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 specific 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 definition, symptoms of TIA resolve within 24 hours, but typically 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 posterior 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 persons per year.
In addition to advancing age, other factors increasing risk of TIA are a history of TIA or stroke in a family member, and black race, thought to be in part because of the 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 incidence rate for any TIA was 68 per 100,000 people. These rates had not changed significantly from those determined during the years 1960 to 1972, suggesting no improvement 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 circulation. The incidence rate of TIA was 41% of the rate of stroke incidence, and it was higher than had been previously reported for other sites throughout the world.
Causes and symptoms
The symptoms of a TIA occur when there is temporary 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 tendency 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 affecting the blood vessels is called arteritis, with specific examples 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 pressure, 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 additional 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 talking 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 indicates 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 symptoms, aid the doctor in diagnosis. Risk factors for atherosclerosis, such as smoking, heart disease, high blood pressure, and family history of heart disease or stroke also suggest the diagnosis of TIA. The specific symptoms associated 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 medical attention, the neurological examination is usually normal, although there may be subtle signs related to previous strokes.
The general physical examination may indicate evidence of atherosclerotic plaques, such as a bruit or abnormal 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 images 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, giving highly detailed cross-sectional images that are very good at detecting small strokes. Magnetic resonance angiography (MRA) uses similar technology to study the arteries in the neck and brain.
The clearest way to see the structure, course, and diameter of brain arteries is with arteriography. Unfortunately, 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 flexible 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 arteries and into the carotid or vertebral artery. An injection of contrast dye through the catheter then allows x-ray images of the arteries in the anterior or posterior circulation.
If the heart is thought to be the source of emboli causing 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 syndromes. Certain procedures may help to rule out other disorders 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 symptoms associated with some seizures may resemble those of a TIA. Other conditions that may be confused with TIA include fainting or migraine headache.
A study reported in the October 2003 issue of Clinical Chemistry describes a blood test which may help to diagnose TIA and to rule out bleeding into the brain, or intracerebral hemorrhage, which can sometimes be confused 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 symptoms as a serious warning of impending neurologic disaster 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, neurologist, cardiologist, and diagnostic technicians all play an important role in TIA management. At stroke centers 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 involved in management of the patient with carotid artery stenosis if surgery is needed to restore blood flow or to bypass 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 usually 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 relationship.
Other antiplatelet agents include dipyridamole; Aggrenox, 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 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 clotting 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 disease 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 accelerates 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) cholesterol 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 occurs naturally in the blood, but in high concentrations it can cause arterial walls to become thicker and scarred, increasing the chances of plaque formation.
Supplementing the diet with B complex vitamins including B6, B12, and folic acid reduces blood levels of homocysteine 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 undesirable 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 exercise 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 improve blood flow and prevent future stroke or TIA. Usually, there is a reduction in artery diameter of more than 70% before surgery is considered. The portion of the artery 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 pressure 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 studies and laboratory research into the biological mechanisms of strokes.
The NINDS is recruiting patients for a study evaluating whether a specific type of carotid artery surgery can reduce subsequent stroke risk in high-risk patients who have recently suffered from stroke or TIA. The surgical procedure, 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 artery 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 information is William J. Powers, MD, 314-362-3317 or wjp@npg.wustl.edu.
Another study for which the NINDS is recruiting patients 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 currently 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 stroke. Contact information is the AstraZeneca Information 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 patient into a false sense of security. After a first TIA, additional episodes may occur later on the same day or at some point in the future. Ironically, patients who recover substantially 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 report in the October 2003 issue of the Annals of Neurology.
TIAs are an ominous sign of increased risk for debilitating 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 person 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 anticoagulants 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 anticoagulant 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 decide 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, regular medical checkups, stopping smoking, avoiding alcohol 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 immediately. 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 warning sign.
Because the symptoms of TIA cannot be distinguished from those of acute stroke, these symptoms must be aggressively treated as soon as possible. Research suggests that emergency care of stroke within the first three to six hours of the first symptom may greatly reduce the disabling, 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 patients 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-DAspartate 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.
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
