Amyloid-Beta Related Angiitis

Amyloid beta related angiitis is a granulomatous inflammation of small and medium cerebral and leptomeningeal vessels associated with amyloid beta deposition in vessel walls. It is a subtype of primary angiitis of the central nervous system and overlaps with cerebral amyloid angiopathy related inflammation.

It is rare, with onset usually in the sixth decade or later, and may be underdiagnosed.

Pathophysiology. Amyloid beta in vessel walls triggers a granulomatous, giant cell mediated immune reaction that damages the vessel wall, causing ischaemia, inflammation and sometimes haemorrhage.

Subacute encephalopathy with cognitive decline, headache, seizures, stroke like episodes and focal deficits. It may be monophasic or relapsing. Fever and systemic symptoms are absent.

Diagnosis is by brain and leptomeningeal biopsy showing vasculitis with amyloid beta deposition. MRI shows infarcts, white matter lesions, leptomeningeal enhancement and sometimes microbleeds; angiography is usually normal because small vessels are affected. CSF often shows a mild lymphocytic pleocytosis and raised protein. Exclude infection (including tuberculosis, syphilis and varicella zoster), systemic vasculitis, lymphoma and malignancy.

Differential diagnosis.

• Cerebral amyloid angiopathy related inflammation.
• Other primary angiitis of the central nervous system and secondary vasculitis.
• Infection, lymphoma and reversible cerebral vasoconstriction syndrome.

Give high dose corticosteroids (methylprednisolone 1 g intravenously daily for 3 to 5 days, then prednisolone 1 mg/kg daily). For severe or relapsing disease add cyclophosphamide 0.5 to 1 g/m2 intravenously monthly for up to 6 months, with mesna and dose reduction for renal impairment, then maintenance with azathioprine 2 mg/kg daily after thiopurine methyltransferase testing, or mycophenolate. Give antiseizure drugs as needed, plus bone and gastric protection and prophylaxis against Pneumocystis jirovecii during prolonged immunosuppression.

Monitoring. Repeat MRI, symptoms, blood counts and liver tests.

Referral and escalation. Refer to neurology and neuropathology early.