Treatment of electrical status epilepticus in sleep

van den Munckhof B, van Dee V, Sagi L, Caraballo RH, Veggiotti P, Liukkonen E, Loddenkemper T, Sánchez Fernández I, Buzatu M, Bulteau C, Braun KP, Jansen FE. e: A Pooled Analysis of 575 Cases. Epilepsia 2015;56:1738–1746.

OBJECTIVE: Epileptic encephalopathy with electrical status epilepticus in sleep (ESES) is a pediatric epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Treatment of ESES is assumed to improve cognitive outcome. The aim of this study is to create an overview of the current evidence for different treatment regimens in children with ESES syndrome. METHODS: A literature search using PubMed and Embase was performed. Articles were selected that contain original treatment data of patients with ESES syndrome. Authors were contacted for additional information. Individual patient data were collected, coded, and analyzed using logistic regression analysis. The three predefined main outcome measures were improvement in cognitive function, electroencephalography (EEG) pattern, and any improvement (cognition or EEG). RESULTS: The literature search yielded 1,766 articles. After applying inclusion and exclusion criteria, 112 articles and 950 treatments in 575 patients could be analyzed. Antiepileptic drugs (AEDs, n = 495) were associated with improvement (i.e., cognition or EEG) in 49% of patients, benzodiazepines (n = 171) in 68%, and steroids (n = 166) in 81%. Surgery (n = 62) resulted in improvement in 90% of patients. In a subgroup analysis of patients who were consecutively reported (585 treatments in 282 patients), we found improvement in a smaller proportion treated with AEDs (34%), benzodiazepines (59%), and steroids (75%), whereas the improvement percentage after surgery was preserved (93%). Possible predictors of improved outcome were treatment category, normal development before ESES onset, and the absence of structural abnormalities. SIGNIFICANCE: Although most included studies were small and retrospective and their heterogeneity allowed analysis of only qualitative outcome data, this pooled analysis suggests superior efficacy of steroids and surgery in encephalopathy with ESES.

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A meta-analysis of 112 published papers involving 950 treatments in 575 patients with ESES/CSWS has been published. Patients were included if there was sufficient data to allow analysis of individual treatment effects on EEG and cognition before and after treatment.

These results indicate that steroids and surgery are the most effective treatments for ESES/CSWS. Normal development prior to onset of ESES and shorter treatment lag were associated with better outcomes. Patients without a structural lesion fared better than those with a lesion (except for those treated surgically).

Other treatments reported to be effective include lacosamide, levetiracetam, ketogenic diet, acetazolamide, sulthiame, and vagus nerve stimulation. Oxcarbazepine and carbamazepine should be avoided as they may worsen ESES. In the presence of a focal cortical lesion, focal resection or hemispherectomy are often successful in eliminating ESES, thereby resulting in cognitive improvement. Multiple subpial transections may be helpful in selected patients with Landau-Kleffner syndrome.

A 2014 survey of 232 neurologists from North America regarding their treatment preferences in a patient with CSWS found that their preferred first choice was high-dose benzodiazepines (47%), followed by valproate (26%) and corticosteroids (15%). Respondents chose ketogenic diet over resective surgery even in the presence of a focal lesion! This survey highlights the disconnect between what neurologists are practicing and what the best available evidence shows. Multicenter controlled trials are needed to evaluate treatments for CSWS, then formal treatment guidelines can be developed.

In summary, CSWS is an epileptic encephalopathy of childhood requiring prompt diagnosis and aggressive treatment (analogous to how one might manage a child with West syndrome). Close follow-up and serial overnight EEGs are helpful to assess the effects of a treatment and may be done cost-effectively using ambulatory EEG. Children not responding to high-dose benzodiazepines and/or valproate should receive a 3-month course of prednisone. Children not responding to steroids or showing steroid dependence (ie, their symptoms reemerge upon weaning steroids) may benefit from intravenous immunoglobulin. Refractory patients should be evaluated at an epilepsy center to determine if they may be candidates for focal resection. Ketogenic diet and vagus nerve stimulation are also useful options. Early reports suggest that patients with CSWS and GRIN2A mutations may benefit from treatment with NMDA receptor antagonists.

http://epilepsycurrents.org/doi/full/10.5698/1535-7597.17.4.214