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Meta-Analysis
. 2019 Jun;26(6):856-864.
doi: 10.1111/ene.13811. Epub 2018 Oct 7.

Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk factors

R Stevelink  1   2 , B P C Koeleman  2 , J W Sander  3   4   5 , F E Jansen  1 , K P J Braun  1
Affiliations
Meta-Analysis

Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk factors

R Stevelink et al. Eur J Neurol. 2019 Jun.

Abstract

Background and purpose: Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and prognostic risk factors for refractoriness of JME.

Methods: We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random-effects meta-analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well-controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta-analysis of risk factors for refractoriness.

Results: Overall, 35% (95% confidence interval, 29-41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52-94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta-analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis-induced seizures.

Conclusion: One-third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.

Keywords: Janz syndrome; epilepsy; meta-analysis; pharmacoresistance; systematic review.

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Conflict of interest statement

The authors declare no financial or other conflicts of interest. J.W.S. reports grants and personal fees from Eisai, grants and personal fees from UCB, grants from WHO, grants from NEF, personal fees from Eisai, and grants and personal fees from UCB, outside the submitted work. His current position is endowed by the Epilepsy Society and he is a member of the Editorial Board of the Lancet Neurology and receives research support from the Marvin Weil Epilepsy Research Fund.

Figures

Figure 1
Figure 1
Flowchart of search strategy and study selection. AED, antiepileptic drug; JME, juvenile myoclonic epilepsy.
Figure 2
Figure 2
Meta‐analysis of the prevalence of refractory juvenile myoclonic epilepsy (JME). The proportion of subjects who were refractory is displayed on the x‐axis. A total of 43 studies describing seizure outcome in 3311 individuals with JME were included. CI, confidence interval; RE, random‐effects. References denoted as ‘e’ are available in the Supporting Information.
Figure 3
Figure 3
Meta‐analyses of the prevalence of refractory juvenile myoclonic epilepsy stratified by definition of seizure freedom. ILAE, International League Against Epilepsy; N, number of studies; I 2, heterogeneity.
Figure 4
Figure 4
Meta‐regression of refractory juvenile myoclonic epilepsy by publication year. The proportion of refractory subjects per study is plotted by publication year. Each study is represented by a circle whose size is proportional to the sample size. A meta‐regression trend line with 95% confidence interval (dotted lines) is plotted as a solid line.
Figure 5
Figure 5
Meta‐analysis of seizure recurrence after antiepileptic drug (AED) withdrawal. The proportion of well‐controlled subjects who experienced recurrence of seizures after AED withdrawal is displayed on the x‐axis. A total of 11 studies describing 246 subjects were included. CI, confidence interval; RE, random‐effects. References denoted as ‘e’ are available in the Supporting Information.
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