Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) — bleeding directly into the brain parenchyma — is the second most common form of stroke and the most lethal. The neuropathology of ICH reflects both the mechanism (which determines the location and pattern) and the temporal evolution (which determines what is found at autopsy). Recognizing the location of an ICH, the appearance of the vessel that bled, and the surrounding tissue reaction allows the cause to be inferred and the time of the hemorrhage to be estimated. This page covers the major causes of ICH, the anatomic distribution by mechanism, the temporal evolution, and the imaging-pathology correlation.

Major Causes of ICH

Hypertensive Hemorrhage

The most common cause of spontaneous ICH. Chronic hypertension damages small penetrating arteries; eventually a vessel ruptures. Substrate:

• Lipohyalinosis: lipid and hyaline deposition in small vessel walls, with replacement of normal architecture.
• Charcot-Bouchard microaneurysms: small (under 1 mm) outpouchings on small penetrating arteries; sites of rupture.

Classical locations (in order of frequency):

1. Putamen (most common location of hypertensive ICH).
2. Thalamus.
3. Pons.
4. Cerebellum.
5. Lobar (deep white matter — less common in hypertensive ICH; raise CAA in older patients).

The combination of deep location + hypertension + lipohyalinosis + Charcot-Bouchard aneurysm is the classic hypertensive ICH picture.

Cerebral Amyloid Angiopathy (CAA)

Beta-amyloid deposition in walls of cortical and leptomeningeal arteries; vessel weakening leads to rupture. Classical features:

• Lobar location (frontal, parietal, occipital, temporal cortex/subcortex).
• Multiple small or larger hemorrhages.
• Microbleeds visible on SWI MRI in cortical and leptomeningeal distribution.
• Patient typically over 60.
• Often associated with Alzheimer disease pathology.

Pathology: Congo red apple-green birefringence in vessel walls; IHC for beta-amyloid (Aβ40 predominant in CAA, vs Aβ42 in parenchymal plaques).

Vascular Malformations

• AVM: tangled abnormal vessels with arteriovenous shunting.
• Cavernous malformation: clusters of dilated thin-walled vascular channels; hemosiderin rim.
• Dural AV fistula: abnormal connection between dural artery and venous sinus.
• Capillary telangiectasia: usually incidental, brainstem location.

Aneurysm Rupture

Saccular (berry) aneurysms at the Circle of Willis rupture into the subarachnoid space (SAH), sometimes with parenchymal extension. Sites:

• Anterior communicating artery (most common).
• Posterior communicating artery.
• Middle cerebral artery bifurcation.
• Basilar tip.

Other Causes

• Anticoagulation-related: increasingly common.
• Antiplatelet-related: less common; mild effect.
• Tumor hemorrhage: melanoma, choriocarcinoma, renal cell, lung, breast — and primary brain tumors (glioblastoma, oligodendroglioma).
• Hemorrhagic transformation of infarct: see ischemic infarction page.
• Trauma: contusion, shear injury.
• Drug-induced: cocaine, methamphetamine, ecstasy.
• Vasculitis: primary CNS angiitis, secondary vasculitis.
• Septic emboli: with hemorrhagic infarction, often mycotic aneurysm.
• Bleeding diatheses: thrombocytopenia, leukemia, DIC.
• Pregnancy-related: eclampsia, postpartum cerebral angiopathy, reversible cerebral vasoconstriction syndrome.

Anatomic Patterns by Cause

Temporal Evolution

Hyperacute (Minutes to Hours)

• Liquid red blood, clot formation.
• Mass effect from the hematoma.
• Gross: red, blood-filled cavity with surrounding parenchyma.

Acute (Hours to Days)

• Clot organization; fibrin and platelets.
• Peri-hematomal edema develops (peaks 3-7 days).
• Hemoglobin breakdown begins — methemoglobin formation.

Subacute (Days to Weeks)

• Macrophage infiltration with phagocytosis of red cells.
• Hemosiderin deposition in macrophages.
• Reactive astrogliosis at margins.
• Liquefactive necrosis of damaged parenchyma.

Chronic (Weeks to Years)

• Cavitation with cyst formation.
• Hemosiderin rim: permanent; Prussian blue positive. Visible on SWI/GRE as low signal.
• Gliotic margin.
• Atrophy and ex vacuo ventricular dilation.

Imaging-Pathology Correlation

Gross Pathology by Location

Putaminal Hemorrhage

Most common location. Often dissects into the external capsule and internal capsule. May extend to ventricles via the caudate. Clinically: contralateral hemiparesis from internal capsule involvement.

Thalamic Hemorrhage

Often dissects to ventricles. Clinically: hemisensory loss + often hemiparesis, sometimes wrong-way eye deviation, vertical gaze palsy.

Pontine Hemorrhage

Hypertensive bleed into the central pons. Often devastating; pinpoint reactive pupils, quadriparesis, decerebrate posturing, hyperthermia, coma. High mortality.

Cerebellar Hemorrhage

Often deep, hemispheric. Mass effect from blood + edema can compress the brainstem and obstruct the fourth ventricle. Surgical evacuation for hematomas > 3 cm or those compressing the brainstem.

Lobar Hemorrhage

Cortical/subcortical white matter. CAA most common cause in elderly. Tumor and vascular malformation in younger patients.

Intraventricular Hemorrhage

From extension of deep ICH (especially thalamus, caudate). Hydrocephalus from outflow obstruction; clinical decline. EVD if hydrocephalus.

Subarachnoid Hemorrhage

Bleeding into the subarachnoid space; pathologically distinct from parenchymal ICH:

• Diffuse subarachnoid blood with rapid spread along basal cisterns.
• Most common cause: aneurysm rupture.
• Other: trauma, AVM, perimesencephalic SAH (often benign, idiopathic).
• Complications: vasospasm (5-14 days), hydrocephalus (early communicating or later from arachnoid scarring), rebleeding, seizures.
• Pathology: blood in subarachnoid space, sometimes coating brain surface; later chronic arachnoid scarring (siderosis).

Superficial Siderosis

Chronic recurrent SAH or recurrent bleeding into CSF deposits hemosiderin on pial surfaces and cranial nerves. Clinical: progressive bilateral hearing loss + cerebellar ataxia + myelopathy. MRI: hemosiderin on T2/SWI on brain surface, cerebellum, cranial nerves.

Secondary Effects of ICH

• Mass effect: peaks at 3-7 days; herniation possible.
• Hydrocephalus: from ventricular extension or obstruction.
• Seizures: from cortical involvement.
• Re-bleeding: in the acute phase; major risk.
• Cerebral edema: peri-hematomal; treatable.
• Vasospasm: SAH-related; rare with pure ICH.
• Cognitive decline: especially with CAA, multiple lobar bleeds.

Special Patterns

Microbleeds

Small (under 5 mm) hemosiderin deposits visible on SWI/GRE. Different distributions reflect different pathologies:

• Deep distribution (basal ganglia, thalamus, pons): hypertensive small vessel disease.
• Lobar/cortical distribution: CAA.
• Mixed: combined disease.

Microbleeds are markers of vascular fragility and predict future ICH risk.

Convexity Subarachnoid Hemorrhage (cSAH)

Localized SAH at the brain convexity, often from CAA. Different from basal cistern SAH from aneurysm rupture. Risk factor for subsequent lobar ICH.

Hemorrhagic Tumor

Some tumors bleed: melanoma metastasis (“hemorrhagic met”), renal cell, choriocarcinoma, lung, breast; among primary tumors, glioblastoma and oligodendroglioma. Tumor cells often visible in or around the hematoma — image at distance from acute hemorrhage to detect tumor.

Imaging Findings to Look For

• Spot sign: contrast extravasation within ICH on CT angiography — predicts hematoma expansion.
• Swirl sign: heterogeneous density within ICH on CT — active bleeding.
• Black hole sign: density variation within ICH — active expansion.
• Hyperdense vessel sign: thrombosed vessel (ischemic stroke); distinguishes from ICH.
• Hemosiderin rim: chronic hemorrhage; SWI/GRE.

🔍 Did You Know?

The neuropathologist can often distinguish hypertensive ICH from cerebral amyloid angiopathy (CAA) at the autopsy table based on location and vessel pathology — and the distinction matters enormously for the patient’s surviving family. Hypertensive ICH is typically deep (putamen, thalamus, pons, cerebellum) and arises from lipohyalinosis of small penetrating arteries — often with Charcot-Bouchard microaneurysms. CAA-related ICH is typically lobar (cortical and subcortical white matter) and arises from beta-amyloid deposition in cortical and leptomeningeal vessels — confirmed by Congo red apple-green birefringence and beta-amyloid IHC. The distinction has practical implications: CAA is associated with increased risk of future lobar ICH (10-15% per year in symptomatic patients), with cognitive impairment, and with Alzheimer disease (the two often coexist). Hypertensive ICH risk is reduced by aggressive BP control, while CAA has no specific treatment but anticoagulation should generally be avoided. The Boston criteria — based on clinical features and MRI findings of lobar bleeds, microbleeds, and superficial siderosis — allow probable CAA to be diagnosed during life without biopsy, but the gold standard remains tissue: Congo red and Aβ IHC on cortical vessel walls. Recognizing the location and the vessel changes is fundamental neuropathology and translates directly into clinical management.

Pitfalls and Pearls

• Hypertensive ICH: deep (putamen > thalamus > pons > cerebellum). Charcot-Bouchard microaneurysms; lipohyalinosis.
• CAA-related ICH: lobar (cortical/subcortical). Congo red + Aβ IHC in vessel walls. Elderly patient.
• Putamen is the most common hypertensive ICH location.
• Pontine hypertensive ICH: pinpoint reactive pupils + quadriparesis + decerebrate + hyperthermia. High mortality.
• Cerebellar ICH > 3 cm or brainstem compression: surgical evacuation.
• Lobar ICH in young patient: image for AVM, tumor, vasculitis, cavernous malformation.
• Lobar ICH in elderly: CAA top of differential.
• Multiple lobar microbleeds on SWI: CAA.
• Multiple deep microbleeds: hypertensive small vessel disease.
• Hemosiderin rim: chronic bleed; permanent.
• Spot sign on CTA: hematoma expansion risk.
• Aneurysm rupture: SAH ± parenchymal extension; PCom aneurysm classic at PCom-ICA junction.
• Convexity SAH: think CAA in elderly.
• Superficial siderosis: chronic recurrent bleeding → bilateral hearing loss + ataxia + myelopathy.
• Tumor hemorrhage: melanoma, renal cell, choriocarcinoma, lung, breast; among primaries, GBM and oligodendroglioma.
• Anticoagulation-related ICH: increasingly common; reverse anticoagulant urgently (4-factor PCC for warfarin; andexanet for factor Xa; idarucizumab for dabigatran).

References

1. Love S, Budka H, Ironside JW, Perry A, eds. Greenfield’s Neuropathology. 9th ed. CRC Press; 2015.
2. Qureshi AI, Mendelow AD, Hanley DF. Intracerebral haemorrhage. Lancet. 2009;373(9675):1632-1644.
3. Greenberg SM, Vernooij MW, Cordonnier C, et al. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8(2):165-174.
4. Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology. 2010;74(17):1346-1350.
5. Mayer SA, Rincon F. Treatment of intracerebral haemorrhage. Lancet Neurol. 2005;4(10):662-672.