SUMMARY 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 post-synaptic 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.

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Objective: To develop and validate a model to predict seizure freedom in children undergoing cerebral hemispheric surgery for the treatment of drug-resistant epilepsy. Methods: We analyzed 1267 hemispheric surgeries performed in pediatric participants across 32 centers and 12 countries to identify predictors of seizure freedom at 3 months after surgery. A multivariate logistic regression model was developed based on 70% of the dataset (training set) and validated on 30% of the dataset (validation set). Missing data were handled using multiple imputation techniques. Results: Overall, 817 of 1237 (66%) hemispheric surgeries led to seizure freedom (median follow-up = 24 months), and 1050 of 1237 (85%) were seizure-free at 12 months after surgery. A simple regression model containing age at seizure onset, presence of generalized seizure semiology, presence of contralateral 18-fluoro-2-d eoxyglucose-positron emission tomography hypometabolism, etiologic substrate, and previous nonhemispheric resective surgery is predictive of seizure freedom (area under the curve = .72). A Hemispheric Surgery Outcome Prediction Scale (HOPS) score was devised that can be used to predict seizure freedom.

Objective:This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri-insular/peri-Sylvian approach to hemispheric surgery is the superior technique in achieving long-term seizure freedom.Methods:We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri-insular/peri-Sylvian, or lateral trans-Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time-to-event method and calculated using the Kaplan-Meier survival method.

BACKGROUND Although ventriculoperitoneal shunts (VPS) remain the first-line option in most instances of pediatric hydrocephalus, the long-term efficacy of ventriculoatrial shunts (VAS) remains unknown. OBJECTIVE To characterize the long-term outcomes and adverse occurrences associated with both VPS and VAS at our institution. METHODS The authors retrospectively analyzed all cerebrospinal fluid (CSF) shunting procedures performed over a 13-yr period at a single institution. A total of 544 pediatric shunt patients were followed for at least 90 d (VPS: 5.9 yr; VAS: 5.3 yr). RESULTS A total of 54% of VPS and 60% of VAS required at least 1 revision. VPS demonstrated superior survival overall; however, if electively scheduled VAS lengthening procedures are not considered true “failures,” no statistical difference is noted in overall survival (P = .08). VPS demonstrated significantly greater survival in patients less than 7 yr of age (P = .001), but showed no difference in older children (P = .4). VAS had a significantly lower rate of infection (P < .05) and proximal failure (P < .001). CONCLUSION VAS can be a useful alternative to VPS when the abdomen is unsuitable, particularly in older children. Although VPS demonstrates superior overall survival, it should be understood that elective VAS lengthening procedures are often necessary, especially in younger patients. If elective lengthening procedures are not considered true failures, then the devices show similar survival.

Summary Objective Drug‐resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on “ultra‐early” epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra‐early epilepsy surgery performed before the age of 3 months. Methods To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. Results Sixty‐four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty‐five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow‐up of 41 months (19–104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1–3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). Significance Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

OBJECTIVESagittal craniosynostosis is managed with a wide variety of operative strategies. The current investigation compares the clinical outcomes of two widely performed techniques: pi craniectomy and minimally invasive endoscopic strip craniectomy (ESC) followed by helmet therapy.METHODSThis IRB-approved retrospective study examined patients diagnosed with nonsyndromic, single-suture sagittal craniosynostosis treated with either pi craniectomy or ESC. Included patients had a minimum postoperative follow-up of 5 months.RESULTSFifty-one patients met the inclusion criteria (pi 21 patients, ESC 30 patients). Compared to patients who underwent ESC, the pi patients were older at the time of surgery (mean age 5.06 vs 3.11 months). The mean follow-up time was 23.2 months for ESC patients and 31.4 months for pi patients. Initial cranial index (CI) was similar between the groups, but postoperatively the ESC patients experienced a 12.3% mean increase in CI (from 0.685 to 0.767) compared to a 5.34% increase for the pi patients (from 0.684 to 0.719), and this difference was statistically significant (p < 0.001). Median hospital length of stay (1 vs 2 days) and operative duration (69.5 vs 93.3 minutes) were significantly less for ESC (p < 0.001 for both). The ESC patients showed a trend toward better results when surgery was done at younger ages. Craniectomy width in ESC cases was positively associated with CI improvement (slope of linear regression = 0.69, p = 0.026).CONCLUSIONSWhile both techniques effectively treated sagittal craniosynostosis, ESC showed superior results compared to pi craniectomy. ESC showed a trend for better outcomes when done at younger ages, although the trend did not reach statistical significance. A wider craniectomy width (up to 2 cm) was associated with better outcomes than smaller craniectomy widths among the ESC patients.

OBJECT Focal cortical dysplasia (FCD) is one of the most common causes of intractable epilepsy leading to surgery in children. The predictors of seizure freedom after surgical management for FCD are still unclear. The objective of this study was to perform a volumetric analysis of factors shown on the preresection and postresection brain MRI scans of patients who had undergone resective epilepsy surgery for cortical dysplasia and to determine the influence of these factors on seizure outcome. METHODS The authors reviewed the medical records and brain images of 43 consecutive patients with focal MRI-documented abnormalities and a pathological diagnosis of FCD who had undergone surgical treatment for refractory epilepsy. Preoperative lesion volume and postoperative resection volume were calculated by manual segmentation using OsiriX PRO software. RESULTS Forty-three patients underwent first-time surgery for resection of an FCD. The age range of these patients at the time of surgery ranged from 2 months to 21.8 years (mean age 7.3 years). The median duration of follow-up was 20 months. The mean age at onset was 31.6 months (range 1 day to 168 months). Complete resection of the area of an FCD, as adjudged from the postoperative brain MR images, was significantly associated with seizure control (p = 0.0005). The odds of having good seizure control among those who underwent complete resection were about 6 times higher than those among the patients who did not undergo complete resection. Seizure control was not significantly associated with lesion volume (p = 0.46) or perilesion resection volume (p = 0.86). CONCLUSIONS The completeness of FCD resection in children is a significant predictor of seizure freedom. Neither lesion volume nor the further resection of perilesional tissue is predictive of seizure freedom.