Sleep-related hypermotor epilepsy: Long-term outcome in a large cohort

Abstract

Objective: To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE).

Methods: We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed.

Results: We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26-14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31-5.85, p = 0.008) were associated with TR.

Conclusions: Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.

Figure 1. Flow diagram of patient recruitment

SHE = sleep-related hypermotor epilepsy. *The final diagnosis was confirmed by 3 experts in sleep medicine and epileptology (P.T., F.P., F.B.). The final agreement required was 100%; otherwise, cases were considered doubtful and excluded. **All cases with video-polysomnographic (VPSG) recording of motor events of uncertain nature/not stereotyped (n = 34) or for which there was no agreement among the experts (n = 3).

Figure 2. Terminal remission rate

The green curve representing the cumulative probability of achieving terminal remission (TR) showed a slow trend of remission: 20.4% at 10 years from onset (97 patients at risk), 23.5% after 20 years (59 patients at risk), and 28.4% after 30 years (24 patients at risk) and after 40 years (13 patients at risk). The gray area represents the 95% confidence interval.

Figure 3. Terminal remission predictors

Terminal remission (TR) as a function of (A) any underlying brain disorder (at least one of the following: intellectual disability, personal history of perinatal insult, pathologic neurologic examination, brain structural abnormalities): absence of any underlying brain disorder (green curve) and presence of any underlying brain disorder (blue curve) identified; (B) typical sleep-related hypermotor epilepsy (SHE; 100% of sleep-related events): patients with typical SHE (green curve) showed a higher TR rate than patients experiencing seizures in wakefulness (blue curve); (C) age at epilepsy onset: the cumulative probability of TR is higher in patients with age at onset ≥6 years (green curve) compared to patients with earlier epilepsy onset (blue curve); (D) combined vs single TR predictors (absence of any underlying brain disorder, typical SHE, and age at onset ≥6 years): the combination of at least 2 of the TR determinants identified (green curve) compared to having one or none of them (blue curve).