumor as safely possible during the same surgery. After the surgery, a pathologist checks the cancer cells to find out the type and grade of brain tumor. The grade of the tumor is based on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. A CT scan or MRI may be used to find out if any cancer cells remain after surgery.

The following tests may be done on the tumor tissue that is removed:

• Immunohistochemistry study: A laboratory test in which a substance such as an antibody, dye, or radioisotope is added to a sample of cancer tissue to test for certain antigens. This type of study is used to tell the difference between different types of cancer.
• Light and electron microscopy: A laboratory test in which cells in a sample of tissue are viewed under regular and high-powered microscopes to look for certain changes in the cells.
• Cytogenetic analysis: A laboratory test in which cells in a sample of tissue are viewed under a microscope to look for certain changes in the chromosomes.

Sometimes a biopsy or surgery cannot be done safely because of where the tumor formed in the brain or spinal cord. These tumors are diagnosed based on the results of imaging tests and other procedures.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options for primary brain tumors depend on the following:

• The type and grade of the tumor.
• Where the tumor is in the brain.
• Whether the tumor can be removed by surgery.
• Whether cancer cells remain after surgery.
• Whether there are certain changes in the chromosomes.
• Whether the cancer has just been diagnosed or has recurred (come back).
• The patient's general health.

The prognosis and treatment options for metastatic brain tumors depend on the following:

• Whether the patient is younger than 60 years.
• Whether there are more than two tumors in the brain or spinal cord.
• Where in the brain or spinal cord the tumors are.
• How well the tumor responds to treatment.
• Whether the primary tumor continues to grow or spread.

The prognosis is better for brain metastases from breast cancer than from other types of primary cancer. The prognosis is worse for brain metastases from colon cancer.

National Cancer Institute

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