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.

BACKGROUND: Computed tomography (CT) is commonly used for children when there is concern for traumatic brain injury (TBI) and is a significant source of ionizing radiation. Our objective was to determine the feasibility and accuracy of fast MRI (motion-tolerant MRI sequences performed without sedation) in young children. METHODS: In this prospective cohort study, we attempted fast MRI in children ,6 years old who had head CT performed and were seen in the emergency department of a single, level 1 pediatric trauma center. Fast MRI sequences included 3T axial and sagittal T2 single-shot turbo spin echo, axial T1 turbo field echo, axial fluid-attenuated inversion recovery, axial gradient echo, and axial diffusion-weighted single-shot turbo spin echo planar imaging. Feasibility was assessed by completion rate and imaging time. Fast MRI accuracy was measured against CT findings of TBI, including skull fracture, intracranial hemorrhage, or parenchymal injury. RESULTS: Among 299 participants, fast MRI was available and attempted in 225 (75%) and completed in 223 (99%). Median imaging time was 59 seconds (interquartile range 52-78) for CT and 365 seconds (interquartile range 340-392) for fast MRI. TBI was identified by CT in 111 (50%) participants, including 81 skull fractures, 27 subdural hematomas, 24 subarachnoid hemorrhages, and 35 other injuries. Fast MRI identified TBI in 103 of these (sensitivity 92.8%; 95% confidence interval 86.3-96.8), missing 6 participants with isolated skull fractures and 2 with subarachnoid hemorrhage. CONCLUSIONS: Fast MRI is feasible and accurate relative to CT in clinically stable children with concern for TBI.

External ventricular drainage (EVD) is one of the most commonly performed neurosurgical procedures. It was first performed as early as 1744 by Claude-Nicholas Le Cat. Since then, there have been numerous changes in technique, materials used, indications for the procedure, and safety. The history of EVD is best appreciated in 4 eras of progress: development of the technique (1850-1908), technological advancements (1927-1950), expansion of indications , and accuracy, training, and infection control (1995-present). While EVD was first attempted in the 18th century, it was not until 1890 that the first thorough report of EVD technique and outcomes was published by William Williams Keen. He was followed by H. Tillmanns, who described the technique that would be used for many years. Following this, many improvements were made to the EVD apparatus itself, including the addition of manometry by Adson and Lillie in 1927, and continued experimentation in cannulation/drainage materials. Technological advancements allowed a great expansion of indications for EVD, sparked by Nils Lundberg, who published a thorough analysis of the use of intracranial pressure (ICP) monitoring in patients with brain tumors in 1960. This led to the application of EVD and ICP monitoring in subarachnoid hemorrhage, Reye syndrome, and traumatic brain injury. Recent research in EVD has focused on improving the overall safety of the procedure, which has included the development of guidance-based systems, virtual reality simulators for trainees, and antibiotic-impregnated catheters.

OBJECT Seizures may cause diagnostic confusion and be a source of metabolic stress after traumatic brain injury (TBI) in children. The incidence of electroencephalography (EEG)-confirmed seizures and of subclinical seizures in the pediatric population with TBI is not well known. METHODS A routine protocol for continuous EEG (cEEG) monitoring was initiated for all patients with moderate or severe TBI at a Level 1 pediatric trauma center. Over a 3.5-year period, all patients with TBI who underwent cEEG monitoring, both according to protocol and those with mild head injuries who underwent cEEG monitoring at the discretion of the treating team, were identified prospectively. Clinical data were collected and analyzed. RESULTS Over the study period, 594 children were admitted with TBI, and 144 of these children underwent cEEG monitoring. One hundred two (71%) of these 144 children had moderate or severe TBI. Abusive head trauma (AHT) was the most common mechanism of injury (65 patients, 45%) in children with cEEG monitoring. Seizures were identified on cEEG in 43 patients (30%). Forty (93%) of these 43 patients had subclinical seizures, including 17 (40%) with only subclinical seizures and 23 (53%) with both clinical and subclinical seizures. Fifty-three percent of patients with seizures experienced status epilepticus. Age less than 2.4 years and AHT mechanism were strongly correlated with presence of seizures (odds ratios 8.7 and 6.0, respectively). Those patients with only subclinical seizures had the same risk factors as the other groups. The presence of seizures did not correlate with discharge disposition but was correlated with longer hospital stay and intensive care unit stay. CONCLUSIONS Continuous EEG monitoring identifies a significant number of subclinical seizures acutely after TBI. Children younger than 2.4 years of age and victims of AHT are particularly vulnerable to subclinical seizures, and seizures in general. Continuous EEG monitoring allows for accurate diagnosis and timely treatment of posttraumatic seizures, and may mitigate secondary injury to the traumatized brain.

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.

OBJECT Nonpowder guns, defined as spring- or gas-powered BB or pellet guns, can be dangerous weapons that are often marketed to children. In recent decades, advances in compressed-gas technology have led to a significant increase in the power and muzzle velocity of these weapons. The risk of intracranial injury in children due to nonpowder weapons is poorly documented. METHODS A retrospective review was conducted at 3 institutions studying children 16 years or younger who had intracranial injuries secondary to nonpowder guns. RESULTS The authors reviewed 14 cases of intracranial injury in children from 3 institutions. Eleven (79%) of the 14 children were injured by BB guns, while 3 (21%) were injured by pellet guns. In 10 (71%) children, the injury was accidental. There was 1 recognized assault, but there were no suicide attempts; in the remaining 3 patients, the intention was indeterminate. There were no mortalities among the patients in this series. Ten (71%) of the children required operative intervention, and 6 (43%) were left with permanent neurological injuries, including epilepsy, cognitive deficits, hydrocephalus, diplopia, visual field cut, and blindness. CONCLUSIONS Nonpowder guns are weapons with the ability to penetrate a child’s skull and brain. Awareness should be raised among parents, children, and policy makers as to the risk posed by these weapons.

Infants with localization-related catastrophic epilepsy can have excellent outcomes from early epilepsy surgery. Complications are common in this patient group and proper diagnosis can be challenging. Young age should not exclude infants with catastrophic epilepsy from consideration for early surgical intervention.

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.