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Introduction: In carefully selected patients with medically refractory epilepsy, disconnective hemispherotomy can result in significant seizure freedom; however, incomplete disconnection can result in ongoing seizures and poses a significant challenge. Completion hemispherotomy provides an opportunity to finish the disconnection. We describe the use of magnetic resonance-guided laser interstitial thermal ablation (MRgLITT) for completion hemispherotomy. Methods: Patients treated with completion hemispherotomy using MRgLITT at our institution were identified. Procedural and seizure outcomes were evaluated retrospectively. Results: Five patients (3 males) underwent six MRgLITT procedures (one child treated twice) for completion hemispherotomy at a median age of 6 years (range 1.8–12.9). Two children had hemimegalencephaly, two had Rasmussen encephalitis, and one had polymicrogyria. All five children had persistent seizures likely secondary to incomplete disconnection after their functional hemispherotomy. The mean time from open hemispherotomy to MRgLITT was 569.5 ± 272.4 days (median 424, range 342–1,095). One patient underwent stereoelectroencephalography before MRgLITT. The mean number of ablation targets was 2.3 ± 0.47 (median 2, range 2–3). The mean length of the procedure was 373 min ± 68.9 (median 374, range 246–475). Four of the five patients were afforded improvement in their neurocognitive functioning and speech performance after ablation, with mean daily seizure frequency at 1 year of 1.03 ± 1.98 (median 0, range 0–5). Two patients achieved Engel Class I outcomes at 1 year after ablation, one was Engel Class III, and two were Engel Class IV. The mean follow-up time was 646.8 ± 179.5 days (median 634, range 384–918). No MRgLITT-related complications occurred. Delayed retreatment (>1 year) occurred in three patients: one child underwent redo ablation and two underwent anatomic hemispherectomy. Conclusion: We have demonstrated the feasibility of a minimally invasive approach for completion hemispherotomy using MRgLITT. Delayed retreatment was needed in three patients; thus, further study of this technique with comparison to other surgical techniques is warranted.

INTRODUCTION: Existing automated seizure detection algorithms report sensitivities between 43% and 77% and specificities between 56% and 90%. The algorithms suffer from false alarms when applied to neonatal EEG because of the high degree of nurse handling and rhythmic patting used to soothe neonates. Computer vision technology that quantifies movement in real time could distinguish artifactual motion and improve automated neonatal seizure detection algorithms. METHODS: The authors used video EEG recordings from 43 neonates undergoing monitoring for seizures as part of the NEOLEV2 clinical trial. The Persyst neonatal automated seizure detection algorithm ran in real time during study EEG acquisitions. Computer vision algorithms were applied to extract detailed accounts of artifactual movement of the neonate or people near the neonate though dense optical flow estimation. RESULTS: Using the methods mentioned above, 197 periods of patting activity were identified and quantified, of which 45 generated false-positive automated seizure detection events. A binary patting detection algorithm was trained with a subset of 470 event videos. This supervised detection algorithm was applied to a testing subset of 187 event videos with 8 false-positive events, which resulted in a 24% reduction in false-positive automated seizure detections and a 50% reduction in false-positive events caused by neonatal care patting, while maintaining 11 of 12 true-positive seizure detection events. CONCLUSIONS: This work presents a novel approach to improving automated seizure detection algorithms used during neonatal video EEG monitoring. This artifact detection mechanism can improve the ability of a seizure detector algorithm to distinguish between artifact and true seizure activity.

OBJECTIVE Periventricular nodular heterotopia (PVNH) is a result of disrupted neuronal migration from the ventricular system and can be a rare cause of refractory focal epilepsy. The goal of this case series was to describe the treatment of pediatric PVNH-related epilepsy with MR-guided laser interstitial thermal ablation. METHODS Patients treated at a single institution with MR-guided laser interstitial thermal therapy (MRgLITT) for PVNH-related epilepsy were identified. Preoperative and postoperative seizure outcomes and procedural information were evaluated. RESULTS Five children with PVNH treated with MRgLITT were reviewed; 1 child was treated twice. Three patients were female; the median age was 10.9 years. Five of 6 treatments were preceded by stereoelectroencephalography phase II monitoring. Three children experienced unilateral PVNH, and 2 had bilateral seizures. The median number of seizures recorded during phase II monitoring was 2; the median number of ablation targets was 2 (range 1–4). All patients experienced a decrease in seizure frequency; 4 patients (80%) had an Engel class ≤ III at the last follow-up (range I–IV). One child experienced right hemianopia posttreatment. CONCLUSIONS This case series investigation has illustrated a novel, minimally invasive approach for treating pediatric PVNH-related epilepsy. Further study of this technique with comparison with other surgical techniques is warranted.

Compared to adult AVMs, there is a paucity of data on the microsurgical treatment of pediatric AVMs. We report our institutional experience with pediatric AVMs treated by microsurgical resection with or without endovascular embolization and radiation therapy. We retrospectively reviewed all patients ≤ 18 years of age with cerebral AVMs that underwent microsurgical resection at Rady Children’s Hospital 2002–2019. Eighty-nine patients met inclusion criteria. The mean age was 10.3 ± 5.0 years, and 56% of patients were male. In total, 72 (81%) patients presented with rupture. Patients with unruptured AVMs presented with headache (n = 5, 29.4%), seizure (n = 9, 52.9%), or incidental finding (n = 3, 17.7%). The mean presenting mRS was 2.8 ± 1.8. AVM location was lobar in 78%, cerebellar/brainstem in 15%, and deep supratentorial in 8%. Spetzler-Martin grade was I in 28%, II in 45%, III in 20%, IV in 6%, and V in 1%. Preoperative embolization was utilized in 38% of patients and more frequently in unruptured than ruptured AVMs (62% vs. 32%, p = 0.022). Radiographic obliteration was achieved in 76/89 (85.4%) patients. Complications occurred in 7 (8%) patients. Annualized rates of delayed rebleeding and recurrence were 1.2% and 0.9%, respectively. The mean follow-up was 2.8 ± 3.1 years. A good neurological outcome (mRS score ≤ 2) was obtained in 80.9% of patients at last follow-up and was improved relative to presentation for 75% of patients. Our case series demonstrates high rates of radiographic obliteration and relatively low incidence of neurologic complications of treatment or AVM recurrence.

PURPOSE Treatment of children with CNS tumors (CNSTs) demands a complex, interdisciplinary approach that is rarely available in low- and middle-income countries. We established the Cross-Border Neuro-Oncology Program (CBNP) between Rady Children’s Hospital, San Diego (RCHSD), and Hospital General, Tijuana (HGT), Mexico, to provide access to neuro-oncology care, including neurosurgic services, for children with CNSTs diagnosed at HGT. Our purpose was to assess the feasibility of the CBNP across the United States-Mexico border and improve survival for children with CNSTs at HGT by implementing the CBNP. PATIENTS AND METHODS We prospectively assessed clinicopathologic profiles, the extent of resection, progression-free survival, and overall survival (OS) in children with CNSTs at HGT from 2010 to 2017. RESULTS Sixty patients with CNSTs participated in the CBNP during the study period. The most common diagnoses were low-grade glioma (24.5%) and medulloblastoma (22.4%). Of patients who were eligible for surgery, 49 underwent resection at RCHSD and returned to HGT for collaborative management. Gross total resection was achieved in 78% of cases at RCHSD compared with 0% at HGT ( P < .001) and was a predictor of 5-year OS (hazard ratio, 0.250; 95% CI, 0.067 to 0.934; P = .024). Five-year OS improved from 0% before 2010 to 52% in 2017. CONCLUSION The CBNP facilitated access to complex neuro-oncology care for underserved children in Mexico through binational exchanges of resources and expertise. Survival for patients in the CBNP dramatically improved. Gross total resection at RCHSD was associated with higher OS, highlighting the critical role of experienced neurosurgeons in the treatment of CNSTs. The CBNP model offers an attractive alternative for children with CNSTs in low- and middle-income countries who require complex neuro-oncology care, particularly those in close proximity to institutions in high-income countries with extensive neuro-oncology expertise.

IntroductionThe Pierre-Robin sequence (PRS) is a pattern of congenital facial abnormalities comprising micrognathia, glossoptosis, and airway obstruction. Associated spinal pathologies have rarely been reported with PRS.MethodsWe explore the molecular genetic basis of this association through a systematic review of spinal disease in patients with PRS. We also present an illustrative case of a PRS patient with tethered cord in the setting of chromosome 10q terminal deletion.ResultsOur systematic literature review of spinal disease in patients with PRS revealed several patterns in the underlying genetic syndromes causing these conditions to co-occur. These principles are illustrated in the case of a 6-month-old female with PRS and a 14.34-Mb terminal deletion of chromosome 10q, who was found to have a sacral dimple during a routine outpatient checkup. Magnetic resonance imaging of the spine revealed a lumbar syrinx associated with tethered spinal cord. Surgical de-tethering was undertaken, with subsequent improvement in motor function and decrease in the size of the syrinx. The deletion of chromosome 10q in our patient had not previously been described in association with tethered cord or PRS.ConclusionSpinal pathologies are understudied contributors to disease burden in patients with PRS. The range of predisposing syndromes and mutations in patients with both PRS and spinal disorders remains poorly characterized but may be more defined than previously conceived. Clinical screening is most critical during neonatal and adolescent developmental periods with continued neurological assessment. This study emphasizes the need for early genetic testing and counseling in this patient population, in parallel with research efforts to develop molecular classifications to guide clinical management.

BACKGROUND Chordomas are rare malignant neoplasms that develop from the primitive notochord with < 5% of the tumors occurring in pediatric patients younger than the age of 20. Of these pediatric chordomas, those affecting the craniocervical junction (C1–C2) are even more rare; therefore, parameters for surgical management of these pediatric tumors are not well characterized. OBSERVATIONS In this case, a 3-year-old male was found to have a clival chordoma on imaging with extension to the craniocervical junction resulting in spinal cord compression. Endoscopic-assisted transoral transclival approach for clival tumor resection was performed first. As a second stage, the patient underwent a left-sided far lateral craniotomy and cervical laminectomy for resection of the skull base chordoma and instrumented fusion of the occiput to C3. He made excellent improvements in strength and dexterity during rehab and was discharged after 3 weeks. LESSONS In pediatric patients with chordoma with extension to the craniocervical junction and spinal cord compression, decompression with additional occipito-cervical fusion appears to offer a good clinical outcome. Fusion performed as a separate surgery before or at the same time as the initial tumor resection surgery may lead to better outcomes.

Author(s): Han, Claudia; Li, Rick; Hansen, Emily; Bennett, Hunter; Poirion, Olivier; Buchanan, Justin; Challacombe, Jean; Fixsen, Bethany; Trescott, Samantha; Schlachetzki, Johannes CM; Preissl, Sebastian; Wang, Allen; O’Connor, Carolyn; Warden, Anna; Shriram, Shreya; Kim, Roy; Nguyen, Celina; Schafer, Danielle; Ramirez, Gabriela; Anavim, Samuel; Johnson, Avalon; Sajti, Eniko; Gupta, Mihir; Levy, Michael; Ben-Haim, Sharona; Gonda, David; Laurent, Louise; Glass, Christopher; Coufal, Nicole | Abstract: The fetal period is a critical time for brain development, characterized by neurogenesis, neural migration, and synaptogenesis 1-3 . Microglia, the tissue resident macrophages of the brain, are observed as early as the fourth week of gestation 4 and are thought to engage in a variety of processes essential for brain development and homeostasis 5-11 . Conversely, microglia phenotypes are highly regulated by the brain environment 12-14 . Mechanisms by which human brain development influences the maturation of microglia and microglia potential contribution to neurodevelopmental disorders remain poorly understood. Here, we performed transcriptomic analysis of human fetal and postnatal microglia and corresponding cortical tissue to define age-specific brain environmental factors that may drive microglia phenotypes. Comparative analysis of open chromatin profiles using bulk and single-cell methods in conjunction with a new computational approach that integrates epigenomic and single-cell RNA-seq data allowed decoding of cellular heterogeneity with inference of subtype- and development stage-specific transcriptional regulators. Interrogation of in vivo and in vitro iPSC-derived microglia models provides evidence for roles of putative instructive signals and downstream gene regulatory networks which establish human-specific fetal and postnatal microglia gene expression programs and potentially contribute to neurodevelopmental disorders.

Background Upper airway obstruction leading to dyspnea and dysphagia after occipitocervical fusion is a rare complication that has significant morbidity. Objective To estimate the frequency of postoperative dyspnea and dysphagia in children after occipitocervical fusion and to identify variables associated with its occurrence. Methods We retrospectively reviewed outcomes from all pediatric occipitocervical fusions at our institution between 2007 and 2014. Pre- and postoperative computed tomography (CT) scans were compared to determine differences in the clivoaxial (OC2) angles. Results Sixty-seven pediatric patients underwent occipitocervical fusions. Median age was 9.6 yr (range 6 mo-18 yr). Fifty-six of 62 patients (90.3%) with at least 1 yr of follow-up had successful fusions. Eleven had pre-existing symptoms or otherwise compromised examination (eg, severe traumatic brain injury). None of 15 patients placed in extension (>2 degrees) relative to preoperative CT in Situ position developed new dyspnea or dysphagia. Nine of forty patients (23%) kept in Situ or flexed position developed new symptoms of dyspnea or dysphagia. Dysphagia in patients fused in the in Situ position was milder and resolved within a few weeks. No patient under age 5 (n = 20) developed symptoms of dyspnea or dysphagia regardless of head position. There were 3 cases of infection, 1 clinically silent vertebral artery injury, and 3 deaths at last follow-up. Conclusion Positioning of the child's head prior to occipitocervical fusion has considerable impact on outcomes, especially in older children. Careful measurements of the OC2 angle during surgery to ensure optimal head positioning in Situ or slightly extended position may prevent postoperative dysphagia or dyspnea.

Background: Nonlesional cingulate gyrus epilepsy is rare, difficult to diagnose, and challenging to treat. Methods: We report the use of ROSA (Medtech Surgical, Inc., New York, NY, USA) robotic assistance for stereotactic EEG (S-EEG) localization and therapeutic thermal laser ablation of a nonlesional cingulate gyrus epileptogenic zone in a 17-year-old female with intractable partial epilepsy. Results: After an inconclusive exhaustive initial workup, robotic-assisted S-EEG localized the patient’s seizure focus to the right cingulate gyrus. Robotic-assisted lesioning of the cingulate gyrus was performed via 5 total ablations with 3 minimally invasive catheters. There were no perioperative complications. The patient was discharged home on postoperative day 2 at her neurologic baseline. She was seizure free for 8 months postoperatively, with a sustained partial response through the 23-month follow-up. Conclusions: This report expands the technical uses, pathologies, and patient populations being treated via robotic-assisted neurosurgery.

BACKGROUND Ventriculoperitoneal shunt (VPS) placement into the reoperative abdomen can be challenging due to intraperitoneal adhesions. Laparoscopic guidance may provide safe abdominal access and identify an area for optimal cerebrospinal fluid drainage. The study aim was to compare laparoscopic-assisted VPS placement to an "open" approach in patients with prior abdominal surgery. MATERIALS AND METHODS A retrospective review was performed of children undergoing VPS placement into a reoperative abdomen from 2009-2019. Clinical data were collected, and patients undergoing laparoscopy (LAP) were compared to those undergoing an open approach (OPEN). RESULTS A total of 120 children underwent 169 VPS placements at a median age of 8 y (IQR 2-15 y), and a mean number of two prior abdominal operations (IQR 1-2). Laparoscopy was used in 24% of cases. Shunt-related complications within 30 d were lower in the LAP group (0% versus 19%, P = 0.001), as were VPS-related postoperative emergency department visits (0% versus 13%, P = 0.003) and readmissions (0% versus 13%, P = 0.013). Shunt malfunction rates were higher (42% OPEN versus 25% LAP, P = 0.03) and occurred sooner in the OPEN group (median 26 versus 78 wk, P = 0.01). The LAP group demonstrated shorter operative times (63 versus 100 min, P < 0.0001), and the only bowel injury. Time to feeds, length of stay, and mortality were similar between groups. CONCLUSIONS Laparoscopic guidance during VPS placement into the reoperative abdomen is associated with a decrease in shunt-related complications, longer shunt patency, and shorter operative times. Prospective study may clarify the potential benefits of laparoscopy in this setting.

OBJECTIVE Children with nonoperative brain tumors, such as diffuse intrinsic pontine gliomas (DIPGs), often have life-threatening hydrocephalus. Palliative shunting is common in such cases but can be complicated by hardware infection and mechanical failure. Endoscopic third ventriculostomy (ETV) is a minimally invasive alternative to treat hydrocephalus without implanted hardware. Herein, the authors report their institutional experience with palliative ETV for primary pediatric brain tumors. METHODS The authors conducted a retrospective review of consecutive patients who had undergone palliative ETV for hydrocephalus secondary to nonresectable primary brain tumors over a 10-year period at Rady Children’s Hospital. Collected variables included age, sex, tumor type, tumor location, presence of leptomeningeal spread, use of a robot for ETV, complications, ETV Success Score (ETVSS), functional status, length of survival, and follow-up time. A successful outcome was defined as an ETV performed without clinically significant perioperative complications or secondary requirement for a new shunt. RESULTS Fifteen patients met the study inclusion criteria (11 males, 4 females; average age 7.9 years, range 0.8–21 years). Thirteen patients underwent manual ETV, and 2 patients underwent robotic ETV. Preoperative symptoms included gaze palsy, nausea/vomiting, headache, lethargy, hemiparesis, and seizures. Tumor types included DIPG (3), intraventricular/thalamic glioblastoma (2), and leptomeningeal spread of medulloblastoma (2), anaplastic oligo-/astrocytoma (2), rhabdoid tumor (2), primitive neuroectodermal tumor (1), ganglioglioma (1), pineoblastoma (1), and embryonal carcinoma (1). The mean preoperative ETVSS was 79 ± 8.8. There was 1 perioperative complication, a wound breakdown consistent with refractory hydrocephalus. The mean follow-up was 4.9 ± 5.5 months overall, and mean survival for the patients who died was 3.2 ± 3.6 months. Two patients remained alive at a mean follow-up of 15.7 months. Palliative ETV was successful in 7 patients (47%) and unsuccessful in 8 (53%). While patients with successful ETV were significantly older (11.9 ± 5.6 vs 4.4 ± 4.1 years, p = 0.010), there were no significant differences in preoperative ETVSS (p = 0.796) or postoperative survival (p = 0.476) between the successful and unsuccessful groups. Overall, functional outcomes were similar between the two groups; there was no significant difference in posttreatment Karnofsky Performance Status scores (68.6 ± 19.5 vs 61.3 ± 16.3, p = 0.454), suggesting that including ETV in the treatment algorithm did not worsen outcomes. CONCLUSIONS Palliative ETV is a safe and potentially efficacious treatment option in selected pediatric patients with hydrocephalus from nonoperative brain tumors. Close follow-up, especially in younger children, is required to ensure that patients with refractory symptoms receive appropriate secondary CSF diversion.

Objective We describe our single-institutional experience with magnetic resonance−guided stereotactic laser ablation (SLA) for the treatment of newly diagnosed and recurrent pediatric brain tumors. Methods Eighteen consecutive ablation procedures were performed in 17 patients from March 2016−April 2020. Patient demographics, indications, procedures, neuroimaging features, and outcomes were reviewed retrospectively. Results Seventeen patients (mean age of 11.4 years, 11 boys, 6 girls) underwent SLA with a mean follow-up of 24 months (range: 3–45 months). Tumor histologies included pilocytic astrocytoma (n = 5), ganglioglioma (n = 3), low-grade glioma not otherwise specified (n = 4), glioblastoma (n = 2), meningioma (n = 1), medulloblastoma (n = 1), and metastatic malignant peripheral nerve sheath tumor (n = 1). SLA was first-line therapy in 10 patients. Mean procedure duration including anesthesia time was 328 minutes (range: 244–529 minutes), and mean postoperative length of stay was 1.5 days (range 1–5 days). The complication rate was 29%, which included 3 patients who experienced postoperative motor changes, which resolved within several weeks of surgery, 1 patient with self-limited intraoperative bradycardia and hypotension, and 1 patient who died postoperatively due to intracranial hemorrhage from a distant lesion. Twelve of 17 patients had a neuroimaging response after SLA (4 complete responses, 8 partial responses, 1 stable disease). Percentage of tumor shrinkage from baseline ranged from 33%−100% (mean 75%). Patients with low-grade glioma exhibited the best responses to SLA (range 3%−100% decrease; mean 90%; 36% complete response rate). Conclusions SLA is a minimally invasive modality for the treatment of newly diagnosed and recurrent low-grade pediatric brain tumors. Low-grade glioma exhibited the best responses. Identification of ideal candidates for SLA, mitigation of perioperative complications, and demonstration of long-term outcomes need to be better defined in a clinical trial setting.

BACKGROUND Removal of the anterior clinoid process (ACP) can expand anterior skull base surgical corridors. ACP development and anatomical variations are poorly defined in children. OBJECTIVE To perform a morphometric analysis of the ACP during pediatric maturation. METHODS Measurements of ACP base thickness (ACP-BT), midpoint thickness (ACP-MT), length (ACP-L), length from optic strut to ACP tip (ACP-OS), pneumatization (ACP-pneumo), and the presence of an ossified carotico-clinoid ligament (OCCL) or interclinoid ligament (OIL) were made from high-resolution computed-tomography scans from 60 patients (ages 0-3, 4-7, 8-11 12-15, 16-18, and >18 yr). Data were analyzed by laterality, sex, and age groups using t-tests and linear regression. RESULTS There were no significant differences in ACP parameters by laterality or sex, and no significant growth in ACP-BT or ACP-MT during development. From ages 0-3 yr to adult, mean ACP-L increased 49%, from 7.7 to 11.5 mm. The majority of ACP-L growth occurred in 2 phases between ages 0-3 to 8-11 and ages 16-18 to adult. Conversely, ACP-OS was stable from ages 0-3 to 8-11 but increased by 63% between ages 8-11 to adult. Variations in ACP morphology (OCCL/OIL/ACP-pneumo) were found in 15% (9/60) of scans. OCCL and OIL occurred in patients as young as 3 yrs, whereas ACP-pneumo was not seen in patients younger than 11 yrs. CONCLUSION The ACP demonstrates stable thickness and a complex triphasic elongation and remodeling pattern with development, the understanding of which may facilitate removal in patients

Compared to adult AVMs, there is a paucity of data on the microsurgical treatment of pediatric AVMs. We report our institutional experience with pediatric AVMs treated by microsurgical resection with or without endovascular embolization and radiation therapy.We retrospectively reviewed all patients ≤ 18 years of age with cerebral AVMs that underwent microsurgical resection at Rady Children's Hospital 2002-2019.Eighty-nine patients met inclusion criteria. The mean age was 10.3 ± 5.0 years, and 56% of patients were male. In total, 72 (81%) patients presented with rupture. Patients with unruptured AVMs presented with headache (n = 5, 29.4%), seizure (n = 9, 52.9%), or incidental finding (n = 3, 17.7%). The mean presenting mRS was 2.8 ± 1.8. AVM location was lobar in 78%, cerebellar/brainstem in 15%, and deep supratentorial in 8%. Spetzler-Martin grade was I in 28%, II in 45%, III in 20%, IV in 6%, and V in 1%. Preoperative embolization was utilized in 38% of patients and more frequently in unruptured than ruptured AVMs (62% vs. 32%, p = 0.022). Radiographic obliteration was achieved in 76/89 (85.4%) patients. Complications occurred in 7 (8%) patients. Annualized rates of delayed rebleeding and recurrence were 1.2% and 0.9%, respectively. The mean follow-up was 2.8 ± 3.1 years. A good neurological outcome (mRS score ≤ 2) was obtained in 80.9% of patients at last follow-up and was improved relative to presentation for 75% of patients.Our case series demonstrates high rates of radiographic obliteration and relatively low incidence of neurologic complications of treatment or AVM recurrence.

OBJECTIVE The middle fossa transpetrosal approach to the petroclival and posterior cavernous sinus regions includes removal of the anterior petrous apex (APA), an area well studied in adults but not in children. To this end, the authors performed a morphometric analysis of the APA region during pediatric maturation. METHODS Measurements of the distance from the clivus to the internal auditory canal (IAC; C-IAC), the distance of the petrous segment of the internal carotid artery (petrous carotid; PC) to the mesial petrous bone (MPB; PC-MPB), the distance of the PC to the mesial petrous apex (MPA; PC-MPA), and the IAC depth from the middle fossa floor (IAC-D) were made on thin-cut CT scans from 60 patients (distributed across ages 0–3, 4–7, 8–11, 12–15, 16–18, and > 18 years). The APA volume was calculated as a cylinder using C-IAC (length) and PC-MPB (diameter). APA pneumatization was noted. Data were analyzed by laterality, sex, and age. RESULTS APA parameters did not differ by laterality or sex. APA pneumatization was seen on 20 of 60 scans (33.3%) in patients ≥ 4 years. The majority of the APA region growth occurred by ages 8–11 years, with PC-MPA and PC-MPB increasing 15.9% (from 9.4 to 10.9 mm, p = 0.08) and 23.5% (from 8.9 to 11.0 mm, p < 0.01) between ages 0–3 and 8–11 years, and C-IAC increasing 20.7% (from 13.0 to 15.7 mm, p < 0.01) between ages 0–3 and 4–7 years. APA volume increased 79.6% from ages 0–3 to 8–11 years (from 834.3 to 1499.2 mm3, p < 0.01). None of these parameters displayed further significant growth. Finally, IAC-D increased 51.1% (from 4.3 to 6.5 mm, p < 0.01) between ages 0–3 and adult, without significant differences between successive age groups. CONCLUSIONS APA development is largely complete by the ages of 8–11 years. Knowledge of APA growth patterns may aid approach selection and APA removal in pediatric patients.

OBJECTIVEBiopsies of tumors located in deep midline structures require highly accurate stereotaxy to safely obtain lesional tissue suitable for molecular and histological analysis. Versatile platforms are needed to meet a broad range of technical requirements and surgeon preferences. The authors present their institutional experience with the robotic stereotactic assistance (ROSA) system in a series of robot-assisted biopsies of pediatric brainstem and thalamic tumors.METHODSA retrospective analysis was performed of 22 consecutive patients who underwent 23 stereotactic biopsies of brainstem or thalamic lesions using the ROSA platform at Rady Children’s Hospital in San Diego between December 2015 and January 2020.RESULTSThe ROSA platform enabled rapid acquisition of lesional tissue across various combinations of approaches, registration techniques, and positioning. No permanent deficits, major adverse outcomes, or deaths were encountered. One patient experienced temporary cranial neuropathy, and 3 developed small asymptomatic hematomas. The diagnostic success rate of the ROSA system was 91.3%.CONCLUSIONSRobot-assisted stereotactic biopsy of these lesions may be safely performed using the ROSA platform. This experience comprises the largest clinical series to date dedicated to robot-assisted biopsies of brainstem and diencephalic tumors.

Laser ablation has become an integral tool within the neurosurgeon’s armamentarium. Applicability to a wide range of pathologies, while maintaining a minimally invasive profile, has been a key driving factor for laser ablation’s success. It has become increasingly utilized in the management of epilepsy and intracranial tumors. Two major laser ablation systems are commercially available at the present time. Neurosurgeons around the world utilize various stereotactic systems for laser insertion. However, the general principles guiding this procedure remain similar. This chapter should serve as a step-by-step how-to guide for operators. Our hope is that neurosurgeons can use this as a manual in their own practice for performing this operation.

OBJECTIVETreatment of hemorrhagic cavernous malformations within the lateral pontine region demands meticulous surgical planning and execution to maximize resection while minimizing morbidity. The authors report a single institution’s experience using the extended middle fossa rhomboid approach for the safe resection of hemorrhagic cavernomas involving the lateral pons.METHODSA retrospective chart review was performed to identify and review the surgical outcomes of patients who underwent an extended middle fossa rhomboid approach for the resection of hemorrhagic cavernomas involving the lateral pons during a 10-year period at Rady Children’s Hospital of San Diego. Surgical landmarks for this extradural approach were based on the Fukushima dual-fan model, which defines the rhomboid based on the following anatomical structures: 1) the junction of the greater superficial petrosal nerve (GSPN) and mandibular branch of the trigeminal nerve; 2) the lateral edge of the porus trigeminus; 3) the intersection of the petrous ridge and arcuate eminence; and 4) the intersection of the GSPN, geniculate ganglion, and arcuate eminence. The boundaries of maximal bony removal for this approach are the clivus inferiorly below the inferior petrosal sinus; unroofing of the internal auditory canal posteriorly; skeletonizing the geniculate ganglion, GSPN, and internal carotid artery laterally; and drilling under the Gasserian ganglion anteriorly. This extradural petrosectomy allowed for an approach to all lesions from an area posterolateral to the basilar artery near its junction with cranial nerve (CN) VI, superior to the anterior inferior cerebellar artery and lateral to the origin of CN V. Retraction of the mandibular branch of the trigeminal nerve during this approach allowed avoidance of the region involving CN IV and the superior cerebellar artery.RESULTSEight pediatric patients (4 girls and 4 boys, mean age of 13.2 ± 4.6 years) with hemorrhagic cavernomas involving the lateral pons and extension to the pial surface were treated using the surgical approach described above. Seven cavernomas were completely resected. In the eighth patient, a second peripheral lesion was not resected with the primary lesion. One patient had a transient CN VI palsy, and 2 patients had transient trigeminal hypesthesia/dysesthesia. One patient experienced a CSF leak that was successfully treated by oversewing the wound.CONCLUSIONSThe extended middle fossa approach can be used for resection of lateral pontine hemorrhagic cavernomas with minimal morbidity in the pediatric population.

Reliable posture labels in hospital environments can augment research studies on neural correlates to natural behaviors and clinical applications that monitor patient activity. However, many existing pose estimation frameworks are not calibrated for these unpredictable settings. In this paper, we propose a semi-automated approach for improving upper-body pose estimation in noisy clinical environments, whereby we adapt and build around an existing joint tracking framework to improve its robustness to environmental uncertainties. The proposed framework uses subject-specific convolutional neural network models trained on a subset of a patient’s RGB video recording chosen to maximize the feature variance of each joint. Furthermore, by compensating for scene lighting changes and by refining the predicted joint trajectories through a Kalman filter with fitted noise parameters, the extended system yields more consistent and accurate posture annotations when compared with the two state-of-the-art generalized pose tracking algorithms for three hospital patients recorded in two research clinics., We propose a semi-automated approach for improving upper-body pose estimation in noisy clinical environments, whereby we adapt and build around an existing joint tracking framework to improve its robustness to environmental uncertainties. The proposed framework uses subject-specific convolutional neural network models trained on a subset of a patient's RGB video recording chosen to maximize the feature variance of each joint. Furthermore, by compensating for scene lighting changes and by refining the predicted joint trajectories through a Kalman filter with fitted noise parameters, the extended system yields more consistent and accurate posture annotations when compared to two state-of-the-art generalized pose tracking algorithms for three hospital patients recorded in two research clinics.

The spontaneous involution and rapid recurrence of a Rathke’s cleft cyst (RCC) is not well described. A 16-year-old female with a putatively incidental nearly 2 cm suprasellar lesion arising from the posterior aspect of the infundibulum found on a brain MRI during workup for aseptic meningitis demonstrated a spontaneous and near-complete involution of this lesion on close follow up (leaving only a thickened infundibulum measuring up to 3.6 mm). After a period of cyclic headaches coinciding with subtle changes in pituitary stalk thickness, she developed progressive fatigue, severe headaches, and bitemporal blurry vision, with rapid re-growth of the suprasellar lesion to near its original size seen on repeat MRI. Due to its purely suprasellar and retro-infundibular location an anterolateral rather than an anterior transnasal approach was recommended. She underwent a successful orbitofrontal craniotomy and cyst fenestration/partial resection, with pathologic analysis confirming an RCC. Post-operatively, she had normal vision and no diabetes insipidus or other hormonal disturbances, and improvement of her headaches on ten-month follow up. Awareness of the potentially dynamic nature of RCCs is important for their timely diagnosis. Purely suprasellar RCCs can require an anterolateral surgical approach, especially when located posterior to the infundibulum.

OBJECTIVEEndoscopic third ventriculostomy (ETV) is a surgical alternative to placing a CSF shunt in certain patients with hydrocephalus. The ETV Success Score (ETVSS) is a reliable, simple method to estimate the success of the procedure by 6 months of postoperative follow-up. The highest score is 90, estimating a 90% chance of the ETV effectively treating hydrocephalus without requiring a shunt. Treatment with ETV fails in certain patients, despite their being the theoretically best candidates for the procedure. In this study the authors attempted to identify factors that further predicted success in patients with the highest ETVSSs.METHODSA retrospective review was performed of all patients treated with ETV at 3 institutions. Demographic, radiological, and clinical data were recorded. All patients by definition were older than 1 year, had obstructive hydrocephalus, and did not have a prior shunt. Failure of ETV was defined as the need for a shunt by 1 year. The ETV was considered a success if the patient did not require another surgery (either shunt placement or a repeat endoscopic procedure) by 1 year. A statistical analysis was performed to identify factors associated with success or failure.RESULTSFifty-nine patients met the entry criteria for the study. Eleven patients (18.6%) required further surgery by 1 year. All of these patients received a shunt. The presenting symptom of lethargy statistically correlated with success (p = 0.0126, odds ratio [OR] = 0.072). The preoperative radiological finding of transependymal flow (p = 0.0375, OR 0.158) correlated with success. A postoperative larger maximum width of the third ventricle correlated with failure (p = 0.0265).CONCLUSIONSThe preoperative findings of lethargy and transependymal flow statistically correlated with success. This suggests that the best candidates for ETV are those with a relatively acute elevation of intracranial pressure. Cases without these findings may represent the failures in this highly selected group.

Linking enhancers to disease Enhancers are genomic regions that regulate gene expression, sometimes in a cell-dependent manner. However, most of our knowledge of human brain cell–type enhancers derives from studies of bulk human brain tissue. Nott et al. examined chromatin and promoter activity in cell nuclei isolated from human brains. Genetic variants associated with brain traits and disease showed cell-specific patterns of enhancer enrichment. These data indicate that Alzheimer's disease is regulated by genetic variants within microglial cells, whereas psychiatric diseases tend to affect neurons. Science , this issue p. 1134

Author(s): Hoshide, Reid; Rennert, Robert C; Calayag, Mark; Gonda, David; Meltzer, Hal; Crawford, John R; Levy, Michael L | Abstract: BACKGROUND:Pediatric intracavernous sinus tumors are exceedingly rare and thus poorly characterized. Their neurosurgical management is challenging and diagnostic, and management guidelines are limited. OBJECTIVE:To report our institutional experience with the surgical resection of pediatric intracavernous sinus tumors. We also compare and contrast our results with the 14 cases of pediatric intracavernous sinus lesions in the current literature. METHODS:A retrospective descriptive analysis of consecutive pediatric patients (ages 0-18 yr) presenting to our institution with a diagnosis of an intracavernous sinus lesion was performed. From January 2012 to January 2017, 5 cases were identified. Eleven patients with secondary invasion of the cavernous sinus (2 meningiomas, 7 pituitary adenomas) or dermoid tumors involving the cavernous sinus (2) were not included in our review. RESULTS:Surgical resection via a frontotemporal orbitozygomatic approach was performed in all cases by a single senior neurosurgeon (M.L.). There were no perioperative or postoperative complications attributable to the surgery or approach. Four of 5 patients remained neurologically stable throughout the perioperative and postoperative period. The fifth patient had a complete resolution of their cranial neuropathies postoperatively. A pathological diagnosis that guided long-term management was obtained in all cases. CONCLUSION:Neurosurgical management of pediatric cavernous sinus lesions can be safely performed and critically guide future therapies. Surgeon familiarity with cavernous sinus and skull-base anatomy is critical to the successful management of these patients. The benefits of surgery should be balanced against the potential complications and need for a tissue diagnosis in children. The senior author had a significant experience with cavernous sinus approaches in adults prior to initiating use of the approach in the pediatric population.

Unique cell type-specific patterns of activated enhancers can be leveraged to interpret non-coding genetic variation associated with complex traits and diseases such as neurological and psychiatric disorders. Here, we have defined active promoters and enhancers for major cell types of the human brain. Whereas psychiatric disorders were primarily associated with regulatory regions in neurons, idiopathic Alzheimer’s disease (AD) variants were largely confined to microglia enhancers. Interactome maps connecting GWAS variants in cell type-specific enhancers to gene promoters revealed an extended microglia gene network in AD. Deletion of a microglia-specific enhancer harboring AD-risk variants ablated BIN1 expression in microglia but not in neurons or astrocytes. These findings revise and expand the genes likely to be influenced by non-coding variants in AD and suggest the probable brain cell types in which they function.One Sentence SummaryIdentification of cell type-specific regulatory elements in the human brain enables interpretation of non-coding GWAS risk variants.

OBJECTIVEThis study aimed to assess the safety and efficacy of MR-guided stereotactic laser ablation (SLA) therapy in the treatment of pediatric brain tumors.METHODSData from 17 North American centers were retrospectively reviewed. Clinical, technical, and radiographic data for pediatric patients treated with SLA for a diagnosis of brain tumor from 2008 to 2016 were collected and analyzed.RESULTSA total of 86 patients (mean age 12.2 ± 4.5 years) with 76 low-grade (I or II) and 10 high-grade (III or IV) tumors were included. Tumor location included lobar (38.4%), deep (45.3%), and cerebellar (16.3%) compartments. The mean follow-up time was 24 months (median 18 months, range 3–72 months). At the last follow-up, the volume of SLA-treated tumors had decreased in 80.6% of patients with follow-up data. Patients with high-grade tumors were more likely to have an unchanged or larger tumor size after SLA treatment than those with low-grade tumors (OR 7.49, p = 0.0364). Subsequent surgery and adjuvant treatment were not required after SLA treatment in 90.4% and 86.7% of patients, respectively. Patients with high-grade tumors were more likely to receive subsequent surgery (OR 2.25, p = 0.4957) and adjuvant treatment (OR 3.77, p = 0.1711) after SLA therapy, without reaching significance. A total of 29 acute complications in 23 patients were reported and included malpositioned catheters (n = 3), intracranial hemorrhages (n = 2), transient neurological deficits (n = 11), permanent neurological deficits (n = 5), symptomatic perilesional edema (n = 2), hydrocephalus (n = 4), and death (n = 2). On long-term follow-up, 3 patients were reported to have worsened neuropsychological test results. Pre-SLA tumor volume, tumor location, number of laser trajectories, and number of lesions created did not result in a significantly increased risk of complications; however, the odds of complications increased by 14% (OR 1.14, p = 0.0159) with every 1-cm3 increase in the volume of the lesion created.CONCLUSIONSSLA is an effective, minimally invasive treatment option for pediatric brain tumors, although it is not without risks. Limiting the volume of the generated thermal lesion may help decrease the incidence of complications.

Objective We studied the relationship between uninstructed, unstructured movements and neural activity in three epilepsy patients with intracranial electroencephalographic (iEEG) recordings. Approach We used a custom system to continuously record high definition video precisely time-aligned to clinical iEEG data. From these video recordings, movement periods were annotated via semi-automatic tracking based on dense optical flow. Main results We found that neural signal features (8-32 Hz and 76-100 Hz power) previously identified from task-based experiments are also modulated before and during a variety of movement behaviors. These movement behaviors are coarsely labeled by time period and movement side (e.g. 'Idle' and 'Move', 'Right' and 'Left'); movements within a label can include a wide variety of uninstructed behaviors. A rigorous nested cross-validation framework was used to classify both movement onset and lateralization with statistical significance for all subjects. Significance We demonstrate an evaluation framework to study neural activity related to natural movements not evoked by a task, annotated over hours of video. This work further establishes the feasibility to study neural correlates of unstructured behavior through continuous recording in the epilepsy monitoring unit. The insights gained from such studies may advance our understanding of how the brain naturally controls movement, which may inform the development of more robust and generalizable brain-computer interfaces.

Objective Current brain-computer interface (BCI) studies demonstrate the potential to decode neural signals obtained from structured and trial-based tasks to drive actuators with high performance within the context of these tasks. Ideally, to maximize utility, such systems will be applied to a wide range of behavioral settings or contexts. Thus, we explore the potential to augment such systems with the ability to decode abstract behavioral contextual states from neural activity. Approach To demonstrate the feasibility of such context decoding, we used electrocorticography (ECoG) and stereo-electroencephalography (sEEG) data recorded from the cortical surface and deeper brain structures, respectively, continuously across multiple days from three subjects. During this time, the subjects were engaged in a range of naturalistic behaviors in a hospital environment. Behavioral contexts were labeled manually from video and audio recordings; four states were considered: engaging in dialogue, rest, using electronics, and watching television. We decode these behaviors using a factor analysis and support vector machine (SVM) approach. Main results We demonstrate that these general behaviors can be decoded with high accuracies of 73% for a four-class classifier for one subject and 71% and 62% for a three-class classifier for two subjects. Significance To our knowledge, this is the first demonstration of the potential to disambiguate abstract naturalistic behavioral contexts from neural activity recorded throughout the day from implanted electrodes. This work motivates further study of context decoding for BCI applications using continuously recorded naturalistic activity in the clinical setting.

BACKGROUND Management of patients afflicted with brain metastasis requires tailoring of therapeutic strategies based on survival expectations. Therefore, the development of prognostic indices is of critical importance in this patient population. OBJECTIVE To determine whether the cumulative intracranial tumor volume (CITV) of brain metastasis augments the prognostic value of the lung-specific Graded Prognostic Assessment (GPA) index. METHODS Patient data were derived from 365 lung cancer patients with brain metastasis who were consecutively treated with stereotactic radiosurgery at the University of California, San Diego/San Diego Gamma Knife Center. CITV was analyzed to determine the volume cutoff that maximized sensitivity and specificity for 1-year survival. Multivariate Cox proportional hazard modeling was performed, and overall survival was estimated by the Kaplan-Meier method risk stratifying with or without this optimal CITV. The prognostic value of these models (lung-specific GPA ± CITV) was quantitatively compared with the use of net reclassification improvement (>0) and integrated discrimination improvement. RESULTS For the University of California, San Diego/San Diego Gamma Knife Center cohort, the CITV cutoff that had the greatest survival discrimination at 1 year was 4 cm. The addition of CITV to the lung-specific GPA indexes significantly improved the prognostic value of lung-specific GPA, with net reclassification improvement >0 of 0.430 (95% confidence interval, 0.228-0.629) and integrated discrimination improvement of 0.029 (95% confidence interval, 0.004-0.073). These findings were validated in an independent cohort of 1638 lung cancer patients with brain metastasis who were treated with stereotactic radiosurgery at the Katsuta Hospital Mito Gamma House in Japan. CONCLUSION In independent cohorts, the addition of CITV to the lung-specific GPA index significantly improved the prognostic value of this index. ABBREVIATIONS AUC, area under the receiver-operating characteristic curveBM, brain metastasisCITV, cumulative intracranial tumor volumeds-GPA, disease-specific Graded Prognostic AssessmentGPA, Graded Prognostic AssessmentIDI, integrated discrimination improvementKHMGH, Katsuta Hospital Mito Gamma HouseKPS, Karnofsky Performance StatusNRI, net reclassification improvementROC, receiver-operating characteristic curveSRS, stereotactic radiosurgeryUCSD/SDGKC, University of California, San Diego/San Diego Gamma Knife Center.

OBJECTIVELesions of the foramen magnum, inferolateral-to-midclival areas, and ventral pons and medulla are often treated using a far-lateral or extreme-lateral infrajugular transcondylar–transtubercular exposure (ELITE) approach. The development and surgical relevance of critical posterior skull base bony structures encountered during these approaches, including the occipital condyle (OC), hypoglossal canal (HGC), and jugular tubercle (JT), are nonetheless poorly defined in the pediatric population.METHODSMeasurements from high-resolution CT scans were made of the relevant posterior skull base anatomy (HGC depth from posterior edge of the OC, OC and JT dimensions) from 60 patients (evenly distributed among ages 0–3, 4–7, 8–11, 12–15, 16–18, and > 18 years), and compared between laterality, sex, and age groups by using t-tests and linear regression.RESULTSThere were no significant differences in posterior skull base parameters by laterality, and HGC depth and JT size did not differ by sex. The OC area was significantly larger in males versus females (174.3 vs 152.2 mm2; p = 0.01). From ages 0–3 years to adult, the mean HGC depth increased 27% (from 9.0 to 11.4 mm) and the OC area increased 52% (from 121.4 to 184.0 mm2). The majority of growth for these parameters occurred between the 0–3 year and 4–7 year age groups. Conversely, JT volume increased nearly 3-fold (281%) from 97.4 to 370.9 mm3 from ages 0–3 years to adult, with two periods of substantial growth seen between the 0–3 to 4–7 year and the 12–15 to 16–18 year age groups. Overall, JT growth during pediatric development was significantly greater than increases in HGC depth and OC area (p < 0.05). JT volume remained < 65% of adult size up to age 16.CONCLUSIONSWhen considering a far-lateral or ELITE approach in pediatric patients, standard OC drilling is likely to be needed due to the relative stability of OC and HGC anatomy during development. The JT significantly increases in size with development, yet is only likely to need to be drilled in older children (> 16 years) and adults.

Normal and pathologic cells secrete extracellular vesicles (EV), which are defined as 30-2,000 nm spherical organelles. It has been found that EV mediate various biological functions including cellular remodeling and export of biomolecules, extracellular communication, immune stimulation and suppression, and modulation of the cellular microenvironment. EV secreted by human glioma cells contain a wealth of tumor-specific proteins and nucleic acids that can be isolated from patients with these neoplasms. Thus, EV contribute to the development of biomarkers, and additionally have certain therapeutic potential for possible use in neuro-oncology and neurosurgery.

OBJECTIVEPediatric traumatic subarachnoid hemorrhage (tSAH) often results in intensive care unit (ICU) admission, the performance of additional diagnostic studies, and ICU-level therapeutic interventions to identify and prevent episodes of neuroworsening.METHODSData prospectively collected in an institutionally specific trauma registry between 2006 and 2015 were supplemented with a retrospective chart review of children admitted with isolated traumatic subarachnoid hemorrhage (tSAH) and an admission Glasgow Coma Scale (GCS) score of 13–15. Risk of blunt cerebrovascular injury (BCVI) was calculated using the BCVI clinical prediction score.RESULTSThree hundred seventeen of 10,395 pediatric trauma patients were admitted with tSAH. Of the 317 patients with tSAH, 51 children (16%, 23 female, 28 male) were identified with isolated tSAH without midline shift on neuroimaging and a GCS score of 13–15 at presentation. The median patient age was 4 years (range 18 days to 15 years). Seven had modified Fisher grade 3 tSAH; the remainder had grade 1 tSAH. Twenty-six patients (51%) had associated skull fractures; 4 involved the petrous temporal bone and 1 the carotid canal. Thirty-nine (76.5%) were admitted to the ICU and 12 (23.5%) to the surgical ward. Four had an elevated BCVI score. Eight underwent CT angiography; no vascular injuries were identified. Nine patients received an imaging-associated general anesthetic. Five received hypertonic saline in the ICU. Patients with a modified Fisher grade 1 tSAH had a significantly shorter ICU stay as compared to modified Fisher grade 3 tSAH (1.1 vs 2.5 days, p = 0.029). Neuroworsening was not observed in any child.CONCLUSIONSChildren with isolated tSAH without midline shift and a GCS score of 13–15 at presentation appear to have minimal risk of neuroworsening despite the findings in some children of skull fractures, elevated modified Fisher grade, and elevated BCVI score. In this subgroup of children with tSAH, routine ICU-level care and additional diagnostic imaging may not be necessary for all patients. Children with modified Fisher grade 1 tSAH may be particularly unlikely to require ICU-level admission. Benefits to identifying a subgroup of children at low risk of neuroworsening include improvement in healthcare efficiency as well as decreased utilization of unnecessary and potentially morbid interventions, including exposure to ionizing radiation and general anesthesia.

Normal and pathologic cells secrete extracellular vesicles (EV), which are defined as 30-2,000 nm spherical organelles. It has been found that EV mediate various biological functions including cellular remodeling and export of biomolecules, extracellular communication, immune stimulation and suppression, and modulation of the cellular microenvironment. EV secreted by human glioma cells contain a wealth of tumor-specific proteins and nucleic acids that can be isolated from patients with these neoplasms. Thus, EV contribute to the development of biomarkers, and additionally have certain therapeutic potential for possible use in neuro-oncology and neurosurgery.

Spine shortening via vertebral osteotomy (SSVO) for recurrent tethered cord syndrome (TCS) is a novel surgical technique that avoids the complication profile associated with revision detethering. While SSVO has previously been described via a posterior approach, we describe a lateral retropleural approach for SSVO in recurrent TCS in a 21-year-old female. Our patient presented with progressive lower extremity weakness, bowel and bladder incontinence, and back pain in the setting of childhood repair of myelomeningocele and two previous detethering procedures. SSVO was offered to the patient as further detethering was deemed to have significant risk. A discectomy at T11-T12 via the lateral retropleural approach was performed, followed by a T12 partial corpectomy removing the vertebral body down to the inferior aspect of the T12 pedicle, followed by the removal of the ipsilateral pedicle. The T10, T11, L1, and L2 pedicle screws were then placed in the prone position and temporary rods were placed for temporary stability, followed by a laminectomy at T12 and a facetectomy for posterior element release. The remaining pedicle was removed, permanent rods were sequentially placed, and spinal column shortening was achieved by compression against the rods. Standing lateral radiographs demonstrated 19 millimeters (mm) of shortening after the intervention. The patient remained at her neurologic baseline postoperatively. At the six-month follow-up, the patient reported decreased lower extremity radicular pain and improved bowel and bladder function. This operative report demonstrates that SSVO via a lateral retropleural approach is a viable treatment for the recurrence of TCS. The advantages of this minimally invasive approach compared to the posterior approach are direct access to the vertebral body and disc space, avoiding the need to operate around the spinal cord. Further studies are necessary to assess this minimally invasive approach to spinal shortening and to see if a complete minimally invasive approach is possible.

OBJECTIVEThe endoscopic third ventriculostomy (ETV) is an established and effective treatment for obstructive hydrocephalus. In its most common application, surgeons plan their entry point and the endoscope trajectory for the procedure based on anatomical landmarks, then control the endoscope freehand. Recent studies report an incidence of neural injuries as high as 16.6% of all ETVs performed in North America. The authors have introduced the ROSA system to their ETV procedure to stereotactically optimize endoscope trajectories, to reduce risk of traction on neural structures by the endoscope, and to provide a stable mechanical holder of the endoscope. Here, they present their series in which the ROSA system was used for ETVs.METHODSAt the authors’ institution, they performed ETVs with the ROSA system in 9 consecutive patients within an 8-month period. Patients had to have a favorable expected response to ETV (ETV Success Score ≥ 70) with no additional endoscopic procedures (e.g., choroid plexus cauterization, septum pellucidum fenestration). The modality of image registration (CT, MRI, surface mapping, or bone fiducials) was dependent on the case.RESULTSNine pediatric patients with an age range of 1.5 to 16 years, 4 girls and 5 boys, with ETV Success Scores ranging from 70 to 90, underwent successful ETV surgery with the ROSA system within an 8-month period. Their intracranial pathologies included tectal tumors (n = 3), communicating hydrocephalus from hemorrhage or meningeal disease (n = 2), congenital aqueductal stenosis (n = 1), compressive porencephalic cyst (n = 1), Chiari I malformation (n = 1), and pineal region mass (n = 1). Robotic assistance was limited to the ventricular access in the first 2 procedures, but was used for the entirety of the procedure for the following 7 cases. Four of these cases were combined with another procedural objective (3 stereotactic tectal mass biopsies, 1 Chiari decompression). A learning curve was observed with each subsequent surgery as registration and surgical times became shorter and more efficient. All patients had complete resolution of their preprocedural symptoms. There were no complications.CONCLUSIONSThe ROSA system provides a stable, precise, and minimally invasive approach to ETVs.

Hydrocephalus is one of the most common diseases managed by pediatric neurosurgeons. Cerebrospinal fluid (CSF) shunting has been the mainstay of durable treatment for hydrocephalus for many decades. There are two main categories of shunt designs for regulating the extent of CSF diversion: (1) Fixed-parameter valves and (2) adjustable valves. Furthermore, these valves can also function with and without an anti-siphon device. Here, we review randomized controlled trials (RCTs) that examined the impact of these valve designs on the clinical outcome of pediatric patients afflicted with hydrocephalus. All three RCTs suggested no significant differences in clinical outcome as a function of shunt design. Implications of these findings are discussed.

Intramedullary spinal cord hematomas are a rare neurosurgical pathological entity typically arising from vascular and neoplastic lesions. Endometriosis is an extremely rare cause of intramedullary spinal cord hematoma, with only 5 previously reported cases in the literature. Endometriosis is characterized by ectopic endometrial tissue, typically located in the female pelvic cavity, that causes a cyclical pain syndrome, bleeding, and infertility. In the rare case of intramedullary endometriosis of the spinal cord, symptoms include cyclical lower-extremity radiculopathies and voiding difficulties, and can acutely cause cauda equina syndrome. The authors report a case of endometriosis of the conus medullaris, the first to include radiological, intraoperative, and histopathological imaging. A brief review of the literature is also presented, with discussion including etiological theories surrounding intramedullary endometriosis.

Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30–2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications.

// Jie Li 1,* , Zachary J. Taich 1,* ,Amit Goyal 1 , David Gonda 1 , Johnny Akers 1 , Bandita Adhikari 1 , Kunal Patel 1 , Scott Vandenberg 2 , Wei Yan 3 , Zhaoshi Bao 3 , Bob S. Carter 1 , Renzhi Wang 4 , Ying Mao 5 , Tao Jiang 3 and Clark C. Chen 1 1 Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, University of California, San Diego 2 Department of Pathology, University of California, San Diego 3 Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, China 4 Department of Neurosurgery, Peking Union Medical College Hospital, Beijing, China 5 Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China * These authors contributed equally to this work Correspondence: Clark C. Chen, email: // Keywords : G-CIMP, EGFR, Glioblastoma, Epigenetic suppression Received : August 10, 2014 Accepted : August 15, 2014 Published : August 16, 2014 Abstract The intrinsic signaling cascades and cell states associated with the Glioma CpG Island Methylator Phenotype (G-CIMP) remain poorly understood. Using published mRNA signatures associated with EGFR activation, we demonstrate that G-CIMP+ tumors harbor decreased EGFR signaling using three independent datasets, including the Chinese Glioma Genome Atlas(CGGA; n=155), the REMBRANDT dataset (n=288), and The Cancer Genome Atlas (TCGA; n=406). Additionally, an independent collection of 25 fresh-frozen glioblastomas confirmed lowered pERK levels in G-CIMP+ specimens (p

Object Using a database that enabled longitudinal follow-up, the authors assessed the long-term outcomes of unruptured cerebral aneurysms repaired by clipping or coiling. Methods An observational analysis of the California Office of Statewide Health Planning and Development (OSHPD) database, which follows patients longitudinally in time and through multiple hospitalizations, was performed for all patients initially treated for an unruptured cerebral aneurysm in the period from 1998 to 2005 and with follow-up data through 2009. Results Nine hundred forty-four cases (36.5%) were treated with endovascular coiling, 1565 cases (60.5%) were surgically clipped, and 76 cases were treated with both coiling and clipping. There was no significant difference in any demographic variable between the two treatment groups except for age (median: 55 years for the clipped group, 58 years for the coiled group, p < 0.001). Perioperative (30-day) mortality was 1.1% in patients with coiled aneurysms compared with 2.3% in those with clipped aneurysms (p = 0.048). The median follow-up was 7 years (range 4–12 years). At the last follow-up, 153 patients (16.2%) in the coiled group had died compared with 244 (15.6%) in the clipped group (p = 0.693). The adjusted hazard ratio for death at the long-term follow-up was 1.14 (95% CI 0.9–1.4, p = 0.282) for patients with endovascularly treated aneurysms. The incidence of intracranial hemorrhage was similar in the two treatment groups (5.9% clipped vs 4.8% coiled, p = 0.276). One hundred ninety-three patients (20.4%) with coiled aneurysms underwent additional hospitalizations for aneurysm repair procedures compared with only 136 patients (8.7%) with clipped aneurysms (p < 0.001). Cumulative hospital costs per patient for admissions involving aneurysm repair procedures were greater in the clipped group (median cost $98,260 vs $81,620, p < 0.001) through the follow-up. Conclusions For unruptured cerebral aneurysms, an observed perioperative survival advantage for endovascular coiling relative to that for surgical clipping was lost on long-term follow-up, according to data from an administrative database of patients who were not randomly allocated to treatment type. A cost advantage of endovascular treatment was maintained even though endovascularly treated patients were more likely to undergo subsequent hospitalizations for additional aneurysm repair procedures. Rates of aneurysm rupture following treatment were similar in the two groups.

Object Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection. Methods The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions. Results A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20–1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06–2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20–2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84–8.18). Conclusions Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.

Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treatment includes surgical resection, irradiation with adjuvant temozolomide and, on recurrence, experimental chemotherapy. However, the survival of patients remains poor. There is a critical need for minimally invasive biomarkers for diagnosis and as measures of response to therapeutic interventions. Glioma shed extracellular vesicles (EVs), which invade the surrounding tissue and circulate within both the cerebrospinal fluid and the systemic circulation. These tumor-derived EVs and their content serve as an attractive source of biomarkers. In this review, we discuss the current state of the art of biomarkers for glioma with emphasis on their EV derivation.

Object There is limited information on the relationship between patient age and the clinical benefit of resection in patients with glioblastoma. The purpose of this study was to use a population-based database to determine whether patient age influences the frequency that gross-total resection (GTR) is performed, and also whether GTR is associated with survival difference in different age groups. Methods The authors identified 20,705 adult patients with glioblastoma in the Surveillance, Epidemiology, and End Results (SEER) registry (1998–2009). Surgical practice patterns were defined by the categories of no surgery, subtotal resection (STR), and GTR. Kaplan-Meier and multivariate Cox regression analyses were used to assess the pattern of surgical practice and overall survival. Results The frequency that GTR was achieved in patients with glioblastoma decreased in a stepwise manner as a function of patient age (from 36% [age 18–44 years] to 24% [age ≥ 75]; p < 0.001). For all age groups, glioblastoma patients who were selected for and underwent GTR showed a 2- to 3-month improvement in overall survival (p < 0.001) relative to those who underwent STR. These trends remained true after a multivariate analysis that incorporated variables including ethnicity, sex, year of diagnosis, tumor size, tumor location, and radiotherapy status. Conclusions Gross-total resection is associated with improved overall survival, even in elderly patients with glioblastoma. As such, surgical decisions should be individually tailored to the patient rather than an adherence to age as the sole clinical determinant.