Long-term outcome of epilepsy and cortical malformations due to abnormal migration and postmigrational development

Laura Licchetta, Luca Vignatelli, Francesco Toni, Andrea Teglia, Laura Maria Beatrice Belotti, Lorenzo Ferri, Veronica Menghi, Barbara Mostacci, Lidia Di Vito, Francesca Bisulli, Paolo Tinuper. Long-term Outcome of Epilepsy and Cortical Malformations Due to Abnormal Migration and Postmigrational Development. A Cohort Study. Neurology Jul 2022, 99 (1) e23-e32; DOI: 10.1212/WNL.0000000000200352

Abstract

Objective To evaluate the long-term outcomes of patients with epilepsy and malformations of cortical development (MCD).

Methods We conducted a historical cohort study of patients with epilepsy and MCD due to impaired neuronal migration and postmigration organization with a follow-up period of ≥5 years. For each patient, MCD was classified after accurate neuroimaging reappraisal by an expert neuroradiologist. The primary outcome was remission, defined as a period of seizure freedom ≥5 years at any time from epilepsy onset. We used Kaplan-Meier estimates for survival analysis and univariate and multivariate Cox regression analyses to evaluate baseline variables as possible factors associated with remission.

Results The cohort included 71 patients (M/F 31/40) with a 17-year median follow-up (1,506 person-years). About half (49.3%) had heterotopia, 35.2% polymicrogyria, 7% lissencephaly, and 8.5% the combination of 2 MCD. The mean age at seizure onset was 12.4 ± 7.2 years. Intellectual disability and neurologic deficits were observed in 30.4% and 40.9%, respectively. More than 60% of patients had refractory epilepsy. In 3 patients who underwent epilepsy surgery, MCD diagnosis was confirmed by histology. At the last visit, 44% of patients had been seizure-free during the previous year, but none of them had stopped antiseizure medication. Thirty patients achieved remission (42.2%) at some point in their disease history, whereas 41 individuals (57.8%) had never been in remission for ≥5 years. The cumulative remission rate was 38% by 20 years from inclusion. In the Cox model, unilateral distribution of MCD (hazard ratio [HR] 2.68, 95% CI 1.04–6.92) and a low seizure frequency at onset (HR 5.01, 95% CI 1.12–22.5) were significantly associated with remission.

Discussion Patients with epilepsy and MCD showed a remission rate of 38% by 20 years from onset. Unilateral distribution of the MCD is associated with a 3-fold probability of achieving remission. About 40% of patients showed a drug-sensitive condition with risk of relapse during their epilepsy course.

Classification of Evidence This study provides Class II evidence that in patients with epilepsy and MCD, unilateral MCD and low seizure frequency at onset are associated with achieving epilepsy remission.