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Lookup NU author(s): Professor Phil WhiteORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Authors. Background: 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. Methods: 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). Findings: 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). Interpretation: 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. Funding: Medical Research Council, Chief Scientist Office of the Scottish Government, and Stroke Association.
Author(s): Sandmann ACA, Vandertop WP, White PM, Verbaan D, Coutinho JM, Al-Shahi Salman R
Publication type: Article
Publication status: Published
Journal: The Lancet Regional Health - Europe
Year: 2025
Volume: 57
Print publication date: 01/10/2025
Online publication date: 01/09/2025
Acceptance date: 18/07/2025
Date deposited: 07/10/2025
ISSN (electronic): 2666-7762
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.lanepe.2025.101410
DOI: 10.1016/j.lanepe.2025.101410
Data Access Statement: The audit and research protocols were published on the SAIVMs website and with the Directory of Clinical Databases (DoCDat). Deidentified individual participant data that underlie the results reported in this article will be made available for scientific purposes upon formal request and consequent approval of the proposal after publication. Reasonable requests should be sent to the corresponding author.
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