GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 857 Transient global amnesia Key Terms Amnesia A general medical term for loss of mem- ory that is not due to ordinary forgetfulness. Amne- sia can be caused by head injuries, brain disease, or epilepsy, as well as by dissociation. Includes: 1) An- terograde amnesia: inability to retain the memory of events occurring after the time of the injury or dis- ease which brought about the amnesic state. 2) Ret- rograde amnesia: inability to recall the memory of events which occurred prior to the time of the injury or disease which brought about the amnesic state. Anterograde amnesia Amnesia for events that oc- curred after a physical injury or emotional trauma but before the present moment. Retrograde amnesia Amnesia for events that oc- curred before a traumatic injury. Valsalva maneuver A strain against a closed air- way combined with muscle tightening, such as hap- pens when a person holds his or her breath and tries to move a heavy object. Most people perform this maneuver several times a day without adverse con- sequences, but it can be dangerous for anyone with cardiovascular disease. Pilots perform this maneuver to prevent black-outs during high-performance flying. centers or other areas of the brain. While the common pre- cipitating factors have been discussed, why these events might trigger a TGA episode are not well understood. Diagnosis TGA is sometimes a difficult condition to diagnose. It is extremely helpful for an observer to contribute in- formation to the physician. Some of the criteria for iden- tifying the event are the impairment of memory, both newly learned and past. There is no loss of consciousness or personal identity. There must be no recent experience of head trauma. Patients must not be epileptics nor can they have experienced any form of a seizure in the last two years. The episode usually lasts for only a few hours and is usually completely resolved by the end of 24 hours. How- ever, rare cases have been documented in which the patient experiences the amnesia for up to a month. Anterograde amnesia, which sometimes also follows head trauma, is a component of TGA. With the antero- grade types of amnesia, the person experiences a memory loss of recent experiences, however, long-term memory persists. Persons with anterograde amnesia often ask ques- tions and, after receiving a response, immediately ask the same question again. Physicians examining a person with amnesia will rule out retrograde amnesia, which is not a part of TGA. Retrograde amnesia is somewhat the oppo- site of anterograde amnesia, whereby the affected person can remember events that occur after the head trauma, but not before. With TGA, a person experiences temporary confusion and lack of memory. The person is disoriented and con- fused, but no loss of personal identity occurs and long- term memories are intact. The person may be frightened and sometimes mildly delusional, but this passes soon and the incidence of recurrence is rare. The initial kinds of tests a physician will request are those that rule out infection, stroke, brain injury, and other physiological conditions. Blood tests such as a CBC with differential help to rule out infection. Another test often performed is running an electrolyte panel. Eletrolytes are common salt minerals such as potassium, calcium, magnesium, etc. Most pro- fessional and amateur athletes are aware of how important proper electrolyte balances are for proper body function- ing. A lowering of electrolytes may cause some of the symptoms described by a person experiencing TGA. Other types of blood tests, including the search for clotting po- tentials, are often performed. To determine whether the pa- tient may be prone to blood clotting, a physician may request a pothrombin time (PT) and activated partial thromboplastin time (aPTT). Quick clotting times could indicate a propensity towards thrombosis (blood clotting), which could lead to stroke. Part of the diagnosis involves conducting several types of imaging tests. The uses of positron emission to- mography (PET) and diffusion-weighted magnetic reso- nance imaging (MRI-DWI) have shown a small degree of ischemia (lack of blood flow) to certain areas of the brain with TGA. However, these same tests have shown con- flicting results in other patients. No definitive tests have been suggested to diagnose the condition. Treatment team Initially, most persons with TGA receive care from a physician in a hospital emergency department. A neurol- ogist usually provides diagnosis and treatment. Both physicians usually order tests to differentiate TGA from other acute neurological events such as a stroke. As there is really no specific treatment for TGA, diagnosis and re- assurance by a physician are important for a person expe- riencing TGA, as well as for family members. LetterT.qxd 10/1/04 11:09 AM Page 857 858 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Transient ischemic attack Treatment After ruling out trauma to the brain from accident, disease, or stroke, most people who have experienced TGA receive very little treatment because the condition is benign. A follow-up appointment with the neurologist is usually recommended. Recovery and rehabilitation Expected average times for recovery are within hours. A TGA patient rarely experiences the symptoms any longer than 24 hours. For most people, the condition lasts only 4–8 hours. Many people even report a shorter dura- tion of one or two hours of disorientation and confusion. They may become frightened, but this is often alleviated with diagnosis and an explanation of the condition. Prognosis The prognosis for TGA patients is excellent. There are no debilitating side effects or any permanent loss of memory. TGA does not portend a serious stroke or simi- lar condition involving the circulatory system. This is one of the reasons that TGA is such a perplexing syndrome for researchers; it is impossible to predict who will experience it. Because repeat occurrences are rare, numerous re-eval- uations by a physician are usually not necessary. Special concerns It is important for people to be aware of the possibil- ity of TGA. Seeking medical help, personal protection, and reassurance are the beneficial to offer someone dis- playing TGA symptoms. Resources BOOKS Adams, R. D., M. Victor, and A. H. Ropper. “Transient Global Amnesia.” In Principles of Neurology. New York: McGraw-Hill, 1997. PERIODICALS Simons, Jon S. and John R. Hodges. “Previous Cases: Transient Global Amnesia.” Neurocases (2000): 6, 211–230. OTHER Tuen, Charles. Neuroland. Transient Global Amnesia. January 4, 2004 (March 24, 2004). <http://neuroland. com/sands/tga.htm>. ORGANIZATIONS National Institute for Neurological Disorders and Stroke. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5761 or (800) 352-9424. <http://www.ninds.nih.gov>. Brook Ellen Hall ❙ Transient ischemic attack Definition A transient ischemic attack (TIA), or “mini-stroke,” is a neurologic episode resembling a stroke but resolving completely within a short period of time. By definition, symptoms of TIA resolve within 24 hours, and symptoms lasting longer than that are termed a stroke. A TIA is caused by brief interruption of the blood supply to a spe- cific brain region, and it may warn of impending stroke. Description Symptoms of TIA begin suddenly and are similar to those of stroke, but leave no residual damage. By defini- tion, symptoms of TIA resolve within 24 hours, but typi- cally they last less than five minutes, or about one minute on average. The symptoms of TIA vary depending on what part of the brain is affected. Anterior circulation TIAs interrupt the blood supply to most of the front part of the brain known as the cerebrum, including the frontal, parietal, and temporal lobes. Symptoms suggesting anterior circulation TIAs may include difficulty speaking or understanding speech. Blindness in one eye suggests amaurosis fugax, a type of TIA caused by decreased blood flow through the carotid artery. This large artery in the neck supplies blood to the optic nerve responsible for vision in the eye on the same side as the artery. Posterior circulation TIAs involve the blood supply to the back part of the brain, including the occipital lobe, cerebellum, and brainstem. Symptoms suggesting poste- rior circulation TIAs include loss of consciousness, dizziness, ringing in the ears, and loss of coordination. Because nerve pathways involved in motor function and sensation pass through multiple brain regions, symptoms of weakness and numbness may occur with either anterior or posterior circulation TIAs. Demographics Every year in the United States, approximately 50,000 individuals experience a TIA, and about one-third of these patients will go on to have a stroke at some point in the future. TIAs rarely affect persons younger than 60 years of age. For individuals 50 to 59 years of age, the incidence of TIA is estimated to be four to eight episodes per 1,000 per- sons per year. In addition to advancing age, other factors increasing risk of TIA are a history of TIA or stroke in a family mem- ber, and black race, thought to be in part because of the LetterT.qxd 10/1/04 11:09 AM Page 858 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 859 Transient ischemic attack higher rates of high blood pressure and diabetes in this group. Although the risk of TIA in older men and women is approximately equal, younger men have a slightly higher risk of stroke than do women of the same age. In a study from the Mayo Clinic reported in Stroke in 1998, the incidence of TIA in Rochester, Minnesota, from 1985 to 1989 was 16 cases per year per 100,000 people aged 45 to 54 years. After adjusting for age and sex, the in- cidence rate for any TIA was 68 per 100,000 people. These rates had not changed significantly from those de- termined during the years 1960 to 1972, suggesting no im- provement in risk factors predisposing to TIA during the intervening time period. In that study, about three-fifths of TIAs affected the anterior circulation, about one-fifth were amaurosis fugax, and the remaining one-fifth affected the posterior circula- tion. The incidence rate of TIA was 41% of the rate of stroke incidence, and it was higher than had been previ- ously reported for other sites throughout the world. Causes and symptoms The symptoms of a TIA occur when there is tempo- rary blockage of an artery supplying part of the brain, causing ischemia, or not enough blood supply to provide the brain with the oxygen and nutrients it needs to function properly. The ischemia does not last long enough to cause permanent damage as would occur with a stroke. When the arterial blockage is reversed, the symptoms of the TIA go away. The underlying causes of the arterial blockage are the same for both TIAs and strokes. The most common cause is a buildup of atherosclerotic plaques, or fatty deposits containing cholesterol, in the wall of the artery. Damage to the arterial lining may cause platelets to stick together around the injured area as a normal part of the clotting and healing process. When cholesterol and other fats are deposited in this area, a plaque forms within the lining of the artery and narrows the channel through which blood passes. This causes blood flow to slow down and become irregular, which increases the natural ten- dency of blood to clot. If a thrombus, or clot, forms at the site of the plaque, it may block the blood vessel at that location. Pieces of the plaque or thrombus may break off and travel downstream to progressively narrower arteries, forming an embolus that can temporarily block these arteries and cause a TIA until it dissolves or is dislodged. In a similar fashion, an embolus moving to the brain from the heart or elsewhere in the body can also cause a TIA. Diseases that increase the tendency of blood to clot may cause TIAs. These include cancer, disorders of blood clotting, sickle cell anemia, and hyperviscosity syndromes in which the blood is very thick. Injury to or inflammation of blood vessels may cause them to narrow or to go into spasm. Inflammation affect- ing the blood vessels is called arteritis, with specific ex- amples including fibromuscular dysplasia, polyarteritis, granulomatous angiitis, systemic lupus erythematosus, and syphilis. In patients with atherosclerotic plaques, conditions which can increase the risk of TIA include low blood pres- sure, high blood pressure, heart disease, migraine headaches, smoking, diabetes, and increasing age. The symptoms of TIA come on suddenly and can be the same as those of a stroke, except that they disappear rapidly, always within 24 hours and usually within five minutes, without leaving any permanent brain injury. Because it is impossible to tell until the symptoms are over whether they were related to a TIA or a stroke, it is crucial to take these symptoms as a serious warning and to seek immediate medical attention. If the blood flow to part of the brain is interrupted for a sufficient length of time, nerve cells supplied by the affected blood vessel may die. Any delay in starting stroke treatment can result in addi- tional irreversible brain damage or even death. Symptoms of either TIA or stroke vary depending on what brain region is affected. Numbness, weakness, or a heavy sensation on one side of the face, arm, and/or leg usually represents an anterior circulation stroke or TIA, whereas these symptoms on both sides suggest posterior circulation stroke or TIA. Confusion, garbled speech, or other difficulty in talk- ing or in understanding speech may occur with decreased anterior circulation affecting the left half of the brain (in right-handed individuals). Difficulty with vision in one eye, often described as a curtain descending over the eye, is a classic symptom of amaurosis fugax. On the other hand, decreased vision involving both eyes usually indi- cates a posterior circulation disturbance. Other symptoms of posterior circulation stroke or TIA may include loss of consciousness, dizziness, loss of balance and coordination, and vertigo (a sensation that the person or the room is moving). A sudden, severe headache with no known cause may occur with any stroke or TIA. Diagnosis The characteristic history or description of a TIA, with its sudden onset, rapid resolution, and typical symp- toms, aid the doctor in diagnosis. Risk factors for athero- sclerosis, such as smoking, heart disease, high blood pressure, and family history of heart disease or stroke also LetterT.qxd 10/1/04 11:09 AM Page 859 860 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Transient ischemic attack suggest the diagnosis of TIA. The specific symptoms as- sociated with the TIA will help the physician determine which portion of the brain and which blood vessels were involved. By the time the person who had a TIA reaches med- ical attention, the neurological examination is usually nor- mal, although there may be subtle signs related to previous strokes. The general physical examination may indicate evi- dence of atherosclerotic plaques, such as a bruit or abnor- mal sound heard with the stethoscope placed over the carotid artery in the neck. Although an audible bruit may be present in the early stages of arterial narrowing when blood flow is turbulent, the sound may disappear when blood flow decreases further. Looking at the back of the eye through an instrument called an ophthalmoscope, the doctor may see cholesterol emboli in the tiny arteries of the retina. Carotid ultrasonography helps determine if there is narrowing, also known as stenosis, or plaque formation in the carotid arteries. In this painless and harmless test, a transducer sends high-frequency sound waves into the neck, and deflections of these waves are analyzed as im- ages on a screen. Computed tomography (CT) scanning creates cross- sectional x-ray images of the brain. The CT may show strokes, but often fails to give sufficiently detailed views of the blood vessels. To improve blood vessel visualization, computerized tomography angiography (CTA) scanning uses injection of a contrast dye into a blood vessel. Magnetic resonance imaging (MRI) uses a strong magnetic field to align water molecules in the brain, giv- ing highly detailed cross-sectional images that are very good at detecting small strokes. Magnetic resonance an- giography (MRA) uses similar technology to study the ar- teries in the neck and brain. The clearest way to see the structure, course, and di- ameter of brain arteries is with arteriography. Unfortu- nately, this test is associated with a low rate of serious complications including bleeding, stroke, and even death. Therefore, it should be performed only if the results would change patient management, for example in guiding the decision of whether surgery is needed. In this test, a radiologist inserts a thin catheter, or flex- ible tube, through a small groin incision into the large femoral artery supplying the leg. Using x-ray guidance, the radiologist threads the catheter through the major ar- teries and into the carotid or vertebral artery. An injection of contrast dye through the catheter then allows x-ray im- ages of the arteries in the anterior or posterior circulation. If the heart is thought to be the source of emboli caus- ing the TIA, testing may include an electrocardiogram and Holter monitoring to detect any changes in heart rhythm, or arrhythmias, occurring during the course of a normal day’s activities. After the technician attaches electrodes to the patient’s chest, the patient can go home overnight with a portable tape recorder. The recordings are later analyzed for arrthymias, during which emboli might tend to leave the heart and cause TIAs. Transesophageal echocardiography (TEE) allows clear, detailed ultrasound images of blood clots within the heart which could act as a source of emboli, but which might be missed by traditional echocardiography. During this test, the doctor passes a flexible probe containing a transducer into the esophagus, which is located directly behind the heart. Other tests may determine if there are any underlying conditions causing TIA, including blood tests for arteritis, sickle cell anemia, diabetes, and hyperviscosity syn- dromes. Certain procedures may help to rule out other dis- orders that may cause symptoms resembling those of TIA. For example, an electroencephalogram (EEG) may determine if there is abnormal electrical activity of the brain diagnostic of a seizure disorder, because the symp- toms associated with some seizures may resemble those of a TIA. Other conditions that may be confused with TIA in- clude fainting or migraine headache. A study reported in the October 2003 issue of Clini- cal Chemistry describes a blood test which may help to di- agnose TIA and to rule out bleeding into the brain, or intracerebral hemorrhage, which can sometimes be con- fused with TIA. The test analyzes antibodies to specialized receptors involved in communication between nerve cells. These N-methyl-D-aspartate receptor antibodies are thought to be key markers of nerve cell damage caused by lack of blood flow to the brain. Treatment team Because time is so critical in preventing damage from acute stroke, and because it is impossible to tell right away whether symptoms of brain ischemia are caused by TIA or acute stroke, the treatment team begins with those who are first aware of the symptoms. The patient and their family must take these symp- toms as a serious warning of impending neurologic disas- ter and seek immediate medical attention by calling 911, rather than by hoping the symptoms will go away. Public awareness of stroke symptoms and their significance is therefore just as important as knowing that crushing chest pain needs to be evaluated right away in the emergency room to rule out or to treat heart attack. The emergency medical technician, internist, neu- rologist, cardiologist, and diagnostic technicians all play an important role in TIA management. At stroke centers LetterT.qxd 10/1/04 11:09 AM Page 860 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 861 Transient ischemic attack Key Terms Amaurosis fugax A type of TIA caused by de- creased blood flow through the carotid artery, char- acterized by blindness or decreased vision in one eye. Anterior circulation The blood supply to most of the front part of the brain known as the cerebrum, in- cluding the frontal, parietal, and temporal lobes. Antiplatelet agents Drugs that reduce the tendency of platelets to clump together, used to reduce the risk of TIA or stroke. Atherosclerotic plaques Fatty deposits containing cholesterol that build up in the wall of arteries, caus- ing narrowing and increased risk of TIA. Atrial fibrillation A condition in which part of the heart is enlarged and beats irregularly, which may cause emboli to travel to the brain. Bruit An abnormal sound heard with the stetho- scope placed over the carotid artery in the neck, sug- gesting decreased blood flow through the vessel. Carotid angioplasty (stenting) Surgery for carotid artery stenosis using a balloon-like device to open the clogged artery, followed by placing a stent, or small wire tube, within the artery to keep it open. Carotid artery A large artery in the neck supplying blood to the brain. Carotid endarterectomy Surgery for carotid artery stenosis in which the atherosclerotic plaques are re- moved through a neck incision. Carotid ultrasonography A painless and harmless test using high-frequency sound waves to determine if there is narrowing or plaque formation in the carotid arteries. Embolus A fragment of plaque or thrombus that breaks off from its original location and travels down- stream to progressively narrower arteries, where it may block the vessel. Ischemia Reduced blood supply to the brain, pre- venting it from getting the oxygen and nutrients it needs to function properly. Posterior circulation The blood supply to the back part of the brain, including the occipital lobe, cere- bellum, and brainstem. Stenosis Narrowing of an artery which reduces blood flow through the vessel. Thrombus A blood clot, which may form at the site of an atherosclerotic plaque and block the artery. Transesophageal echocardiography (TEE) A test using sound waves to reveal blood clots or other ab- normalities within the heart that might be missed by traditional echocardiography. and larger hospitals, members of a specialized stroke team designated for rapid response may be the first health care professionals to see the patient with TIA. Other providers who may become involved in helping the patient reduce their risk factors for TIA and stroke may include nutritionists, dieticians, and nurses specializing in lifestyle counseling for issues such as quitting smoking. Neurosurgeons or vascular surgeons will become in- volved in management of the patient with carotid artery stenosis if surgery is needed to restore blood flow or to by- pass the obstruction. Treatment Ideally, patients with symptoms suggesting TIA or acute stroke should be evaluated within 60 minutes. Even if the symptoms resolve by the time the patient reaches the emergency room, prompt evaluation is needed to identify the specific cause of the TIA and to begin appropriate treatment. Patients who have had a TIA within 48 hours are usu- ally admitted to the hospital for observation, diagnostic testing, and treatment planning in a controlled situation, in case the TIA recurs or a stroke develops. If there are any medical conditions causing the TIA, such as sickle cell anemia or arteritis, these should be treated. Drugs that reduce the tendency of platelets to clump together, known as antiplatelet agents, may reduce the risk of future TIA or stroke. Within this drug class, aspirin is the most often prescribed, least expensive, and safest treatment in terms of possible side effects. Although the optimal dose of aspirin to prevent stroke and TIA has long been debated, there may not be a clear dose-response re- lationship. Other antiplatelet agents include dipyridamole; Ag- grenox, which is a combination of low-dose aspirin and dipyridamole; clopidogrel (Plavix), which may be given alone or together with aspirin; and ticlopidine (Ticlid). If the medical evaluation reveals a condition called atrial fibrillation, in which part of the heart is enlarged and LetterT.qxd 10/1/04 11:09 AM Page 861 862 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Transient ischemic attack beats irregularly, causing emboli to travel to the brain, blood thinners or anticoagulants may be prescribed. These drugs inhibit proteins involved in blood clotting but do not affect platelet function. Warfarin (Coumadin) is the best known drug of this class for long-term use, whereas heparin is typically given only for a limited period, usually while the patient is still in the hospital. Because anticoagulants reduce blood clot- ting and hence TIAs, they can also cause serious bleeding. Drug levels must therefore be monitored with blood tests usually done at least once weekly. Atrial fibrillation or other conditions in which the heart beats erratically, known as arrythmias, may be treated with antiarrhythmic agents that stabilize electrical impulses in the heart to allow a more regular heart beat. A vital part of TIA treatment is to reduce treatable risk factors for stroke, including cardiovascular disease, smoking, diabetes, hyperlipidemia, and obesity. Heart dis- ease caused by previous heart attack, abnormalities of the heart valve, and arrythmias may prevent the heart from pumping blood efficiently. Cigarette smoking increases blood clotting and ac- celerates development of atherosclerotic plaques. Nicotine makes the heart work harder by increasing heart rate and blood pressure, and carbon monoxide in cigarette smoke decreases the amount of oxygen reaching the brain. In a similar fashion to smoking, diabetes makes atherosclerosis worse and speeds its progression, as do high blood levels of low-density lipoprotein (LDL) cho- lesterol and low levels of high-density lipoprotein (HDL) cholesterol. Increased homocysteine level is another risk factor for atherosclerosis that may be treatable. This amino acid oc- curs naturally in the blood, but in high concentrations it can cause arterial walls to become thicker and scarred, in- creasing the chances of plaque formation. Supplementing the diet with B complex vitamins in- cluding B6, B12, and folic acid reduces blood levels of ho- mocysteine and may protect against heart disease, but it is not yet known whether this will reduce stroke risk. High blood pressure, heart disease, diabetes, and un- desirable cholesterol levels may require treatment with specific drugs, or they may be controlled by lifestyle changes alone. Whether or not medications are needed, lifestyle changes should include stopping smoking, weight control, avoiding heavy drinking, and eating a balanced diet low in saturated fats, salt, and sugar and high in vegetables, fruits, and fiber. Nutritional or lifestyle counseling, structured ex- ercise programs, and/or support groups may help patients achieve these goals. If carotid artery testing reveals moderate or severe narrowing or stenosis, surgery may be indicated to im- prove blood flow and prevent future stroke or TIA. Usu- ally, there is a reduction in artery diameter of more than 70% before surgery is considered. The portion of the ar- tery downstream from the site of blockage also needs to be relatively free of narrowing or obstruction for surgery to be successful. Carotid endarterectomy involves opening the artery through a neck incision, removing atherosclerotic plaques, then closing the artery. In some cases, carotid angioplasty or stenting may be a viable alternative. Using a balloon- like device, the surgeon opens the clogged artery and then places a stent, or small wire tube, within the artery to keep it open. According to a study by the Carotid Endarterectomy Trialists’ Collaboration, published in the November 2003 issue of Stroke, blood pressure control needs to be more closely regulated in patients with carotid stenosis than in other patients. Overly aggressive reduction of blood pres- sure in these patients may actually decrease blood flow through the obstructed artery. Clinical trials The National Institutes of Neurological Disorder and Stroke (NINDS) is the primary sponsor of research on stroke and TIA in the United States, including patient stud- ies and laboratory research into the biological mechanisms of strokes. The NINDS is recruiting patients for a study evaluat- ing whether a specific type of carotid artery surgery can re- duce subsequent stroke risk in high-risk patients who have recently suffered from stroke or TIA. The surgical proce- dure, known as extracranial-intracranial bypass surgery, involves removing an artery from the scalp, making a small hole in the skull, and then connecting the scalp ar- tery to a brain artery within the skull. By circumventing the carotid artery obstruction in the neck, the rationale is to provide more blood flow to the brain. Contact informa- tion is William J. Powers, MD, 314-362-3317 or wjp@ npg.wustl.edu. Another study for which the NINDS is recruiting pa- tients is the “Aspirin or Warfarin to Prevent Stroke” study, designed to determine whether aspirin or warfarin is more effective in preventing stroke in patients with narrowing of one of the arteries in the brain. Contact information is Harriet Howlett Smith, RN, 1-404-778-3153 or hhowlet@ emory.edu. The pharmaceutical company AstraZeneca is cur- rently recruiting patients for a study testing the safety and effectiveness of their drug NXY-059 when given within six hours of limb weakness suggesting TIA or acute LetterT.qxd 10/1/04 11:09 AM Page 862 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 863 Transient ischemic attack stroke. Contact information is the AstraZeneca Informa- tion Center, 800-236-9933. Prognosis A single TIA is by definition very brief, and recovery is complete, but that good outcome should not lull the pa- tient into a false sense of security. After a first TIA, addi- tional episodes may occur later on the same day or at some point in the future. Ironically, patients who recover sub- stantially within 24 hours of acute brain ischemia may be at greater risk of subsequent neurological deterioration than those who take longer to recover, according to a re- port in the October 2003 issue of the Annals of Neurology. TIAs are an ominous sign of increased risk for debil- itating stroke. Although most strokes are not preceded by TIAs, approximately one-third of patients who have a TIA will have an acute, major stroke days, weeks, or even months later. About half of the time, the stroke occurs within one year of the TIA. Stroke risk is higher in a per- son who has had one or more TIAs than in someone of the same age and sex who has never suffered a TIA. Even among patients given antiplatelet agents or an- ticoagulants after a TIA or stroke, 10% will have a stroke within 90 days. Stroke can have devastating consequences, as it is the third leading cause of death and the primary cause of disability in the United States. Besides recurrent TIA and stroke, complications of TIA may include injury from falls, if the patient becomes weak or loses balance with the TIA, or bleeding from an- ticoagulant drugs used to treat the TIA. Although a single episode of TIA is not fatal, the TIA reflects generalized atherosclerosis. The leading cause of death after a TIA is coronary artery disease causing a heart attack. For that reason, a patient with TIA should have a heart evaluation to determine cardiovascular risk and de- cide on management of potential coronary artery disease. Special concerns Preventing TIA is a worthwhile goal, especially since the same strategies will help prevent heart disease, stroke, high blood pressure, and diabetes. Healthy lifestyle, reg- ular medical checkups, stopping smoking, avoiding alco- hol and illegal drugs, regular exercise, and nutritionally sound diet all have additional benefits beyond their effects on cardiovascular and stroke risk. When the symptoms of TIA strike, it is no time to be brave or stoic. It is a medical emergency demanding that 911 or other local emergency number be called immedi- ately. Even if the symptoms resolve, they are an urgent warning that must not be ignored, and require immediate attention to prevent stroke. Having a TIA may in some ways be a blessing in disguise if the warning is heeded, as most patients who suffer a stroke do so without this warn- ing sign. Because the symptoms of TIA cannot be distin- guished from those of acute stroke, these symptoms must be aggressively treated as soon as possible. Research sug- gests that emergency care of stroke within the first three to six hours of the first symptom may greatly reduce the dis- abling, long-term effects of stroke. Sadly, the average time elapsed between experiencing the first symptoms of stroke and seeking medical attention is 13 hours, and 42% of pa- tients wait as long as 24 hours. Recognizing the symptoms of stroke and obtaining immediate emergency care can prevent disability and even death. Resources PERIODICALS Adams, Harold P. Jr., Robert J. Adams, Thomas Brott, et al. “Guidelines for the Early Management of Patients with Ischemic Stroke.” Stroke 34 (2003): 1056-1083. Brown, R. D. Jr., G. W. Petty, W. M. O’Fallon, et al. “Incidence of Transient Ischemic Attack in Rochester, Minnesota, 1985-1989.” Stroke 29, no. 10 (October 1998): 2109-13. Dambinova, S. A., G. A. Khounteev, G. A. Izykenova, et al. “Blood Test Detecting Autoantibodies to N-Methyl-D- Aspartate Neuroreceptors for Evaluation of Patients with Transient Ischemic Attack and Stroke.” Clinical Chemistry 49, no. 10 (October 2003): 1752-62. Goldstein, Larry B., Robert Adams, Kyra Becker, et al. “Primary Prevention of Ischemic Stroke.” Circulation 32 (2001): 280-299. Johnson, E. S., S. F. Lanes, C. E. Wentworth, et al. “A Metaregression Analysis of the Dose-Response Effect of Aspirin on Stroke.” Archives of Internal Medicine 159 (June 14, 1999): 1248-53. Johnston, S. C., E. C. Leira, M. D. Hansen, and H. P. Adams Jr. “Early Recovery After Cerebral Ischemia Risk of Subsequent Neurological Deterioration.” Annals of Neurology 54, no. 4 (October 2003): 439-44. Rothwell, P. M., S. C. Howard, and J. D. Spence. “Relationship Between Blood Pressure and Stroke Risk in Patients with Symptomatic Carotid Occlusive Disease.” Stroke 34, no. 11 (November 2003): 2583-90. Scott, P. A., and R. Silbergleit. “Misdiagnosis of Stroke in Tissue Plasminogen Activator-Treated Patients: Characteristics and Outcomes.” Annals of Emergency Medicine 42, no. 5 (November 2003): 611-18. WEBSITES American Heart Association. <http://www.americanheart.org>. Clinical Trials. <http://www.clinicaltrials.gov/ct/action/ GetStudy>. eMedicine. <http://www.emedicine.com/emerg/byname/ transient-ischemic-attack.htm>. Mayo Clinic. <http://www.mayoclinic.com/invoke.cfm? id=DS00220>. LetterT.qxd 10/1/04 11:09 AM Page 863 864 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Transverse myelitis National Institute of Neurological Disorders and Stroke. NIH Neurological Institute. <http://www.ninds.nih.gov/ health_and_medical/disorders/tia_doc.htm>. National Stroke Association. <http://www.stroke.org>. U.S. National Library of Medicine. <http://www.nlm.nih.gov/ medlineplus/transientischemicattack.html>. Laurie Barclay Transmissible spongiform encephalopathies see Prion diseases ❙ Transverse myelitis Definition Transverse myelitis is an inflammation of the full width of the spinal cord that disrupts communication to the muscles, resulting in pain, weakness, and muscle paralysis. Description The symptoms of transverse myelitis are due to dam- age and/or destruction of the myelin sheath, the fatty white covering of nerve fibers that serves both to insulate the nerve fibers and to speed nervous conduction along them. Areas of missing myelin and areas of scarring along the affected nerves result in slowed or disrupted nervous con- duction and muscle dysfunction. Transverse myelitis may have a gradual onset or a re- markably quick onset. Symptoms of transverse myelitis may reach their peak within 24 hours of onset for some pa- tients (considered the hyperacute form of the condition). Other patients experience a more gradual increase in symp- tom severity, with peak deficits occurring days (acute form of transverse myelitis) to weeks (subacute form of trans- verse myelitis) after the initial symptoms first presented. Patients with the quicker onset form and who experience more severe initial symptoms tend to have more compli- cations and a greater likelihood of permanent disability. Transverse myelitis often occurs in people who are re- covering from a recent viral illness, including chickenpox, herpes simplex, cytomegalovirus, Epstein-Barr, influenza, and measles. When this association is present, the condi- tion often follows the more sudden hyperacute course. Demographics In the United States, there are only about 4.6 cases of transverse myelitis per million people per year. In the Unites States, about 1,400 people a year develop trans- verse myelitis; about 33,000 people in the United States have disabilities due to transverse myelitis. Individuals of all ages can be affected; reports have been made of pa- tients ranging from the age of six months to 88 years. The peak ages appear to be 10-19 years and 30-39 years. About 30-60% of all cases of transverse myelitis occur in individuals who have just recovered (within the previous 8 weeks) from a relatively minor viral infection. Recent vaccination is another risk factor for transverse myelitis. Other individuals at higher risk for transverse myelitis include patients with preexisting autoimmune dis- eases (such as multiple sclerosis, systemic lupus erythe- matosus, or Devic’s disease); patients with recent histories of infections such as Lyme disease, tuberculosis, or syphilis; and intravenous drug abusers who inject heroine and/or amphetamines. Causes and symptoms Although the specific mechanism of transverse myelitis has not been delineated, the basic cause is thought to be an autoimmune response. Under normal conditions, the immune system reacts to the presence of a viral or bac- terial illness by producing a variety of immune cells de- signed to attack the invading viruses or bacteria. Unfortunately, in the case of transverse myelitis, the im- mune cells mistake the body’s own tissues as foreign, and attack those tissues as well. These errant immune cells are called autoantibodies; that is, antibodies that actually at- tack the body’s own tissues. Symptoms of transverse myelitis can develop over several hours, days, or weeks. The types of symptoms and their severity are dependent on the area of the spinal cord affected. When the transverse myelitis occurs in the neck, the arms and legs will be affected; when the transverse myelitis occurs lower in the back, only the legs will be affected. Symptoms of transverse myelitis often begin with back pain, headache, achy muscles, flu-like symptoms, and stiff neck. Over hours or days, symptoms expand to in- clude loss of sensation, numbness, dysesthesia (sensations of burning, lightning flashes of pain, prickly pinpoints), muscle weakness, partial or complete paralysis, and im- paired bladder and bowel function. Symptoms of weak- ness and then paralysis usually begin in the feet, ascending over time to the legs, and then to the trunk and arms when the lesion is in the neck. Symptoms are bilateral, meaning that they affect both sides of the body simultaneously. Over time, muscles become increasingly tight and spastic, further limiting mobility. When the muscles of respiration are affected, breathing can be compromised. Diagnosis Diagnosis involves meeting specific symptom crite- ria, as well as demonstrating spinal cord involvement with MRI scanning and examination of cerebrospinal fluid. LetterT.qxd 10/1/04 11:09 AM Page 864 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 865 Transverse myelitis Key Terms Myelin The fatty white substance that wraps around nerve fibers, providing insulation and speed- ing electrical conduction of nerve impulses along the fibers. Symptom criteria include the evolution of symptoms peak- ing over four hours to 21 days, with symptoms clearly traceable to spinal cord dysfunction, and including muscle weakness or paralysis and sensory defects such as numb- ness occurring on both sides of the body. The presence of a spinal cord tumor or another condition that is exerting pressure on the spinal cord, vitamin B12 deficiency, or a history of radiation therapy to or cyclophosphamide in- jection into the spinal cord excludes the possibility of a di- agnosis of transverse myelitis. Treatment team The mainstay of the treatment team for patients with transverse myelitis will be a neurologist. A rheumatolo- gist, specializing in autoimmune illness, may also be con- sulted. In order to regain maximum function, a physiatrist (a physician specializing in rehabilitation medicine) may be required, as well as the services of both physical and occupational therapists. Treatment Treatment is aimed at calming the immune response that caused the spinal cord injury in the first place. To this end, high doses of intravenous and then oral steroids are the first-line treatments for transverse myelitis. In se- vere cases of transverse myelitis, the very potent im- munosupressant cyclophosphamide may be administered. In patients with moderately severe transverse myelitis unimproved by five to seven days of steroid treatment, a procedure called plasma exchange may be utilized. This procedure involves removing blood from the patient, and separating it into the blood cells and the plasma (fluid). The blood cells are then mixed into a synthetic plasma re- placement solution and returned to the patient. Because the immune cells are in the plasma, this effectively re- moves the damaging immune cells from the body, hope- fully quelling the myelin destruction. Treatments to reverse the process involved in trans- verse myelitis should be attempted for about six months from the onset of the condition. After that point, treatment efforts should be shifted to effective rehabilitation. Pain and other dysesthesias (uncomfortable sensa- tions, such as burning, pins-and-needles, or electric shock sensations) are treated with a variety of medications, such as gabapentin, carbamazepine, nortriptyline, or tra- madol. Another treatment for pain and dysesthesias is tran- scutaneous electrical nerve stimulation, called TENS therapy. This involves the use of a device that stimulates the painful area with a small electrical pulse, which seems to disrupt the painful sensation. Because constipation and urinary retention are fre- quent problems in the patient with transverse myelitis, medications may be necessary to treat these problems. Oxybutinin, hyoscyamine, tolterodine, and propantheline can treat some of the bladder problems common to trans- verse myelitis patients. When urinary retention is an issue, sacral nerve stimulation may help the patient avoid re- peated bladder catheterizations. Dulcolax, senekot, and bisacodyl can help improve constipation. Tight, spastic muscles may improve with baclofen, ti- zanidine, or diazepam. When these medications are given orally, they sometimes result in untenable side effects. Recovery and rehabilitation Rehabilitation has both short- and long-term compo- nents. Even in the earliest stages of the condition, passive exercises should be performed. Passive exercises involve a physical therapist putting a particular muscle group or joint through range of motion and strengthening exercise, even when the patient cannot assist in its movement. Dur- ing the recovery phase, the patient should be given pro- gressive exercises to improve strength and range of motion, and to attempt to regain mobility. Physical thera- pists can also be helpful with pain management, using such techniques as heat and/or cold application, nerve stimulation, ultrasound, and massage. Physical therapy may also be helpful to retrain muscles necessary for im- proved bladder and bowel control and relief of constipa- tion and urinary retention. Occupational therapists can help the patient relearn old skills for accomplishing the ac- tivities of daily living, or strategize new techniques that take into account the patient’s disabilities. Braces or assistive devices such as walkers, wheel- chairs, crutches, or canes may be necessary during reha- bilitation or permanently. Prognosis The area on the spinal cord affected by transverse myelitis will determine the individual’s level of function- ing. The higher-up the lesion, the greater the disability. High cervical lesions will require complete care; as lesions drop lower and lower in the cervical, thoracic, or lumbar region, the chance to participate in self-care or even to ambulate increases. LetterT.qxd 10/1/04 11:09 AM Page 865 866 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Traumatic brain injury Recovery from transverse myelitis seems to follow the law of thirds: about a third of all patients make a full recovery from their level of functioning at the condition’s peak, a third make a partial recovery, and a third make no recovery at all. Most patients make a good or even a com- plete recovery within one to three months of the onset of their symptoms. Patients who have not begun to improve by month three after symptom onset usually will not ac- complish a complete recovery from their disability. Fac- tors that do not bode well include abrupt onset of symptoms, prominent pain upon onset, and severe dis- ability and deficit at the peak of the condition. Resources BOOKS Aminoff, Michael J. “Inflammatory disorders affecting the spinal cord.” In Cecil Textbook of Internal Medicine, edited by Lee Goldman, et al. Philadelphia: W. B. Saunders Company, 2000. Schneider, Deborah Ross. “Transverse Myelitis.” In Essentials of Physical Medicine and Rehabilitation, 1st ed., edited by Walter R. Frontera. Philadelphia: Hanley and Belfus, 2002. PERIODICALS Transverse Myelitis Consortium Working Group. “Proposed diagnostic criteria and nosology of acute transverse myelitis.” In Neurology 59, no. 4 (27 August 2002): 499–505 WEBSITES National Institute of Neurological Disorders and Stroke (NINDS). NINDS Transverse Myelitis Information Page. July 1, 2001 (June 10, 2004). <http://www.ninds.nih.gov/ health_and_medical/disorders/transversemyelitis_ doc.htm>. ORGANIZATIONS Transverse Myelitis Association. 1787 Sutter Parkway, Powell, OH 43065. (614) 766-1806. ssiegel@myelitis.org. <http://www.myelitis.org/index.html>. The Johns Hopkins Transverse Myelitis Center. 600 N. Wolfe Street, Baltimore, MD 21287. (410) 502-7099; Fax: (410) 502-6736. dkerr@jhmi.edu. <http://www.hopkins medicine.org/jhtmc/>. Rosalyn Carson-DeWitt, MD ❙ Traumatic brain injury Definition Traumatic brain injury (TBI) is the result of physical trauma to the head causing damage to the brain. This dam- age can be focal, or restricted to a single area of the brain, or diffuse, affecting more than one region of the brain. By definition, TBI requires that there be a head injury, or any physical assault to the head leading to injury of the scalp, skull, or brain. However, not all head trauma is associated with TBI. Description TBI is sometimes known as acquired brain injury. The least severe and most common type of TBI is termed a concussion, which is technically defined as a brief loss of consciousness after a head injury without any physical ev- idence of damage on an imaging study such as a CT or MRI scan. In common parlance, concussion may refer to any minor injury to the head or brain. Symptoms, complaints, and neurological or behav- ioral changes following TBI depend on the location(s) of the brain injury and on the total volume of injured brain. Usually, TBI causes focal brain injury involving a single area of the brain where the head is struck or where an ob- ject such as a bullet enters the brain. Although damage is typically worst at the point of direct impact or entry, TBI may also cause diffuse brain injury involving several other brain regions. Closed head injury refers to TBI in which the head is hit by or strikes an object without breaking the skull. In a penetrating head injury, an object such as a bullet fractures the skull and enters brain tissue. Diffuse brain damage associated with closed head in- jury may result from back-and-forth movement of the brain against the inside of the bony skull. This is some- times called coup-contrecoup injury. “Coup,” or French for “blow,” refers to the brain injury directly under the point of maximum impact to the skull. “Contrecoup,” or French for “against the blow,” refers to the brain injury op- posite the point of maximum impact. For example, coup-contrecoup injury may occur in a rear-end collision, with high speed stops, or with violent shaking of a baby, because the brain and skull are of dif- ferent densities, and therefore travel at different speeds. The impact of the collision causes the soft, gelatinous brain tissue to jar against bony prominences on the inside of the skull. Because of the location of these prominences and the position of the brain within the skull, the frontal lobes (be- hind the forehead) and temporal lobes (underlying the temples) are most susceptible to this type of diffuse dam- age. These lobes house major brain centers involved in speech and language, so problems with communication skills often follow closed head injuries of this type. Depending on which areas of the brain are injured, other symptoms of closed head injury may include diffi- culty with concentration, memory, thinking, swallowing, LetterT.qxd 10/1/04 11:09 AM Page 866 [...]... P.O Box 27 4, Millboro, VA 24 460 (540) 8 6 2- 9437; Fax: (540) 8 6 2- 9 485 ncpoa@cfw.org National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 31 Centre Dr., Rm 4Co2 MSC 23 50, Bethesda, MD 20 8 9 2- 2350 (301) 49 6 -8 190 or (87 7) 22 6 426 7 info@mail.nih.gov American Chronic Pain Association (ACPA) P.O Box 85 0, Rocklin, CA 9567 7-0 85 0 (916)... impinging of an artery The nerve damage that results in ulnar neuropathy can involve the main body of the nerve, the branching region at the end of the nerve known as the axon (which is involved in the movement of the nerve impulse to the adjacent nerve), and the protective myelin coating around the nerve When the main body of the nerve is involved, the problem is usually a block in the passage of the impulse... Organisation of Tuberous Sclerosis Associations) ORGANIZATIONS Tuberous Sclerosis Alliance 80 1 Roeder Road, Suite 750, Silver Spring, MD 20 910 30 1-5 6 2- 989 0 or 80 0 -2 2 5 68 72; Fax: 30 1-5 6 2- 987 0 ntsa@ntsa.org The Tuberous Sclerosis Association, U.K Janet Medcalf, P.O Box 9644, Bromsgrove, England B61 OFP +44 (0)1 527 87 189 8; Fax: +44 (0)1 527 5794 52 . against bony prominences on the inside of the skull. Because of the location of these prominences and the position of the brain within the skull, the frontal lobes (be- hind the forehead) and temporal. structure is part of the basal ganglia, a part of the brain involved in the con- trol of willed (voluntary) movement of the muscles. Parkinson’s disease A slowly progressive disease of that destroys. increasing risk of TIA are a history of TIA or stroke in a family mem- ber, and black race, thought to be in part because of the LetterT.qxd 10/1/04 11:09 AM Page 85 8 GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 85 9 Transient