Original articleTreatment of electrical status epilepticus in sleep: Clinical and EEG characteristics and response to 147 treatments in 47 patients
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)
- et al.
Electrical status epilepticus in sleep
Semin Pediatr Neurol
(2008) - et al.
Cognitive deterioration and electrical status epilepticus during slow sleep
Epilepsy Behav
(2005) - et al.
Impaired slow wave sleep downscaling in encephalopathy with status epilepticus during sleep (ESES)
Clin Neurophysiol
(2011) - et al.
Long-term follow-up of cognitive functions in patients with continuous spike–waves during sleep (CSWS)
Epilepsy Behav
(2016) - et al.
The serum level of interleukin-6 in patients with intellectual disability and refractory epilepsy
Epilepsy Res
(2011) - et al.
Subclinical ‘electrical status epilepticus’ induced by sleep in children
Arch Neurol
(1971) Proposal for revised classification of epilepsies and epileptic syndromes
Epilepsia
(1989)- et al.
Continuous spikes and waves during sleep: electroclinical presentation and suggestions for management
Epilepsy Res Treat
(2013) - et al.
Syndrome of acquired aphasia with convulsive disorder in children
Neurology
(1957) - et al.
Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES)
Epilepsia
(2009)
Treatment of electrical status epilepticus in sleep: a pooled analysis of 575 cases
Epilepsia
Cited by (36)
Treatment Practices and Outcomes in Continuous Spike and Wave during Slow Wave Sleep: A Multicenter Collaboration
2021, Journal of PediatricsCitation Excerpt :Choice of treatment was not obviously driven by patients’ demographic or clinical variables, which suggests that initial therapy may reflect provider preference or experience rather than specific patient characteristics. In agreement with prior literature,8,24,25 we find that benzodiazepines and steroids are more effective against CSWS than ASMs. Though we restricted enrollment from some of the largest centers, it is still notable that there were only 81 subjects over a 2-year window, supporting that CSWS is a rare condition.
Clinical spectrum and treatment outcome of 95 children with continuous spikes and waves during sleep (CSWS)
2021, European Journal of Paediatric NeurologyCitation Excerpt :With increasing availability of genetic testing an increasing number of genes were identified as underlying causes of CSWS, such as GRIN2A [9,10]. Early therapy is thought to reduce the risk of irreversible long-term cognitive sequelae of CSWS [1,11–13], while it has remained unclear which specific anti-seizure medication (ASM) is most effective [8,11,14,15]. As outlined in the previous paragraphs, CSWS has not been sufficient examined regarding different definitions of SWI and treatment goals.