Long-term outcomes of untreated cerebral cavernous malformations: a prospective, population-based cohort study.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 41132766.
- Also identified by DOI 10.1016/j.lanepe.2025.101410 and PMC identifier 12541635.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Treatment decisions for cerebral cavernous malformations (CCM) currently rely on risk extrapolation from short-term studies, despite potential variations over time. This study aims to quantify the risks and functional outcomes of untreated CCMs during long-term follow-up. This population-based study included people aged ≥16 years in Scotland who were newly diagnosed with CCM between 1 January 1999 and 31 December 2003 or 1 January 2006 and 31 December 2010, using brain MRI or pathology. We analysed clinical events and functional outcomes using the Oxford Handicap Scale (OHS) during prospective follow-up without CCM intervention until 31 December 2023. The primary outcome was a composite of symptomatic intracranial haemorrhage (ICH) or new, non-haemorrhagic, persistent/progressive focal neurological deficit (FND) definitely or possibly related to CCM (ICH/FND). Among 300 patients (median age 44 years [IQR 32-57], 159 [53%] female, 48 [16%] brainstem CCM) included during 1999-2003 or 2006-2010, 81 (27%) presented with ICH/FND, 88 (29%) with epileptic seizure(s), and 131 (44%) incidentally. Over 4779 person-years of follow-up (completeness 95%), 44 patients were censored after microsurgical resection (n = 41) and stereotactic radiosurgery (n = 3). During a median untreated follow-up of 15 years (IQR 8-20), 40 (13%) patients experienced ICH/FND, 72 (24%) experienced dependence (OHS score 3-5), and 53 (18%) died (n = 7 [2%] related to CCM). The hazard of recurrent ICH/FND was higher than the first-event hazard (hazard ratio 8.66 [95% CI 4.44-16.90], p < 0.0001). The hazard rate of recurrent ICH/FND declined approximately 50-fold from 0.109 (95% CI 0.074-0.160) over the first five years to 0.002 (0.000-0.015) in the subsequent 20 years (p < 0.0001). The risk of a first ICH/FND from CCM is low, while the risk of recurrence is significantly higher, although the recurrence risk declines dramatically five years after a first ICH/FND. These long-term findings can guide clinical decision-making, and suggest focussing on a 5-year risk horizon rather than extrapolating annual risks to patients' lifetimes. Medical Research Council, Chief Scientist Office of the Scottish Government, and Stroke Association.