Describe a case of cerebral amyloid angiopathy-related inflammation (CAA-ri) without obvious radiographic features of cerebral amyloid angiopathy (CAA).

CAA-ri is a rare neuroinflammatory disease associated with beta-amyloid deposition in cerebral and leptomeningeal vessels. In addition to the Boston criteria for CAA, criteria have also been proposed for diagnosis of CAA-ri, including asymmetric white matter hyperintensities and cortical-subcortical hemorrhagic lesions. Diagnostic challenges emerge when these classic radiographic features are absent.

Case report.

A 71-year-old man with minimal prior medical history presented to the hospital with profound encephalopathy. He was found to have diffuse leptomeningeal enhancement in addition to scattered small areas of cortical diffusion restriction, without cerebral microhemorrhages or cortical superficial siderosis. A lumbar puncture was performed, which revealed an elevated opening pressure of 32 cmH2O, a total nucleated cell count of 298 cells/mcL (neutrophilic predominant), protein of 476 mg/dL, and glucose of 58 mg/dL (serum 116 mg/dL). Broad infectious and inflammatory testing was negative including metagenomic sequencing and autoimmune/paraneoplastic antibodies. He was treated with meningitis-dosed antibiotics and dexamethasone. Although he had some apparent initial clinical improvement, follow-up imaging revealed progression of diffuse leptomeningitis, new infarcts, and he developed focal seizures. Biopsy of brain and leptomeninges was pursued and ultimately revealed diffuse circumferential deposition of amyloid beta surrounding leptomeningeal and cortical vessels, colocalized with mixed inflammatory infiltrates, consistent with CAA-ri. He was treated with high-dose steroids but ultimately transitioned to comfort cares after a protracted hospitalization.

This case illustrates leptomeningeal-predominant CAA-ri in the absence of cerebral microhemorrhages or characteristic subcortical T2/FLAIR hyperintensities. CAA-ri should be considered in the differential diagnosis for patients presenting with an undifferentiated leptomeningitis, particularly in the setting of multifocal ischemic stroke, but even in the absence of other classic imaging features. Early recognition of CAA-ri is imperative given implications for treatment and patient outcomes.