Cerebral amyloid angiopathy (CAA) commonly presents with intracerebral hemorrhage due to amyloid deposition in the leptomeningeal and small/medium vessels. CAA-related inflammation (CAA-ri) is an acute/subacute inflammatory response to amyloid and typically presents with cognitive changes, headache, seizure and/or focal neurological deficits. While both CAA and CAA-ri can be supported by clinical and radiographic findings, atypical cases generally require biopsy.

A 77-year-old right-handed-man with recently diagnosed Miller-Fisher Syndrome presented with one day of aphasia. Exam was notable for a transcortical sensory aphasia and right homonymous hemianopsia. CT head showed a left occipital intracerebral hemorrhage. MRI brain with contrast showed perihematomal edema and leptomeningeal enhancement in the left temporal and occipital lobes. MRA of the vessel walls was without vasculitis. EEG showed left temporal slowing. Pan CT and whole body PET scan did not demonstrate malignancy. LP revealed minimally elevated protein with negative infectious studies, paraneoplastic panel, flow cytometry and cytology. Extensive rheumatological testing was unremarkable, aside from ESR(65mm/hr), RF(18.6IU/mL), and GQ1B IGG/IGM(358IV).

Given persistent aphasia, repeat MRI was done on hospital day 7 which showed stable occipital hemorrhage but worsening left temporal, occipital, and parietal lobe leptomeningeal enhancement. An occipital lobe and leptomeningeal biopsy was performed on hospital day 13. IV methylprednisolone was started on hospital day 14 with significant improvement in his aphasia. Pathology showed CAA without evidence of perivascular or transmural inflammation. Despite unsupportive biopsy, steroids were continued and long-term immunosuppression for CAA-ri is planned.

While brain biopsy confirmed CAA as the cause of occipital hemorrhage, it did not elucidate the etiology of the leptomeningeal enhancement. However, CAA-ri is most likely the source of his leptomeningeal enhancement given the extensive, negative workup and response to steroids. This case highlights the challenge of diagnosing CAA-ri even when biopsy is pursued given the segmental distribution of inflammation.