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OBJECTIVE The utilization of telemedicine in healthcare has increased dramatically during the recent COVID-19 pandemic. This study aimed to investigate the feasibility to perform remote patient monitoring after full endoscopic spine surgery via a smartphone application that also allows communication with patients. METHODS A smartphone application (SPINEhealthie) was designed at the University of Washington and used to collect patient-reported outcome measures (PROMs) and to provide chat communication between patients and their care team. A total of 71 patients were included in the study and prospectively followed for 3 months postoperatively. Patient demographic characteristics, compliance with surveys, and frequency of chat utilization were recorded. The ease of use, the participants’ experiences with the app interface design, and the usefulness of the app were assessed by using the mHealth App Usability Questionnaire (MAUQ). RESULTS Of all eligible patients, 71/78 (91.0%) agreed to participate. Of these, 60 (85%) patients provided at least 1 postoperative PROM. There was good coverage of the immediate postoperative period with 45 (63.4%) patients providing ≥ 5 PROMs within the 1st week after surgery. The authors observed a 33.2% increase in patient compliance in postoperative PROMs and a 45.7% increase in chat function utilization between the first and last of the three enrollment periods of the study, during which continuous updates were made to improve the app’s functionality. Sixty-two (87.3%) patients responded to the user satisfaction survey after using the app for at least 40 days. The MAUQ results revealed excellent rates of satisfaction for ease of use (78.6% of the maximum score), app interface design (71.4%), and usefulness (71.4%), resulting in a total mean MAUQ score of 110 (74.8%). Communication with the doctor (38 votes) was found to be the top feature of the app. Additionally, physical therapy instructions (33 votes) and imaging review (29 votes) were the top two features that patients would like to see in future app versions. Lastly, the authors have presented a case example of a 68-year-old man who used the app for postoperative monitoring and communication after undergoing a two-level lumbar endoscopic unilateral laminotomy for bilateral decompression. CONCLUSIONS Postoperative remote patient monitoring and communication after full endoscopic surgery is feasible using the SPINEhealthie app. Importantly, patients were willing to share their medical information using a mobile device, and they were eager to use it postoperatively as a supplementary tool.

OBJECTIVE Brain arteriovenous malformations (bAVMs) most commonly present with rupture and intraparenchymal hemorrhage. In rare cases, the hemorrhage is large enough to cause clinical herniation or intractable intracranial hypertension. Patients in these cases require emergent surgical decompression as a life-saving measure. The surgeon must decide whether to perform concurrent or delayed resection of the bAVM. Theoretical benefits to concurrent resection include a favorable operative corridor created by the hematoma, avoiding a second surgery, and more rapid recovery and rehabilitation. The objective of this study was to compare the clinical and surgical outcomes of patients who had undergone concurrent emergent decompression and bAVM resection with those of patients who had undergone delayed bAVM resection. METHODS The authors conducted a 15-year retrospective review of consecutive patients who had undergone microsurgical resection of a ruptured bAVM at their institution. Patients presenting in clinical herniation or with intractable intracranial hypertension were included and grouped according to the timing of bAVM resection: concurrent with decompression (hyperacute group) or separate resection surgery after decompression (delayed group). Demographic and clinical characteristics were recorded. Groups were compared in terms of the primary outcomes of hospital and intensive care unit (ICU) lengths of stay (LOSs). Secondary outcomes included complete obliteration (CO), Glasgow Coma Scale score, and modified Rankin Scale score at discharge and at the most recent follow-up. RESULTS A total of 35/269 reviewed patients met study inclusion criteria; 18 underwent concurrent decompression and resection (hyperacute group) and 17 patients underwent emergent decompression only with later resection of the bAVM (delayed group). Hyperacute and delayed groups differed only in the proportion that underwent preresection endovascular embolization (16.7% vs 76.5%, respectively; p < 0.05). There was no significant difference between the hyperacute and delayed groups in hospital LOS (26.1 vs 33.2 days, respectively; p = 0.93) or ICU LOS (10.6 vs 16.1 days, respectively; p = 0.69). Rates of CO were also comparable (78% vs 88%, respectively; p > 0.99). Medical complications were similar in the two groups (33% hyperacute vs 41% delayed, p > 0.99). Short-term clinical outcomes were better for the delayed group based on mRS score at discharge (4.2 vs 3.2, p < 0.05); however, long-term outcomes were similar between the groups. CONCLUSIONS Ruptured bAVM rarely presents in clinical herniation requiring surgical decompression and hematoma evacuation. Concurrent surgical decompression and resection of a ruptured bAVM can be performed on low-grade lesions without compromising LOS or long-term functional outcome; however, the surgeon may encounter a more challenging surgical environment.

OBJECTIVE The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p < 0.0001), fewer patients with > 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p > 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.

Following neurosurgical repair of spinal dysraphism defects, soft-tissue reconstruction is often required to obtain robust coverage of the dura. Layered closure utilizing local muscle and muscle fascia has proven reliable for this purpose, but it often results in significant dead space necessitating closed suction drainage. Progressive-tension sutures have been reported as an alternative to drains for prevention of fluid collection in several other procedures. In this study, the use of progressive-tension sutures for eliminating subcutaneous dead space and obtaining tension-free skin closure was prospectively evaluated in pediatric patients undergoing soft-tissue reconstruction for congenital spinal anomalies. Primary outcomes of interest included wound breakdown, seroma, hematoma, and cerebrospinal fluid leak. Patients were excluded if a lumbar, submuscular, or subcutaneous drain was placed during the index procedure. Over a 3-year period, 45 patients underwent muscle flap reconstruction for coverage of dural defects. The primary diagnoses were myelomeningocele (10 patients), lipomyelomeningocele (eight patients), myelocystocele (three patients), tethered cord release (15 patients), meningocele (three patients), spinal tumor (two patients), and hardware exposure following spinal instrumentation (three patients). During the follow-up period, three patients (6.7 percent) had postoperative wound complications. One patient had superficial dehiscence, one had cerebrospinal fluid leak requiring operative revision, and one had a surgical site infection necessitating operative drainage. No patients developed hematomas, seromas, cerebrospinal fluid fistulae, or wound breakdown requiring operative revision. The use of progressive-tension sutures is an effective method for eliminating subcutaneous dead space in pediatric soft-tissue reconstruction and eliminates the need for drain placement.Therapeutic, IV.

SCH Clinical and Sequencing Data

Supplementary Figure 1 from Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci

3 Tables & 2 Figures from The SmoA1 Mouse Model Reveals That Notch Signaling Is Critical for the Growth and Survival of Sonic Hedgehog-Induced Medulloblastomas

Supplementary Figures 1-9, Methods from Specific Targeting of Brain Tumors with an Optical/Magnetic Resonance Imaging Nanoprobe across the Blood-Brain Barrier

To develop a genetically faithful model of medulloblastoma with increased tumor incidence compared with the current best model we activated the Sonic Hedgehog (Shh) pathway by transgenically expressing a constitutively active form of Smoothened in mouse cerebellar granule neuron precursors (ND2:SmoA1 mice). This resulted in early cerebellar granule cell hyper-proliferation and a 48% incidence of medulloblastoma formation. Gene expression studies showed an increase in the known Shh targets Gli1 and Nmyc that correlated with increasing hyperplasia and tumor formation. Notch2 and the Notch target gene, HES5, were also significantly elevated in Smoothened-induced tumors showing that Shh pathway activation is sufficient to induce Notch pathway signaling. In human medulloblastomas reverse transcription-PCR for Shh and Notch targets revealed activation of both of these pathways in most tumors when compared with normal cerebellum. Notch pathway inhibition with soluble Delta ligand or γ secretase inhibitors resulted in a marked reduction of viable cell numbers in medulloblastoma cell lines and primary tumor cultures. Treatment of mice with D283 medulloblastoma xenografts with a γ secretase inhibitor resulted in decreased proliferation and increased apoptosis, confirming that Notch signaling contributes to human medulloblastoma proliferation and survival. Medulloblastomas in ND2:SmoA1 mice and humans have concomitant increase in Shh and Notch pathway activities, both of which contribute to tumor survival.

Supplementary Table 1 from Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci

Supplementary Figure 2 from Tumor Paint: A Chlorotoxin:Cy5.5 Bioconjugate for Intraoperative Visualization of Cancer Foci

Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies. [Cancer Res 2007;67(14):6882–8]

It is important to determine whether sagittal synostosis-associated scaphocephaly is static in the presurgical period, or whether there are morphologic differences with time to include in surgical decision-making. The authors' purpose was to perform cross-sectional analysis of cranial morphology before any surgical intervention in children with sagittal synostosis younger than 9 months compared to matched controls.The authors performed morphometric analysis on computed tomographic scans from 111 untreated isolated sagittal synostosis patients younger than 9 months and 37 age-matched normal controls. The authors divided the patients into three age groups and performed statistical comparison between sagittal synostosis and controls for each group.Sagittal synostosis cephalic indices were stable and lower in patients than in controls across groups. Total cranial volume was equivalent, but sagittal synostosis patients had a greater posterior volume than controls at all ages and a smaller middle fossa volume at older ages. Pterional width was greater in sagittal synostosis patients than in controls for each age group. Frontal bossing vectors were most severe in the youngest age groups and least in the older group. Occipital protuberance was consistent across the age groups.Upper parietal narrowing and occipital protuberance were the consistent deformities across age groups, with the most parietal constriction seen in older patients. Frontal bossing was not consistent and was more severe in the younger patients. The authors did not detect significant pterional constriction, and the appearance of constriction is relative to adjacent morphology and not absolute.Risk, II.

OBJECTIVE The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p < 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002], dysconjugate gaze [p = 0.03], hearing loss [p = 0.003], gait instability [p = 0.003], tremor [p = 0.021], or dysmetria [p < 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p < 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p < 0.001), higher estimated blood loss (p < 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p < 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p < 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.

The neocortex is disproportionately expanded in human compared with mouse1,2, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth3. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer’s disease4,5. Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease., Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

PURPOSE: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature. METHODS: A systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression. RESULTS: We identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression. CONCLUSION: Our IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.

Human cortical interneurons have been challenging to study due to high diversity and lack of mature brain tissue platforms and genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in brain slices to define the signature morpho-electric properties of GABAergic neurons in the human neocortex. Viral targeting greatly facilitated sampling of the SST subclass, including primate specialized double bouquet cells which mapped to two SST transcriptomic types. Multimodal analysis uncovered an SST neuron type with properties inconsistent with original subclass assignment; we instead propose reclassification into PVALB subclass. Our findings provide novel insights about functional properties of human cortical GABAergic neuron subclasses and types and highlight the essential role of multimodal annotation for refinement of emerging transcriptomic cell type taxonomies.One Sentence SummaryViral genetic labeling of GABAergic neurons in humanex vivobrain slices paired with Patch-seq recording yields an in-depth functional annotation of human cortical interneuron subclasses and types and highlights the essential role of multimodal functional annotation for refinement of emerging transcriptomic cell type taxonomies.

Chiari Malformation type 1 (CM-I) is a neurological disorder characterized by morphological defects such as excessive cerebral tonsils herniation and vast associated symptomatology. Given that these structural defects cannot explain the underlying symptomatology, and might result in misdiagnosis, in this work, we studied the brain’s intrinsic motion to better understand the mechanisms of CM-I. We acquired 3D cine MRI of 14 healthy and 14 CM-I subjects and used 3D amplified MRI (3D aMRI) to visualize and measure the brain’s intrinsic motion during the cardiac cycle. We observed that the regional brain motion in CM-I was significantly higher than the healthy subjects, with anterior-posterior (AP) and superior-inferior (SI) displacements in cerebral tonsils and medulla having the highest differences between the healthy and CM-I (∽45% ∽73% increased motion in the CM-I group). The motion of the cerebellum, and brainstem in AP directions (∽42% and ∽31% increased motion in the CM-I group, respectively), followed by the motion of the cerebral tonsils and medulla in medial-lateral (ML) directions were other significant differences found between the two groups (∽16% increased motion in the CM-I group). Additionally, for the CM-I subjects, we measured morphological parameters including the tonsil herniation, ratio of neural tissue in the foramen magnum, and 4thventricle volume. We then used the morphometrics and brain’s intrinsic motion to analyze the symptomatology of the CM-I patients and their surgical outcomes. Interestingly, we found the ratio of neural tissue in the foramen to be directly correlated with the SI motion of the tonsils (r= 0.58). We also found the tonsil herniation to be directly correlated with the AP motion of the tonsils (r= 0.61), and AP and ML motions of the medulla (r= 0.66, andr= 0.57). Additionally, we found the ML motion of the tonsils to be the only indicator of the surgical outcome (AUC= 0.95), in which subjects with higher motion had an improved outcome. Although we did not observe a significant correlation between the brains motion and morphometrics on the CM-I symptoms due to our small sample size, illustrative cases increase our hope for the development of a future tool based on the brain biomechanics.

Neocortical layer 1 (L1) is a site of convergence between pyramidal neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neuron types with extensive branching in L1, but whether L1 interneurons are similarly diverse is underexplored. Using patch-seq recordings from human neurosurgically resected tissues, we identified four transcriptomically defined subclasses, unique subtypes within those subclasses and additional types with no mouse L1 homologue. Compared with mouse, human subclasses were more strongly distinct from each other across all modalities. Accompanied by higher neuron density and more variable cell sizes compared with mouse, these findings suggest L1 is an evolutionary hotspot, reflecting the increasing demands of regulating the expanding human neocortical circuit.One Sentence SummaryUsing transcriptomics and morpho-electric analyses, we describe innovations in human neocortical layer 1 interneurons.

Patients with severe polyethylene glycol (PEG) allergies face broad challenges, especially when presenting to the hospital for surgery, as PEG is used often as an excipient in medications and in medical supplies. Although rare, this allergy is increasingly reported and likely underdiagnosed. We present a patient with known past anaphylactic reaction to PEG and a detailed account of her perioperative course. More broadly, we provide recommendations and resources for the safe management of similar patients with a severe PEG allergy.

Telemedicine has received increased attention in recent years as a potential solution to expand clinical capability and patient access to care in many fields, including neurosurgery. Although patient and physician attitudes are rapidly shifting toward greater telemedicine use in light of the COVID-19 pandemic, there remains uncertainty about telemedicine's regulatory future. Despite growing evidence of telemedicine's utility, there remain a number of significant medicolegal barriers to its mass adoption and wider implementation. Herein, we examine recent progress in state and federal regulations in the United States governing telemedicine's implementation in quality of care, finance and billing, privacy and confidentiality, risk and liability, and geography and interstate licensure, with special attention to how these concern teleneurosurgical practice. We also review contemporary topics germane to the future of teleneurosurgery, including the continued expansion of reciprocity in interstate licensure, expanded coverage for homecare services for chronic conditions, expansion of Center for Medicare and Medicaid Services reimbursements, and protections of store-and-forward technologies. Additionally, we discuss recent successes in teleneurosurgery, stroke care, and rehabilitation as models for teleneurosurgical best practices. As telemedicine technology continues to mature and its expanse grows, neurosurgeons’ familiarity with its benefits, limitations, and controversies will best allow for its successful adoption in our field to maximize patient care and outcomes.

OBJECTIVE Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.

Background Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI. Objective To provide key insight for operative management and RTP following SRSBI using a (1) focused systematic review and (2) survey of expert opinions. Methods A systematic literature review of SRSBI from 2012 to present in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a cross-sectional survey of RTP in SRSBI by 31 international neurosurgeons was conducted. Results Of 27 included articles out of 241 systematically reviewed, 9 (33.0%) case reports provided RTP information for 12 athletes. To assess expert opinion, 31 of 32 neurosurgeons (96.9%) provided survey responses. For acute, asymptomatic SRSBI, 12 (38.7%) would not operate. Of the 19 (61.3%) who would operate, midline shift (63.2%) and hemorrhage size > 10 mm (52.6%) were the most common indications. Following SRSBI with resolved hemorrhage, with or without burr holes, the majority of experts (>75%) allowed RTP to high-contact/collision sports at 6 to 12 mo. Approximately 80% of experts did not endorse RTP to high-contact/collision sports for athletes with persistent hemorrhage. Following craniotomy for SRSBI, 40% to 50% of experts considered RTP at 6 to 12 mo. Linear regression revealed that experts allowed earlier RTP at higher levels of play (β = -0.58, 95% CI -0.111, -0.005, P = .033). Conclusion RTP decisions following structural brain injury in athletes are markedly heterogeneous. While individualized RTP decisions are critical, aggregated expert opinions from 31 international sports neurosurgeons provide key insight. Level of play was found to be an important consideration in RTP determinations.

OBJECTIVE Surgical treatment for symptomatic Chiari I malformation involves surgical decompression of the craniovertebral junction. Given the proximity of critical brainstem structures, intraoperative neuromonitoring (IONM) is employed for safe decompression in some institutions. However, IONM adds time and cost to the operation, and the benefit to the patient has not been defined. Given the diversity in surgical practices, there is no evidence-based standard of care regarding when to use IONM and which modalities are most helpful. The purpose of this study was to review a single-surgeon experience with IONM in order to determine the sensitivity, specificity, and predictive values of various IONM modalities routinely used in pediatric Chiari I decompression; to examine the associations between patient, clinical, and radiographic characteristics and IONM alerts; and to obtain data regarding the usefulness of these modalities during the surgical process to improve patient outcomes. METHODS A retrospective review was performed for 300 consecutive pediatric patients who underwent suboccipital craniectomy and C1 laminectomy for Chiari decompression performed by a single surgeon over a 15-year period. Clinical, radiographic, and IONM data were collected. Radiographic measurements of the skull base morphological abnormalities, including clival angle, Chamberlain’s line, and Grabb-Oakes line, were compared between patients with and without true IONM signal changes. RESULTS A total of 291 cases were included, with an age range of 6 months to 19 years. Among 291 cases, somatosensory evoked potentials (SSEPs) were monitored in 291, motor evoked potentials (MEPs) in 209, cranial nerve spontaneous electromyography (sEMG) in 290, and brainstem auditory evoked potentials (BAEPs) in 110. Sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were as follows: 1.00, 1.00, 1.00, and 1.00 for SSEPs; 1.00, 0.99, 0.67, and 1.00 for MEPs; 0.00, 0.88, 0.00, and 1.00 for sEMG; and not appliable, 1.00, not applicable, and 1.00 for BAEPs. Six patients had true IONM signal changes. These patients had radiographic evidence of more severe concomitant craniocervical instability and basilar invagination, with steeper clival angles (124° vs 146°, p = 0.02) and larger Grabb-Oakes lines (10.1 mm vs 6.7 mm, p = 0.02), when compared with the patients without any true IONM changes. CONCLUSIONS Intraoperative neuromonitoring may be best utilized for patients who show radiographic features of abnormal skull base morphology, defined as a clival angle < 135° or Grabb-Oakes line > 9 mm. When IONM is employed, SSEP and MEP monitoring are the most useful modalities.

Post-operative seizure rates after endoscopic third ventriculostomy (ETV) are not definitively known. We analyzed our institution’s experience for all causes of hydrocephalus in pediatric patients undergoing ETV to determine rates of post-ETV seizure. A retrospective review of institutional pediatric patients undergoing ETV from May 2014 to December 2018. Included were < 21 years, with 1-year follow-up. Exclusion criteria included ventriculoperitoneal shunts (VPS) prior to ETV, VPS within 7 days post-ETV, and prior seizure disorder. Data included age, gender, diagnosis, early post-operative seizure (within 7 days post-ETV), late post-operative seizures (after first 7 days and within first year post-ETV), concomitant choroid plexus cauterization (CPC), VPS conversion within 1 year, and administration of prophylactic antiepileptics. Sixty of 81 ETV cases were included; 41% underwent concomitant CPC. Of these, 53% (n = 32) were male, 46% (n = 28) female, averaging 5.8 years, with the most common diagnosis neoplasm-related obstructive hydrocephalus (38.3%, n = 23). Early post-operative seizure occurred in 6.7% (n = 4); late post-operative seizure occurred in 8.3% (n = 5). Late post-operative seizures were higher in patients experiencing early post-operative seizure versus those without (75% vs 3.7%, p = 0.003). Late post-operative seizure occurred in 13.6% (n = 3 patients) requiring VPS versus 5.3% (n = 2 patients) with successful ETV (p = 0.36). Rates did not correlate with pathology. No patients received prophylactic antiepileptics prior to surgery or exhibiting a seizure. Patients with early post-operative seizures have an increased likelihood of developing late post-operative seizures. Pediatric ETV patients may have a lower rate of both early and late post-operative seizure; underlying pathology may influence these rates.

OBJECTIVEWhile a select population of pediatric patients with Chiari malformation type I (CM-I) remain asymptomatic, some patients present with tussive headaches, neurological deficits, progressive scoliosis, and other debilitating symptoms that necessitate surgical intervention. Surgery entails a variety of strategies to restore normal CSF flow, including increasing the posterior fossa volume via bone decompression only, or bone decompression with duraplasty, with or without obex exploration. The indications for duraplasty and obex exploration following bone decompression remain controversial. The objective of this study was to describe an institutional series of pediatric patients undergoing surgery for CM-I, performed by a single neurosurgeon. For patients presenting with a syrinx, the authors compared outcomes following bone-only decompression with duraplasty only and with duraplasty including obex exploration. Clinical outcomes evaluated included resolution of syrinx, scoliosis, presenting symptoms, and surgical complications.METHODSA retrospective review was conducted of the medical records of 276 consecutive pediatric patients with CM-I operated on at a single institution between 2001 and 2015 by the senior author. Imaging findings of tonsillar descent, associated syrinx (syringomyelia or syringobulbia), basilar invagination, and clinical assessment of CM-I–attributable symptoms and scoliosis were recorded. In patients presenting with a syrinx, clinical outcomes, including syrinx resolution, symptom resolution, and impact on scoliosis progression, were compared for three surgical groups: bone-only/posterior fossa decompression (PFD), PFD with duraplasty (PFDwD), and PFD with duraplasty and obex exploration (PFDwDO).RESULTSPFD was performed in 25% of patients (69/276), PFDwD in 18% of patients (50/276), and PFDwDO in 57% of patients (157/276). The mean follow-up was 35 ± 35 months. Nearly half of the patients (132/276, 48%) had a syrinx. In patients presenting with a syrinx, PFDwDO was associated with a significantly higher likelihood of syrinx resolution relative to PFD only (HR 2.65, p = 0.028) and a significant difference in time to symptom resolution (HR 2.68, p = 0.033). Scoliosis outcomes did not differ among treatment groups (p = 0.275). Complications were not significantly higher when any duraplasty (PFDwD or PFDwDO) was performed following bone decompression (p > 0.99).CONCLUSIONSIn this series of pediatric patients with CM-I, patients presenting with a syrinx who underwent expansile duraplasty with obex exploration had a significantly greater likelihood of syrinx and symptom resolution, without increased risk of CSF-related complications, compared to those who underwent bone-only decompression.

OBJECTIVEThe high global burden of traumatic brain injury (TBI) disproportionately affects low- and middle-income countries (LMICs). These settings also have the greatest disparity in the availability of surgical care in general and neurosurgical care in particular. Recent focus has been placed on alleviating this surgical disparity. However, most capacity assessments are purely quantitative, and few focus on concomitantly assessing the complex healthcare system needs required to care for these patients. The objective of the present study was to use both quantitative and qualitative assessment data to establish a comprehensive approach to inform capacity-development initiatives for TBI care at two hospitals in an LMIC, Cambodia.METHODSThis mixed-methods study used 3 quantitative assessment tools: the World Health Organization Personnel, Infrastructure, Procedures, Equipment, Supplies (WHO PIPES) checklist, the neurosurgery-specific PIPES (NeuroPIPES) checklist, and the Neurocritical Care (NCC) checklist at two hospitals in Phnom Penh, Cambodia. Descriptive statistics were obtained for quantitative results. Qualitative semistructured interviews of physicians, nurses, and healthcare administrators were conducted by a single interviewer. Responses were analyzed using a thematic content analysis approach and coded to allow categorization under the PIPES framework.RESULTSOf 35 healthcare providers approached, 29 (82.9%) participated in the surveys, including 19 physicians (65.5%) and 10 nurses (34.5%). The majority had fewer than 5 years of experience (51.7%), were male (n = 26, 89.7%), and were younger than 40 years of age (n = 25, 86.2%). For both hospitals, WHO PIPES scores were lowest in the equipment category. However, using the NCC checklist, both hospitals scored higher in equipment (81.2% and 62.7%) and infrastructure (78.6% and 69.6%; hospital 1 and 2, respectively) categories and lowest in the training/continuing education category (41.7% and 33.3%, hospital 1 and 2, respectively). Using the PIPES framework, analysis of the qualitative data obtained from interviews revealed a need for continuing educational initiatives for staff, increased surgical and critical care supplies and equipment, and infrastructure development. The analysis further elucidated barriers to care, such as challenges with time availability for experienced providers to educate incoming healthcare professionals, issues surrounding prehospital care, maintenance of donated supplies, and patient poverty.CONCLUSIONSThis mixed-methods study identified areas in supplies, equipment, and educational/training initiatives as areas for capacity development for TBI care in an LMIC such as Cambodia. This first application of the NCC checklist in an LMIC setting demonstrated limitations in its use in this setting. Concomitant qualitative assessments provided insight into barriers otherwise undetected in quantitative assessments.

BACKGROUND: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology. OBJECTIVE: To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD. METHODS: The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD. RESULTS: All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P

Operation Desert Storm (ODS) was an astounding success for combat arms and logistical units of the US Military. In contrast, Department of Defense (DOD) medical units struggled to keep pace with combat operations and were fortunate that casualty estimates for a Cold War–era battle failed to materialize. The medical support plan included a large contingent of active-duty and reserve neurosurgeons in anticipation of care requirements for more than 500,000 deploying service members engaged in a large-scale combat operation. Here, the authors review the clinical experience and operational challenges encountered by neurosurgeons deployed in support of this conflict and discuss legacies of ODS for both surgeons and the military medical system.

Consent and assent are important concepts to understand in the care of pediatric neurosurgery patients. Recently it has been recommended that although pediatric patients generally do not have the legal capacity to make medical decisions, they be encouraged to be involved in their own care. Given the paucity of information on this topic in the neurosurgery community, the objective is to provide pediatric neurosurgeons with recommendations on how to involve their patients in medical decision-making. We review the essential elements and current guidelines of consent and assent for pediatric patients using illustrative neurosurgical case vignettes. The pediatric population ranges widely in cognitive and psychological development making the process of consent and assent quite complex. The role of the child or adolescent in medical decision-making, issues associated with obtaining assent or dissent, and informed refusal of treatment are considered. The process of obtaining consent and assent represents a critical yet often overlooked aspect to care of pediatric neurosurgical patients. The pediatric neurosurgeon must be able to distill immensely complex and high-risk procedures into simple, understandable terms. Furthermore, they must recognize when the child’s dissent or refusal to treatment is acceptable. In general, allowing children to be involved in their neurosurgical care is empowering and gives them both identity and agency, which is the vital first step to a successful neurosurgical intervention.

OBJECTIVE A variety of factors contribute to an increasingly challenging environment for neurological surgery residents to develop psychomotor skills in microsurgical technique solely from operative training. While adjunct training modalities such as cadaver dissection and surgical simulation are embraced and practiced at our institution, there are no formal educational milestones defined to help residents develop, measure, and advance their microsurgical psychomotor skills in a stepwise fashion when outside the hospital environment. The objective of this report is to describe an efficient and convenient “home microsurgery lab” (HML) assembled and tested by the authors with the goal of supporting a personalized stepwise advancement of microsurgical psychomotor skills. METHODS The authors reviewed the literature on previously published simulation practice models and designed adjunct learning modules utilizing the HML. Five milestones were developed for achieving proficiency with each graduated exercise, referencing the Accreditation Council for Graduate Medical Education (ACGME) guidelines. The HML setup was then piloted with 2 neurosurgical trainees. RESULTS The total cost for assembling the HML was approximately $850. Techniques for which training was provided included microinstrument handling, tissue dissection, suturing, and microanastomoses. Five designated competency levels were developed, and training exercises were proposed for each competency level. CONCLUSIONS The HML offers a unique, entirely home-based, affordable adjunct to the operative neurosurgical education mandated by the ACGME operative case logs, while respecting resident hospital-based education hours. The HML provides surgical simulation with specific milestones, which may improve confidence and the microsurgical psychomotor skills required to perform microsurgery, regardless of case type.

Introduction Beyond focal radiation, there is no consensus standard therapy for pediatric high-grade glioma (pHGG) and outcomes remain dismal. We describe the largest molecularly-characterized cohort of children with pHGG treated with a 3-drug maintenance regimen of temozolomide, irinotecan, and bevacizumab (TIB) following radiation. Methods We retrospectively reviewed 36 pediatric patients treated with TIB at Seattle Children's Hospital from 2009 to 2018 and analyzed survival using the Kaplan-Meier method. Molecular profiling was performed by targeted DNA sequencing and toxicities, steroid use, and palliative care utilization were evaluated. Results Median age at diagnosis was 10.9 years (18 months-18 years). Genetic alterations were detected in 26 genes and aligned with recognized molecular subgroups including H3 K27M-mutant (12), H3F3A G34-mutant (2), IDH-mutant (4), and hypermutator profiles (4). Fifteen patients (42%) completed 12 planned cycles of maintenance. Side effects associated with chemotherapy delays or modifications included thrombocytopenia (28%) and nausea/vomiting (19%), with temozolomide dosing most frequently modified. Median event-free survival (EFS) and overall survival (OS) was 16.2 and 20.1 months, with shorter survival seen in DIPG (9.3 and 13.3 months, respectively). Survival at 1, 2, and 5 years was 80%, 10% and 0% for DIPG and 85%, 38%, and 16% for other pHGG. Conclusion Our single-center experience demonstrates tolerability of this 3-drug regimen, with prolonged survival in DIPG compared to historical single-agent temozolomide. pHGG survival was comparable to analogous 3-drug regimens and superior to historical agents; however, cure was rare. Children with pHGG remain excellent candidates for the study of novel therapeutics combined with standard therapy.

OBJECTIVEFactors associated with syrinx size in pediatric patients undergoing posterior fossa decompression (PFD) or PFD with duraplasty (PFDD) for Chiari malformation type I (CM-I) with syringomyelia (SM; CM-I+SM) are not well established.METHODSUsing the Park-Reeves Syringomyelia Research Consortium registry, the authors analyzed variables associated with syrinx radiological outcomes in patients (< 20 years old at the time of surgery) with CM-I+SM undergoing PFD or PFDD. Syrinx resolution was defined as an anteroposterior (AP) diameter of ≤ 2 mm or ≤ 3 mm or a reduction in AP diameter of ≥ 50%. Syrinx regression or progression was defined using 1) change in syrinx AP diameter (≥ 1 mm), or 2) change in syrinx length (craniocaudal, ≥ 1 vertebral level). Syrinx stability was defined as a < 1-mm change in syrinx AP diameter and no change in syrinx length.RESULTSThe authors identified 380 patients with CM-I+SM who underwent PFD or PFDD. Cox proportional hazards modeling revealed younger age at surgery and PFDD as being independently associated with syrinx resolution, defined as a ≤ 2-mm or ≤ 3-mm AP diameter or ≥ 50% reduction in AP diameter. Radiological syrinx resolution was associated with improvement in headache (p < 0.005) and neck pain (p < 0.011) after PFD or PFDD. Next, PFDD (p = 0.005), scoliosis (p = 0.007), and syrinx location across multiple spinal segments (p = 0.001) were associated with syrinx diameter regression, whereas increased preoperative frontal-occipital horn ratio (FOHR; p = 0.007) and syrinx location spanning multiple spinal segments (p = 0.04) were associated with syrinx length regression. Scoliosis (HR 0.38 [95% CI 0.16–0.91], p = 0.03) and smaller syrinx diameter (5.82 ± 3.38 vs 7.86 ± 3.05 mm; HR 0.60 [95% CI 0.34–1.03], p = 0.002) were associated with syrinx diameter stability, whereas shorter preoperative syrinx length (5.75 ± 4.01 vs 9.65 ± 4.31 levels; HR 0.21 [95% CI 0.12–0.38], p = 0.0001) and smaller pB-C2 distance (6.86 ± 1.27 vs 7.18 ± 1.38 mm; HR 1.44 [95% CI 1.02–2.05], p = 0.04) were associated with syrinx length stability. Finally, younger age at surgery (8.19 ± 5.02 vs 10.29 ± 4.25 years; HR 1.89 [95% CI 1.31–3.04], p = 0.01) was associated with syrinx diameter progression, whereas increased postoperative syrinx diameter (6.73 ± 3.64 vs 3.97 ± 3.07 mm; HR 3.10 [95% CI 1.67–5.76], p = 0.003), was associated with syrinx length progression. PFD versus PFDD was not associated with syrinx progression or reoperation rate.CONCLUSIONSThese data suggest that PFDD and age are independently associated with radiological syrinx improvement, although forthcoming results from the PFDD versus PFD randomized controlled trial (NCT02669836, clinicaltrials.gov) will best answer this question.

Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis. The tumors underwent next-generation sequencing on a panel of 340 genes. Chromosomal copy gains and losses were present and differed between the tumors. No mutations or amplifications, including none specific to pineoblastoma, were identified.

Key Points Question Are different patterns of intracranial injury on head computed tomography associated with prognosis after mild traumatic brain injury (mTBI)? Findings In this cohort study, subarachnoid hemorrhage, subdural hematoma, and contusion often co-occurred and were associated with both incomplete recovery and more severe impairment out to 12 months after injury, while intraventricular and/or petechial hemorrhage co-occurred and were associated with more severe impairment up to 12 months after injury; epidural hematoma was associated with incomplete recovery at some points but not with more severe impairment. Some intracranial hemorrhage patterns were more strongly associated with outcomes than previously validated demographic and clinical variables. Meaning In this study, different pathological features on head computed tomography carried different implications for mild traumatic brain injury prognosis to 1 year., The longitudinal, observational study aims to identify pathological computed tomography features associated with adverse outcomes after mild traumatic brain injury., Importance A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale–Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures Acute nonpenetrating head trauma. Main Outcomes and Measures Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores