Stroke

Fall 2000
Volume 11, Number 2

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Stroke in young adults is surprisingly common. The differential diagnosis for potential etiologies is broader than that for older adults. Elements of the initial workup, including neuroimaging, bloodwork, and other ancillary studies, are reviewed. Emphasis is placed on areas in which the diagnostic approach to stroke in young adults differs from that for older patients. Clinical manifestations and management are usually similar to, but prognosis is often better than, those in an older population.

Introduction. This article will emphasize aspects of a diagnostic approach to young adults (up to 45 years of age) with stroke as it differs from a standard approach for older adults, with emphasis on initial work-up.

Stroke in young adults is surprisingly common. The annual stroke incidence was estimated at 34/100000 in Swedish adults under 55 years of age, and 10/100000 in a Mayo Clinic study of women ages 15 to 29. Ischemic stroke is much more common than hemorrhagic, the latter comprising 12% of strokes in the Lausanne registry for patients 30 to 45 years old.1 The ubiquity of stroke in young adults and its potential for devastating consequences mean that healthcare providers must have a high index of suspicion for stroke. This is especially true when a patient’s clinical picture is not easily explained otherwise.

Etiologies. The range of potential etiologies for stroke in young adults is broader than that for older adults. (Table) Like in older adults, stroke in younger adults is typically categorized as primarily ischemic or hemorrhagic. Ischemic etiologies include cardioembolic, atherosclerotic disease, and nonatherosclerotic cerebral vasculopathies. Hemorrhagic strokes include subarachnoid and intraparenchymal types. Of particular note in young adults are stroke causes such as hematologic disorders, substance abuse, trauma, dissections, oral contraceptive use, pregnancy and postpartum states, and migraine.

Clinical Manifestations. The clinical presentations for stroke in young adults are not unique to this age group. Sudden or subacute onset of neurologic symptoms referable to the brain should suggest stroke as a potential explanation. The presence of a given stroke risk factor does not assure that it is causative. Many young patients have multiple risk factors. Detailed history and examination, oriented toward common and uncommon etiologies, are especially important. Stroke mimics in the young adult population include multiple sclerosis and malignancy.

The physical exam should include neurologic, cardiovascular, ophthalmologic and dermatologic assessments. Relevant ocular findings include corneal arcus (hypercholesterolemia) or corneal opacity (Fabry’s disease); Lisch nodules, optic atrophy (neurofibromatosis); lens subluxation (Marfan’s syndrome, homocystinuria); and retinal perivasculitis (sickle-cell disease, syphilis, connective tissue diseases, inflammatory bowel disease), occlusions (emboli), angioma (cavernous malformation), or hamartoma (tuberous sclerosis). Among dermatologic associations are splinter hemorrhages or needle tracks (endocarditis); xanthoma (hyperlipidemia); café-au-lait spots, neurofibromas (neurofibromatosis); purpura (coagulopathy); and capillary angiomata (cavernous malformation).3

One-fifth to one-third of strokes in the young may be caused by cardioembolic phenomena. Transesophageal echocardiography (TEE) is usually indicated. Causes include congenital heart disease, valvular disease (including endocarditis) and arrhythmias. Mitral valve prolapse and patent foramen ovale are common but are typically not causes of stroke when present. An atrial septal aneurysm is less likely to be associated with stroke when found in isolation than when it occurs with other cardiac abnormalities.

Premature atherosclerotic cerebrovascular disease can be symptomatic in young adults, just as atherosclerosis can begin in childhood. The symptoms and signs are similar to those for older adults.

Cervicocephalic arterial dissections can involve the extracranial internal carotid, the vertebrobasilar system, or, less commonly, the intracranial carotid system. They are associated with major or minimal trauma, chiropractic manipulation, or can occur spontaneously. Other associations include fibromuscular dysplasia, Marfan syndrome, Ehlers-Danlos syndrome type IV, moyamoya and sympathomimetic drug abuse. Symptoms and signs may include neck pain, transient or lasting ischemia of retina, cerebral hemispheres, or posterior fossa, Horner’s syndrome, hemicranial pain, or subarachnoid hemorrhage. Extracranial ultrasound or magnetic resonance angiography (MRA) may confirm the clinical impression. Often catheter angiography is required for diagnosis.

Cerebral vasculitis should be considered for cases of ischemic or hemorrhagic stroke, recurrent strokes, stroke with encephalopathy, and stroke with fever, multifocal symptoms, skin abnormalities, or abnormal renal function or sedimentation rate. Infectious vasculitis (eg, with syphilis, tuberculosis, purulent meningitis), necrotizing vasculitis (eg, polyarteritis nodosa), vasculitis with collagen vascular disease (eg, lupus, rheumatoid arthritis), giant cell arteritis, and hypersensitivity vasculitis (eg, drug-induced) are seen much more often than primary central nervous system vasculitis.

Moyamoya is a noninflammatory vasculopathy associated with extensive collateral vasculature. It can present with transient ischemic attacks, headaches, hemiparesis, seizures, cerebral infarction, or hemorrhage. MRA screening is useful. Angiographic findings are distinctive and resemble in part a “puff of smoke”.4

Hypercoagulable states may be responsible for 2% to 7% of cases in young adults.4 Inherited (primary) thrombophilic disorders include entities that are recently described (hyperhomocysteinemia, factor V Leiden, prothrombin G20210A), well- established (deficiencies of antithrombin, protein S or protein C), and extremely rare (dysfibrinogenemia, thrombomodulin deficiency, heparin cofactor II deficiency).5 Acquired (secondary) causes include malignancy, pregnancy/postpartum states, oral contraceptive use and sickle-cell disease. Prior thromboembolic disease in a young patient or in family members should raise suspicion.4 Please refer to Dr. Trevarthen’s accompanying article for further information on this topic.

Cerebral venous thrombosis can cause ischemic or hemorrhagic strokes. Septic thrombosis usually occurs at the cavernous sinus as a complication of facial infection. Signs include proptosis, chemosis, and gaze palsies. Aseptic thromboses are seen disproportionately in women during pregnancy or postpartum periods, or while taking oral contraceptives. Presenting symptoms include headache, emesis, lethargy, and seizures. Papilledema may accompany focal signs.4, 6

Strokes induced by migraines are rare, considering that perhaps 20% of US adults may suffer migraines. Symptoms include persistent visual, motor, sensory or aphasic deficits, which began in the course of a typical migraine attack, where other causes are excluded. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are inherited causes of stroke which can include migraine as part of the clinical presentation.1, 4

Up to 45% of strokes in young adults are due to spontaneous intracerebral hemorrhage.4 Approximately half are lobar; one-quarter are in basal ganglia or internal capsule.7 Vascular malformations, aneurysms, hypertension, and illicit drug use are the main causes.4, 7

Investigations. The initial work-up should be as expeditious as possible to allow consideration of acute therapies, such as tissue plasminogen activator (t-PA).8 Brain computed tomography (CT) is usually the initial imaging study of choice as it is readily available and is highly sensitive for acute hemorrhage. Blood work should include a complete blood count with differential and platelet count, prothrombin time (international normalized ratio), activated partial thromboplastin time, glucose, chemistries, electrolytes, serology for syphilis, and an erythrocyte sedimentation rate.

A more detailed coagulation profile (anticardiolipin antibodies, lupus anticoagulants, protein S, protein C, activated protein C resistance, antithrombin III) is requested in patients without a firmly identified cause of stroke or if the patient or family members have a history of thromboses. It is advantageous to send such a profile prior to initiating anticoagulation, as heparin can alter interpretation of some of those assays. Therefore, consider ordering these assays at the beginning of the work-up.

Most patients should have high-quality brain magnetic resonance imaging (MRI) and often MRA.4, 9 Where available, MRI with diffusion-weighted imaging (DWI) and perfusion imaging (PI) is becoming standard. DWI-PI has the potential to distinguish irreversibly injured tissue from that which may be salvageable.10

Additional studies in initial screening include pregnancy testing, a chest roentgenogram, and an electrocardiogram. An echocardiogram (consider transesophageal), and extracranial (carotid-vertebral) Doppler ultrasound are routinely obtained, although often after initial antiplatelet or anticoagulation therapy is started.

Keep in mind the limitations of studies performed. CT will miss a minority of acute bleeds. MRI with DWI, quite sensitive for acute stroke, has an occasional false negative result (17 out of 782 patients in a recent study).11 Also, MRA’s resolution is not yet on par with conventional angiography.

Consider conventional angiography of cerebral and neck vessels for patients in whom dissection is suspected or in whom no other cause is found. Transcranial Doppler ultrasound can be helpful. Please see Dr. Ricci’s article in this issue for more information on neuroimaging.

Toxicologic studies are often productive, even when drug use is not acknowledged.

Other blood tests may include homocysteine, fibrinogen, antinuclear antibody, lipid panel, lipoprotein (a), serum protein electrophoresis, hemoglobin electrophoresis, and sickle-cell assay. Cerebrospinal fluid analysis is indicated for cases suspicious for infectious, vasculitic, or occult hemorrhage origins. Telemetry monitoring for arrhythmias is occasionally revealing.4

Prothrombin mutation G20210A testing is of uncertain utility in cerebrovascular disease, but may be appropriate for patients with a personal history of thromboembolic disease or family history of thrombophilia.5

A patient with one or more risk factors, such as migraine or diabetes, should be thoroughly investigated for other possibilities. The cause of stroke in young patients may remain undetermined in 20% to 30% of cases, even after a detailed work-up.4

Management. General management of ischemic8, 12, 13 and hemorrhagic14 strokes is similar to that for older adults and is beyond the scope of this article. Additional specific measures are oriented toward any underlying etiology found.4, 15  Primary16 and secondary17 preventive measures have recently been reviewed.

Prognosis. The outcome of stroke in young adults is better than that for older adults. In a recent study of 330 patients with first stroke or transient ischemic attack, followed for an average of 96 months, 8% died, 3% had another stroke, and 3% had a myocardial infarction. Approximately 16% were dependent, but 56% had returned to work. Unfortunately, only a minority of those who smoked at the time of their stroke subsequently stopped using tobacco.18 The overall annual recurrence rate is less than 1%.1 Prognosis is often closely associated with the underlying cause. A relatively good outcome may be found after many cases of arterial dissection. Risk of stroke recurrence is low (2% over 5 years) in women whose first stroke occurred in pregnancy.19

Conclusion. Strokes in young adults make up a significant proportion of strokes in general. A thorough investigation is recommended, looking into a broad array of potential etiologies, common and uncommon. Management is similar overall to that for older adults, with some aspects of treatment dictated by specific causes found. Health care providers must stress prevention with all of their young adult patients, especially those with identifiable risk factors. The potential for devastation is great in any case of stroke but prognosis in this population is better than that for older adults.
  

Address comments and questions to:
 
Marc Marcoux, MD
499 E. Hampden Avenue, Suite 280
Englewood, CO 80113

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