Electrical status epilepticus in sleep (ESES) - Treatment pattern and EEG outcome in children with very high spike-wave index.

OBJECTIVE: The objective of the study was to determine electrical status epilepticus in sleep (ESES) outcome in children with very high spike-wave index (SWI; ≥85%), and assess treatment pattern. METHODS: Medical records of children 1-17 years old with ESES were reviewed. In this study, ESES is defined as SWI in non-rapid eye movement (non-REM) sleep of ≥85%. Electrical status epilepticus in sleep resolution is defined as reduction of SWI to <50%. RESULTS: Complete data were available in 33 children. Age at ESES diagnosis ranged from 32 to 165 months, median 76 months. The median duration of follow-up was 33 months. Two-thirds of the children were on one or more antiepileptic drugs (AED) at ESES diagnosis. Antiepileptic drugs were used as first treatment for ESES in 24/33 (73%). Electrical status epilepticus in sleep initially resolved in 76%, but 56% had subsequent relapse. The relapse rate was higher for steroids (89%) and benzodiazepines (60%) as compared with nonbenzodiazepine AEDs (29%). At last follow-up, ESES resolved in 21 children (64%). Electrical status epilepticus in sleep resolution was associated with seizure freedom (Fisher's exact, p < 0.05). SIGNIFICANCE: Using electroencephalogram (EEG) criteria, ESES resolved in 64%. We found high failure rate of first-line AEDs in preventing ESES, and high relapse rate. Standardization of ESES management is urgently needed.

Measure thrice, cut twice: On the benefit of reoperation for failed pediatric epilepsy surgery.

OBJECTIVE: To determine whether clinical outcomes are improved after repeat surgery for medically refractory epilepsy in children. METHODS: This is a single-center retrospective cohort analysis of all patients who received repeat resective surgery for ongoing seizures from 2000-2017. From a total of 251 consecutive individual epilepsy surgical patients for focal resection, 53 patients met study inclusion criteria and had adequate follow-up documented. RESULTS: Median age of seizure-onset was 2.0-years-old (IQR 0.3-5.5 years). The median age at first epilepsy surgery was 6.3-years-old (IQR 2.9-9.2 years) and at second epilepsy surgery was 8.4-years-old (IQR 4.7-12.6 years). Overall, 53 % (n = 28) of this series achieved Engel Class I (seizure freedom); with improved seizure control (Engel Class I-II) in 83 % (n = 44) of the cohort. 64 % (n = 34) had one reoperation; 26 % (n = 14) had two; and 9% (n = 5) had three. Pathology: 58 % (n = 31) had focal cortical dysplasia; 13 % (n = 10) tumor; 9% (n = 5) encephalitis; 6% (n = 3) gliosis; 4% (n = 2) mesial temporal sclerosis; and 2% (n = 1) hemimegalencephaly. Tumor pathology was associated with increased chance (p = 0.01) for seizure freedom (90 % of tumor patients had Engel Class I outcome). MTS had worse outcome with both patients having ongoing seizures (Engel II-IV). There were 6 patients who developed post-operative hemiparesis; one was unplanned but resolved. SIGNIFICANCE: Reoperation for pediatric epilepsy surgery can lead to seizure freedom in many cases and improved seizure control in most cases. Reoperation for brain tumor pathology is associated with a high rate of seizure freedom.

Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy.

Because molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we generated and tested the Emx-Cre; Clockflox/flox and PV-Cre; Clockflox/flox mouse lines with targeted deletions of the Clock gene in excitatory and parvalbumin (PV)-expressing inhibitory neurons, respectively. The Emx-Cre; Clockflox/flox mouse line alone has decreased seizure thresholds, but no laminar or dendritic defects in the cortex. However, excitatory neurons from the Emx-Cre; Clockflox/flox mouse have spontaneous epileptiform discharges. Both neurons from Emx-Cre; Clockflox/flox mouse and human epileptogenic tissue exhibit decreased spontaneous inhibitory postsynaptic currents. Finally, video-EEG of Emx-Cre; Clockflox/flox mice reveals epileptiform discharges during sleep and also seizures arising from sleep. Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy.