Disease Progression in Iatrogenic Cerebral Amyloid Angiopathy

Iatrogenic cerebral amyloid angiopathy (iCAA), likely caused by transmission of amyloid-beta by medical procedures, is a rare but distinct cerebral amyloid angiopathy (CAA) subtype, with rising numbers of patients identified globally. However, given its relatively recent recognition, data on long-term outcomes and prognosis are scarce. Therefore, we aimed to investigate the clinical disease progression in patients diagnosed with iCAA.

After a systematic literature search for larger case series of iCAA (n ≥ 5), we included patients from 4 European countries (Austria, Italy, The Netherlands, and the United Kingdom) meeting modified Queen Square criteria for possible or probable iCAA. Clinical outcomes of interest were symptomatic intracerebral hemorrhage (ICH), convexity subarachnoid hemorrhage (cSAH), cognitive status at last follow-up, and mortality. We used Cox regression to investigate clinical variables associated with those outcome events.

We included 82 patients (59.8% male, median age at presentation 50 years, median latency from exposure 39 years); 50% of patients initially presented with ICH and 32.9% with cSAH/transient focal neurologic episodes. During a median follow-up time of 3.8 years (IQR 1.8-5.9; total follow-up 385 patient-years), 74 symptomatic ICH occurred, corresponding to a rate of 19.2 per 100 patient-years after first presentation. Patients who initially presented with ICH had an increased rate of recurrent ICH compared with other presentations (hazard ratio 3.14, 95% CI 1.55-6.33, p = 0.001) with a recurrence rate of 24.6 per 100 patient-years (95% CI 18.2-32.6). Patients with spinal surgery as an exposure (n = 24) had a lower rate of ICH compared with brain surgery or embolization (hazard ratio 0.34, 95% CI 0.13-0.87, p = 0.02). Six patients (7.3%) died during the follow-up period (initial presentation with ICH in 3, cSAH in 3). Cognitive impairment at last available cognitive evaluation (median 1.9 years from first presentation) was recorded in 42 patients (51.2%).

Following a long latency from presumed exposure, patients diagnosed with iCAA have a high rate of subsequent symptomatic ICH (∼20% yearly risk), with recurrence risk being the highest among patients initially presenting with ICH and those exposed by brain rather than spinal surgery. The mortality rate was low despite the high frequency of ICH.