We report somatic variants in SLC35A2 as an explanation for a substantial fraction of NLFE, a largely unexplained condition, as well as focal MCD, previously shown to result from somatic mutation but until now only in PI3K-AKT-mTOR pathway genes. Collectively, our findings suggest a larger role than previously recognized for glycosylation defects in the intractable epilepsies. Ann Neurol 2018.

Summary Objective Medically refractory epilepsy is a debilitating disorder that is particularly challenging to treat in patients who have already failed a surgical resection. Evidence regarding outcomes of further epilepsy surgery is limited to small case series and reviews. Therefore, our group performed the first quantitative meta-analysis of the literature from the past 30 years to assess for rates and predictors of successful reoperations. Methods A PubMed search was conducted for studies reporting outcomes of repeat epilepsy surgery. Studies were excluded if they reported fewer than 5 eligible patients or had average follow ups < 1 year, and patients were excluded from analysis if they received a non-resective intervention. Outcomes were stratified by each variable of interest and quantitative meta-analysis was performed to generate odds ratios (OR) and 95% confidence intervals (CI). Results 782 patients who received repeat resective epilepsy surgery from 36 studies were included. Engel I outcome was observed in 47% (N=369) of patients. Significant predictors of seizure freedom in included congruent over non-congruent electrophysiology data (OR 3.6, 95% CI 1.6–8.2), lesional over non-lesional epilepsy (OR 3.2, 95% CI 1.9–5.3), and surgical limitations over disease-related factors associated with failure of the first surgery (OR 2.6, 95% CI 1.3–5.3). Among patients with at least one of these predictors, seizure freedom was achieved in 58%. Conversely, the use of invasive monitoring was associated with worse outcome (OR 0.4, 95% CI 0.2–0.9). Temporal lobe over extratemporal/multilobe resection (OR 1.5, 95% CI 0.8–3.0) and abnormal over normal pre-operative MRI (OR 1.9, 95% CI 0.6–5.4) showed non-significant trends toward seizure freedom. Significance This analysis supports considering further resection in patients with intractable epilepsy who continue to have debilitating seizures after an initial surgery, especially in the context of factors predictive of a favorable outcome.

OBJECTIVEIn children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty.METHODSThe authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty.RESULTSA total of 359 patients met the inclusion criteria. The patients’ mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17–4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03–5.79), and ventilator dependence (OR 8.45, 95% CI 1.10–65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection.Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98–0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts.CONCLUSIONSThis is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.

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