Introduction The global shortage of neurosurgeons demands tools to geographically extend the reach of expert surgeons. Technology allowing a remote, experienced surgeon to provide real-time guidance to local surgeons has great potential for training and capacity building in medical centers worldwide. Virtual interactive presence and augmented reality (VIPAR), an iPad®-based tool, allows surgeons to provide long-distance virtual assistance wherever a wireless internet connection is available. Local and remote surgeons view a composite image of video feeds at each station, allowing for intraoperative telecollaboration in real time. Methods Local and remote stations were established in Ho Chi Minh City, Vietnam, and Birmingham, Alabama, as part of an ongoing neurosurgical collaboration. An endoscopic third ventriculostomy with choroid plexus coagulation (ETV/CPC) utilizing VIPAR was used for subjective and objective evaluation of system performance. Results VIPAR allowed both surgeons to engage in complex visual and verbal communication during the procedure. Analysis of five video clips revealed video delay of 237msec (range: 93–391msec) relative to the audio signal. Excellent image resolution allowed the remote neurosurgeon to visualize all critical anatomy. The remote neurosurgeon could gesture to structures with no detectable difference in accuracy between stations, allowing for sub-millimeter precision. Both local and remote neurosurgeons felt the system improved procedural safety and efficacy. Conclusion Evolving technologies allowing long-distance, intra-operative guidance and knowledge transfer hold great potential for highly efficient international neurosurgical education. VIPAR is one example of an inexpensive, scalable platform for increasing global neurosurgical capacity. Efforts to create a network of Vietnamese neurosurgeons using VIPAR for collaboration are underway.

In this review the authors demonstrate that decompression of the cervicomedullary junction in the setting of achondroplasia may be accomplished safely with significant clinical benefit and minimal morbidity.

This study provides reference charts detailing AFC frequency and AF SA as a function of age. Wide variability of AFC timing and AF size among healthy infants suggest that early or delayed AFC may represent normal variants.

ObjectiveMany genetic studies of intractable epilepsy in pediatric patients primarily focus on inherited, constitutional genetic deficiencies identified in patient blood. Recently, studies have revealed somatic mosaicism associated with epilepsy in which genetic variants are present only in a subset of brain cells. We hypothesize that tissue-specific, somatic mosaicism represents an important genetic etiology in epilepsy and aim to discover somatic alterations in epilepsy-affected brain tissue.MethodsWe have pursued a research study to identify brain somatic mosaicism, using next-generation sequencing (NGS) technologies, in patients with treatment refractory epilepsy who have undergone surgical resection of affected brain tissue.ResultsWe used an integrated combination of NGS techniques and conventional approaches (radiology, histopathology, and electrophysiology) to comprehensively characterize multiple brain regions from a single patient with intractable epilepsy. We present a 3-year-old male patient with West syndrome and intractable tonic seizures in whom we identified a pathogenic frameshift somatic variant in SLC35A2, present at a range of variant allele fractions (4.2%–19.5%) in 12 different brain tissues detected by targeted sequencing. The proportion of the SLC35A2 variant correlated with severity and location of neurophysiology and neuroimaging abnormalities for each tissue.ConclusionsOur findings support the importance of tissue-based sequencing and highlight a correlation in our patient between SLC35A2 variant allele fractions and the severity of epileptogenic phenotypes in different brain tissues obtained from a grid-based resection of clinically defined epileptogenic regions.

Objective Epilepsy‐associated developmental lesions, including malformations of cortical development and low‐grade developmental tumors, represent a major cause of drug‐resistant seizures requiring surgical intervention in children. Brain‐restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified. Methods We enrolled 50 children who were undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA sequencing to identify somatic variation and we confirmed our findings using high‐depth targeted DNA sequencing. Results We uncovered candidate disease‐causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). In agreement with previous studies, we identified somatic variation affecting solute carrier family 35 member A2 (SLC35A2) and mechanistic target of rapamycin kinase (MTOR) pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) of patients with Type I focal cortical dysplasia (FCD)s. Somatic variation in mitogen‐activated protein kinase (MAPK) pathway genes (i.e., fibroblast growth factor receptor 1 [FGFR1], FGFR2, B‐raf proto‐oncogene, serine/threonine kinase [BRAF], and KRAS proto‐oncogene, GTPase [KRAS]) was associated with low‐grade epilepsy‐associated developmental tumors. RNA sequencing enabled the detection of somatic structural variation that would have otherwise been missed, and which accounted for more than one‐half of epilepsy‐associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease‐causing variants in genes not yet associated with focal cortical dysplasia. Significance These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

OBJECTIVE Subjective evaluations typically guide craniosynostosis repair. This study provides normative values of anthropometric cranial indices that are clinically useful for the evaluation of multiple types of craniosynostosis and introduces 2 new indices that are useful in the evaluation and management of metopic and bicoronal synostosis. The authors hypothesize that normative values of the new indices as well as for established measures like the cephalic index can be drawn from the evaluation of CT scans of normal individuals. METHODS High-resolution 3D CT scans obtained in normal infants (age 0-24 months) were retrospectively reviewed. Calvarial measurements obtained from advanced imaging visualization software were used to compute cranial indices. Additionally, metopic sutures were evaluated for patency or closure. RESULTS A total of 312 participants were included in the study. Each monthly age group (total 24) included 12-18 patients, yielding 324 head CT scans studied. The mean cephalic index decreased from 0.85 at age 0-3 months to 0.81 at 19-24 months, the mean frontoparietal index decreased from 0.68 to 0.65, the metopic index from 0.59 to 0.55, and the towering index remained comparatively uniform at 0.64 and 0.65. Trends were statistically significant for all measured indices. There were no significant differences found in mean cranial indices between sexes in any age group. Metopic suture closure frequency for ages 3, 6, and 9 months were 38.5%, 69.2%, and 100.0%, respectively. CONCLUSIONS Radiographically acquired normative values for anthropometric cranial indices during infancy can be used as standards for guiding preoperative decision making, surgical correction, and postoperative helmeting in various forms of craniosynostosis. Metopic and towering indices represent new cranial indices that are potentially useful for the clinical evaluation of metopic and bicoronal synostoses, respectively. The present study additionally shows that metopic suture closure appears ubiquitous after 9 months of age.

OBJECTIVEDespite perioperative risks, epilepsy surgery represents a legitimate curative or palliative treatment approach for children with drug-resistant epilepsy (DRE). Several factors characterizing infants and toddlers with DRE create unique challenges regarding optimal evaluation and management. Epilepsy surgery within children < 3 years of age has received moderate attention in the literature, including mainly case series and retrospective studies. This article presents a systematic literature review and explores multidisciplinary considerations for the preoperative evaluation and surgical management of infants and toddlers with DRE.METHODSThe study team conducted a systematic literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, targeting studies that investigated children < 3 years of age undergoing surgical treatment of DRE. Using the PubMed database, investigators selected peer-reviewed articles that reported seizure outcomes with or without developmental outcomes and/or perioperative complications. Studies were eliminated based on the following exclusion criteria: sample size < 5 patients; and inclusion of patients > 3 years of age, when demographic and outcomes data could not be separated from the cohort of patients < 3 years of age.RESULTSThe study team identified 20 studies published between January 1990 and May 2017 that satisfied eligibility criteria. All selected studies represented retrospective reviews, observational studies, and uncontrolled case series. The compiled group of studies incorporated 465 patients who underwent resective or disconnective surgery (18 studies, 444 patients) or vagus nerve stimulator insertion (2 studies, 21 patients). Patient age at surgery ranged between 28 days and 36 months, with a mean of 16.8 months (1.4 years).DISCUSSIONThe study team provided a detailed summary of the literature review, focusing on the etiologies, preoperative evaluation, surgical treatments, seizure and developmental outcomes, and potential for functional recovery of infants and toddlers with DRE. Additionally, the authors discussed special considerations in this vulnerable age group from the perspective of multiple disciplines.CONCLUSIONSWhile presenting notable challenges, pediatric epilepsy surgery within infants and toddlers (children < 3 years of age) offers significant opportunities for improved seizure frequency, neuro-cognitive development, and quality of life. Successful evaluation and treatment of young children with DRE requires special consideration of multiple aspects related to neurological and physiological immaturity and surgical morbidity.

Object. Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column. Methods. Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 μL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 μL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL-1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed. Results. There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups. Conclusions. These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.