Foundational Principles of Intracerebral Hemorrhage

1. Epidemiology of Intracerebral Hemorrhage

ICH is less common than ischemic stroke but carries a disproportionate burden of mortality and disability. Understanding incidence, outcomes, and population‐based risk factors informs resource allocation and early recognition strategies.

Incidence and Prevalence

• Global incidence: 10–30 cases per 100,000 person-years
• Higher rates in low- and middle-income countries; stable or rising trends in aging populations

Mortality and Morbidity

• 30-day case fatality ≈40% among contemporary cohorts
• Only 15–25% of survivors achieve functional independence at 6 months

Demographic Risk Factors

• Age: risk doubles each decade after 55 years
• Sex: male predominance with narrowing gap in older age
• Ethnicity: higher incidence in Asian, Black, and Hispanic populations

2. Risk Factors for ICH

ICH risk arises from immutable factors (age, genetics, vessel pathology) and modifiable exposures (hypertension, antithrombotic use, lifestyle). Pharmacists play a critical role in identifying and mitigating modifiable risks.

Non-modifiable Risk Factors

• Advanced age (>55 years)
• Genetic predisposition: APOE ε2/ε4 genotype, cerebral amyloid angiopathy (CAA)
• Vascular malformations: arteriovenous malformations, cavernomas

Modifiable Risk Factors

• Chronic hypertension: leading risk for deep (basal ganglia, thalamus) hemorrhages
• Anticoagulants: warfarin (INR >3), DOACs; antiplatelet agents carry smaller risk
• Illicit drugs: cocaine, amphetamines
• Lifestyle: heavy alcohol use, smoking, diabetes, hyperlipidemia

Pharmacist’s Role in Risk Mitigation

• Comprehensive medication reconciliation to identify antithrombotics and interacting agents
• Protocols for blood pressure monitoring and escalation
• Patient education on adherence to antihypertensive therapy and warning signs of ICH

3. Pathophysiology of ICH

ICH begins with rupture of small cerebral vessels, leading to hematoma formation, mass effect, expansion, perihematomal edema, and secondary injury cascades. Each phase offers potential intervention targets.

Vessel Rupture Mechanisms

• Lipohyalinosis from chronic hypertension weakens deep perforating arterioles
• Amyloid β deposition in cortical vessels causes lobar hemorrhages (CAA)
• Structural defects in vascular malformations predispose to bleeding

Hematoma Formation and Expansion

• Primary bleed creates focal mass effect and raised intracranial pressure
• Early hematoma expansion occurs in ~30% of patients within 24 hours
• CT “spot sign” predicts active bleeding and risk of growth

Perihematomal Edema and Inflammation

• Cytotoxic edema (hours): ionic shifts cause intracellular swelling
• Vasogenic edema (peaks days 3–5): blood–brain barrier disruption allows plasma leakage
• Inflammatory mediator release and microglial activation exacerbate tissue injury

Secondary Brain Injury Pathways

• Excitotoxicity: glutamate release, calcium influx
• Oxidative stress: free radical formation from blood breakdown products
• Cell death via apoptosis and necrosis pathways

4. Clinical Presentation of ICH

Clinical features depend on hemorrhage location and size. Prompt recognition of focal deficits, headache, altered consciousness, and signs of elevated intracranial pressure guides emergent imaging and triage.

Focal Neurological Deficits

• Deep ICH (basal ganglia/thalamus): contralateral hemiparesis, sensory loss
• Lobar ICH: aphasia, visual field deficits, hemispatial neglect
• Cerebellar: ataxia, dysarthria, vertigo; brainstem: cranial nerve palsies, rapid decline

Headache and Pain Patterns

• Sudden, severe headache (“worst of life”) more common in lobar and cerebellar bleeds
• Nausea/vomiting often accompany raised intracranial pressure
• Differentiation from SAH: focal deficits favor ICH; SAH more diffuse headache without focal signs

Altered Level of Consciousness

• Glasgow Coma Scale quantifies impairment; lower scores correlate with larger hemorrhages
• Fluctuations may indicate ongoing bleeding or rising ICP

Signs of Elevated Intracranial Pressure

• Cushing triad: hypertension, bradycardia, irregular respiration
• Pupillary asymmetry or sluggish reaction; posturing indicates impending herniation