Original article
Treatment of electrical status epilepticus in sleep: Clinical and EEG characteristics and response to 147 treatments in 47 patients

https://doi.org/10.1016/j.ejpn.2017.08.006Get rights and content

Highlights

  • Treatment of ESES syndrome aims to improve cognitive outcome.

  • Improvement of daily functioning after treatment was strongly associated with SWI decrease.

  • Improvement of daily functioning and SWI change were not reflected by IQ change.

  • Steroid treatment was most successful in improving cognitive performance.

  • Higher age at diagnosis was related to cognitive improvement after treatment.

Abstract

Objective

Electrical status epilepticus in sleep (ESES) syndrome is characterized by near-continuous sleep-induced epileptiform activity and acquired cognitive deficits. Treatment is assumed mandatory to improve cognitive outcome. We aimed to compare EEG characteristics, subjective evaluation and objective neuropsychological assessment as measures to evaluate treatment efficacy, and to analyze possible predictors.

Methods

We retrospectively included patients with ESES syndrome treated in our center. Treatment effect was analyzed on sleep EEG spike wave index (SWI) and cognitive functioning.

Results

47 patients had 147 (43 steroid and 104 non-steroid) treatments. Cognitive improvement was reported after 36% of treatments at first follow-up and 45% of treatments at last follow-up. The median SWI change for treatments resulting in subjective cognitive improvement was −44%, and 0% for those not resulting in subjective cognitive improvement at first follow-up (p = 0.008) and −50% vs. +5% at last follow-up (p = 0.002). No clear association between subjective cognitive improvement and IQ change, and between SWI and IQ change was found. By means of logistic regression we found that steroid treatment, as compared to non-steroid treatment, was associated with cognitive improvement at first follow-up (multivariate OR after multiple imputation 2.5, 95% CI 1.1–5.7), while at last follow-up, higher age at diagnosis was related to cognitive improvement only in univariate analysis (OR 1.02, 95% CI 1.01–1.04).

Conclusions

We found that in children with ESES, cognitive improvement after treatment was strongly associated with SWI decrease, while it was not reflected by a significant IQ increase. Steroid treatment was most successful in improving cognitive performance.

Introduction

Encephalopathy with electrical status epilepticus in sleep (ESES), ESES syndrome and continuous spikes and waves during sleep (CSWS) have been used interchangeably to define patients with an EEG pattern of near-continuous spike and wave discharges during non-REM sleep and acquired neuropsychological deficits. Typical cases have a spike wave index (SWI) of at least 85% during non-REM sleep, while in recent years cases with a SWI of 50–85% were added to the spectrum.1, 2, 3, 4, 5 This epilepsy syndrome is typically age related, presenting at an age between 2 and 14 years, with a peak at 4–8 years. Although seizures are present in the majority of patients and can form a serious burden, cognitive decline is the most frightening symptom of the disorder.2, 6, 7 While the ESES EEG pattern resolves during puberty, cognitive deficits often remain.2

Structural brain abnormalities have been reported in 20–50% of patients with ESES and an important role of the thalamus has become evident from recent studies.8, 9, 10, 11, 12 Also, etiological as well as treatment studies have linked inflammation to ESES.13, 14 How ESES leads to cognitive decline is incompletely understood. The epileptiform activity has been suggested to interfere with normal recuperative functions of sleep, thereby adversely affecting learning abilities, language, memory and other cognitive domains.15, 16

Early and adequate treatment of ESES is assumed mandatory to prevent further cognitive decline and possibly recover skills that were lost. A recent study has shown that treatment strategies vary widely between clinicians.17 No adequately powered randomized controlled trials are available and evidence is limited to mostly small and retrospective case series. A pooled analysis of 575 cases reported in literature revealed that conventional anti-epileptic drugs are often not successful in improving cognitive outcome, while benzodiazepines and steroids seem better alternatives. Surgery is highly successful in selected cases.8 Although a causative relation is assumed, it is unclear whether resolution of the ESES EEG pattern is necessary for treatment efficacy or can serve as a predictive biomarker.18 Cognitive improvement should be leading, but its assessment is often based on subjective measures (parents' opinion, clinician's judgment).

In a large, single center cohort study of patients with ESES syndrome we aimed to address the following questions: (1) What is the effect of treatment on cognitive functioning and EEG-abnormalities? (2) Is there an association between EEG response to treatment, measured as a change of the spike-wave index, subjective cognitive functioning and IQ test results?, and (3) what are predictors of cognitive outcome?

Section snippets

Patients

We retrospectively selected all children with epileptic encephalopathy with ESES, further called ESES syndrome, who consulted the pediatric neurology clinic of the UMC Utrecht, the Netherlands between January 2002 and December 2013. The study was approved by the medical ethics committee who judged that the Dutch Medical Research Involving Human Subjects Act did not apply.

Patients were selected according to predefined inclusion criteria: 1) a diagnosis of ESES syndrome before the age of 12

Patient characteristics

Of 57 patients who were diagnosed with ESES syndrome, 47 (82.5%) met the inclusion criteria. Nine patients were excluded because SWIs did not exceed 50%, one patient never received treatment. The mean age at diagnosis of the included patients was 6.8 years and a male preponderance was seen (61.7%). Twenty-two patients had MRI abnormalities: 13 patients had vascular abnormalities, 7 patients had developmental malformations and 2 patients had hippocampal sclerosis. Genetic abnormalities included

Discussion

In this study we investigated the effect of treatment on – subjectively assessed – cognitive functioning, IQ test results and spike-wave index in 47 patients with ESES syndrome treated in our center. We found that, in general, cognitive improvement is reported after a minority of treatments (36% at first follow-up and 45% at last follow-up). IQ results showed on average no clear change after treatment, while the EEG on average revealed a decrease in spike-wave index (−21 and −24% at first and

Competing interests

Dr. van den Munckhof and Dr. Jansen report grants from the Dutch Epilepsy Fund (epilepsiefonds) and Wilhelmina Children's Hospital Research Fund and non-financial support by the European Clinical Research Infrastructure Network (ECRIN) during the conduct of the study. The other authors have no potential conflicts of interest to declare.

Acknowledgments

This work was supported by grants from the Dutch Epilepsy Fund (13-17) and the Wilhelmina Children's Hospital Research Fund (R2634). The funding sources had no direct involvement in this study.

References (23)

  • B. van den Munckhof et al.

    Treatment of electrical status epilepticus in sleep: a pooled analysis of 575 cases

    Epilepsia

    (2015)
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