Iatrogenic Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Case Series.

Abstract

Background and objectives: Variants of cerebral amyloid angiopathy (CAA) have been increasingly reported. Iatrogenic CAA (iCAA) is a subtype arising in patients with a history of neurosurgery. Current etiopathogenetic hypotheses focus on previous exposure to contaminated materials, such as cadaveric dura, followed by a prion-like mechanism. CAA-related inflammation (CAA-ri) represents the inflammatory variant of CAA, usually with a good response to immunosuppressive therapy. To date, the association between iCAA and CAA-ri has not been clarified yet. This study reports cases of iCAA evolving into CAA-ri, emphasizing the clinical and radiologic overlaps between these conditions.

Methods: This retrospective observational study included patients with clinical and radiologic features of CAA-ri and a history of neurosurgical intervention, observed at 2 Italian neurologic centers. Patients were identified from CAA databases and screened for neurosurgical history before 1990. Eligible cases met diagnostic criteria for CAA-ri. Clinical data were anonymized and included surgical details, evidence of amyloid-β in the CNS (amyloid-PET, CSF biomarkers, genetic screening), and CAA-ri features (symptoms, imaging findings, treatment, and outcomes).

Results: We identified 6 patients with iCAA who developed clinical and instrumental features of CAA-ri during their follow-up. The mean age at neurosurgery was 17.2 years (range: <1-43) while the onset of CAA-ri occurred at 61.8 years (range: 48-79), with an average latency of 44.7 years (range: 36-59). Despite immunosuppressive treatment, 2 patients experienced a rapid decline in their clinical condition and deceased within a few months from CAA-ri onset.

Discussion: This study increases awareness about the potential occurrence of CAA-ri in patients with iCAA, confirming its aggressive nature and highlighting the importance of neuroinflammation in the pathogenesis of the disease. In these patients, CAA-ri seems to be associated with a severe clinical course and a poor response to steroid treatment, often resulting in a fatal outcome in the short term.