Cerebral Amyloid Angiopathy-Related Inflammation

Cerebral amyloid angiopathy related inflammation is a subacute inflammatory encephalopathy in people with cerebral amyloid angiopathy, caused by an immune response to amyloid beta deposits in cerebral vessel walls. It responds to immunosuppression, so early recognition matters.

It is rare and usually affects people in their sixties and seventies. It is a cause of treatable rapid cognitive decline.

Pathophysiology. An autoimmune reaction to vascular amyloid beta produces perivascular inflammation and vasogenic oedema. Carriage of two APOE e4 alleles is a strong risk factor. A similar mechanism underlies amyloid related imaging abnormalities during anti-amyloid antibody treatment.

Subacute cognitive decline over weeks, headaches, seizures, focal neurological deficits, behavioural change, and sometimes altered consciousness.

Red flags.

• Rapid cognitive decline over weeks.
• New seizures or focal deficits.
• Fever or immunosuppression (consider infection).

MRI shows asymmetric, patchy white matter hyperintensities on T2 and FLAIR sequences with mass effect, often extending to cortex, plus microbleeds or cortical superficial siderosis on susceptibility sequences. Contrast enhancement of the leptomeninges may be present. CSF may show raised protein with mild pleocytosis; test also for infection and autoimmune encephalitis. Biopsy is reserved for atypical cases.

Differential diagnosis.

• Primary angiitis of the central nervous system and amyloid beta related angiitis.
• Brain tumour, infection and progressive multifocal leukoencephalopathy.
• Posterior reversible encephalopathy syndrome and autoimmune encephalitis.
• Creutzfeldt-Jakob disease.

Give methylprednisolone 1 g intravenously daily for 3 to 5 days, then oral prednisolone 1 mg/kg daily, tapered slowly over several months, with bone protection, gastric protection and glucose monitoring. Add a steroid sparing agent (such as mycophenolate or cyclophosphamide) for relapse or steroid dependence. Treat seizures (for example levetiracetam 500 mg twice daily). Avoid antithrombotics and anticoagulants unless strongly indicated, because of the haemorrhage risk. Relapses occur in about a third.

Monitoring. MRI at 4 to 8 weeks and during taper, with symptom review.

Referral and escalation. Refer urgently to neurology.