Risk of Clinical Events in Presymptomatic Familial Cerebral Cavernous Malformations

Familial cerebral cavernous malformations (fCCM) may cause focal neurological deficits (FND) due to hemorrhagic or non-hemorrhagic events and epileptic seizures (ES). With the widespread use of magnetic resonance imaging (MRI) and genetic testing, diagnosis is now frequently established at a presymptomatic stage, before any clinical manifestation. However, the subsequent risk of a first clinical event in these individuals remains poorly defined.

We conducted a cohort-based analysis of retrospectively collected longitudinal data from 79 patients with fCCM who were asymptomatic at diagnosis (median age, 41.7 years) and managed in a national referral center.

Over 649.6 patient-years (median follow-up, 4.0 years), 23 patients (29%) experienced a first clinical event. Post-diagnostic event-free survival was approximately 97% at 1 year, 79% at 5 years, and 69% at 10 years. Incidence rates for a first event were 35.4 per 1000 person-years for any first event (FND or ES), 23.1 per 1000 person-years for a first FND, and 15.4 per 1000 person-years for a first ES. Male sex was independently associated with higher risk (HR 4.20; 95% CI, 1.60-11.04; p = 0.0036).

These data provide pragmatic post-diagnostic risk estimates to guide counseling and surveillance in asymptomatic fCCM.