What is the possible cause of multiple intracerebral hemorrhages in a patient with a history of hypertension, potential bleeding disorders, and previous strokes?

Multiple Intracerebral Hemorrhage: Causes and Diagnostic Approach

Multiple simultaneous intracerebral hemorrhages are uncommon but have distinct etiologies that must be systematically evaluated, with cerebral amyloid angiopathy, coagulopathy, and underlying vascular malformations being the primary causes in patients without hypertension, while hypertensive vasculopathy remains the most common cause overall. 1, 2, 3

Primary Etiologic Categories

Cerebral Amyloid Angiopathy (CAA)

• CAA is the predominant cause of multiple lobar hemorrhages, particularly in elderly patients over 70 years without hypertension history. 1, 4
• This condition results from β-amyloid peptide deposition in cortical and leptomeningeal arteriolar walls, making vessels prone to rupture at multiple sites. 1
• The presence of microbleeds on MRI gradient-echo sequences indicates significantly elevated risk for recurrent hemorrhage. 1

Hypertensive Vasculopathy

• Chronic hypertension causes lipohyalinosis and microaneurysm formation in small penetrating arteries, predisposing multiple vessels to simultaneous rupture. 2
• Hypertensive hemorrhages typically occur in deep structures (basal ganglia, thalamus, pons, cerebellum) but can also manifest as multiple lobar hemorrhages. 1, 2
• Even when hypertension is present, the causal pathway is multifactorial, and attributing hemorrhage solely to hypertension is oversimplistic. 3

Coagulopathy and Anticoagulation

• Severe thrombocytopenia significantly increases risk of spontaneous multiple intracerebral hemorrhages. 1
• Deficiencies of coagulation factors (Factor VIII, Factor XIII, vitamin K) predispose to multiple simultaneous bleeds. 1
• Anticoagulant-related hemorrhages require immediate reversal: discontinue warfarin and administer 4-factor PCC (25-50 IU/kg) plus IV vitamin K (5-10 mg) without waiting for INR results. 4

Vascular Malformations

• Arteriovenous malformations and fistulas account for approximately 32.4% of intracerebral hemorrhages in children and remain important causes in adults. 1
• Vascular imaging is mandatory for patients under 70 years with lobar hemorrhage, under 55 years regardless of location, those without hypertension history, or when subarachnoid blood is present. 4
• Aneurysms and dural arteriovenous fistulas can cause multiple hemorrhages, though less commonly than other etiologies. 1, 4

Tumors

• Approximately 13.2% of intracerebral hemorrhages in children are tumor-associated, with metastases being particularly prone to multiple hemorrhagic sites in adults. 1, 4

Iatrogenic Causes

• Massive cerebrospinal fluid overdrainage can precipitate multiple simultaneous hemorrhages affecting both supratentorial and infratentorial regions, even in patients without prior bleeding risk factors. 5

Diagnostic Algorithm

Initial Evaluation

• Non-contrast CT is the standard initial diagnostic tool for detecting acute hemorrhages. 1
• Document hemorrhage locations (deep vs. lobar), number of lesions, and presence of intraventricular extension. 6
• Verify platelet count and coagulation profile immediately. 1, 7

Age-Based Assessment

• For patients >70 years with multiple lobar hemorrhages and no hypertension: presume CAA until proven otherwise. 1, 4
• For patients <55 years or those with atypical locations: pursue aggressive vascular imaging. 4

MRI Evaluation

• Perform MRI with gradient-echo sequences when stable to identify microbleeds (suggesting CAA), cortical superficial siderosis (CAA), or underlying masses. 1, 4
• MRI is superior to CT for detecting chronic hemorrhages and underlying structural lesions. 1

Vascular Imaging

• CT angiography or catheter angiography should be performed for younger patients, those without clear hypertensive or CAA patterns, or when subarachnoid blood is present. 4
• Note that conventional angiography may miss multiple lesions, as CT is more sensitive for detecting multiple simultaneous hemorrhages. 7

Critical Clinical Pitfalls

• Multiple hemorrhages with identical CT density profiles indicate simultaneous bleeding events, not sequential hemorrhages. 7
• Only 17% of patients with multiple hemorrhages in one series had hypertension history, challenging the assumption that hypertension explains all cases. 7
• Five of twelve patients with multiple hemorrhages presented without lateralizing signs—only headache, altered mentation, and nuchal rigidity—mimicking subarachnoid hemorrhage or meningitis. 7
• The diagnosis of multiple lesions is often missed on angiography and other studies, making CT essential for accurate diagnosis. 7