BACKGROUND AND CLINICAL INFORMATION: Head

Summary: Cerebral amyloid angiopathy (CAA) is a very common cause of intracerebral hemorrhage, perhaps only second to hypertensive intracerebral hemorrhage in frequency. They are usually seen in normotensive adults over 60 years of age. They are almost always cerebral. Hemorhages due to CAA tend to be superficially located and have a distribution distinctly different from those resulted from hypertension. The amyloid can be detected by Congo red, thioflavin S, and immunostaining. The commonest form is due to deposition of Ab peptide in the blood vessels, the two known heditary types (Icelandic and Dutch types) are transmitted in an autosomal dominant fashion.

Age: Most commonly seen in normotensive adults over 60 years of age.

Incidence: Very common, probably only second to hypertensive intracerebral hemorrhage. It is responsible for about 10-20% of all cases of spontaneous intracerebral hemorrhage.

Association: The most common form is resulted from deposition of Ab peptide, a 4 kD peptide product of cleavage of the amyloid precursor protein (APP), and is closely associated with Alzheimer’s disease. The Icelandic form (hereditary cystatin C amyloid angiopathy) and the Dutch form (hereditary cerebral hemorrhage with amyloidosis-Dutch) are must less frequent, both are transmitted as autosomal dominant traits.

Genetics:

Icelandic form (hereditary cystatin C amyloid angiopathy): Single nucletide substitution at codon 68 of cystatin C/gamma trace leading to replacement of glutamine by leucine. Patients also have abnormally low level of cystin in the CSF.
Dutch form (hereditary cerebral hemorrhage with amyloidosis-Dutch): Mutation at codon 692 and 693 of APP.

GROSS PATHOLOGY: Head

Superficial: They tend to be more superficial and, in rare occasions, they may be subarachnoid. For the larger hemorrhagee, if is often difficult to tell if they have a superficial origin or not.

Multiple: On autopsy, there are often evidnce of hemorrhage at different stages of resorption in the same brain.

Distribution: They are almost always cerebral; the brainstem and cerebellum is seldom affected. They have a distribution that is different from that of hypertensive intracerebral hemorrhage; deep structures are not usually affected. In addition, they do not rupture into the ventricle as often as does hypertensive intracerebral hemorrhage.