Clinical-radiological presentation and natural history of iatrogenic cerebral amyloid angiopathy

Background We aimed to describe neuroimaging features, clinical profiles and long-term outcomes in patients with iatrogenic cerebral amyloid angiopathy (iCAA). Methods We performed a systematic literature search for case series of iCAA and included individual patients and their longitudinal clinical and neuroimaging data in this pooled cohort study. Patients meeting a modified version of the Queen Square criteria for iCAA were included. Baseline and follow-up MRIs were centrally analysed for markers of CAA using validated rating scales. Results We included 51 patients (68.6% male, median age at presentation 48 years), 51.0% with probable and 49.0% with possible iCAA. We evaluated 219 MRIs acquired over a median follow-up time of 3.7 years (IQR 1.8–6.4). There were 43 symptomatic intracerebral haemorrhages (ICH) in 24 patients during follow-up, a rate of 16.7 per 100 patient-years. Patients with previous supratentorial brain surgery had an ipsilateral-dominant distribution and spread of haemorrhagic markers on MRI. 14/51 (27.5%) patients had transient inflammatory changes (cortical or parenchymal oedema, sulcal hyperintensities). Haemorrhagic markers progressed during follow-up. In addition to 43 symptomatic ICH, 36 asymptomatic ICH (mostly smaller intragyral haemorrhages) were detected on follow-up scans. Besides numerous lobar microbleeds (median 16 at baseline, 53 at last followup), deep microbleeds were present in 19.6% of patients at baseline and 44.4% at follow-up. Severe perivascular spaces in centrum semiovale were common at baseline (64.7%) and follow-up (95.6%). Conclusions Patients with iCAA appear to have distinctive MRI characteristics, which might differentiate iCAA from other CAA subtypes and provide new insights into underlying disease mechanisms.