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Pediatric arteriovenous malformations (AVMs) are rare but carry a risk of devastating neurological morbidity and mortality. Rupture of a cerebral AVM is the most common cause of spontaneous intracranial hemorrhage in children, with an unruptured AVM having an approximate hemorrhage risk of 2%-4% per year. The complex etiology of pediatric AVMs persists as an impediment to a comprehensive understanding of pathogenesis and subsequent targeted gene therapies. While AVMs secondary to vascular malformation syndromes have a clearer pathogenesis, a variety of gene mutations have been identified within sporadic AVM cases. The Ephrin B2/EphB4 (RASA-1, KRAS, and MEK) signaling axis, hemorrhagic telangiectasia, NOTCH, and TIE2 receptor complexes (PIK3CA and mTOR), in addition to other isolated gene variants, have been implicated in AVM pathogenesis. Furthering the understanding of the molecular mechanisms of AVM pathogenesis will lead to future novel therapies and treatment paradigms. Given the expected lifespan of a child, pediatric patients have an unacceptably high cumulative lifetime risk of hemorrhage. AVM treatment strategies are dependent on AVM grade, provider preference, and institutional resources. While open microsurgery is the mainstay of treatment for some AVMs, radiosurgery for definitive treatment and adjunctive endovascular embolization are also used extensively. There is increasing evidence indicating that all three modalities play important and potentially synergistic roles in the armamentarium for pediatric AVM treatment. This review serves to report current understanding in the genetic and molecular mechanisms of pediatric AVMs, review clinical diagnostic and classification criteria, and detail treatment options and subsequent outcomes of pediatric AVM patients.

Background: Focal epilepsy caused by a posterior fossa lesion is a rare phenomenon. In these cases, seizure onset typically occurs during the first few months of life, with episodes of epileptic hemifacial spasms and abnormal eye movements. Patients often present with drug-resistant epilepsy and often require resection for the best chance of seizure freedom., Observations: The authors present the case of a 19-month-old male with intractable epileptic hemifacial spasms and a dorsally exophytic right brainstem and middle cerebellar peduncle hamartoma, following 2 prior subtotal resections. The authors recommended a third suboccipital craniotomy with intraoperative electrocorticography, which revealed interictal spiking from an intralesional depth electrode. Near-total resection led to durable seizure freedom., Lessons: Although posterior fossa lesions are rarely associated with epileptiform activity, this case demonstrates that pediatric patients with epileptic hemifacial spasms associated with a posterior fossa lesion may respond favorably to resection. Furthermore, this case demonstrates that intralesional electrocorticography can detect epileptic activity in posterior fossa lesions, which may predict postoperative seizure outcomes. https://thejns.org/doi/10.3171/CASE2452.

Somatic mosaic variants contribute to focal epilepsy, but genetic analysis has been limited to patients with drug-resistant epilepsy (DRE) who undergo surgical resection, as the variants are mainly brain-limited. Stereoelectroencephalography (sEEG) has become part of the evaluation for many patients with focal DRE, and sEEG electrodes provide a potential source of small amounts of brain-derived DNA. We aimed to identify, validate, and assess the distribution of potentially clinically relevant mosaic variants in DNA extracted from trace brain tissue on individual sEEG electrodes. We enrolled a prospective cohort of eleven pediatric patients with DRE who had sEEG electrodes implanted for invasive monitoring, one of whom was previously reported. We extracted unamplified DNA from the trace brain tissue on each sEEG electrode and also performed whole-genome amplification for each sample. We extracted DNA from resected brain tissue and blood/saliva samples where available. We performed deep panel and exome sequencing on a subset of samples from each case and analysis for potentially clinically relevant candidate germline and mosaic variants. We validated candidate mosaic variants using amplicon sequencing and assessed the variant allele fraction (VAF) in amplified and unamplified electrode-derived DNA and across electrodes. We extracted DNA from >150 individual electrodes from 11 individuals and obtained higher concentrations of whole-genome amplified vs unamplified DNA. Immunohistochemistry confirmed the presence of neurons in the brain tissue on electrodes. Deep sequencing and analysis demonstrated similar depth of coverage between amplified and unamplified samples but significantly more called mosaic variants in amplified samples. In addition to the mosaic PIK3CA variant detected in a previously reported case from our group, we identified and validated four potentially clinically relevant mosaic variants in electrode-derived DNA in three patients who underwent laser ablation and did not have resected brain tissue samples available. The variants were detected in both amplified and unamplified electrode-derived DNA, with higher VAFs observed in DNA from electrodes in closest proximity to the electrical seizure focus in some cases. This study demonstrates that mosaic variants can be identified and validated from DNA extracted from trace brain tissue on individual sEEG electrodes in patients with drug-resistant focal epilepsy and in both amplified and unamplified electrode-derived DNA samples. Our findings support a relationship between the extent of regional genetic abnormality and electrophysiology, and suggest that with further optimization, this minimally invasive diagnostic approach holds promise for advancing precision medicine for patients with DRE as part of the surgical evaluation.

In 1994, the use of interfacet spacer placement was for joint distraction, reduction, and fusion to supplement atlantoaxial or occipitocervical fixation. Here, we present a unique case of bilateral atlantoaxial interfacet fixation using cervical facet cages (CFC) in a pediatric patient with basilar invagination. In addition, we review the literature on atlantoaxial facet fixation. We present a 12-year-old boy with Wiedemann-Steiner syndrome who presented with multiple episodes of sudden neck jerking, described as in response to a sensation of being shocked, and guarding against neck motion, found to have basilar invagination with cervicomedullary compression. He underwent an occiput to C3 fusion with C1-C2 CFC fixation. We also conducted a literature review identifying all publications using the following keywords: "C1" AND "C2" OR "atlantoaxial" AND "facet spacer" OR "DTRAX." The patient demonstrated postoperative radiographic reduction of his basilar invagination from 6.4 to 4.1 mm of superior displacement above the McRae line. There was a 4.5 mm decrease in the atlantodental interval secondary to decreased dens retroflexion. His postoperative course was complicated by worsening of his existing dysphagia but was otherwise unremarkable. His neck symptoms completely resolved. We illustrate the safe use of CFC for atlantoaxial facet distraction, reduction, and instrumented fixation in a pediatric patient with basilar invagination. Review of the literature demonstrates that numerous materials can be safely placed as a C1-C2 interfacet spacer including bone grafts, titanium spacers, and anterior cervical discectomy and fusion cages. We argue that CFC may be included in this arsenal even in pediatric patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Hemimegalencephaly (HME) is a rare diffuse malformation of cortical development characterized by unihemispheric hypertrophy, drug-resistant epilepsy (DRE), hemiparesis, and developmental delay. Definitive treatment for HME-related DRE is hemispheric surgery through either anatomic (AH) or functional hemispherectomy (FH). This individual patient data meta-analysis assessed seizure outcomes of AH and FH for HME with pharmacoresistant epilepsy, predictors of Engel I, and efficacy of different FH approaches., Methods: PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were searched from inception to Jan 13th, 2023, for primary literature reporting seizure outcomes in >3 patients with HME receiving AH or FH. Demographics, neurophysiology findings, and Engel outcome at the last follow-up were extracted. Postsurgical seizure outcomes were compared through 2-tailed t -test and Fisher exact test. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of Engel I outcome., Results: Data from 145 patients were extracted from 26 studies, of which 89 underwent FH (22 vertical, 33 lateral), 47 underwent AH, and 9 received an unspecified hemispherectomy with a median last follow-up of 44.0 months (FH cohort) and 45.0 months (AH cohort). Cohorts were similar in preoperative characteristics and at the last follow-up; 77% (n = 66) of the FH cohort and 81% (n = 38) and of the AH cohort were Engel I. On multivariate analysis, only the presence of bilateral ictal electroencephalography abnormalities (hazard ratio = 11.5; P = .002) was significantly associated with faster time-to-seizure recurrence. A number-needed-to-treat analysis to prevent 1 additional case of posthemispherectomy hydrocephalus reveals that FH, compared with AH, was 3. There was no statistical significance for any differences in time-to-seizure recurrence between lateral and vertical FH approaches (hazard ratio = 2.59; P = .101)., Conclusion: We show that hemispheric surgery is a highly effective treatment for HME-related DRE. Unilateral ictal electroencephalography changes and using the FH approach as initial surgical management may result in better outcomes due to significantly lower posthemispherectomy hydrocephalus probability. However, larger HME registries are needed to further delineate the predictors of seizure outcomes., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Low-grade epilepsy-associated tumors (LEATs) are a common cause of drug-resistant epilepsy in children. Herein, we demonstrate the feasibility of using tumor tissue derived from stereoelectroencephalography (sEEG) electrodes upon removal to molecularly characterize tumors and aid in diagnosis. An 18-year-old male with focal epilepsy and MRI suggestive of a dysembryoplastic neuroepithelial tumor (DNET) in the left posterior temporal lobe underwent implantation of seven peri-tumoral sEEG electrodes for peri-operative language mapping and demarcation of the peri-tumoral ictal zone prior to DNET resection. Using electrodes that passed through tumor tissue, we show successful isolation of tumor DNA and subsequent analysis using standard methods for tumor classification by DNA, including Glioseq targeted sequencing and DNA methylation array analysis. This study provides preliminary evidence for the feasibility of molecular diagnosis of LEATs or other lesions using a minimally invasive method with microscopic tissue volumes. The implications of sEEG electrodes in tumor characterization are broad but would aid in diagnosis and subsequent targeted therapeutic strategies., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Corpus callosotomy (CC) is an important treatment for atonic seizures in patients with generalized or multifocal drug-resistant epilepsy (DRE). Traditionally, CC is performed via an open microsurgical approach, but more recently, MR-guided stereotactic laser interstitial thermal therapy (LITT) corpus callosum ablation (CCA) has been developed to leverage the safety and minimally invasive nature of LITT. Given the recent adoption of CCA at select centers, how CCA compares to CC is unknown. We aim to compare the clinical seizure outcomes of CCA and CC after extended follow-up., Methods: We performed a retrospective cohort study to compare the effectiveness and safety of CC to CCA from 1994 to 2022. The primary outcome was a 50% reduction in target seizure. Secondary outcome measures were postoperative length of stay, adverse events, and other effectiveness metrics. Comparative statistics were executed using Stata. Normality for continuous variables was assessed, and parametric statistics were utilized as needed. Frequency was compared with chi-squared or Fischer's exact tests, when applicable., Results: Data from 47 operations performed on 36 patients were included in this study, of which 13 (36%) patients underwent 17 CCA. Patients who received CCA had similar rates of meaningful reduction (>50%) of atonic seizures as their CC counterparts (55% vs 70% P = 0.15). Patients undergoing CCA had significantly shorter hospitalizations than those receiving CC (2.5 vs 6.0 days P < 0.001). There was no significant difference in rates of postoperative complications between the groups, although the magnitude of the complication rates was lower in the CCA cohort (12% vs 28%)., Significance: This early experience suggests CCA has similar outcomes to traditional CC, albeit with a shorter hospital stay. However, future studies are necessary to investigate the noninferiority between these two approaches. Large multicenter studies are necessary to investigate differences in adverse events and whether these findings generalize across other centers., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Hemimegalencephaly (HME) is a rare congenital brain malformation presenting predominantly with drug-resistant epilepsy. Hemispheric disconnective surgery is the mainstay of treatment; however, little is known about how postoperative outcomes compare across techniques. Thus we present the largest single-center cohort of patients with HME who underwent epilepsy surgery and characterize outcomes., Methods: This observational study included patients with HME at University of California Los Angeles (UCLA) from 1984 to 2021. Patients were stratified by surgical intervention: anatomic hemispherectomy (AH), functional hemispherectomy (FH), or less-than-hemispheric resection (LTH). Seizure freedom, functional outcomes, and operative complications were compared across surgical approaches. Regression analysis identified clinical and intraoperative variables that predict seizure outcomes., Results: Of 56 patients, 43 (77%) underwent FH, 8 (14%) underwent AH, 2 (4%) underwent LTH, 1 (2%) underwent unknown hemispherectomy type, and 2 (4%) were managed non-operatively. At median last follow-up of 55 months (interquartile range [IQR] 20-92 months), 24 patients (49%) were seizure-free, 17 (30%) required cerebrospinal fluid (CSF) shunting for hydrocephalus, 9 of 43 (21%) had severe developmental delay, 8 of 38 (21%) were non-verbal, and 15 of 38 (39%) were non-ambulatory. There was one (2%) intraoperative mortality due to exsanguination earlier in this cohort. Of 12 patients (29%) requiring revision surgery, 6 (50%) were seizure-free postoperatively. AH, compared to FH, was not associated with statistically significant improved seizure freedom (hazard ratio [HR] = .48, p = .328), although initial AH trended toward greater odds of seizure freedom (75% vs 46%, p = .272). Younger age at seizure onset (HR = .29, p = .029), lack of epilepsia partialis continua (EPC) (HR = .30, p = .022), and no contralateral seizures on electroencephalography (EEG) (HR = .33, p = .039) independently predicted longer duration of seizure freedom., Significance: This study helps inform physicians and parents of children who are undergoing surgery for HME by demonstrating that earlier age at seizure onset, absence of EPC, and no contralateral EEG seizures were associated with longer postoperative seizure freedom. At our center, initial AH for HME may provide greater odds of seizure freedom with complications and functional outcomes comparable to those of FH., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: Brain-limited pathogenic somatic variants are associated with focal pediatric epilepsy, but reliance on resected brain tissue samples has limited our ability to correlate epileptiform activity with abnormal molecular pathology. We aimed to identify the pathogenic variant and map variant allele fractions (VAFs) across an abnormal region of epileptogenic brain in a patient who underwent stereoelectroencephalography (sEEG) and subsequent motor-sparing left frontal disconnection., Methods: We extracted genomic DNA from peripheral blood, brain tissue resected from peri-sEEG electrode regions, and microbulk brain tissue adherent to sEEG electrodes. Samples were mapped based on an anatomic relationship with the presumed seizure onset zone (SOZ). We performed deep panel sequencing of amplified and unamplified DNA to identify pathogenic variants with subsequent orthogonal validation., Results: We detect a pathogenic somatic PIK3CA variant, c.1624G>A (p.E542K), in the brain tissue samples, with VAF inversely correlated with distance from the SOZ. In addition, we identify this variant in amplified electrode-derived samples, albeit with lower VAFs., Discussion: We demonstrate regional mosaicism across epileptogenic tissue, suggesting a correlation between variant burden and SOZ. We also validate a pathogenic variant from individual amplified sEEG electrode-derived brain specimens, although further optimization of techniques is required., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Rudimentary meningoceles of the spine with dural extension are very rare and warrant surgical excision to prevent infection and long-term neurological deficits in pediatric patients. We present the case of a 5-month-old infant with a tethered spinal cord secondary to a rudimentary meningocele. The patient presented shortly after birth with a midline cervical dimple that was evaluated for a suspected dermal sinus tract. Magnetic resonance imaging scan of the spine showed a sinus tract with intradural extension to C2-3 and external opening at the level of spinous process C5. En bloc surgical excision and spinal cord release were successfully performed. Histological analysis of the specimen confirmed the presence of two blunt sinus tracts and staining was consistent with a rudimentary meningocele. Intradural rudimentary meningoceles in infants can successfully be managed with surgical intervention. Surgery is indicated to prevent future motor complications from spinal cord tethering and neoplastic growth from the rudimentary meningocele., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background and Objectives: Hemispheric surgery effectively treats unihemispheric pediatric drug-resistant epilepsy (DRE) by resecting and/or disconnecting the epileptic hemisphere. Modifications to the original anatomic hemispherectomy have generated multiple functionally equivalent, disconnective techniques for performing hemispheric surgery, termed functional hemispherotomy. While a myriad of hemispherotomy variants exist, all of them can be categorized according to the anatomic plane they are performed in, which includes vertical approaches at or near the interhemispheric fissure and lateral approaches at or near the Sylvian fissure. This meta-analysis of individual patient data (IPD) aimed to compare seizure outcomes and complications between the hemispherotomy approaches to better characterize their relative efficacy and safety in the modern neurosurgical treatment of pediatric DRE, given emerging evidence that outcomes may differ between them., Methods: CINAHL, Embase, PubMed, and Web of Science were searched from inception to September 9, 2020, for studies reporting IPD from pediatric patients with DRE who underwent hemispheric surgery. Outcomes of interest were seizure freedom at last follow-up, time-to-seizure recurrence, and complications including hydrocephalus, infection, and mortality. The χ 2 test compared the frequency of seizure freedom and complications. Multivariable mixed-effects Cox regression controlling for predictors of seizure outcome was performed on propensity score-matched patients to compare time-to-seizure recurrence between approaches. Kaplan-Meier curves were made to visualize differences in time-to-seizure recurrence., Results: Fifty-five studies reporting on 686 unique pediatric patients treated with hemispheric surgery were included for meta-analysis. Among the hemispherotomy subgroup, vertical approaches resulted in a greater proportion of seizure free patients (81.2% vs 70.7%, p = 0.014) than lateral approaches. While there were no differences in complications, lateral hemispherotomy had higher rates of revision hemispheric surgery due to incomplete disconnection and/or recurrent seizures than vertical hemispherotomy (16.3% vs 1.2%, p < 0.001). After propensity score matching, vertical hemispherotomy approaches independently conferred longer time-to-seizure recurrence than lateral hemispherotomy approaches (hazard ratio 0.44, 95% CI 0.19-0.98)., Discussion: Among functional hemispherotomy techniques, vertical hemispherotomy approaches confer more durable seizure freedom than lateral approaches without compromising safety. Future prospective studies are required to definitively determine whether vertical approaches are indeed superior and how it should influence clinical guidelines for performing hemispheric surgery., (© 2023 American Academy of Neurology.)

Objective: To characterize ictal EEG change in the centromedian (CM) and anterior nucleus (AN) of the thalamus, using stereoelectroencephalography (SEEG) recordings., Methods: Forty habitual seizures were analyzed in nine patients with pediatric-onset neocortical drug-resistant epilepsy who underwent SEEG (age 2-25 y) with thalamic coverage. Both visual and quantitative analysis was used to evaluate ictal EEG signal in the cortex and thalamus. The amplitude and cortico-thalamic latencies of broadband frequencies at ictal onset were measured., Results: Visual analysis demonstrated consistent detection of ictal EEG changes in both the CM nucleus and AN nucleus with latency to thalamic ictal EEG changes of less than 400ms in 95% of seizures, with low-voltage fast activity being the most common ictal pattern. Quantitative broadband amplitude analysis showed consistent power changes across the frequency bands, corresponding to ictal EEG onset, while while ictal EEG latency was variable from -18.0 seconds to 13.2 seconds. There was no significant difference between detection of CM and AN ictal activity on visual or amplitude analysis. Four patients with subsequent thalamic responsive neurostimulation (RNS) demonstrated ictal EEG changes consistent with SEEG findings., Conclusions: Ictal EEG changes were consistently seen at the CM and AN of the thalamus during neocortical seizures., Significance: It may be feasible to use a closed-loop system in the thalamus to detect and modulate seizure activity for neocortical epilepsy.

Background: The occurrence of both an intracranial aneurysm and epilepsy, especially drug-resistant epilepsy (DRE), is rare. Although the overall incidence of aneurysms associated with DRE is unclear, it is thought to be particularly infrequent in the pediatric population. Surgical ligation of the offending aneurysm has been reported in conjunction with resolving seizure activity, although few cases have cited a combined approach of aneurysm ligation and resection of an epileptogenic focus., Observations: We present the case of a 14-year-old female patient with drug-resistant temporal lobe epilepsy and an ipsilateral supraclinoid internal carotid artery aneurysm. Seizure semiology, electroencephalography monitoring, and magnetic resonance imaging all indicated a left temporal epileptogenic focus, in addition to an incidental aneurysm. The authors recommended a combined surgery involving resection of the temporal lesion and surgical clip ligation of the aneurysm. Near-total resection and successful ligation were achieved, and the patient has remained seizure free since surgery at 1 year postoperatively., Lessons: In patients with focal DRE and an adjacent intracranial aneurysm, a combined surgical approach involving both resection and surgical ligation can be used. Several surgical timing and neuroanesthetic considerations should be made to ensure the overall safety and efficacy of this procedure.

Mesial temporal lobe epilepsy (mTLE) is an important cause of drug-resistant epilepsy (DRE) in adults and children. Traditionally, the surgical option of choice for mTLE includes a frontotemporal craniotomy and open resection of the anterior temporal cortex and mesial temporal structures. Although this technique is effective and durable, the neuropsychological morbidity resulting from temporal neocortical resections has resulted in the investigation of alternative approaches to resect the mesial temporal structures to achieve seizure freedom while minimizing postoperative cognitive deficits. Outcomes supporting the use of selective temporal resections have resulted in alternative approaches to directly access the mesial temporal structures via endoscopic approaches whose direct trajectory to the epileptogenic zone minimizes retraction, resection, and manipulation of surrounding cortex. The authors reviewed the utility of the endoscopic transmaxillary, endoscopic endonasal, endoscopic transorbital, and endoscopic supracerebellar transtentorial approaches for the treatment of drug-resistant mesial temporal lobe epilepsy. First, a review of the literature demonstrated the anatomical feasibility of each approach, including the limits of exposure provided by each trajectory. Next, clinical data assessing the safety and effectiveness of these techniques in the treatment of DRE were analyzed. An outline of the surgical techniques is provided to highlight the technical nuances of each approach. The direct access to mesial temporal structures and avoidance of lateral temporal manipulation makes endoscopic approaches promising alternatives to traditional methods for the treatment of DRE arising from the temporal pole and mesial temporal lobe. A dearth of literature outlining clinical outcomes, a need for qualified cosurgeons, and a lack of experience with endoscopic approaches remain major barriers to widespread application of the aforementioned techniques. Future studies are warranted to define the utility of these approaches moving forward.

Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown., Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE., Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022., Exposures: Drug-resistant MTLE., Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex., Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P = .01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism., Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery.

Background: Cerebral hemispherectomy can effectively treat unihemispheric epilepsy. However, posthemispherectomy hydrocephalus (PHH), a serious life-long complication, remains prevalent, requiring careful considerations in technique selection and postoperative management. In 2016, we began incorporating open choroid plexus cauterization (CPC) into our institution's hemispherectomy procedure in an attempt to prevent PHH., Objective: To determine whether routine CPC prevented PHH without exacerbating hemispherectomy efficacy or safety., Methods: A retrospective review of consecutive patients who underwent hemispherectomy for intractable epilepsy between 2011 and 2021 was performed. Multivariate logistic regression was used to identify factors independently associated with PHH requiring cerebrospinal fluid (CSF) shunting., Results: Sixty-eight patients were included in this study, of whom 26 (38.2%) underwent CPC. Fewer patients required CSF shunting in the CPC group (7.7% vs 28.7%, P = .033) and no patients who underwent de novo hemispherectomy with CPC developed PHH. Both cohorts experienced seizure freedom (65.4% vs 59.5%, P = .634) and postoperative complications, including infection (3.8% vs 2.4%, P = .728), hemorrhage (0.0% vs 2.4%, P = .428), and revision hemispherectomy (19.2% vs 14.3%, P = .591) at similar rates. Patients without CPC had greater odds of developing PHH requiring CSF shunting (odds ratio = 8.36, P = .026). The number needed to treat with CPC to prevent an additional case of PHH was 4.8, suggesting high effectiveness., Conclusion: Preventing PHH is critical. Our early experience demonstrated that routinely incorporating CPC into hemispherectomy effectively prevents PHH without causing additional complications, especially in first-time hemispherectomies. A multicenter randomized controlled trial with long-term follow-up is required to corroborate the findings of our single-institutional case series and determine whether greater adoption of this technique is justified., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Pediatric brain tumors are the most common solid malignancies in children. Advances in the treatment of pediatric brain tumors have come in the form of imaging, biopsy, surgical techniques, and molecular profiling. This has led the way for targeted therapies and immunotherapy to be assessed in clinical trials for the most common types of pediatric brain tumors. Here we review the latest efforts and challenges in targeted molecular therapy, immunotherapy, and newer modalities such as laser interstitial thermal therapy., Competing Interests: The authors declare no conflict of interest.

Objective: Long-term seizure outcomes of pediatric epilepsy surgery are understudied. A systematic review and independent patient data meta-analysis was performed to study seizure outcomes ≥ 10 years following pediatric resective epilepsy surgery., Methods: Electronic literature searches of PubMed, Web of Science, and CINAHL were conducted for relevant articles from inception to April 2020. The following search terms were used in various combinations: "pediatric", "child", "adolescent", "epilepsy", "resective", "surgery", "long-term", "longitudinal", "10 year". Two reviewers (W.B.H., T.B.C.) performed title, abstract, and full-text screening. All relevant perioperative factors reported that may be associated with long-term seizure outcomes were recorded at a study or individual participant level. The primary outcome was long-term (≥ 10 year) seizure freedom measured by the Engel Classification scale, and available data on functional outcomes were also reviewed., Results: Twenty-five articles met criteria for inclusion in the study, which were analyzed for proportions of 10-year seizure freedom ranging from 57.6% at the study level to 64.8% at the individual patient level. At the study level, the proportion of patients remaining seizure free at least 10 years postoperatively (61.2%; 95% CI 52.5-69.3) was significantly less than at 1 year (74.2%; 95% CI 69.3-78.6; p = 0.008) but not at 2 years (67.9%; 95% CI 58.6-76.0) or 5 years (63.7%; 95% CI 55.4-71.2). No differences in long-term seizure freedom were detected by etiology or surgery type. At the individual patient level, univariate logistic regression analyses of all variables putatively associated with seizure freedom demonstrated that lobectomy (OR 0.280, 95% CI 0.117-0.651, p = 0.003) was associated with decreased long-term seizure freedom (41.9%) compared to lesionectomy (75.7%) and hemispherectomy (69.4%), which achieved similar results., Conclusion: Resective surgery is a durable and potentially curative treatment option for select pediatric patients with refractory epilepsy. On a group level, two-thirds of children have long-term seizure freedom ≥ 10 years after resective epilepsy surgery. Given the greatest rate of change occurs in the first 2 years, this may serve as the best short-term follow-up period to predict long-term outcome. Although lobectomy appears to be a strong predictor for lower likelihood of long-term seizure freedom, long-term prognostication on an individual patient level is still not possible. Uniform data reporting and prospective, multicenter studies collecting high quality, stratified (e.g., by etiology, surgery type) data over an extended postoperative interval are recommended to further examine the durability of resective surgery as a treatment for pediatric epilepsy., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: The prevalence of long-term postoperative sensorimotor deficits in children undergoing perirolandic resective epilepsy surgery is unclear. The risk of developing these deficits must be weighed against the potential reduction in seizure frequency after surgery. In this study, the authors investigated the prevalence of sensorimotor deficits after resective surgery at ≥ 1 year postoperatively., Methods: A systematic review and individual patient data meta-analysis was conducted using PubMed, Embase, and Scopus databases. Subgroups of patients were identified and categorized according to their outcomes as follows: group A patients were denoted as seizure free with no postoperative sensorimotor deficits; group B patients experienced seizure recurrence with no deficit; group C patients were seizure free with deficits; and group D patients were not seizure free and with deficits. Rates of sensory deficits were examined in patients undergoing postcentral gyrus resection, and rates of motor deficits were aggregated in patients undergoing precentral gyrus resection., Results: Of 797 articles resulting from the database searches, 6 articles including 164 pediatric patients at a mean age of 7.7 ± 5.2 years with resection for drug-resistant perirolandic epilepsy were included in the study. Seizure freedom was observed in 118 (72.9%) patients at a mean follow-up of 3.4 ± 1.8 years. In total, 109 (66.5%) patients did not develop sensorimotor deficits at last follow-up, while 55 (33.5%) had permanent deficits. Ten (14.3%) of 70 patients with postcentral gyrus resection had permanent sensory deficits. Of the postcentral gyrus resection patients, 41 (58.6%) patients were included in group A, 19 (27.1%) in group B, 7 (10.0%) in group C, and 3 (4.3%) in group D. Forty (37.7%) of 106 patients with precentral resections had permanent motor deficits. Of the precentral gyrus resection patients, 50 (47.2%) patients were in group A, 16 (15.1%) in group B, 24 (22.6%) in group C, and 16 (15.1%) in group D. Patients without focal cortical dysplasia were more likely to have permanent motor deficits relative to those with focal cortical dysplasia in the precentral surgery cohort (p = 0.02)., Conclusions: In total, 58.6% of patients were seizure free without deficit, 27.1% were not seizure free and without deficit, 10.0% were seizure free but with deficit, and 4.3% were not seizure free and with deficit. Future studies with functional and quality-of-life data, particularly for patients who experience seizure recurrence with no deficits (as in group B in the present study) and those who are seizure free with deficits (as in group C) after treatment, are necessary to guide surgical decision-making.

Background: Hemispherectomy and its modern variants are effective surgical treatments for medically intractable unihemispheric epilepsy. Although some complications such as posthemispherectomy hydrocephalus are well documented, midline brain shift (MLBS) after hemispheric surgery has only been described anecdotally and never formally studied., Objective: To assess the natural history and clinical relevance of MLBS and determine whether cerebrospinal fluid (CSF) shunting of the ipsilateral surgical cavity exacerbates MLBS posthemispheric surgery., Methods: A retrospective review of consecutive pediatric patients who underwent hemispheric surgery for intractable epilepsy and at least 6 months of follow-up at UCLA between 1994 and 2018 was performed. Patients were grouped by MLBS severity, shunt placement, valve type, and valve opening pressure (VOP). MLBS was evaluated using the paired samples t-test and analysis of covariance adjusting for follow-up time and baseline postoperative MLBS., Results: Seventy patients were analyzed, of which 23 (33%) required CSF shunt placement in the ipsilateral surgical cavity for posthemispherectomy hydrocephalus. MLBS increased between first and last follow-up for nonshunted (5.3 ± 4.9-9.7 ± 6.6 mm, P < .001) and shunted (6.6 ± 3.5-16.3 ± 9.4 mm, P < .001) patients. MLBS progression was greater in shunted patients (P = .001). Shunts with higher VOPs did not increase MLBS relative to nonshunted patients (P = .834), whereas MLBS increased with lower VOPs (P = .001). Severe MLBS was associated with debilitating headaches (P = .048)., Conclusion: Patients undergoing hemispheric surgery often develop postoperative MLBS, ie, exacerbated by CSF shunting of the ipsilateral surgical cavity, specifically when using lower VOP settings. MLBS exacerbation may be related to overshunting. Severe MLBS is associated with debilitating headaches., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Cranioplasty is the surgical repair of cranial defects. Throughout its history, a number of different materials have been used, however, there is still no consensus on which material or method is best. The purpose of this study was to analyze the viability of polyetheretherketone (PEEK) cranioplasty to autologous cranioplasty modalities., Methods: A single-institution retrospective analysis of patients undergoing cranioplasties was performed. Patients were divided to PEEK and autologous cranioplasty cohorts. Parameters of interest included patient demographics and perioperative outcomes. A p-value <0.05 was considered statistically significant., Results: A total of 66 patients met the inclusion criteria (PEEK: 22, autologous: 44). There were 36 males (54.5%) and 30 females (45.5%). Mean age of the entire cohort was 51.7 years (range 19-85 years). Baseline demographics were similar in both cohorts as measured by the modified frailty index (mFI) (p = 0.67). Univariate analysis revealed a significantly longer hospital length of stay (LoS) associated with the autologous group (p = 0.02). However, multivariate analysis did not yield such an association (p = 0.06) after controlling for mFI. Although the individual postoperative complication rates were similar between the two cohorts, autologous cranioplasty was associated with a significantly higher rate of total postoperative complications (65.9% vs 36.4%, p = 0.02)., Conclusion: Overall, PEEK biomaterials may offer a superior complication profile with similar hospital LoS compared to autologous bone implants used in cranioplasty. Future studies are warranted to validate our findings and further evaluate the utility of PEEK in cranioplasty., (Copyright © 2022. Published by Elsevier B.V.)

Background: Superior semicircular canal dehiscence (SSCD) is an abnormality of the otic capsule, which normally overlies the superior semicircular canal. Surgical management is indicated in patients with persistent and debilitating symptoms. Given the complexity of the disease, there are patients who experience less favorable surgical outcomes and require revision surgery. The purpose of this study was to report to the rate of postoperative symptomatic improvement in patients who required revision surgery., Methods: A retrospective analysis of patients undergoing SSCD surgical repair at a single institution was performed. Information on patient demographics, primary and secondary surgical approaches, surgical outcomes, and follow-up length was collected., Results: Seventeen patients underwent 20 revision surgeries. There were eleven (65%) females and six (35%) males. Mean age of the cohorts was 50 years (range 30-68 years), and mean follow-up length was 6.8 months (range 0.1-31.1 months). Cerebrospinal fluid leak was noted in 67% of cases. The greatest postoperative symptomatic resolution was reported in oscillopsia (100%), headache (100%), and internal sound amplification (71%), while the least postoperative symptomatic resolution was reported in tinnitus (42%), aural fullness (40%), and dizziness (29%)., Conclusions: Revision surgery can provide symptomatic improvement in select SSCD patients; however, patients should be cautioned about the possibility of less favorable outcomes than in index surgery. Revision surgeries are associated with a considerably higher rate of perioperative cerebrospinal fluid leak., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Despite the well-documented utility of responsive neurostimulation (RNS, NeuroPace) in adult epilepsy patients, literature on the use of RNS in children is limited., Objective: To determine the real-world efficacy and safety of RNS in pediatric epilepsy patients., Methods: Patients with childhood-onset drug-resistant epilepsy treated with RNS were retrospectively identified at 5 pediatric centers. Reduction of disabling seizures and complications were evaluated for children (<18 yr) and young adults (>18 yr) and compared with prior literature pertaining to adult patients., Results: Of 35 patients identified, 17 were <18 yr at the time of RNS implantation, including a 3-yr-old patient. Four patients (11%) had concurrent resection. Three complications, requiring additional surgical interventions, were noted in young adults (2 infections [6%] and 1 lead fracture [3%]). No complications were noted in children. Among the 32 patients with continued therapy, 2 (6%) achieved seizure freedom, 4 (13%) achieved ≥90% seizure reduction, 13 (41%) had ≥50% reduction, 8 (25%) had <50% reduction, and 5 (16%) experienced no improvement. The average follow-up duration was 1.7 yr (median 1.8 yr, range 0.3-4.8 yr). There was no statistically significant difference for seizure reduction and complications between children and young adults in our cohort or between our cohort and the adult literature., Conclusion: These preliminary data suggest that RNS is well tolerated and an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients as young as 3 yr of age. Data regarding long-term efficacy and safety in children will be critical to optimize patient selection., (© Congress of Neurological Surgeons 2021.)

Background: Venous thromboembolism (VTE) represents a rare but preventable postoperative complication. Unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are used to prevent VTE, but comparative studies of their safety and efficacy in the neurosurgical context are limited., Objective: To determine the relative safety and efficacy of UH and LMWH for prophylaxis after cranial surgery., Methods: We performed a retrospective analysis of 3204 elective intracranial surgical admissions in 2901 patients over the period 2013 to 2018. From chart review, we extracted demographic and clinical features, including diagnosis and procedure, drugs administered, and the occurrence of VTE events. To compare postoperative outcomes, we performed propensity score matching of patients receiving different drugs, and reviewed postoperative cranial imaging. To contextualize our results, we selected 14 prior neurosurgical studies of VTE prophylaxis to compare our outcomes to the existing literature., Results: In our sample of 3204 admissions, the overall rate of VTE was 0.8% (n = 27). Rates of VTE were not statistically different in matched cohorts receiving UH and LMWH (1.7% vs 1.0%, respectively); however, LMWH was associated with a higher rate of clinically significant intracranial hemorrhage (ICH) (3.4% vs 0.5%, P = .008). Literature review and meta-analysis supported these findings. Across studies, UH and LMWH were associated with similar rates of VTE. Studies in which patients received LMWH reported significantly higher rates of ICH (4.9% higher, P = .005)., Conclusion: We find that LMWH and UH show similar efficacy in preventing VTE; however, LMWH is associated with higher rates of ICH., (© Congress of Neurological Surgeons 2021.)

Traumatic brain injury (TBI) is responsible for the majority of trauma-related deaths and is a leading cause of disability. It is characterized by an inflammatory process involved in the progression of secondary brain injury. TBI is measured by the Glasgow Coma Scale (GCS) with scores ranging from 15-3, demonstrating mild to severe brain injury. Apart from this clinical assessment of TBI, compendiums of literature have been published on TBI-related serum markers.Herein we create a comprehensive appraisal of the most prominent serum biomarkers used in the assessment and care of TBI.The PubMed, Scopus, Cochrane, and Web of Science databases were queried with the terms "biomarker" and "traumatic brain injury" as search terms with only full-text, English articles within the past 10 years selected. Non-human studies were excluded, and only adult patients fell within the purview of this analysis. A total of 528 articles were analyzed in the initial search with 289 selected for screening. A further 152 were excluded for primary screening. Of the remaining 137, 54 were included in the final analysis. Serum biomarkers were listed into the following broad categories for ease of discussion: immune markers and markers of inflammation, hormones as biomarkers, coagulation and vasculature, genetic polymorphisms, antioxidants and oxidative stress, apoptosis and degradation pathways, and protein markers. Glial fibrillary acidic protein(GFAP), S100, and neurons specific enolase (NSE) were the most prominent and frequently cited markers. Amongst these three, no single serum biomarker demonstrated neither superior sensitivity nor specificity compared to the other two, therefore noninvasive panels should incorporate these three serum biomarkers to retain sensitivity and maximize specificity for TBI., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2021, Mozaffari et al.)

Complete surgical resection of abnormal brain tissue is the most important predictor of seizure freedom following surgery for cortical dysplasia. While lesional tissue is often visually indiscernible from normal brain, anecdotally, it is subjectively stiffer. We report the first experience of the use of a digital tonometer to understand the biomechanical properties of epilepsy tissue and to guide the conduct of epilepsy surgery. Consecutive epilepsy surgery patients (n = 24) from UCLA Mattel Children's Hospital were recruited to undergo intraoperative brain tonometry at the time of open craniotomy for epilepsy surgery. Brain stiffness measurements were corrected with abnormalities on neuroimaging and histopathology using mixed-effects multivariable linear regression. We collected 249 measurements across 30 operations involving 24 patients through the pediatric epilepsy surgery program at UCLA Mattel Children's Hospital. On multivariable mixed-effects regression, brain stiffness was significantly associated with the presence of MRI lesion (β = 32.3, 95%CI 16.3-48.2; p < 0.001), severity of cortical disorganization (β = 19.8, 95%CI 9.4-30.2; p = 0.001), and recent subdural grid implantation (β = 42.8, 95%CI 11.8-73.8; p = 0.009). Brain tonometry offers the potential of real-time intraoperative feedback to identify abnormal brain tissue with millimeter spatial resolution. We present the first experience with this novel intraoperative tool for the conduct of epilepsy surgery. A carefully designed prospective study is required to elucidate whether the clinical application of brain tonometry during resective procedures could guide the area of resection and improve seizure outcomes.

Object: The use of stereotactic radiosurgery (SRS) has increased. SRS training has not risen congruently. Neurosurgeons have conducted surveys and advocated implementation of widespread, standardized radiosurgery training. Here we analyze the SRS surveys conducted throughout the past decade., Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic literature review. A broad search of the literature was conducted in October 2018 through the PubMed, Scopus, Embase, and Web of Science databases. This study included surveys evaluating SRS training in neurosurgery and excluded those regarding other specialties., Results: An overview of surveys showed that neurosurgery residents possess gaps in SRS knowledge and procedural competency that have persisted through the past decade. There is an overwhelming sentiment that current radiosurgery training is not adequate to prepare residents for future practice. Our recommendation is for residency programs to integrate formal SRS training electives, with a movement towards creating more options for extended SRS fellowships post-residency., Conclusions: We present data from SRS competency and current training surveys. Although resident SRS training still lags behind other subspecialties, we see indications for growth. To keep up with the role of SRS in neurosurgery, residencies need more formalized SRS rotations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Rasmussen encephalitis (RE) is a rare inflammatory neurological disorder typically involving one hemisphere and resulting in drug-resistant epilepsy and progressive neurological decline. Here, the authors present seizure outcomes in children who underwent epilepsy surgery for RE at a single institution., Methods: The records of consecutive patients who had undergone epilepsy surgery for RE at the UCLA Mattel Children's Hospital between 1982 and 2018 were retrospectively reviewed. Basic demographic information, seizure history, procedural notes, and postoperative seizure and functional outcome data were analyzed., Results: The cohort included 44 patients, 41 of whom had sufficient data for analysis. Seizure freedom was achieved in 68%, 48%, and 22% of the patients at 1, 5, and 10 years, respectively. The median time to the first seizure for those who experienced seizure recurrence after surgery was 39 weeks (IQR 11-355 weeks). Anatomical hemispherectomy, as compared to functional hemispherectomy, was independently associated with a longer time to postoperative seizure recurrence (HR 0.078, p = 0.03). There was no statistically significant difference in postoperative seizure recurrence between patients with complete hemispherectomy and those who had less-than-hemispheric surgery. Following surgery, 68% of the patients could ambulate and 84% could speak regardless of operative intervention., Conclusions: A large proportion of RE patients will have seizure relapse after surgery, though patients with anatomical hemispherectomies may have a longer time to postoperative seizure recurrence. Overall, the long-term data in this study suggest that hemispheric surgery can be seen as palliative treatment for seizures rather than a cure for RE.

Objective: The objective of this study was to perform an individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Rasmussen's encephalitis (RE) undergoing resective or hemispheric epilepsy surgery., Methods: Electronic databases (PubMed, Web of Science, CINAHL) were searched with no language or date restrictions to identify cohort studies of consecutive participants undergoing resective surgery that reported seizure outcomes. The authors recorded all preoperative factors that could plausibly be associated with seizure outcomes and used Cox regression analysis to identify which of these variables were associated with seizure freedom (i.e., Engel class I)., Results: Of 720 citations, 19 articles reporting on 187 participants were eligible. Seizure freedom (Engel class I) was observed in 113 participants (60.4%). On univariate analyses, younger age at disease onset (hazard ratio [HR] 0.906, p = 0.001), younger age at surgery (HR 0.928, p < 0.001), shorter time to surgery (HR 0.921, p = 0.001), and hemispherectomy (HR 0.283, p < 0.001) were all associated with longer time to postoperative seizure recurrence. Additionally, multivariable analysis including the aforementioned variables showed that younger age at surgery (HR 0.946, p = 0.043) and hemispherectomy (HR 0.297, p < 0.001) were independently and significantly associated with a greater time to seizure recurrence and longer duration of seizure freedom., Conclusions: The majority of pediatric patients undergoing resective or hemispheric surgery for RE achieve good seizure outcome. Although small retrospective cohort studies are inherently prone to bias, the best available evidence utilizing individual participant data suggests hemispheric surgery and younger age at surgery are associated with good seizure outcomes following epilepsy surgery. Large, multicenter observational studies with long-term follow-up are required to evaluate the risk factors identified in this review.

Background: Since the debut of Facebook in 2004, social media (SoMe) has garnered increased popularity and usage worldwide. Given its appeal and visibility, many industries have used SoMe to promote products for professional purposes. Specialized sites have subsequently been created to connect users in similar disciplines. Although SoMe sites have amassed over 1-billion followers, SoMe usage in the neurosurgical community has not yet been well described., Methods: We present an online survey administered to neurosurgery faculty, fellows, and residents in 102 U.S. accredited programs to gauge usage and perception of SoMe for professional purposes., Results: Of all surveys distributed, 241 neurosurgeons responded with an attending, resident, to fellow breakdown of 137, 96, and 8, respectively. A total of 55.97% of respondents were under the age of 34, 2% were over the age of 75, and 81% of respondents identified as men. An overwhelming majority cited conferences (83%) and in-person meetings as their preferred method of networking. However, 70% state they use SoMe for professional purposes with Doximity and LinkdIn listed as the most popular (49% and 48%, respectively) platforms. Lack of time and perceived value, in addition to privacy concerns, were noted to be the main factors for those refraining from SoMe use., Conclusions: As SoMe becomes increasingly popular and its use expands, the majority of neurosurgeon respondents are also using SoMe for professional purposes. Although lack of time, lack of perceived value, and privacy concerns were hindrances to usage, other factors like age do not seem to correlate with SoMe adoption for professional aims., (Copyright © 2019. Published by Elsevier Inc.)

Background: Vestibular schwannomas (VSs) are benign neoplasms of the Schwann cells of cranial nerve VIII, and treatment of VS typically involves surgical resection. However, tumor recurrence may necessitate reintervention, and secondary treatment modalities include repeat surgical resection or adjuvant radiosurgery. The purpose of this study is to examine the scientific literature in order to determine whether surgical resection or radiosurgery for recurrent VS results in better tumor control, hearing preservation, and preservation of facial nerve function., Methods: The PubMed, Scopus, Embase, Cochrane, and Web of Science databases were searched for studies reporting on patients undergoing either radiosurgery or repeat surgical resection after primary surgical resection for recurrent VS. Statistical analyses were performed on the compiled data, primarily outcome data involving tumor control, hearing preservation, and preservation of facial nerve function., Results: We analyzed the data of 15 individual studies involving 359 total patients, and our results reveal that tumor control rates are comparable between adjuvant radiosurgery (91%, CI: 88-94%) and secondary resection (92%, CI 75-98%). However, adjuvant radiosurgery was shown to preserve good facial nerve function better (94%, CI 84-98%) compared to secondary surgical resection (56%, CI 41-69%)., Conclusion: With comparable tumor control rates and better preservation of good facial nerve function, this study suggests that secondary radiosurgery for recurrent VS is associated with both optimal tumor control and preservation of good facial nerve function.

Although the pre-surgical management of patients with acute traumatic subdural hematoma prioritizes rapid transport to the operating room, there is conflicting evidence regarding the importance of time interval from injury to surgery with regards to outcomes. We sought to determine the association of surgical timing with outcomes for subdural hematoma. A retrospective review was performed of 522 consecutive patients admitted to a single center from 2006-2012 who underwent emergent craniectomy for acute subdural hematoma. After excluding patients with unknown time of injury, penetrating trauma, concurrent cerebrovascular injury, epidural hematoma, or intraparenchymal hemorrhage greater than 30 mL, there remained 45 patients identified for analysis. Using a multiple regression model, we examined the effect of surgical timing, in addition to other variables on in-hospital mortality (primary outcome), as well as the need for tracheostomy or gastrostomy (secondary outcome). We found that increasing injury severity score (odds ratio [OR] 1.146; 95% confidence interval [CI] 1.035-1.270; p=0.009) and age (OR1.066; 95%CI 1.006-1.129; p=0.031) were associated with in-hospital mortality in multivariate analysis. In this model, increasing time to surgery was not associated with mortality, and in fact had a significant effect in decreasing mortality (OR 0.984; 95%CI 0.971-0.997; p=0.018). Premorbid aspirin use was associated with a paradoxical decrease in mortality (OR 0.019; 95%CI 0.001-0.392; p=0.010). In this patient sample, shorter time interval from injury to surgery was not associated with better outcomes. While there are potential confounding factors, these findings support the evaluation of rigorous preoperative resuscitation as a priority in future study., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: To determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE)., Methods: We identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision., Results: Forty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5 months)., Significance: More than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Studies suggest that a lack of standardized knowledge may lead to underreporting and undertreatment of sports-related concussion. However, there has been little work done to establish how this knowledge may affect athletes' behaviors toward reporting their concussions and removing themselves from play. We conducted an anonymous online survey to assess athletes' knowledge of signs and symptoms of concussion, and also sought to estimate the potential frequency of underreporting in a collegiate athlete cohort. Among 262 athletes who responded to the survey, 43% of those with a history of concussion reported that they had knowingly hidden symptoms of a concussion to stay in a game, and 22% of athletes overall indicated that they would be unlikely or very unlikely to report concussion symptoms to a coach or athletic trainer in the future. These data suggest that there may be a substantial degree of underreporting of concussion among collegiate athletes, despite most acknowledging that they have been formally educated about the risks of concussion.

Treatment options for triple negative breast cancer (TNBC) are generally limited to cytotoxic chemotherapy. Recently, anti-epidermal growth factor receptor (EGFR) therapy has been introduced for TNBC patients. We engineered a novel nanobioconjugate based on a poly(β-L-malic acid) (PMLA) nanoplatform for TNBC treatment. The nanobioconjugate carries anti-tumor nucleosome-specific monoclonal antibody (mAb) 2C5 to target breast cancer cells, anti-mouse transferrin receptor (TfR) antibody for drug delivery through the host endothelial system, and Morpholino antisense oligonucleotide (AON) to inhibit EGFR synthesis. The nanobioconjugates variants were: (1) P (BioPolymer) with AON, 2C5 and anti-TfR for tumor endothelial and cancer cell targeting, and EGFR suppression (P/AON/2C5/TfR), and (2) P with AON and 2C5 (P/AON/2C5). Controls included (3) P with 2C5 but without AON (P/2C5), (4) PBS, and (5) P with PEG and leucine ester (LOEt) for endosomal escape (P/mPEG/LOEt). Drugs were injected intravenously to MDA-MB-468 TNBC bearing mice. Tissue accumulation of injected nanobioconjugates labeled with Alexa Fluor 680 was examined by Xenogen IVIS 200 (live imaging) and confocal microscopy of tissue sections. Levels of EGFR, phosphorylated and total Akt in tumor samples were detected by western blotting. In vitro western blot showed that the leading nanobioconjugate P/AON/2C5/TfR inhibited EGFR synthesis significantly better than naked AON. In vivo imaging revealed that 2C5 increased drug-tumor accumulation. Significant tumor growth inhibition was observed in mice treated with the lead nanobioconjugate (1) [P = 0.03 vs. controls; P<0.05 vs. nanobioconjugate variant (2)]. Lead nanobioconjugate (1) also showed stronger inhibition of EGFR expression and Akt phosphorylation than other treatments. Treatment of TNBC with the new nanobioconjugate results in tumor growth arrest by inhibiting EGFR and its downstream signaling intermediate, phosphorylated Akt. The nanobioconjugate represents a new generation of nanodrugs for treatment of TNBC.

Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (l-3,4-dihydroxyphenylalanine at 100 mg/kg or l-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.