Cerebral Ischemia and Hemorrhage

Disease

Diagnostic test

Hypoglycemia

Serum glucose

Hyperglycemia

Serum glucose, ketone bodies, lactate, osmolarity, K⁺, BGA

Hepatic coma

NH₃, GOT, GPT, bilirubin, BGA

Renal failure

Urea, creatinine, electrolytes, BGA

Thyrotoxic/hypothyroid crisis

T₃, T₄, TSH

Addisonian crisis, hypophyseal coma

Na⁺, K⁺, Cl⁻, glucose, cortisol, TSH, BGA

Postictal confusion

CK, prolactin

Sepsis

CRP, ESR, coagulation, Na⁺, K⁺, creatinine, urea

Severe electrolyte imbalance

Na⁺, K⁺, Ca²⁺

CO intoxication

COHb

Alcohol intoxication

Ethanol in the serum

Substance intoxication (recreational and pharmaceutical drugs)

Direct detection in the serum and/or urine

**Table 12.2** Contribution of laboratory analysis to determining the etiology of cerebral infarction
*Thrombophilia*	• Protein C activity • Protein S activity • Activated protein C resistance (factor V Leiden mutation) • Antithrombin III concentration • Plasminogen concentration • Prothrombin polymorphism • Lupus anticoagulant • Anti-cardiolipin antibodies
*Hematological diseases*	• Essential thrombocythemia: thrombocyte count → • Polycythemia vera: erythrocyte count →, Hct → Hb → • Lymphoma: idiopathic thrombocytopenic purpura, acquired von Willebrand-Jürgens disease • Sickle cell anemia: hypochromic anemia, differential blood count, Hb electrophoresis
*Systemic vasculitis*	• Chap. 10, “Systemic Vasculitis and Connective Tissue Diseases”
*Pathogen-induced vasculitis*	• Hepatitis B serology, perhaps HBV PCR • Hepatitis C serology, perhaps HCV PCR • HIV test • Varicella antibody index if varicella-associated vasculitis is suspected, perhaps VZV PCR • Syphilis diagnosis in the serum and CSF if syphilitic vasculitis is suspected (Chap. 10, “Neurosyphilis”) • Diagnostic tests for Borrelia in serum and CSF if Borrelia-associated vasculitis is suspected (Chap. 10, “Neuroborreliosis”) • Mycobacterium tuberculosis PCR if tuberculous vasculitis is suspected • Cerebral mycosis: lymphocytic CSF pleocytosis, direct detection in the CSF and/or serological findings • Cerebral cysticercosis: lymphocytic CSF pleocytosis, CSF protein →, serology
*Isolated angiitis of the CNS*	There may be mild CSF pleocytosis and/or blood–brain barrier dysfunction
*Genetically determined arteriopathy*	• CADASIL: skin biopsy and/or molecular genetic confirmation • MELAS: serum and CSF lactate →, aerobic lactate ischemia test, molecular genetics • Vascular dissection in Marfan’s syndrome and Ehlers-Danlos syndrome
*Other rare causes*	• Homocystinuria: homocysteine in serum and urine →, methionine load test • Heparin-induced thrombocytopenia: thrombocytes decreased under heparin therapy, detection by antibody diagnosis

• Temporal arteritis: There are no specific laboratory parameters for temporal arteritis, which in rare cases can also involve the extracranial arteries supplying the brain. Raised ESR, increased CRP level, and thrombocytosis are indicative; the diagnosis is made by biopsy.

• Immune complex-mediated forms of vasculitis: These include cryoglobulinemic vasculitis, hypersensitivity vasculitis, infection-associated endoperiarteritis, systemic lupus erythematosus, rheumatoid arthritis, and Sharp’s syndrome. They often cause hypocomplementemia.

• Isolated angiitis: Isolated angiitis of the CNS is extremely rare. In most cases (about 60%) headache occurs; otherwise the manifestations are very varied, and include encephalopathy, focal neurological deficits, and cranial nerve dysfunction. Laboratory results for systemic markers are normal. In about 90% of cases, CSF exhibits mild lymphocytic pleocytosis with elevated protein and normal glucose levels. In some cases, positive oligoclonal bands have been reported. Diagnosis is on the basis of meningeal biopsy, since in up to 50% of cases even angiography reveals no abnormalities.

Thrombocythemia, plasmacytoma. The risk of cerebral infarction is markedly increased in essential thrombocythemia and polycythemia vera, whereas leukemic diseases (with the exception of plasmacytoma) carry a much lower risk. In addition to the patient’s history and clinical findings, changes in the blood count results may show thrombocythemia and polycythemia, whereas a raised ESR usually indicates plasmacytoma.

Homocystinuria. Homocystinuria is caused by a rare autosomal recessive defect (incidence 1:40 000 to 1:330 000). Severe juvenile atherosclerosis unassociated with any known risk factor suggests the heterozygous form of homocystinuria; homozygous carriers usually die in childhood of atherothrombotic complications. The characteristic symptoms are excessively high homocysteine levels in the serum (> 100 mmol/L) and the presence of homocysteine in the urine. The methionine load test (oral administration of 0.1 g/kg methionine followed by determination of the homocysteine concentration in the serum after 4–6 hours) may be used to screen for heterozygous carriers. Homocystinuria is caused by defects in methionine and vitamin B₁₂ metabolism and can be detected by molecular genetic analysis. There are three types of the disease, the most common being a defect in cystathionine synthetase (type 1).

**Table 12.3** Laboratory analysis of treatable risk factors in primary and secondary stroke prevention
*Risk factor*	*Target value*
*Hypercholesterolemia*
Primary prevention
• Slightly elevated global risk: no CHD, 0–1 risk factors • Moderately elevated global risk: no CHD and ≥ 2 risk factors • High global risk: no CHD, ≥ 2 risk factors, and peripheral occlusive arterial disease	• LDL cholesterol ≤ 160 mg/dL • LDL cholesterol ≤ 130 mg/dL • LDL cholesterol ≤ 100 mg/dL
Secondary prevention
• Very high global risk: manifest CHD or secondary prevention • After cerebral infarction or TIA or diabetes	• LDL cholesterol ≤ 100 mg/dL • HDL cholesterol ≥ 40 mg/dL • Triglycerides < 200 mg/dL
*Diabetes*
Fasting blood sugar	≤ 100 mg/dL
Blood sugar 1 hour postprandial	≤ 135 mg/dL
Urinary glucose	0 mg/dL
Glycohemoglobin (HbA_1c)	<6.5%
*Hyperhomocysteinemia*
Normal range	11.15 ± 2.15 mmol/L
Risk factors: age > 45 years (men) or > 55 years (women), family history of early CHD, smoking, arterial hypertension, diabetes mellitus, HDL cholesterol < 35 mg/dL, trunk obesity.