GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 351 Epilepsy myoclonic epilepsy. As the genetics of the epilepsies be- come better understood, the classification scheme will evolve. With epilepsy, symptoms vary considerably depend- ing on the type. The common link among the epilepsies is, of course, seizures. The different epilepsies can sometimes be associated with more than one seizure type. This is the case with Lennox-Gastaut syndrome. Diagnosis Arriving at a diagnosis of epilepsy is relatively straightforward: when people suffer two or more seizures, they would be considered to have epilepsy. However, di- agnosing the specific epilepsy syndrome is much more complex. The first step in the evaluation process is to ob- tain a very detailed history of the illness, not only from the patient but from the family as well. Since seizures can im- pair consciousness, the patient may not be able to recall the specifics of the attacks. In these cases, family or friends that have witnessed the episodes can fill in the gaps about the particulars of the seizure. The description of the behaviors during a seizure can go a long way to catego- rizing the type of seizure and help with the overall diag- nosis. Moreover, in the initial visit with the physician, the entire history of the patient is obtained. In a child, this would include birth history, complications, if any, mater- nal history, and developmental milestones. At any age, so- called co-morbidities (other medical problems) are considered. Medications that have been taken or currently being prescribed are documented. A complete physical examination is performed, espe- cially a neurological exam. Because seizures are an episodic disorder, abnormal neurological findings may not be present. Frequently, people with epilepsy have a normal exam. However, in some, there can be abnormal findings that can provide clues to the underlying cause of epilepsy. For example, if someone has had a stroke that subse- quently caused seizures, then the neurological exam can be expected to reveal a focal neurological deficit such as weakness or language difficulties. In some children with seizures, there can be a variety of associated neurologic abnormalities such as mental retardation and cerebral palsy that are themselves non-specific but indicate that the brain has suffered, at some point in development, an injury or malformation. Also, subtle findings on examination can lead to a diagnosis such as in tuberous sclerosis. This is an autosomal dominantly inherited disorder associated with infantile spasms in 25% of cases. On examination, patients have so-called ash-leaf spots and adenoma se- baceum on the skin. There can also be a variety of sys- temic abnormalities that involve the kidneys, retina, heart, and gums, depending on severity. In the course of evaluating epilepsy, a number of tests are typically ordered. Usually, magnetic resonance image (MRI) of the brain is obtained. This is a scan that can help in finding many known causes of epilepsy such as tumors, strokes, trauma, and congenital malformations. However, while MRI can reveal incredible details of the brain, it can- not visualize the presence of abnormalities in the micro- scopic neuronal environment. Another test that is routinely ordered is an electroencephalogram (EEG). Unlike the MRI scan, this can be considered a functional test of the brain. The EEG measures the electrical activity of the brain. Some seizure disorders or epilepsies have a charac- teristic EEG with particular abnormalities that can help in diagnosis. Other tests that are frequently ordered are var- ious blood tests that are also ordered in many medical con- ditions. These blood tests help to screen for abnormalities that can be a factor in the cause of seizures. Occasionally, genetic testing is performed in those instances where a known genetic cause is suspected and can be tested. A major concern in the course of an evaluation of epilepsy is to identify the presence of life-threatening causes such as brain tumors, infections, and cerebrovascular disease. Also, an accurate diagnosis can expedite the most effective treatment plan. The symptoms of epilepsy are dependent in part on the particular seizures that occur and other medical prob- lems that may be associated. Seizures, themselves, can take on a variety of features. A simple sustained twitch- ing of an extremity could be a focal seizure. If a seizure arises in the occipital lobes of the brains, then a visual ex- perience can occur. Aura is a term often used to describe symptoms that a person may feel prior to the loss of con- sciousness of a seizure. However, auras are, themselves, small focal seizures that have not spread in the brain to in- volve consciousness. Smells, well-formed hallucina- tions, tingling sensations, or nausea have each occurred in auras. The particular sensation can be a clue as to the lo- cation in the brain where a seizure starts. Focal seizures can then spread to involve other areas of the brain and lead to an alteration of consciousness, and possibly con- vulsions. In certain epilepsy syndromes such as Lennox- Gastaut, there can be more than one type of seizure experienced, such as atonic, atypical absence, and tonic- axial seizures. Treatment One challenge in predicting the course of epilepsy is that for any type, there can be a variable response to treat- ment. Sometimes, seizures may play a rather small role in the manifestation of a medical condition. For example, a severe head injury could result in seizures that readily re- spond to medication, but severe neurological impairments and disabilities may still be present. On the other hand, a LetterE.qxd 10/1/04 11:05 AM Page 351 352 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Epilepsy different head injury may result in relatively mild neuro- logical problems, but there may be seizures that are severe and be resistant to medications. Whatever the case, the ultimate goals when treating epilepsy are to: • strive for complete freedom from seizures • have little to no side effects from medications • be able to follow an easy regimen so that compliance with treatment can be maintained Up to 60% of patients with epilepsy can be expected to achieve control of seizures with medication(s). How- ever, in the remaining 40%, epilepsy appears to be resist- ant, to varying degrees, to medications. In these cases, the epilepsy is termed medically intractable. Generally, the choice of medication is somewhat trial and error. There are, however, a number of considerations that guide the choice of treatment. Each medication has a particular side effect profile and mechanism of action. Some medications seem to be particularly effective for certain epilepsy syndromes. For example, juvenile my- oclonic epilepsy responds well to valproic acid. On the other hand, ethosuxamide is primarily used for absence seizures. As with any medication, individuals can have very different experiences with same drug. Consequently, it is difficult to predict the efficacy of treatment in the begin- ning. A key concept of treatment is to first strive for monotherapy (or single drug therapy). This simplifies treatment and minimizes the chance of side effects. Some- times, however, two or more drugs may be necessary to achieve satisfactory control of seizures. As with any treat- ment, potential side effects can be worse than the disease itself. Moreover, there is little point in controlling seizures if severe side effects limit quality of life. If a seizure dis- order is characterized by mild, focal, or brief symptoms that do not interfere with day-to-day life, then aggressive treatments may not be justified. Epilepsy medications do not cure epilepsy; the medications can only control the frequency and severity of seizures. A list of the most com- monly used medications in the management of epilepsy includes: • phenobarbital • phenytoin (Dilantin, Phenytek) • clonazepam (Klonipin) • ethosuxamide (Zarontin) • carbamazepine (Tegretol, Carbatrol) • divalproex sodium (Depakote, Depakene) • felbamate (Felbatol) • gabapentin (Neurontin) • lamotrigine (Lamictal) • topiramate (Topamax) • tiagabine (Gabatril) • zonisamide (Zonegran) • oxcarbazepine (Trileptal) • leviteracetam (Keppra) It has been found that the initial, thoughtfully chosen medication can be expected to make almost 50% of pa- tients seizure free for extended periods of time. If the ini- tial drug fails, another well-chosen drug may make an additional 14% of people seizure free. If that drug fails, then the likelihood of rendering someone with epilepsy seizure free is poor. This does not mean that trying more medications or combinations of them may not be suc- cessful, but rather, these statistics give the neurologist and the patient an understanding of the realities of epilepsy treatment. In cases where medications do not fully control epilepsy, it is recommended that a more extensive evalua- tion at a comprehensive epilepsy center be conducted where an epileptologist (a specialist in epilepsy) will more thoroughly assess the particular aspects of the seizures. When medications are clearly ineffective, the other types of therapy that can be considered are the ketogenic diet, brain surgery, and vagal nerve stimulation. Ketogenic diet The ketogenic diet is based on high-fat, low-carbo- hydrate, and low-protein meals. The ketogenic diet is named because of the production of ketones by the break- down of fatty acids. The most common version of the diet involves long-chain triglycerides. These are present in whole cream, butter, and fatty meats. The ketogenic diet is administered with the support of a nutritionist with experience in this treatment modal- ity. It is mostly used in children with medically in- tractable epilepsy and whose diet can be controlled. The ketogenic diet can be considered a pharmacologic treat- ment. As such, there are potential side effects that limit its tolerance. This includes hair thinning, lethargy, weight loss, kidney stones, and possibly cardiac problems. Sugar-free vitamin and mineral supplementation is nec- essary. The diet may not be appropriate for certain indi- viduals, particularly in children, who may have certain metabolic diseases. Overall, the diet has been very helpful in the control of seizures in many patients. Roughly 50% of patients can hope to achieve complete control of seizures, 25% of the patients see improvements, and another 25% are non-re- sponders. There are some patients who have an improve- ment in behavior. If the diet is well tolerated with good results, then it can be maintained for up to two years, fol- lowed by a careful gradual transition to regular meals. LetterE.qxd 10/1/04 11:05 AM Page 352 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 353 Epilepsy Elizabeth Rudy, who suffers from epilepsy, sits hooked up to brain wave monitor. Her left hand strokes her seizure- predicting dog, Ribbon. (A/P Wide World Photos. Reproduced by permission.) Epilepsy surgery Epilepsy surgery is an option in the attempt to either cure or significantly reduce the severity of medically re- sistant cases. It is thought that up to 100,000 patients in the United States could be potential candidates for a surgical treatment. However, only about 5,000 cases are performed throughout the United States annually. This is likely due to several factors, including the belief that any brain surgery is a last resort, the lack of awareness or understanding of the benefits of surgery, and the false hope that some med- ication will come along that will be effective. There are several kinds of surgery that are available depending on the nature of the seizure disorder. A list of operations that are utilized regularly for epilepsy include: • lobectomy • lesionectomy • corpus collosotomy • multiple subpial transection • hemispherectomy The type of surgery that is performed depends on the nature of the individual seizure disorder. If a seizure can be localized to a particular area in the brain, then this ab- normal region can potentially be surgically removed. Epileptic brain tissue is abnormal and its removal can pro- vide a chance of a cure. Generally, surgery should be a consideration when the risk and benefits of it outweigh the long-term risks of uncontrolled epilepsy. The approach taken in any brain surgery for epilepsy is highly individualized and great care is taken to avoid in- jury to essential brain tissue. The most common epilepsy surgery performed is the temporal lobectomy. Brain tu- mors are frequently associated with seizures. In many cases, surgery to remove the tumor is planned so that re- gions that may be causing seizures are removed as well. However, in many cases, epilepsy surgery cannot be done. Vagus nerve stimulation Another non-medicinal approach to treating epilepsy is a novel method that became available in July 1997. The Food and Drug Administration (FDA) approved the use of the vagal nerve stimulator (VNS) as add-on therapy in pa- tients who experience seizures of partial onset. The VNS is designed to intermittently deliver small electrical stim- ulations to a nerve in the neck called the vagus nerve. LetterE.qxd 10/1/04 11:05 AM Page 353 354 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Epilepsy There are two vagal nerves, one on each side of the neck near the carotid arteries, making a pair of cranial nerves (there are 12 different paired cranial nerves). The vagus nerve carries information from the brain to many parts of the thoracic and abdominal organs. The nerve also carries information from these same organs back to the brain. VNS takes advantage of this fact and, by intermittent stim- ulation, there is an effect on many brain areas that can be involved in seizures. About 50% of patients experience at least 50% re- duction in the frequency of their seizures. The responses to VNS range from complete control of seizures (less than 10% of patients) to no noticeable improvement. The de- vice is not a substitute for epilepsy surgery and should be considered only after there is an evaluation for epilepsy surgery. The implantation of the device requires relatively minor surgery with two incisions, one in the neck and the other in the left upper chest area. The battery in the device lasts up to eight to ten years, after which the device can be replaced. Side effects of VNS therapy include voice hoarseness that typically does not impair communication. Like any surgery, there is an initial risk of infection, bleeding, and pain. Recovery takes a few weeks. Individuals can return to their usual activities once the incisions have healed. Clinical trials The National Institute of Neurological Disorders and Stroke list a number of clinical trials. There are also a number of studies being conducted at a more basic science stage evaluating the role of the following in seizures and epilepsy: neurotransmitters, non-neuronal cells, and ge- netic factors. Treatment strategies including deep brain stimulation and intracranial early seizure detection de- vices are being studied at different stages. Prognosis The prognosis of epilepsy varies widely depending on the cause, severity, and patient’s age. Even individuals with a similar diagnosis may have different experiences with treatment. For example, in benign epilepsy of child- hood with centrotemporal spikes (also called benign rolandic epilepsy), the prognosis is excellent with nearly all children experiencing remission by their teens. With childhood absence epilepsy, the prognosis is variable. In this case, the absence seizures become less frequent with time, but almost half of patients may eventually develop generalized tonic-clonic seizures. Overall, the seizures are responsive to an appropriate anticonvulsant. On the other hand, the seizures in Lennox-Gastaut syndrome are very difficult to control. In this case, however, the ketogenic diet can help. In seizures that begin in adulthood, one can expect that medications will control seizures in up to 60–70% of cases. However, in some of the more than 30% of medically intractable cases, epilepsy surgery can im- prove or even cure the problem. Overall, most patients have a good chance of con- trolling seizures with the available options of treatment. The goal of treatment is complete cessation of seizures since a mere reduction in seizure frequency and/or sever- ity may continue to limit patients’ quality of life: they may not be able to drive, sustain employment, or be productive in school. Resources BOOKS Browne, T. R., and G. L. Holmes. Handbook of Epilepsy, 2nd edition. Philadelphia: Lippincott Williams & Wilkins. 2000. Devinski, O. A Guide to Understanding and Living with Epilepsy. Philadelphia: F.A. Davis Company. 1994. Engel, J., Jr., and T. A. Pedley. Epilepsy: A Comprehensive Textbook. Philadelphia: Lippincott-Raven. 1998. Freeman, M. J., et al. The Ketogenic Diet: A Treatment for Epilepsy, 3rd Edition. New York: Demos Medical Publishing, 2000. Hauser, W. A., and D. Hesdorffer. Epilepsy: Frequency, Causes, and Consequences. New York: Demos Medical Publishing, 1990. Pellock, J. M., W. E. Dodson, and B. F. D. Bourgeois. Pediatric Epilepsy Diagnosis and Therapy, 2nd Edition. New York: Demos Medical Publishing, 2001. Santilli, N. Managing Seizure Disorders: A Handbook for Health Care Professionals. Philadelphia: Lippincott- Raven. 1996. Schachter, S. C., and D. Schmidt. Vagus Nerve Stimulation, 2nd Edition. Oxford, England: Martin Dunitz, 2003. Wyllie, E. The Treatment of Epilepsy: Principles and Practice, 3rd Edition. Philadelphia: Lippincott Williams & Wilkins, 2001. PERIODICALS Kwan, P., and M. J. Brodie. “Early Identification of Refractory Epilepsy.” New England Journal of Medicine no. 342 (2000): 314–319. ORGANIZATIONS American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507. 860.586.7505. <www.aesnet.org>. Epilepsy Foundation of America. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. <www.epilepsyfoundation.org>. International League Against Epilepsy. Avenue Marcel Thiry 204, B-1200, Brussels, Belgium. + 32 (0) 2 774 9547; Fax: + 32 (0) 2 774 9690. <www.epilepsy.org>. Roy Sucholeiki, MD Erb’s palsy see Brachial plexus injuries LetterE.qxd 10/1/04 11:05 AM Page 354 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 355 Exercise Erb-Duchenne and Dejerine-Klumpke palsies see Brachial plexus injuries ❙ Exercise Definition Exercise is physical activity that is undertaken in order to improve one’s health. Physicians, physical thera- pists, and researchers have found that exercise plays an important role in the maintenance of brain, nerve, and muscle function in the human body. New research sug- gests that exercise may delay mental deterioration with age and disease, and perhaps even promote neurogenesis (nerve cell growth). Description Health care professionals recommend regular exercise because it increases energy, contributes to overall health, improves sleep, increases life expectancy, and enhances lifestyle. In terms of specific medical disorders, exercise has been shown to prevent or delay the onset of coronary artery disease, bone loss and osteoporosis, some types of cancer, and stroke. Generally, exercise is categorized into the following four types: • Aerobic exercise focuses on strengthening the heart, lungs, and circulatory system. Its major goal is to in- crease the heart rate and breathing rate. Examples of aer- obic exercise include jogging, bicycling, swimming, and racket sports. • Strength training focuses on strengthening muscles and joints. It also improves balance and increases metabo- lism. Weightlifting is the most common form of strength training. • Balance exercises are used to improve stability. They stimulate the vestibular system, which includes muscles, joints, sensory organs, the inner ear, and the brain. • Stretching exercises improve flexibility, which helps pre- vent injury during other forms of exercises and may de- crease chronic pain. Stretching exercises include yoga, tai chi, and basic stretches. All four types of exercises have been found to be im- portant to maintaining brain, nerve, and muscle health. Exercise and the brain Exercise is particularly beneficial to the health of the brain. It has long been known that exercise causes the en- docrine system to release serotonin and dopamine, hor- mones in the brain that produce feelings of euphoria and peacefulness. These hormones often allow people who ex- ercise to think more clearly and perform mental tasks more easily. Exercise has also been successfully used as a treatment for depression, used in lieu of prescription antidepressants. A 2003 study on mice suggests that new brain cells can grow as a result of exercise. This neurogenesis, previ- ously thought not to occur in adult mammals, is concen- trated in the hippocampus, the part of the brain responsible for learning and spatial memory. In addition, the study found that the mice subjected to an exercise regimen had stronger synapses than the mice that were sedentary. Other research shows that nerve growth factors, called neu- rotropins, are stimulated by exercise. Finally, exercise in- creases blood flow to the brain, as well as collateral circulation, enhancing mental function and nerve cell stimulation. Exercise and aging Aging naturally affects a variety of processes in the human body. Exercise has many positive benefits that pre- vent or slow the age-related deterioration of brain, nerve, and muscle functions. In 2001, a study reported by the Mayo Clinic showed that regular exercise in older people slowed rates of men- tal deterioration, including Alzheimer’s disease and de- mentia. On tests of mental acuity, older people who exercised regularly performed just as well as younger people who did not exercise. Another study found that regular walking greatly slowed rates of mental decline in older women. Between the ages of 30 and 90, natural aging processes result in the loss of 15–25% of the brain tissue. In particular, losses are significant in the parts of the brain consisting of gray matter, which is associated with learn- ing and memory. The February 2003 issue of Journal of Gerontology: Medical Sciences reported that this natural degradation of gray matter in older people was signifi- cantly decreased in people who exercised regularly com- pared to those who did not exercise. In the study, fitness levels were determined by treadmill-walking tests and tis- sue degradation was measured using magnetic reso- nance imaging (MRI). Balance is often affected as people age. Balance de- pends on input from the eyes, ears, and other sensory or- gans, all of which are affected by age. In addition, muscle strength and tone are required for balance. The natural aging process includes contraction of muscle tissue, and sedentary lifestyles only exacerbate the weakening of muscles. Joints supported by strong muscles are more sta- ble than joints that are supported by weak muscles. Strength training, in particular, has the potential to coun- teract loss of muscle strength. LetterE.qxd 10/1/04 11:05 AM Page 355 356 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Exercise Physical therapy and the brain, nerves, and muscles Therapeutic exercises have been designed to enhance a variety of aspects of physical fitness in patients suffer- ing from diseases and dysfunctions. Goals of physical therapy include improving circulation, coordination, bal- ance, and respiratory capacity. Exercises may be geared toward mobilizing joints and releasing contracted muscles and tendons. Patients suffering from neurological disorders can be treated with a variety of physical therapies. For example, motor neuron damage or partial peripheral nerve damage may respond to a specific type of physical therapy called proprioceptive neuromuscular facilitation (PNF). PNF fo- cuses on exercises that build muscle strength by applying resistance to muscle contraction. Patients who have expe- rienced cerebrovascular accidents may undergo PNF com- bined with training for muscle strength, balance, and coordination. Multiple sclerosis is treated with PNF along with physical fitness training. Physical therapies for Parkinson disease focus on general physical fitness train- ing, along with stretching exercises. Resources BOOKS Putnam, Stephen C. Nature’s Ritalin for the Marathon Mind. Hinesburg, VT: Upper Access Book Publishers, 2001. Ratey, John. A User’s Guide to the Brain: Perception, Attention, and the Four Theaters of the Brain. Vancouver, WA: Vintage Books, 2002. OTHER Effects on Neurologic Diseases and Mental Decline. Health and Age. (March 18, 2004). <http://www.healthandage.com/ Home/gm=0!gc=2!gid6=2908>. Frankenfield, Gay. “Exercise May Improve Learning and Memory.” WebMD January 4, 2004 (March 18, 2004). <http://my.webmd.com/content/article/17/1676_50120.ht m?lastselectedguid={5FE84E90-BC77-4056-A91C- 9531713CA348>. Lawrence, Star. “Train Your Brain with Exercise.” WebMD July 28, 2003 (March 18, 2004). <http://my.webmd.com/ content/article/67/79909.htm?lastselectedguid={5FE84E9 0-BC77-4056-A91C-9531713CA348>. Warner, Jennifer. “Exercise Saves Brain Cells.” WebMD January 29, 2003 (March 18, 2004). <http:// my.webmd.com/content/article/60/66925.htm? lastselectedguid={5FE84E90-BC77-4056-A91C- 9531713CA348>. ORGANIZATIONS Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion. Division of Nutrition and Physical Activity, 4770 Buford Highway, NE, Atlanta, GA 30341-3724. (888) CDC- 4NRG ((888) 232-4674). <http://www.cdc.gov>. The President’s Council on Physical Fitness and Sports. Department W, 200 Independence Ave., SW, Room 738-H, Washington, DC 20004. (202) 690-9000; Fax: (202) 690-5211. <http://fitness.gov/index.html>. Juli M. Berwald LetterE.qxd 10/1/04 11:05 AM Page 356 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 357 F ❙ Fabry disease Definition Fabry disease is a genetic condition that typically af- fects males. It is caused by deficiency of an enzyme, a chemical that speeds up another chemical reaction. Fabry disease can affect many parts of the body including the kidneys, eyes, brain, and heart. Pain in the hands and feet and a characteristic rash are classic features of this disease. Description The symptoms of Fabry disease were first described by Dr. Johann Fabry and Dr. William Anderson in 1898. The enzyme deficiency that leads to the disease was iden- tified in the 1960s. The symptoms of Fabry disease are variable. Some in- dividuals with Fabry disease have severe complications, while others have very mild symptoms. The first sign of the disease may be a painful burning sensation in the hands and feet (acroparesthesias). A red rash, most commonly between the belly button and the knees (angiokeratoma) is also common. The outer portion of the eye (cornea) may also become clouded in individuals with Fabry disease. The progressive buildup of globotriaosylceramide can also lead to kidney problems and heart disease in adulthood. Demographics Fabry disease affects approximately one in 40,000 live births. It occurs evenly among all ethnic groups. Al- most always, only male children are affected. Although fe- male carriers of the disease occasionally develop symptoms of the disease, it is rare for a female carrier to be severely affected. Causes and symptoms Fabry disease is caused by a change (mutation) in the GLA gene. This gene is responsible for the production of the enzyme alpha-galactosidase A. Alpha-galactosidase A normally breaks down globotriaosylceramide. Globo- triaosylceramide is a natural substance in the body, made of sugar and fat. A mutation in the GLA gene leads to a de- crease in alpha-galactosidase A activity which, in turn, leads to an excess of globotriaosylceramide. The excess globotriaosylceramide builds up in blood vessels (veins, arteries, and capillaries) and obstructs normal blood flow. It also builds up in parts of the skin, kidneys, heart, and brain. It is this buildup that inhibits normal function and leads to the symptoms associated with the disease. The gene that produces alpha-galactosidase A is lo- cated on the X chromosome. It is called the GLA gene. Since the GLA gene is located on the X chromosome, Fabry disease is considered to be X-linked. This means that it generally affects males. The signs and symptoms of Fabry disease vary. Some individuals with Fabry disease have many severe symp- toms, while other individuals’ symptoms may be few and mild. The symptoms typically increase or intensify over time. This progression is caused by the slow buildup of globotriaosylceramide as the person ages. A painful burning sensation in the hands and feet (acroparesthesias) is one of the first symptoms of Fabry disease. This pain can be severe and may grow worse with exercise, stress, illness, extreme heat, or extreme cold. Another symptom of Fabry disease typically present dur- ing childhood is a red rash (angiokeratoma). This rash typ- ically develops between the navel and the knees. Children with Fabry disease may also have a clouding of the outer most portion of the eye (cornea). This symptom is usually diagnosed by an eye doctor (ophthalmologist). The cloudiness may increase with time. A decreased ability to sweat is another common symptom of Fabry disease. Due to the progressive nature of Fabry disease, most affected individuals develop additional symptoms by age 40. The buildup of globotriaosylceramide in the heart can lead to heart problems. These heart problems can include changes in the size of the heart (left ventricular enlarge- ment), differences in the heart beat, and leaky heart valves. LetterF.qxd 10/1/04 11:05 AM Page 357 358 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Fabry disease 22 21 11 12 11 13 1 1 2 Renpenning syndrome DMD: Duchenne muscular dystrophy Spondyloepiphyseal dysplasia X-linked hydrocephaly STA: Emery-Dreifuss muscular dystrophy FMR1: Fragile X syndrome SGBS1: Simpson-Golabi-Behmel syndrome p q 27 26 28 24 25 23 22 21 2 ALD: Adrenoleukodystrophy ATRX: Smith-Fineman-Myers syndrome ATP7A: Menkes syndrome Sutherland-Hann syndrome OCRL1: Lowe syndrome IL2RG: X-linked severe combined immunodeficiency GLA: Fabry disease PIG-A: Paroxysomal nocternal hemoglobinuria Chromosome X Asplenia (x) KAL: Kallman syndrome (x) Fabry disease, on chromosome X. (Gale Group.) Mitral valve prolapse is a particular type of leaky heart valve that is common in Fabry disease, even in childhood. The excess globotriaosylceramide can also disrupt normal blood flow in the brain. In some cases this can cause dizzi- ness, seizures, and stroke. The kidneys are other organs affected by Fabry disease. Kidney problems can lead to an abnormal amount of protein in the urine (proteinuria). Se- vere kidney problems can lead to kidney failure. Although the symptoms of Fabry disease usually occur in males, female carriers may occasionally exhibit symptoms of the disease. Some carriers experience pain in their hands and feet. Carrier females may also have pro- teinuria and clouding of their cornea. It is rare for a female to experience all of the symptoms associated with Fabry disease. Diagnosis Initially, the diagnosis of Fabry disease is based on the presence of the symptoms. It should also be suspected if there is a family history of the disorder. The diagnosis of Fabry disease is definitively made by measuring the ac- tivity of the alpha-galactosidase A enzyme. When the ac- tivity is very low, it is diagnostic of Fabry disease. This enzyme analysis can be performed through a blood test. Measuring the activity of the enzyme can also detect fe- male carriers. Women who are carriers of Fabry disease have enzyme activity that is lower than normal. Prenatal diagnosis is possible by measuring the alpha- galactosidase A activity in fetal tissue drawn by amnio- centesis or chorionic villus sampling (CVS). Fetuses should be tested if the mother is a carrier. A woman is at risk of being a carrier if she has a son with Fabry disease or someone in her family has Fabry disease. Treatment team A number of specialized practitioners are necessary to care for patients with Fabry disease. Depending on the specific manifestations, these specialists may include a dermatologist to treat skin problems; a neurologist to treat such complications as dizziness, seizure, stroke; an oph- thalmologist to treat eye problems; a nephrologist to treat kidney problems; a cardiologist to treat heart problems. A pain specialist may be helpful, as well. Treatment There is currently no cure for Fabry disease. Until such time as enzyme replacement therapy is proven to be safe and effective, individuals with Fabry disease must rely on traditional treatments. Pain can be treated with medications such as carbamazepine and dilantin. Indi- viduals with Fabry disease are recommended to have rou- tine evaluations of their heart and kidneys. Some individuals with kidney disease require a special diet that is low in sodium and protein. Dialysis and kidney trans- plantation may be necessary for patients with severe kid- ney disease. Certain medications may reduce the risk of stroke. Finally, individuals with Fabry disease are recom- mended to avoid the situations that cause the pain in their hands and feet to grow worse. In some situations medica- tion may be required to reduce the pain. Clinical trials A number of clinical trials are underway. Some are studying the specific nervous system effects of the disase. Others are giving individuals with Fabry disease the alpha- galactosidase A enzyme (Replagal) as a form of enzyme replacement therapy. If successful, this enzyme replace- ment therapy may reduce or eliminate the symptoms as- sociated with Fabry disease. Clopidogrel, a blood thinner, is also being studied to see if its administration may de- crease the rate/severity of such complications as stroke and heart attack. LetterF.qxd 10/1/04 11:05 AM Page 358 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 359 Facial synkinesis Key Terms Acroparesthesias Painful burning sensation in hands and feet. Amniocentesis A procedure performed at 16–18 weeks of pregnancy in which a needle is inserted through a woman’s abdomen into her uterus to draw out a small sample of the amniotic fluid from around the baby. Either the fluid itself or cells from the fluid can be used for a variety of tests to obtain informa- tion about genetic disorders and other medical con- ditions in the fetus. Angiokeratoma Skin rash comprised of red bumps. Rash most commonly occurs between the navel and the knees. Blood vessels General term for arteries, veins, and capillaries that transport blood throughout the body. Chorionic villus sampling (CVS) A procedure used for prenatal diagnosis at 10-12 weeks gestation. Under ultrasound guidance a needle is inserted ei- ther through the mother’s vagina or abdominal wall and a sample of cells is collected from around the fetus. These cells are then tested for chromosome ab- normalities or other genetic diseases. Cornea The transparent structure of the eye over the lens that is continuous with the sclera in forming the outermost protective layer of the eye. Dialysis Process by which special equipment puri- fies the blood of a patient whose kidneys have failed. Enzyme replacement therapy Giving an enzyme to a person who needs it for normal body function. It is given through a needle that is inserted into the body. Left ventricular enlargement Abnormal enlarge- ment of the left lower chamber of the heart. Mitral valve prolapse A heart defect in which one of the valves of the heart (which normally controls blood flow) becomes floppy. Mitral valve prolapse may be detected as a heart murmur, but there are usually no symptoms. Mutation A permanent change in the genetic ma- terial that may alter a trait or characteristic of an in- dividual, or manifest as disease, and can be transmitted to offspring. Proteinuria Excess protein in the urine. Prognosis The prognosis for individuals with Fabry disease is good, especially with the arrival of enzyme replacement therapy. Currently, affected individuals survive into adult- hood with the symptoms increasing over time. Resources BOOKS Desnick, Robert J., Yiannis Ioannou, and Christine Eng. “Galactosidase A Deficiency: Fabry Disease.” In The Molecular Bases of Inherited Disease. 8th ed. New York: McGraw Hill, 2001. ORGANIZATIONS Alliance of Genetic Support Groups. 4301 Connecticut Ave. NW, Suite 404, Washington, DC 20008. (202) 966-5557. Fax: (202) 966-8553. <http://www.geneticalliance.org>. Deptartment of Human Genetics, International Center for Fabry Disease. Box 1497, Fifth Ave. at 100th St., New York, NY 10029. (866) 322-7963. <http://www.mssm.edu/genetics/fabry>. Fabry Support and Information Group. PO Box 510, 108 NE 2nd St., Suite C, Concordia, MO 64020. (660) 463-1355. <http://www.cpgnet.com/fsig.nsf>. National Institute of Neurological Disorders and Stroke. 31 Center Drive, MSC 2540, Bldg. 31, Room 8806, Bethesda, MD 20814. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov>. National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>. WEBSITES Fabry Disease Home Page. <http://www.sci.ccny.cuny.edu/ ~fabry/>. Online Mendelian Inheritance in Man (OMIM). <http:// www.ncbi.nlm.nih.gov/htbin-post/Omim/ dispmim?301500>. Holly Ann Ishmael, MS, CGC Rosalyn Carson-DeWitt, MD ❙ Facial synkinesis Definition Facial synkinesis is the involuntary movement of fa- cial muscles that accompanies purposeful movement of some other set of muscles; for example, facial synkinesis may result in the mouth involuntarily closing or grimacing when the eyes are purposefully closed. LetterF.qxd 10/1/04 11:05 AM Page 359 360 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Fainting Description Facial synkinesis occurs during recuperation from conditions or injuries that affect the facial nerve, for ex- ample during recovery from Bell’s palsy. During recovery, as the facial nerve tries to regenerate, some new nerve twigs may accidentally regrow in close proximity to mus- cles that they wouldn’t normally innervate (stimulate). Fa- cial synkinesis may occur transiently, during recovery, or may become a permanent disability. As with all facial injuries or palsies, facial synkinesis can cause considerable emotional distress. Lack of control over one’s facial expressions is known to be a serious psy- chological stressor. Causes and symptoms Facial synkinesis can follow any injury or condition causing palsy or paralysis of the facial nerve. The most common associated disorder is Bell’s palsy; about 40% of all individuals who are recovering from Bell’s palsy will experience facial synkinesis during recovery. Other con- ditions that may prompt the development of facial synki- nesis include stroke, head injury, birth trauma, head injury, trauma following tumor removal (such as acoustic neuroma), infection, Lyme disease, diabetes, and multi- ple sclerosis. Facial synkinesis can cause a number of abnormali- ties in the facial muscles. For example, when a patient with facial synkinesis tries to close his or her eyes, the muscles around the mouth may twitch or grimace. Con- versely, when the patient tries to smile, the eyes may in- voluntarily close. The phenomenon of purposeful mouth movements resulting in involuntary eye closing is often re- ferred to as “jaw winking.” Unfortunately, as with any fa- cial deformity or disability, facial synkinesis carries with it a high risk of concomitant depression, anxiety, and dis- ruption of interpersonal relationships and employment. Diagnosis Diagnosis is usually apparent on physical examina- tion. When the patient is asked to move certain facial mus- cles (i.e., smile), other facial muscles will be activated (e.g., the eyes may close involuntarily). When the under- lying condition is unclear, a variety of tests may be required, such as CT or MRI scanning or EMG (elec- tromyographic) testing to evaluate the functioning of the facial nerves and muscles. Treatment team Facial synkinesis may be treated by neurologists or otorhinolaryngologists. Treatment Treatment may include: • surgery, to remove causative tumors or other sources of pressure on and damage to the facial nerve • steroid medications, to decrease inflammation of the fa- cial nerve • facial exercises • electrical stimulation (this remains controversial, and may, in fact, worsen facial synkinesis in some patients) • intensive video-assisted, electromyographic feedback fa- cial muscle retraining • injections of the paralytic agent botox into the muscle groups that are contracting involuntarily Prognosis The prognosis of facial synkinesis is quite variable, depending largely on the prognosis of the underlying con- dition that caused its development. Resources BOOKS Goetz, Christopher G., ed. Textbook of Clinical Neurology. Philadelphia: W. B. Saunders Company, 2003. PERIODICALS Armstrong, M. W., R. E. Mountain, and J. A. Murray. “Treatment of facial synkinesis and facial asymmetry with botulinum toxin type A following facial nerve palsy.” Clin Otolaryngol 21, no. 1 (February 1996): 15–20. Messé, S. R. “Oculomotor synkinesis following a midbrain stroke.” Neurology 57, no. 6 (September 2001): 1106–1107. Münevver, Çelik, Hulki Forta, and Çetin Vural. “The Development of Synkinesis after Facial Nerve Paralysis.” European Neurology 43 (2000): 147–151. Zalvan, C., B. Bentsianov, O. Gonzalez-Yanes, and A. Blitzer. “Noncosmetic uses of botulinum toxin.” Dermatol Clin 22, no. 2 (April 2004): 187–195. WEBSITES Diels, H. Jacqueline. New concepts in Non-Surgical Facial Nerve Rehabilitation. Bell’s Palsy Infosite. (June 2, 2004). <http://www.bellspalsy.ws/printretrain.htm>. Rosalyn Carson-DeWitt, MD ❙ Fainting Definition Fainting is a temporary loss of consciousness, weak- ness of muscles, and inability to stand up, all caused by sudden loss of blood flow to the brain. Fainting is a rela- tively common symptom caused by a variety of problems LetterF.qxd 10/1/04 11:05 AM Page 360 [...]... Bay, CA 95746 ( 916 ) 79 7-3 700; Fax: ( 916 ) 79 7-3 707 research@childrensgaucher.org National Gaucher Foundation 5 410 Edson Lane, Suite 260, Rockville, MD 2 085 2- 313 0 (3 01) 81 6 -1 5 15 or 80 0GAUCHER (42 8- 2 437); Fax: (3 01) 81 6 -1 5 16 ngf@ gaucherdisease.org Lipid A fatty substance in use throughout the body Prognosis The prognosis of Gaucher disease... ataxia GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 2 24 23 22 21 1 p q CDKN2: Malignant melanoma 13 12 11 11 FRDA: Friedreich’s ataxia 12 1 13 21 2 22 Familial dysautonomia 3 31 32 33 OWR1: Olser-Weber-Rendu syndrome 34 Distal arthrogryposis syndrome (9) Friedreich ataxia, on chromosome 9 (Gale Group.) Demographics FRDA is the most common inherited ataxia and affects between 3,000–5,000 people in the. .. National Heart, Blood and Lung Institute P.O Box 3 010 5, Bethesda, MD 2 082 4- 010 5 (3 01) 59 2 -8 573; Fax: (3 01) 59 2 -8 563 National Institute of Neurological Disorders and Stroke P.O Box 58 01, Bethesda, MD 2 082 4 (3 01) 49 6-5 7 51 or (80 0) 35 2-9 424 Juli M Berwald 362 Familial spastic paralysis see Hereditary... specific muscles of the ankle and the foot The affected muscles participate in the downward and upward movement of the ankle and the foot The specific muscles include the anterior tibialis, extensor hallucis longus, and the extensor digitorum longus The normal function of these muscles is to allow the toes to swing up from the ground during the beginning of a stride and to control the movement of the foot... within the specimen Other cells can be examined to demonstrate decreased activity of the enzyme beta-glucosidase DNA testing can also reveal the specific mutation responsible for the disease, particularly within Ashkenazi Jewish populations 33 32 31 22 2 21 Marshall syndrome Treatment team 13 p q 1 12 11 11 1 12 GBA: Gaucher disease 21 PKLR: Pyruvate kinase deficiency 22 2 23 Factor V deficiency HPC1:... drop Second, the muscles themselves may be damaged Third, there can be some skeletal or other anatomical abnormality that affects the movement of the ankle or foot A combination of these factors can also be involved, as is the case with the drop foot malady known as Charcot foot Diagnosis Diagnosis of foot drop is based on the visual appearance of the altered behavior of the foot Analysis of blood can... (FARA) 20 01 Jefferson Davis Highway, Suite 209, Arlington, VA 22202 (703) 413 -4 4 68; Fax: (703) 413 -4 467 fara@frda.org Muscular Dystrophy Association 3300 East Sunrise Drive, Tucson, AZ 85 7 18 (520) 52 9-2 000 or (80 0) 572 -1 7 17; Fax: (520) 52 9-5 300 mda@mdausa.org National Ataxia Foundation (NAF) 2600 Fernbrook Lane, Suite 11 9, Minneapolis, MN 55447 (763) 55 3-0 020;... occur because of the inability of the eyes to maintain proper alignment Description Depending on the nature of the cause of foot drop, recovery can be partial or complete Physical therapy and an ankle foot orthotic device worn in the shoe are important aspects of rehabilitation Clinical trials As of mid-2004, there were no clinical trials recruiting participants for the study or treatment of foot drop,... Box 18 426, Kansas City, MO 6 413 3 ( 81 6 ) 313 -2 000 80 85 % of all febrile seizures, and last less than 15 minutes They usually do not recur within 24 hours Complex febrile seizures, which suggest a more serious illness, account for 15 –20% of all cases, last more than 15 minutes, and can recur within 24 hours Children with febrile seizures often lose consciousness and shake, moving limbs on both sides of the. .. Center for Jewish Diseases, Department of Human Genetics, Mount Sinai Medical Center Fifth Avenue at 10 0th Street, New York, NY 10 029 ( 212 ) 65 9-6 774 or ( 212 ) 2 4 1- 6947 382 Rosalyn Carson-DeWitt, MD S Gene therapy Definition Classic gene therapy is the direct use of genetic material in the treatment of disease This usually involves inserting a functional . beat, and leaky heart valves. LetterF.qxd 10 /1/ 04 11 :05 AM Page 357 3 58 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Fabry disease 22 21 11 12 11 13 1 1 2 Renpenning syndrome DMD: Duchenne muscular. 31, Room 88 06, Bethesda, MD 20 81 4 . (3 01) 49 6-5 7 51 or (80 0) 35 2-9 424. <http://www.ninds.nih.gov>. National Organization for Rare Disorders (NORD). PO Box 89 23, New Fairfield, CT 06 81 2 -8 923 con- traction of muscles on both sides of the body, usually fa- cial muscles, trunk, arms, and legs. The force of the LetterF.qxd 10 /1/ 04 11 :05 AM Page 366 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 367 Febrile