Intracerebral Hemorrhage: Macrobleeds and Microbleeds

• Poststroke mortality is ~10% at 30 days, ~20% at 1 year, and ~40% at 5 years

Intracerebral Hemorrhage

• Bleeding in the brain parenchyma, not in the epidural, subdural, or subarachnoid space
• Presents as focal stroke, indistinguishable from ischemic stroke on imaging studies
• Requires imaging for definitive diagnosis
• Can be cerebral macrobleeds or cerebral microbleeds

Cerebral Macrobleeds

• Macroscopic
• Almost always symptomatic
• Often neurologically devastating
• Most often caused by head trauma or chronic hypertension

Cerebral Microbleeds

• 1-10 mm in diameter
• Individually asymptomatic
• Reflect cerebral small vessel disease

Common Causes of Cerebral Microbleeds

• Hypertension, associated with microbleeds in the deep subcortical gray matter and brainstem
• Cerebral amyloid angiopathy, which tends to produce lobar microbleeds at the cortical gray matter-white matter junction

Less Frequent Causes of Cerebral Microbleeds

• CADASIL
• Moyamoya
• Infective endocarditis
• Fat embolism
• Cerebral malaria

Microbleeds

• Associated with cognitive dysfunction and an increased risk of large intracerebral hemorrhages
• Nonlobar microbleeds are also predictive of ischemic stroke
• Treatment involves controlling hypertension
• Does not preclude usage of antiplatelet agents, anticoagulants, thrombolytics, or statins for concurrent ischemic cerebrovascular disease

Hypertensive Hemorrhage Epidemiology

• Causes ~10% of strokes, independent of age
• Hypertension is the most common underlying cause of nontraumatic hemorrhage

Chronic Hypertension Pathophysiology

• Promotes changes in the walls of penetrating small cerebral arteries and arterioles in the subcortical white matter, basal ganglia, thalamus, pons, and cerebellum
• Consists of lipohyalinosis (collagenous thickening and inflammation of the vessel wall) and fibrinoid necrosis (vessel-wall destruction with perivascular inflammation)
• Associated with ischemic (lacunar) stroke and may also lead to the development of miliary (Charcot–Bouchard) aneurysms, which predispose to hemorrhage

Acute Hypertension

• Uncertainty regarding the role of acute elevation of blood pressure in intracerebral hemorrhage
• Patients are hypertensive after intracerebral hemorrhage, from baseline chronic hypertension and the vasopressor response to increased intracranial pressure (Cushing reflex)
• Can occur following sympathomimetic drug (eg, amphetamine or cocaine) use

Hematoma Effects

• Hypertensive hemorrhage causes both destruction and compression of brain tissue
• Breakdown products of extravasated blood may cause inflammation and secondary injury
• Perihematoma edema correlates with hematoma size, which predicts a poor outcome
• Increased intracranial pressure results in tamponade of the ruptured vessel, but can also lead to brain herniation and death

Hydrocephalus

• May result from hematomal compression of the ventricular system or its obstruction by intraventricular or subarachnoid blood
• Especially common after cerebellar hemorrhage

Rebleeding

• Occurs in up to ~15% of cases
• Associated with clinical worsening

Deep Cerebral Hemorrhage

• Most common sites of hypertensive hemorrhage are the putamen and thalamus, which are separated by the posterior limb of the internal capsule
• Putaminal hemorrhage leads to more severe motor deficit
• Thalamic hemorrhage to more marked sensory disturbance
• Common sites are the putamen and thalamus

Putaminal Hemorrhage

• Produces tonic eye deviation toward the affected side of the brain

Thalamic Hemorrhage

• Tonic downward and medial deviation from pressure on the midbrain center for upgaze

Lobar Hemorrhage

• Hypertensive hemorrhages also occur in subcortical white matter underlying the frontal, parietal, temporal, and occipital lobes
• Symptoms and signs vary according to the location, but can include headache, vomiting, hemiparesis, hemisensory deficits, aphasia, and visual field defects
• Seizures are more frequent than with hemorrhages in other locations, whereas coma is less so

Pontine Hemorrhage

• Bleeding into the pons produces coma within seconds to minutes and usually death within 48 hours
• Key findings are pinpoint pupils and absent or impaired horizontal eye movements; vertical eye movements may be preserved
• Patients are commonly quadriparetic with decerebrate posturing, and hyperthermia may be present

Cerebellar Hemorrhage

• Headache, dizziness, and vomiting of sudden onset, and inability to stand or walk within minutes
• Can lead to coma within 12 to 24 hours in most cases
• Impaired gaze toward or forced deviation away from the lesion
• The pupils are small and reactive
• Impaired upgaze indicates upward transtentorial herniation of the cerebellar vermis and midbrain, and implies a poor prognosis
• Stance and gait should be examined in any patient who presents acutely with headache, dizziness, or vomiting

Investigative Studies

• Noncontrast CT scan should be obtained to confirm the diagnosis of intracerebral hemorrhage and assess the likelihood of a cause other than chronic hypertension
• Lobar hemorrhage, deep hemorrhage in an atypical location, or disproportionate subarachnoid blood or perihematomal edema should prompt a search for such alternative etiologies, using CT angiography or MR angiography
• Blood tests should be obtained to identify coagulopathy or thrombocytopenia as a possible cause of hemorrhage or complicating factor
• Lumbar puncture yields bloody cerebrospinal fluid, but should not be performed because of the risk of brain herniation

Treatment

• Initial management includes airway support with ventilatory assistance if required
• Hypertension should be treated by reducing systolic blood pressure to 140-179 mm Hg with intravenous nicardipine and, if needed, intravenous labetalol
• Coagulopathy should be reversed by clotting factor replacement with prothrombin complex concentrate or fresh frozen plasma
• Hyperglycemia and hypoglycemia should both be avoided and insulin or glucose administered as needed
• Seizures may occur, especially with lobar hemorrhages, but prophylactic administration of anticonvulsants is not recommended

Surgical Treatment

• Cerebellar hemorrhage - Neurologic deterioration, brainstem compression, and hydrocephalus are indications for decompressive posterior fossa surgery, which may avert a fatal outcome
• Lobar hemorrhage - Surgical evacuation can also be useful for lobar hematomas, especially those larger than 30 mL in volume and located within approximately 1 cm of the brain surface

Hemorrhagic Transformation

• Hemorrhagic transformation into a cerebral infarct is common
• Predisposing factors include thrombolytic therapy, anticoagulation, cardioembolic stroke, massive infarction, cortical gray matter infarction, and thrombocytopenia
• Treatment consists of discontinuing thrombolytic or anticoagulant drugs where applicable

Intracerebral Hemorrhage Complications

• Can complicate disorders involving either clotting factors or platelets

Cerebral Amyloid Angiopathy

• Characterized by β-amyloid deposits in the walls of leptomeningeal and cortical capillaries, arterioles, and small arteries
• Most common in elderly patients
• Typically produces lobar hemorrhage, including microbleeds, at multiple sites
• Risk factors include apolipoprotein E ε4 and ε2 alleles, anticoagulation or antiplatelet therapy, head trauma, and hypertension
• Rare hereditary cases are inherited in autosomal dominant fashion

Vascular Malformations

• Cerebrovascular malformations can affect arteries (saccular, or berry, aneurysms), veins (cavernous malformations), or their interconnections (arteriovenous malformations, or AVMs), and rupture can cause intracerebral hemorrhage
• AVMs are usually sporadic, but may also be features of Mendelian disorders, such as hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu disease)
• For unruptured AVMs, the risk of rupture is 1-3% per year
• However, when rupture occurs it carries a 10-30% mortality rate and, for survivors, a 6% risk of re-rupture over the next year

Amphetamine or Cocaine Abuse

• Can cause intracerebral hemorrhage, typically within minutes to hours after the drug is taken
• Most such hemorrhages are located in subcortical white matter and may be related to acutely elevated blood pressure, rupture of a preexisting vascular anomaly, or drug-induced arteritis