TOPLINE:

The long-term risk for a first-ever symptomatic intracranial haemorrhage (ICH) or new, non-haemorrhagic, persistent/progressive focal neurologic deficit (FND) from cerebral cavernous malformations (CCMs) was low, but the risk for recurrence was significantly higher, declining markedly after 5 years from the first event.

METHODOLOGY:

• Researchers conducted a prospective, population-based study to evaluate outcomes and risks for untreated CCMs over a long follow-up period.
• They included 300 patients (median age, 44 years; 53% women) newly diagnosed with CCMs in Scotland during two time periods (1999-2003 and 2006-2010).
• The primary outcome was a composite of symptomatic ICH or new, non-haemorrhagic, persistent/progressive FND related to CCMs (ICH/FND).

TAKEAWAY:

• Overall, 29% of patients presented with epileptic seizure, 27% with ICH/FND, and 44% incidentally; 16% had a brainstem CCM.
• During a median follow-up of 15 years without treatment, 13% of patients experienced ICH/FND. Presentation with ICH/FND (adjusted HR [aHR], 5.52) and the presence of a brainstem CCM (aHR, 4.62; both P < .0001) were strong predictors of future ICH/FND events.
• The risk for a recurrent ICH/FND was 8.66 times higher than the risk for a first event (P < .0001), with the risk for recurrence declining by 50-fold from 0.109 over the first 5 years to 0.002 in the subsequent 20 years (P < .0001).
• Of the 219 patients who presented incidentally or with epileptic seizure(s), only 12 experienced a first ICH/FND, with a 10-year risk of 5% (95% CI, 2%-8%).

IN PRACTICE:

"These long-term findings are reassuring for patients who escape recurrent ICH/FND over five years after a first ICH/FND and focus future randomised controlled trials and everyday clinical practice on a 5-year time horizon to which the up-front risks of CCM interventions are compared, as thereafter CCMs often become quiescent," the authors wrote.

SOURCE:

The study was led by Abel Clemens Adriaan Sandmann, Amsterdam UMC, Department of Neurology, University of Amsterdam, Amsterdam, the Netherlands, and was published online on September 1, 2025, in The Lancet Regional Health - Europe.

LIMITATIONS:

The study may have missed certain outcomes as it relied on events being reported to general practitioners or resulting in hospitalisations. Moreover, rates of ICH may have been underestimated. Additionally, the follow-up time for some patients included in both the first and recurrent event analyses may have overlapped.

DISCLOSURES:

The study was funded by the Medical Research Council, the Chief Scientist Office of the Scottish Government, and the Stroke Association. The authors reported no direct compensation for this article; however, some received institutional grants or travel support or held equity in companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.