Seizures and Epilepsy in Patients With Untreated Cerebral Cavernous Malformations: A Prospective, Population-Based Cohort Study.
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BACKGROUND AND OBJECTIVES: Treatment decisions for patients with epileptic seizures due to cerebral cavernous malformations (CCMs) are challenging because of a paucity of studies. We aimed to assess the rates and risk factors of CCM-related seizures during long-term follow-up without CCM intervention. METHODS: This population-based study included people aged 16 years or older in Scotland who were newly diagnosed with CCM during 1999-2003 or 2006-2010, using brain MRI or pathology. From the initial presentation that led to CCM diagnosis, during prospective follow-up without CCM intervention, we analyzed the rates and risk factors for epileptic seizure(s) after any presentation, a first-ever epileptic seizure, seizure recurrence after a first unprovoked epileptic seizure, and 2-year/5-year seizure freedom among patients with CCM-related epilepsy (CRE). RESULTS: We included 300 patients with CCM (median age 44 years, interquartile range [IQR] 32-57, 159 [53%] female). During a median follow-up of 15 years (IQR 8-20), 98 (33%) patients experienced epileptic seizure(s) after any presentation, which was associated with age (adjusted hazard ratio [aHR] 0.82, 95% CI 0.71-0.95, per 10-year increment, p = 0.008) and initial presentation with epileptic seizure(s) (aHR 12.94, 95% CI 7.11-23.52, p < 0.001). Of 189 patients who had never experienced epileptic seizures at initial presentation, 6% (95% CI 2%-9%) experienced a first-ever epileptic seizure within 10 years. For 64 patients with a first unprovoked epileptic seizure at initial presentation or during follow-up, the risk of seizure recurrence within 10 years was 80% (95% CI 70%-91%), which was lower with antiseizure medicine(s) therapy after the first seizure (aHR 0.36, 95% CI 0.19-0.70, p = 0.003). Among 110 patients who had CRE at initial presentation or developed CRE during follow-up, 82% (95% CI 74%-91%) became 2-year seizure-free and 62% (95% CI 51%-72%) 5-year seizure-free at 10 years, mostly while on antiseizure medicine monotherapy (44/75 [59%] and 40/60 [67%], respectively). DISCUSSION: The risk of a first-ever epileptic seizure from CCM is low. Four of 5 patients who experience a first unprovoked epileptic seizure develop a recurrent seizure within 10 years, justifying diagnosis of CRE after a first unprovoked epileptic seizure due to CCM. Most of the patients with CRE achieve 2-year/5-year seizure freedom within 10 years. These long-term findings can inform patients and guide clinical practice.