Transient ischemic attacks (TIAs), defined as neurologic deficits with complete clinical resolution within 24 hours, usually last only 10 to 15 minutes. The deficits generally occur when platelet aggregates form on atheromatous plaques, cause embolization, and temporarily occlude a distal cerebral or ophthalmic arteriole. Stroke from occlusive carotid disease is preceded by TIAs in 50% to 75% of patients. Up to 64% of patients with complete resolution of symptoms within 24 hours still have radiographic evidence of infarction by computed tomography (CT) scan; the distinction, therefore, between TIA, cerebral infarct with transient signs and symptoms, and stroke has become increasingly difficult with the use of both CT scans and magnetic resonance imaging (MRI).

• Emboli of platelets and fibrin or atheromatous plaques or emboli from cardiac lesions secondary to mitral valve pathology; ventricular aneurysm, clot, or dyskinesia; atrial fibrillation or clot; interarterial shunts—temporarily occlude a distal cerebral or ophthalmic artery
• Carotid stenosis with >70% occlusion in conjunction with transient hypotension
• Coagulation abnormalities (especially in young people); antiphospholipid antibodies; protein C or S deficiency; oral contraceptives; rare association with stroke which is more likely to occur when other co-founding risk factors exist such as HTN, smoking, and/or age > 35
• Chlamydia pneumoniae IgG antibody titers is associated with stroke and TIA

Non-modifiable:

• > 65—risk doubles each decade over 65 years of age
• Men > women
• Family history
• Race-ethnicity: African-American and Japanese-American > Caucasian

Modifiable:

• Hypertension
• Diabetes
• History of stroke
• Cardiac disease, including atrial fibrillation
• Hyperlipidemia/hypercholesterolemia
• Smoking
• Heavy alcohol consumption
• Physical inactivity

Carotid symptoms, more focal:

• Transient monocular blindness
• Dysphasia, aphasia
• Amaurosis fugax
• Hemiparesis, clumsiness, weakness
• Carotid bruit

Vertebrobasilar symptoms, more general:

• Visual blurring—binocular
• Vertigo
• Paresthesias
• Ataxia
• Dysarthria
• Diplopia
• Weakness
• Loss of consciousness
• Transient global amnesia

Brain stem involvement:

• Headache
• Vomiting
• Ataxia

• Thrombocytosis
• Mass lesions—e.g. meningiomas
• Subdural hematomas
• Cerebral hemorrhage
• Focal seizures
• Migraine
• Protruding cervical disk
• Infection—e.g. endocarditis, sepsis; rarely, cryptococcal meningitis or meningoencephalitis; syphilis
• Hypoglycemia
• Drug use—e.g. cocaine, crack, amphetamines, LSD, PCP, heroin; sharing unclean needles may precipitate infections (see above)

Focal deficits should be noted, and accurate neurologic examination performed. Airway, breathing, circulation, vital signs as well as presence of heart murmurs, dysrhythmias, and hypertension require immediate assessment. Carotid arteries are gently auscultated for presence of a bruit. The head is examined for trauma and the arms for signs of needle tracks. Signs of systemic disease should be evaluated as well, including petechiae and ecchymosis.

• Blood sugar evaluation
• Complete blood count (CBC) with platelet count (identifies thrombocytosis, thrombocytopenia); coagulation studies; toxicology screening
• Blood cultures should be considered in appropriate clinical setting
• VDRL should be considered

• See etiology

• CT scan, noncontrast, differentiates hemorrhagic from ischemic infarction (ischemic strokes not visualized for at least six hours – 5% visualized by CT within 12 hours; 50% between 24 and 48 hours; 90% within seven days); identifies abscesses, tumors, hematomas
• MRI identifies ischemic infarcts faster than CT scans; able to show silent or prior infarction
• Magnetic resonance angiography (MRA) for large-vessel occlusion at base of skull; images blood flow
• Angiogram detects subtle abnormalities, stenosis (distinguishes 95% from complete occlusion), occlusion, subarachnoid hemorrhage, aneurysm; screen prior to endarterectomy and/or with borderline stenoses to determine endarterectomy vs. anticoagulation
• Doppler and B-mode ultrasound reveals carotid arterial lesion, lumen size; differentiates occlusion from tightly stenosed carotid artery

Other Diagnostic Procedures to consider

• National Institutes of Health (NIH) stroke scale
• Funduscopy looking for hypertensive changes, papilledema, diabetic retinopathy, bacterial endocarditis, retinal artery branch embolism
• More detailed and extensive neurologic examination of cranial nerve, brain stem, cortical, motor, sensory, sensorimotor, cerebellar
• ECG to identify MI and atrial fibrillation
• Transesophageal echocardiogram detects intracardiac and aortic embolisms
• Holter monitor may be indicated to r/o arrhythmia
• Antiphospholipid antibodies

Treatment strategy depends on clinical presentation and evaluation including physical exam, lab work, and radiologic tests. It is often desirable that patients be admitted to an acute care facility; Henneman and Lewis, writing in Annals of Emergency Medicine, conclude that admitting all patients with TIA is medically justified because ER evaluation cannot reliably identify which patients' conditions are likely to worsen. The 1994 American Heart Association (AHA) guidelines for treatment of TIAs conclude that hospitalization is often justified to expedite evaluation and lessen the possibility of stroke; this is particularly true when a patient is seen within one week of a TIA since the guidelines recommend that the work-up be completed within one week or less. The 1999 AHA update with new guidelines for treatment does not specifically address this recommendation, implying that the approach to hospital care remains the same.

Patient may require oxygen to aid breathing; in addition, oxygen supplementation may be necessary to lessen effects of ischemia. Intubation may be needed if patient loses consciousness or is unable to breathe on his or her own. Medical risk factors, such as volume overload, dehydration, hypoglycemia, and hypertension, need immediate control.

Antiplatelet agents:

• Aspirin—25 mg/day to 1300 mg/day decreases risk of TIA, stroke and MI; generally, reduces stroke risk by 15%; no linear dose-response level effect has been established for ASA, supporting low-dose ASA whenever possible; the lowest effective dose has not been established
• Ticlopidine—250 mg/bid; thought to be superior to aspirin for prevention of stroke following TIA; however, side effect profile limits use; generally reserved for aspirin failures or aspirin intolerance; may cause neutropenia (2.4% of those taking ticlopidine) requiring CBC every two weeks for initial three months; thrombotic thrombocytopenic purpura (TTP) reported
• Clopidogrel—75 mg QD; potentially better side-effect profile than ticlopidine
• Dipyridamole—200 mg QD to BID, extended release; in combination with ASA; 1994 AHA recommendations concluded no evident benefit over ASA alone or ticolopidine; 1999 AHA update reports European Stroke Prevention Study (ESPS-2) showing marked improvement over ASA or dipyridamole alone; AHA update states that dipyridamole and ASA combination has greater stroke risk reduction than clopidogrel
• Anticoagulant—INR should generally be between 2.0 and 3.0; therapy of choice for atrial fibrillation with TIA; appropriate in case of TIA when at high risk for cardiac embolization – e.g. mechanical prosthetic heart valve, recent MI, LV thrombus, dilated cardiomyopathy; INR > 3.0 is not safe in case of recent TIA d/t risk of hemorrhage; studies with low dose anticoagulation (INR 1.4 to 2.8) in combination with ASA for stroke prevention are currently under way; may be indicated while awaiting endarterectomy when stenosis is severe or in case of antiphospholipid antibody syndrome

• Carotid endarterectomy—is procedure of choice if >70% stenosis and one or more TIAs in last two years; determine surgical candidacy (cardiac risk); superior to medical management with > 70% stenosis and in the hands of a skilled surgeon; should be considered in the case of recent TIA even with stenosis between 50% and 69% because reduced stroke rate has been suggested by research compared to medical management, particularly for men and patients with hemispheric symptoms; women benefit much less from surgery
• Angioplasty and stent placement for carotid stenosis under investigation
• Extracranial-intracranial bypass – high patency rate of the bypass; however, no benefit over medical therapy has been demonstrated to date

Dietary factors figure prominently in the prevention and treatment of vascular disease. Specific nutrients and herbs may provide protection against oxidative stress and ischemic injury. Acupuncture plays a role in altering cerebral hemodynamics and in reducing adverse effects of reperfusion.

In the Framingham Study (a pivotal, population-based, longitudinal study which has been ongoing since 1948), researchers investigated the association of diet and relative risk of transient ischemic attacks (TIAs) and completed stroke in 832 men aged 45 to 65 with no known history of vascular disease. Increased intake of fruits and vegetables was associated with a decreased overall risk of all causes of stroke and TIAs. Age-adjusted risk of stroke decreased as the quintiles of servings of fruits and vegetables per day increased (Gillman et al. 1995).

As part of the Physicians' Health Study, a prospective study of 14,916 male subjects aged 40 to 84, the relationship of homocysteine to ischemic stroke using a nested case-control design was examined. Subjects, who had no prior history of stroke or related incidents, provided baseline blood samples and were followed for 5 years. Although not statistically significant, homocysteine levels assayed in samples from 109 subjects who subsequently developed ischemic stroke were slightly higher than the 427 controls (11.1 +/- 4.0 nmol/mL compared to 10.6 +/- 3.4 nmol/mL respectively). In subgroup analyses, homocysteine levels seemed to be a better predictor of stroke risk in normotensive individuals and men <= 60 years old than the group at large (Verhoef et al. 1994). Folic acid, vitamin B6, vitamin B12, and betaine are essential to homocysteine metabolism; therefore, supplementation with these nutrients is thought to be beneficial for controlling homocysteine levels (Miller and Kelly 1997). Please see individual monographs on folic acid and vitamins B6 and B12 for detailed information about these supplements.

A review of the role of magnesium in vascular disease shows a strong association between the dietary intake of magnesium, the concentration of magnesium in the myocardium and vasculature, and the risk for development of TIAs and other vascular pathologies (Altura and Altura 1985).

Acetyl-L-carnitine has been found to improve cerebral blood flow in patients with cerebrovascular disease. Ten patients, who had suffered an ischemic stroke at least six months before the study, were administered acetyl-L-carnitine (1.5 g IV) and evaluated with Single Photon Emission Computerized Tomography (SPECT scan) before and after injection. Cerebral blood flow improved in the areas surrounding the ischemic site but not in the stroke corresponding zone itself (Postiglione et al. 1990). In an animal model, pre-ischemic treatment with acetyl-L-carnitine (100 mg/kg) provided neuronal protection (Shuaib et al. 1995). This supplement may hold potential benefit as primary prevention for high-risk patients and/or secondary prevention for those who have already suffered from a TIA or ischemic stroke.

Free radical damage and lipid peroxidation play a crucial role in the pathogenesis of cerebral ischemia (van der Worp et al. 1999). Vitamin E inhibits platelet adhesion and platelet-induced lipid peroxidation (Steiner et al. 1995). A randomized, double-blind, controlled study of 100 patients with a history of cerebrovascular events was performed over a period of two years. Patients received either aspirin (325 mg/day) monotherapy or aspirin combined with vitamin E (alphatocopheral) (400 mg/day). The combination of alpha-tocopherol (antiadhesive) and aspirin (antiaggregating) therapy reduced platelet adhesion by 40% and significantly reduced the incidence of ischemic events in patients with history of ischemic cerebrovascular disease (Steiner et al. 1995). Several animal studies have also supported findings of the protective effect of vitamin E alpha-tocopherol on the effects of ischemia (Altura and Gebrewold 1996; Hara et al. 1990; van der Worp et al. 1999). Vitamin E inhibited neuronal damage secondary to pro-oxidant events such as alcohol-induced cerebrovascular and brain damage, common carotid artery occlusion, and iron-induced lipid peroxidation.

Other areas of animal research which may prove beneficial to the treatment of TIAs in humans include post-ischemia treatment with nicotinamide (vitamin B₃). In rat studies using models of permanent middle cerebral artery occlusion, post-ischemia treatment with vitamin B₃ was neuroprotective and reduced the infarct volume; the theory is that ischemia depletes ATP and that nicotinamide, a precursor of NAD+, helps regenerate ATP or energy reserve, which, in turn, is neuroprotective (Sakakibara et al. 2000).

Ginkgo (Ginkgo biloba) increases cerebral circulation, improves hypoxic tolerance in cerebral tissues, inhibits cerebral edema, improves cognitive function, provides neuronal protection, and inhibits platelet-activating factor (Blumenthal et al. 1998). It is often used in a standardized form, EGb 761.

In patients with cerebrovascular ischemia secondary to developmental anomalies and deformities of major brain arteries, blood serum antioxidant activity increased and cognitive measures improved after administration of the preparation Tanakan, also known as EGb 761 (Dziak and Golik 1998). In animal models, pre-treatment with ginkgo (EGb 761) prior to intentional ischemic injury preserves membrane integrity, presumably by preventing Na,K-ATPase injury and by reducing lipoperoxidation induced by ischemia (Pierre et al. 1999).

Although there is no known literature specifically evaluating the application of homeopathy for prevention or treatment of TIAs, a trained specialist would determine value and appropriateness of this approach on a case by case basis. Homeopathic treatment can address both constitutional and acute aspects of disease in general. In homeopathic terminology, the constitutional state reflects a pattern of underlying vulnerability or weakness that is unique to the individual and persists throughout that person's life. Symptoms tend to alternate over time, and treatment consists of selecting the appropriate remedy specific for the patient's constitutional type. By contrast, in acute conditions a remedy can be administered without reference to any particular constitutional state (Ullman 1995).

In an animal study of focal cerebral ischemia, scalp acupuncture improved neurologic symptoms, promoted proliferation and repair of neogenetic capillaries and gliocytes in necrotic regions, and reduced blood viscosity, infarct size, edema, and inflammatory changes at the necrotic site (Lei et al. 1997). In patients with cerebrovascular disease, electro-acupuncture (EA) stimulation induced greater change in cerebral blood flow compared to needle retention, assessed via SPECT scan (Wang and Jia 1996). Animal studies have confirmed the benefit of electro-acupuncture, indicating that it could reduce EEG inhibition during global ischemia and improve recovery after reperfusion (Ying and Cheng 1994).

Pointed massage, or massage on acupuncture points (such as that performed in the practice of acupressure), improved cerebral blood flow in 120 patients with encephalopathy due to poor circulation and a history of TIAs in the vertebrobasilar bed (Gusarova et al. 1997).

Oren-gedo ku-to (TJ15), a Chinese herbal preparation, reduced neuronal damage in mice with oxidative stress induced by transient forebrain ischemia (Kondo et al. 2000) . An acupuncturist trained in Chinese approach and technique would determine if this herb or others are appropriate for a particular person with history of TIA or stroke.

Following TIAs, 50% of strokes occur within a year, 20% within five months. Patient monitoring is essential for stroke and MI prevention.

• Lifestyle factors—no smoking, regular exercise, dietary factors (e.g., reducing homocysteine levels with folate, vitamins B₆ and B₁₂; AHA Step II diet), maintain ideal body weight
• Eliminate excessive alcohol intake (definied as ³ seven drinks per day)—moderate alcohol consumption (no more than two drinks per day) may confer benefit for prevention of ischemic stroke only
• Control hypertension—regular screenings; weight control; antihypertensive drugs; SBP should be maintained below 140 mm Hg and DBP below 90 mm Hg, for diabetics these numbers should be 130 and 85 mm Hg respectively
• Modify other risks of CAD as well—e.g. lipid-lowering agents—decrease risk of stroke, TIAs following MI; FDA has approved pravastatin, simvastatin
• Control diabetes—control blood sugar levels; controlling co-morbidity is particularly important for diabetics to reduce the risk of stroke and TIA
• Treat carotid artery disease—consider endarterectomy; see section entitled "Surgical Procedures" for indications; can be considered for > 50% stenosis, particularly for men
• Treat CAD, cardiac arrhythmias, CHF and valvular disease appropriately
• Maintenance of Hormone Replacement Therapy (HRT) if already on it—i.e. discontinuation not recommended

• TIAs—warning signs of stroke
• Myocardial Infarction—more patients with TIA die from MI than stroke
• Incapacitated stroke victim may be found one to two days following event—results in complications, including pneumonia, hypothermia, dehydration, rhabdomyolysis
• Brain stem lesions—airway compromised
• Hemorrhaging transformation—several days following stroke presentation; may be clinically silent
• Cerebral edema—occurs one to two days after TIA
• Multiple strokes increase risk of seizure, pulmonary embolism, thrombosis, dementia

• Interval between TIAs seems to be most important predictor of stroke; frequency of TIAs as well as location or duration of symptoms are not predictive of stroke risk
• Severity of carotid stenosis—predictor of stroke (e.g., lumen < 1 mm)
• Carotid disease is more likely cause of stroke than vertebrobasilar disease

Hypercoagulability during pregnancy increases risks.

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