Impact of the Occurrence While Sleeping of First Unprovoked Seizure on Seizure Recurrence: A Systematic Review

Abstract

Background and purpose: The impact of the occurrence while sleeping of first unprovoked seizure (FUS) on seizure recurrence in people with FUS is currently unclear. This uncertainty makes it challenging for physicians to determine whether to apply antiseizure medications (ASMs) to people with FUS while sleeping (FUS-S). This study aimed to determine the impact of the occurrence while sleeping of FUS.

Methods: We searched the MEDLINE, Embase, Cochrane Library, Web of Science, and Scopus electronic databases. Among retrieved studies, we selected those that provided information on the number of people with FUS, and relapsed people among these in each instance of FUS-S and FUS when waking (FUS-W). We used a random-effects model for meta-analyses.

Results: Of the 3,582 identified studies, 13 were eligible for systematic review. Seven of these 13 studies were deemed adequate for inclusion in a meta-analysis since they provided information at the time point of 2 years follow-up after FUS. The seven studies were of high quality regarding their risk of bias. When combining these 7 studies, the total sample comprised 1,659 people, of which 626 had FUS-S and 1,033 had FUS-W. The relative risk of seizure recurrence between FUS-S and FUS-W was 1.627. The seizure recurrence rates (SRRs) were 59.8% and 36.5% in the FUS-S and FUS-W groups, respectively.

Conclusions: We verified that the SRR was higher among people with FUS-S than FUS-W. After 2 years of follow-up, the SRR in people with FUS-S was about 60%. It is preferable to initiate an ASM for people with FUS-S.

Systematic review registration: PROSPERO registration number CRD42021266191.

Keywords: epilepsy; meta-analysis; prevalence; recurrence; seizures.

Fig. 1. Identification of relevant studies based on the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020). Among 3,582 studies identify by database searching, we removed 1,016 studies that represented duplicated data. There were 68 studies left after screening the remaining 2,566 studies. After excluding 21 studies through a preliminary review, we evaluated whether the remaining 47 were eligible for inclusion in this systematic review by carefully assessing their full texts. We eventually included 13 studies in this review after removing 34 of the 47 articles for various reasons.

Fig. 2. Increasing seizure recurrence risk (SRR) after 2 years of follow-up if a first unprovoked seizure (FUS) occurs while sleeping. The total number of patients was 1,659 when combining the 7 cohort studies, with 626 people with the FUS occurring while sleeping (FUS-S) and 1,033 persons with it occurring when waking (FUS-W). The occurrence of FUS-S increased the SRR in people with FUS by 62.7%, according to the relative risk (RR) integrated using a random-effects model (RR=1.627, 95% CI=1.463–1.809, p<0.0001, I²=0.0%). CI, confidence interval.

Fig. 3. Higher seizure recurrence rate (SRR) after 2 years of follow-up in first unprovoked seizures while sleeping (FUS-S) than those while waking (FUS-W). After integrating the seven cohort studies, the SSR was 59.8% in the FUS-S group (A) and 36.5% in the FUS-W group (B). CI, confidence interval.

Fig. 4. No significant changes of RRs of seizure recurrence after 2 years of follow-up in subgroup analyses by subject age or sleep definition. The RR was 1.722 in the three adult studies and 1.600 in the four pediatric studies (A). The RR was 1.482 in the two studies that defined sleep as nighttime and 1.673 in the five studies that defined it as actually being asleep (B). FUS, first unprovoked seizure; FUS-S, FUS while sleeping, FUS-W, FUS when waking; RR, relative risk.