The Inflammatory Side of Iatrogenic Cerebral Amyloid Angiopathy: Rethinking Therapeutic Opportunities

Background: Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA occurring decades after neurosurgical procedures involving cadaveric dural grafts. While typically associated with recurrent lobar intracerebral hemorrhages, recent reports suggest a possible overlap with CAA-related inflammation (CAAri). We report a case of iCAA with features indicative of active neuroinflammation that demonstrated a positive response to immunosuppressive therapy. Methods: Over a 12-year natural history, the patient underwent a comprehensive work-up, including serial clinical assessments, brain MRIs, core CSF biomarker analysis, amyloid PET imaging, and next-generation sequencing panel testing. Results: Previous clinical charts confirmed the use of cadaveric graft (Lyodura) in a neurosurgical intervention thirty years before. During hospitalization for seizures, brain MRI revealed, along with a severe form of CAA, an area of vasogenic edema. Given the suspicion of an active inflammatory process, corticosteroid and subsequent methotrexate maintenance therapy were introduced, leading to clinical and radiological improvement. Over 30 months of follow-up, the patient has remained clinically and radiologically stable, with no new hemorrhagic or inflammatory events. Conclusions: This case highlights the potential interplay between iCAA and neuroinflammation. The absence of new hemorrhages following immunosuppression suggests a possible disease-modifying effect, warranting further investigation into the role of neuroinflammation in iCAA and its therapeutic implications.