Stroke in young adults

Diagnostic workup
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By Bartlomiej Piechowski-Jozwiak MD, Jorge Moncayo-Gaete MD, and Julien Bogousslavsky MD

A careful patient history, physical examination, and laboratory evaluation, as well as specific diagnostic techniques in appropriate patients can elucidate many etiologies of stroke in this group of patients. The history can provide clues to the cause of the stroke. A history of deep venous thrombosis or miscarriage may alert the physician to an occult coagulation abnormality. Repeated questioning of patients and family members regarding possible illicit drug use may clarify this issue. Subtle head trauma or rapid or prolonged head and neck extension may be helpful historical points. A family history of headache or early onset stroke may be relevant as well. The physical examination should include a careful evaluation of the cardiovascular system and skin, a formal ophthalmologic evaluation (Table 6), and a complete neurologic assessment.

Table 6. Clues from Examination of the Eyes and Skin




Possible cause



Corneal arcus



Corneal opacity

Fabry disease


Lisch nodules



Lens subluxation

Marfan syndrome, homocystinuria


Retinal perivasculitis

Eales disease, Behçet disease, syphilis, connective tissue diseases, sarcoidosis, inflammatory bowel disease


Retinal arteriolar occlusions

Emboli, microangiopathy with sensorineural hearing loss and multiple small strokes


Retinal angioma

Cavernous malformation, von Hippel-Lindau disease


Optic atrophy



Retinal hamartoma

Tuberous sclerosis



Osler nodes, splinter hemorrhages, needle tracks


Infective endocarditis

Xanthoma, xanthelasma



Cafe-au-lait spots, axillary and inguinal freckles, neurofibromas



Thin, fragile skin with easy bruising, bluish sclera


Ehlers-Danlos syndrome type IV


Osler-Weber-Rendu disease, scleroderma



Coagulopathy, Henoch-Schönlein purpura, cryoglobulinemia


Capillary angioma

Cavernous malformation


Aphthous or genital ulcers

Behçet disease



Fabry disease


Livedo reticularis

Sneddon syndrome


Facial angiofibromas, ash leaf spot, ungual fibroma, shagreen patch


Tuberous sclerosis

Papules, atrophic lesions

Degos disease (malignant atrophic papulosis)





Yellow-orange papules/plaques (resembling xanthomas)

Pseudoxanthoma elasticu

Adapted from (Stern and Wityk 1994).

An organized and stepwise evaluation should follow as needed regarding ancillary testing. Complete blood count with differential, erythrocyte sedimentation rate, electrolytes, glucose, coagulation panel, platelet count, liver and renal function tests, lipid panel, and pregnancy test (if appropriate) are routinely performed (Singhal et al 2013). Specialized investigations to rule out specific etiologies in young adults with stroke may involve toxicological, rheumatological, infectious, hematological, and hypercoagulable panel tests, CSF examination, advanced brain-imaging techniques, brain and leptomeningeal biopsy, and genetic tests (Singhal et al 2013).

Neuroimaging with a CT or MRI (preferred) of the head can confirm the diagnosis and differentiate between an ischemic stroke and a hemorrhagic event. A carotid ultrasound can evaluate for high-grade stenosis of a symptomatic vessel, whereas transcranial Doppler, CT angiography, or MR angiography may be useful to evaluate the intracranial vasculature for stenosis or collateral flow. Transcranial Doppler sonography can increase the detection of right-to-left intracardiac shunts. Cerebral angiography remains the most sensitive method of vascular imaging and is particularly useful when a dynamic evaluation of the intracranial circulation is required (eg, hemodynamically significant stenosis, leptomeningeal collateral supply, venous hypertension, or early venous drainage from a vascular malformation). Further evaluation should be performed as indicated, based on the suspected stroke etiology. A cerebrospinal fluid sample should be obtained when vasculitis is suspected or when the history is concerning for subarachnoid hemorrhage and the CT is unrevealing. CT and MR venography (CTV and MRV) are useful for evaluating cerebral venous thrombosis, particularly when a sinus is involved. If cortical venous thrombosis is strongly suspected, despite a negative head CTV/MRV, a diagnostic cerebral angiogram should be performed. Transesophageal echocardiography is helpful for identifying cardioembolic and aortoembolic sources; transesophageal echocardiography is superior for detection of left atrial appendage thrombus. Transcranial Doppler sonography can increase the detection of right to left intracardiac shunts (Topcuoglu et al 2003). In patients with patent foramen ovale, pelvic MR venography can uncover pelvic vein thrombosis as the source of blood clots (Cramer et al 2004). Cerebral angiography often provides a wealth of information and remains the most sensitive vessel imaging method. Further evaluation should be performed as indicated, based on the suspected stroke etiology. For example, a cerebrospinal fluid sample should be obtained when vasculitis is suspected or when the history is concerning for subarachnoid hemorrhage and the CT is unrevealing.

The diagnostic yield of tests in 215 young adults (mean age of 37) with cerebral infarct involving the anterior (65%) and posterior (30%) circulation has recently been reported. An extensive diagnostic workup, including prothrombotic and vasculitis panel, toxicology screening, CSF examination, Holter monitoring, echocardiography, and neuroimaging, was performed in almost all patients (Ji et al 2012). Cerebral angiography disclosed an embolic occlusion, severe stenosis, or other vasculopathy, mainly in the proximal segment of the middle cerebral artery, in 64% of the patients. Echocardiography (contrast transthoracic in 91% and transesophageal in 40%) was abnormal in half of the patients; patent foramen ovale was the most common abnormality, affecting 96 patients, and was the only finding in 83 patients; in 76, it was implicated as stroke etiology. Screening for hypercoagulable state gave a diagnostic yield of 16%; functional protein S deficiency and prothrombin 20201 mutation were the most and least commonly observed abnormalities, respectively. Cerebrospinal fluid examination was abnormal in 15% of the patients. A low diagnostic yield (less than 5%) was observed in both toxicological screening and vasculitis panel whereas Holter monitoring had the lowest diagnostic yield (Ji et al 2012).

Table 7. Ischemic Infarction Diagnostic Testing

Laboratory studies

  • Complete blood count
  • Erythrocyte sedimentation rate
  • Chemistry profile
  • Fasting glucose, hemoglobin A1C level
  • Prothrombin time, activate partial thromboplastin time, platelets
  • Toxicology
  • Rapid plasma reagin/venereal disease research laboratory
  • Fasting lipid profile
  • Sickle cell prep
  • Blood cultures
  • Pregnancy test

Brain imaging

  • Head CT without contrast
  • Head MRI without gadolinium
  • High-resolution (3T) contrast enhanced T1-weighted MRI

Vascular imaging

  • Carotid duplex ultrasound
  • Trans/cranial Doppler sonography
  • MRA/CTA of head and neck
  • Cerebral angiography
  • Lower extremity ultrasound, pelvic CT or MR venography (in patients with patent foramen ovale)

Cardiac studies

  • ECG
  • Transesophageal echocardiogram with bubble
  • Holter

Hypercoagulable screen

  • Protein C activity and free protein S antigen
  • Antithrombin III
  • Activated protein C resistance
  • Factor V Leiden mutation
  • Russell viper venom time or other screen for lupus anticoagulant and antiphospholipid antibodies (IgG & IgM)/beta2-glycoprotein I antibody
  • Thrombin time
  • Fibrinogen
  • Prothrombin gene 20210A mutation
  • MTHFR C677T
  • PAI-1


  • CSF analysis (if vasculitis or infection suspected)
  • HIV serology
  • ANA
  • Lactic acid
  • Homocysteine
  • ESR
  • CRP
  • Cryoglobulin level
  • Complement levels
  • ANCA
  • Neutrophil cytoplasm antibody (cANCA and pANCA)
  • Scl-70 antibody
  • Anti-centromere antibody
  • Anti-Ro (SSA) and anti-La (SSB)
  • Serum angiotensin-converting enzyme
  • Antiproteinase 3
  • Lipoprotein (A)
  • Brain and meningeal biopsy (suspected vasculitis)
  • Skin biopsy
  • Sural nerve biopsy
  • Muscle biopsy

Adapted from (Stern and Wityk 1994; Singhal et al 2013).

In This Article

Historical note and nomenclature
Clinical manifestations
Clinical vignette
Pathogenesis and pathophysiology
Differential diagnosis
Diagnostic workup
Prognosis and complications
References cited