Inherited Cerebrovascular Diseases

Not a distinct disease, except in rare genetic forms

Found in 98% of confirmed cases of Alzheimer's disease

Usual age range: 70 to 80 years; rarely symptoms may be present in fifth to sixth decades

Leads to increased risk for microscopic and large lobar hemorrhages

Hemorrhage typically involves superficial regions of cerebral cortex

Symptoms depend on anatomic location of hemorrhage

Any lobe of the brain can be affected, occipital most common

Lobar hemorrhages tend to be peripheral and usually involve the cerebral cortex

Contralateral neglect syndrome when right parietal lobe affected

Hemorrhages can present as a massive stroke or recurrent hemorrhagic infarctions

Cognitive impairment worsens as the disease progresses

Acute lobar hemorrhage may cause death resulting from herniation and mass effect

Removal of blood is often indicated, but bleeding from amyloid-laden blood vessels can complicate surgery

Immunosuppressants are indicated in ABRA and can lead to dramatic responses

CT is the most effective imaging tool for detection of acute hemorrhage

Gradient-echo (GE) MRI can detect millimeter-sized foci of blood products in brain and thus can be used to determine hemorrhagic burden over time

β-amyloid deposits can be visualized on imaging by specific probes and positron emission tomography

If hemorrhage is present, it will be located in a superficial or peripheral location—cerebral cortex and leptomeninges

Can often have multiple hemorrhages or hemorrhagic necrosis (infarcts) of different ages; hemosiderin deposition seen with remote hemorrhage

Hyalinized-appearing blood vessels with mural thickening and effacement by eosinophilic, homogeneous, acellular material

Amyloid accumulates in the basement membrane around smooth muscle cells, eventually leading to destruction of the muscularis

Generally, the endothelium is spared until late-stage disease

Late-stage vessels often have “double-barrel contour” of amyloid accumulation

Inflammation in ABRA: lymphocytes, plasma cells, macrophages, and multinucleated giant cells

Congo red staining has characteristic “apple-green” birefringence under polarization

Immunohistochemical stain for Aβ-amyloid peptide can detect the accumulations, as well as neuritic (amyloid) plaques (like those seen in Alzheimer's disease) in the cerebral cortex

Rare genetic forms with accumulation of transthyretin, gelsolin, cystatin C, and prion protein

Primary angiitis of the central nervous system (PACNS)

Hypertensive vasculopathy