Slow (Ͻ0.1 Hz), spontaneous fluctuations in the functional magnetic resonance imaging blood oxygen level-dependent (BOLD) signal have been shown to exhibit phase coherence within functionally related areas of the brain. Surprisingly, this phenomenon appears to transcend levels of consciousness. The genesis of coherent BOLD fluctuations remains to be fully explained. We present a resting state functional connectivity study of a 6-year-old child with a radiologically normal brain imaged both before and after complete section of the corpus callosum for the treatment of intractable epilepsy. Postoperatively, there was a striking loss of interhemispheric BOLD correlations with preserved intrahemispheric correlations. These unique data provide important insights into the relationship between connectional anatomy and functional organization of the human brain. Such observations have the potential to increase our understanding of large-scale brain systems in health and disease as well as improve the treatment of neurologic disorders.

Objective-To describe initial experience with resting state correlation mapping as a potential aid for presurgical planning of brain tumor resections.Methods/Technique-Resting state blood oxygenation dependent (BOLD) fMRI was acquired in seventeen healthy young adults and four patients with brain tumors invading sensorimotor cortex. Conventional fMRI motor mapping (finger tapping protocol) was also performed in the patients. Intraoperatively, motor hand area was mapped using cortical stimulation.Results-Robust and consistent delineation of sensorimotor cortex was obtained using the resting state BOLD data. Resting state functional mapping in patients showed localization to sensorimotor areas consistent with cortical stimulation mapping (CSM) and in all cases performed as well or better than task-based fMRI.Conclusions-Resting state correlation mapping is a promising tool for reliable functional localization of eloquent cortex. This method compares well with "gold standard" CSM and offers several advantages in comparison to conventional motor mapping fMRI.

Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10), SMARCC1 (p = 8.15 × 10), and PTCH1 (p = 1.06 × 10). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10). Together, these probands account for ∼10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.

OBJECT Pediatric sports-related concussions are a growing public health concern. The factors that determine injury severity and time to recovery following these concussions are poorly understood. Previous studies suggest that initial symptom severity and diagnosis of attention deficit hyperactivity disorder (ADHD) are predictors of prolonged recovery (> 28 days) after pediatric sports-related concussions. Further analysis of baseline patient characteristics may allow for a more accurate prediction of which patients are at risk for delayed recovery after a sports-related concussion. METHODS The authors performed a single-center retrospective case-control study involving patients cared for at the multidisciplinary Concussion Clinic at Children's of Alabama between August 2011 and January 2013. Patient demographic data, medical history, sport concussion assessment tool 2 (SCAT2) and symptom severity scores, injury characteristics, and patient balance assessments were analyzed for each outcome group. The control group consisted of patients whose symptoms resolved within 28 days. The case group included patients whose symptoms persisted for more than 28 days. The presence or absence of the SCAT2 assessment had a modifying effect on the risk for delayed recovery; therefore, stratum-specific analyses were conducted for patients with recorded SCAT2 scores and for patients without SCAT2 scores. Unadjusted ORs and adjusted ORs (aORs) for an association of delayed recovery outcome with specific risk factors were calculated with logistic regression analysis. RESULTS A total of 294 patients met the inclusion criteria of the study. The case and control groups did not statistically significantly differ in age (p = 0.7). For the patients who had received SCAT2 assessments, a previous history of concussion (aOR 3.67, 95% CI 1.51–8.95), presenting SCAT2 score < 80 (aOR 5.58, 95% CI 2.61–11.93), and female sex (aOR 3.48, 95% CI 1.43–8.49) were all associated with a higher risk for postconcussive symptoms lasting more than 28 days. For patients without SCAT2 scores, female sex and reporting a history of ADHD significantly increased the odds of prolonged recovery (aOR 4.41, 95% CI 1.93–10.07 and aOR 3.87, 95% CI 1.13–13.24, respectively). Concussions resulting from playing a nonhelmet sport were also associated with a higher risk for prolonged symptoms in patients with and without SCAT2 scores (OR 2.59, 95% CI 1.28–5.26 and OR 2.17, 95% CI 0.99–7.73, respectively). Amnesia, balance abnormalities, and a history of migraines were not associated with symptoms lasting longer than 28 days. CONCLUSIONS This case-control study suggests candidate risk factors for predicting prolonged recovery following sports-related concussion. Large prospective cohort studies of youth athletes examined and treated with standardized protocols will be needed to definitively establish these associations and confirm which children are at highest risk for delayed recovery.

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✓ Selective dorsal rhizotomy is a well-established surgical procedure for improving lower-extremity spasticity in children with cerebral palsy. The standard technique requires an L1–S1 laminectomy or laminoplasty for visualization of all dorsal nerve roots exiting at their respective foramina. The authors describe a rhizotomy procedure that requires a single-level laminectomy at the level of the conus, with the advantages of decreased operating time and postoperative pain as well as a minimal risk of progressive lumbar instability. This procedure is both effective and well tolerated in appropriately selected children and adults, and has had one cerebrospinal fluid lead requiring operative repair in more than 1500 patients treated at the authors' institution since 1991.

BACKGROUND-Outcomes in children and adolescents with recurrent or progressive highgrade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric highgrade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.

IntroductionPediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive brain tumor that arises from the sellar/suprasellar region. Despite a high survival rate with current surgical and radiation therapy (75–95 % at 10 years), ACP is associated with debilitating visual, endocrine, neurocognitive and psychological morbidity, resulting in excheptionally poor quality of life for survivors. Identification of an effective pharmacological therapy could drastically decrease morbidity and improve long term outcomes for children with ACP.ResultsUsing mRNA microarray gene expression analysis of 15 ACP patient samples, we have found several pharmaceutical targets that are significantly and consistently overexpressed in our panel of ACP relative to other pediatric brain tumors, pituitary tumors, normal pituitary and normal brain tissue. Among the most highly expressed are several targets of the kinase inhibitor dasatinib – LCK, EPHA2 and SRC; EGFR pathway targets – AREG, EGFR and ERBB3; and other potentially actionable cancer targets – SHH, MMP9 and MMP12. We confirm by western blot that a subset of these targets is highly expressed in ACP primary tumor samples.ConclusionsWe report here the first published transcriptome for ACP and the identification of targets for rational therapy. Experimental drugs targeting each of these gene products are currently being tested clinically and pre-clinically for the treatment of other tumor types. This study provides a rationale for further pre-clinical and clinical studies of novel pharmacological treatments for ACP. Development of mouse and cell culture models for ACP will further enable the translation of these targets from the lab to the clinic, potentially ushering in a new era in the treatment of ACP.