Amyloid Angiopathy

Background: Cerebral amyloid angiopathy (CAA) refers to the deposition of b-amyloid in the media and adventitia of small- and mid-sized arteries (and less frequently, veins) of the cerebral cortex and the leptomeninges. It is a component of any disorder in which amyloid is deposited in the brain, and it is not associated with systemic amyloidosis. CAA has been recognized as one of the morphologic hallmarks of Alzheimer disease (AD), but it also is found often in the brains of elderly patients who are neurologically healthy. While often asymptomatic, CAA can present as intracranial hemorrhage (ICH), dementia, or transient neurologic events. ICH is the most consistent effect of CAA. Although the vast majority of cases are sporadic, 2 familial forms exist (ie, hereditary cerebral hemorrhage with amyloidosis [HCHWA]-Dutch type and HCHWA-Icelandic type).

Pathophysiology: Deposition of amyloid damages the media and adventitia of cortical and leptomeningeal vessels, leading to thickening of the basal membrane, stenosis of the vessel lumen, and fragmentation of the internal elastic lamina. This can result in fibrinoid necrosis and microaneurysm formation, predisposing to hemorrhage. Some evidence suggests that the amyloid is produced in the smooth muscle cells of the tunica media as a response to damage of the vessel wall (perhaps by arteriosclerosis or hypertension). Impaired elimination and accumulation of soluble and insoluble b-amyloid peptide may underlie the pathogenesis of CAA and may explain the link between CAA and AD.

Frequency:

• In the US: The true incidence and prevalence are hard to specify, as definite CAA can be diagnosed only at postmortem. However, estimates can be made based on autopsy series and the incidence of lobar ICH. A series of 400 autopsies found evidence of CAA in the brains of 18.3% of men and 28% of women aged 40-90 years. In a series of 117 brains of patients with confirmed AD, 83% had evidence of CAA. The prevalence of CAA increases with advancing age; in some autopsy series it has been found in 5% of individuals in the seventh decade but in 50% of those older than 90 years.

Sex: Although CAA may be found more commonly in women than men at autopsy, the incidence of ICH is the same in women and men. Hemorrhage occurs at the same age in men and women.

Treatment
Medical Care:

• CAA is largely untreatable at this time.

• The management of CAA-related ICH is identical to the standard management of ICH. Pay special attention to reversing anticoagulation, managing intracranial pressure, and preventing complications.

• If coexisting vasculitis is found on angiography and brain biopsy, long-term treatment (up to 1 y) with steroids and cyclophosphamide is indicated.

• A syndrome of subacute cognitive decline, seizures, and white matter changes on MRI with perivascular inflammatory changes on biopsy was recently described. Some patients improved clinically (but not to baseline) when given corticosteroids or cyclophosphamide.

Surgical Care:

• Hematoma evacuation can be life saving when the hematoma causes significant mass effect and predisposes to herniation, particularly when there has been no response to medical management of increased intracranial pressure. The goal of therapy is to lower intracranial pressure.

• No evidence is available from well-designed, randomized clinical trials that can help determine which patients benefit from evacuation of the hematoma. However, that the intervention should be considered in patients with intermediate-sized hematomas (20-60 cc) who have a progressive deterioration in their level of consciousness is agreed.

• Surgery should be performed before coma develops.

• Surgery is not beneficial for small or very large hematomas. Patients with small (<20>60 cc) and the patient is lethargic or comatose, the prognosis is poor despite surgical evacuation.

• Early concerns about the safety of hematoma evacuation in patients with CAA-related ICH were unfounded. Several recent series have reported low rates of mortality and postoperative hematoma; surgical evacuation of the hematoma should be performed when clinically indicated.

• No evidence supports the belief that evacuation leads to an increased rate of recurrence. A recent large series that evaluated 50 neurosurgical procedures in 37 patients with CAA-related ICH found a mortality rate of 11% and a 5% rate of postoperative hematoma that required intervention. Risk factors associated with an adverse postoperative outcome were age >75 years and the presence of a parietal hematoma.

• Although transoperative oozing from the walls of the hematoma was a common occurrence, it could be controlled easily with an absorbable hemostat (eg, oxidized cellulose, gelatin sponge) or fibrin glue.

• When determining whether evacuation of the hematoma is appropriate, consider the patient's cognitive status.

Consultations:

• Neurosurgical consultation in cases of ICH

• Neuropsychological assessment for cognitive impairment

Diet: No special diet

Activity: Activities should not be restricted. However, patients should avoid head trauma of any degree.