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Objective: Spinal cord injury (SCI) trials have historically underrepresented pediatric patients. There are limited pediatric data examining the influence of surgical timing on complications and mortality for children and adolescents who have sustained complete traumatic SCI., Methods: The following multicenter cohort study used Trauma Quality Improvement Program data from 2010 to 2020. The authors identified pediatric patients (aged < 18 years) who sustained complete traumatic SCI and underwent surgical intervention within 7 days of admission. Propensity score matching was performed between patients who underwent surgery within 24 hours versus ≥ 24 hours. The authors then assessed differences for the following outcomes: major in-hospital complications, immobility-related complications, length of stay (LOS), and mortality., Results: There were 837 patients with complete traumatic SCI managed across 297 trauma centers identified for study inclusion (70% underwent early surgery). After matching, 494 patients were available for analysis. Patients undergoing delayed surgery experienced longer ICU LOS (mean difference 3.74 days, 95% CI 0.91-6.57 days) and more major in-hospital complications (OR 1.77, 95% CI 1.16-2.73) and immobility-related complications (OR 2.09, 95% CI 1.25-3.56). There were no differences in mortality between groups. Younger age, non-White race, penetrating injuries, lower Glasgow Coma Scale score at admission, severe concomitant abdominal injuries, and motor vehicle collision injury mechanisms were associated with increased time to surgery., Conclusions: The authors demonstrated an association between early surgery and shorter ICU LOS and reduced in-hospital complications. Future work is needed to quantify the impact of surgical timing on functional neurological outcomes and to explore upstream social determinants of health influencing timing of surgery.

Aim: To describe the experiences of children with self-injurious behavior (SIB) through the lens of family caregivers to inform the development of relevant interventions., Method: SIB in children with autism spectrum disorder is challenging to understand and manage. Furthermore, our understanding of the impact of SIB on families is limited. We performed an exploratory qualitative study using interpretive description methodology. Semi-structured one-on-one interviews were conducted as the primary data collection technique. A purposive convenience sampling technique was used for the recruitment of participants through several clinics at one institution. Enrollment continued until 12 participants were recruited, at which time consensus was reached by the study team that sufficient data had been obtained to develop a depth of understanding of key elements of the caregiver perspective. Data were then analysed using a thematic analysis approach to develop overarching themes., Results: Three main themes were developed from the analysis of the data: the pervasive impact of SIB; lack of resources to turn toward; and the presence of silver linings. Participants described in some detail the many elements of their children's condition that led to a pervasive impact far beyond the child themselves. This experience was augmented by stigma and the lack of available resources. Despite these challenges, there was a strong sense of resilience and hope., Interpretation: Our study provides insights into the patterns of experiences of family caregivers of children with SIB. These results have far-reaching implications ranging from the clinical need for enhanced care and collaboration with affected families, the call for researchers to further develop effective treatments, and lastly highlighting the need to work with policymakers to advocate for resources to support children with SIB and their families., (© 2024 Mac Keith Press.)

Objective: We systematically reviewed the existing literature on the efficacy of corpus callosotomy (CC) in children and adults with refractory epileptic spasms (ES) and analyzed clinical determinants of seizure outcomes., Methods: The Preferred Report Items for Systematic Reviews and Meta-Analysis Guidelines (PRISMA) were followed. We systematically searched MEDLINE, EMBASE and Cochrane databases up to December 2023 for original research articles on using CC to treat refractory ES. The primary outcome measure was the proportion of study participants who achieved seizure freedom following initial CC at the last follow-up. Meta-regression using mixed-effects models was performed to obtain clinical determinants of seizure outcomes., Results: A total of 12 studies were included (253 individuals). Initial complete total CC was most common (n = 218/253, 86%), followed by anterior CC (n = 29/253, 12%) and other forms of CC (i.e., anterior to posterior, posterior, staged total) (n = 6/253, 2%). The pooled proportion of patients achieving spasm freedom following CC was 0.31 (95% CI: 0.22, 0.42) (mean follow-up 47 months). Meta-regression showed that structural etiology and mean age at the time of CC were significant moderators of the pooled effect. For every 1% increase in the proportion of structural etiology, the proportion of spasm-free outcome was found to reduce by 0.45 (95% CI: -0.86, -0.03, p < 0.0001). In addition, increasing the mean age by 1 month led to a reduction in the proportion of spasms-free patients by 0.003 (95% CI: -0.005, -0.0006, p = 0.01). Sixty-two individuals (24%) from seven studies underwent further surgery for residual ES; 34 became spasm free (55%)., Conclusions: Corpus callosotomy may be an effective treatment option in selected individuals with refractory epileptic spasms. Structural aetiologies and increased age at the time of corpus callosotomy are important clinical determinants. In some cases, CC may lead to further epilepsy surgery., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Developmental and epileptic encephalopathies (DEEs) are a group of childhood-onset epilepsy syndromes characterized by frequent seizures, severe cognitive and behavioral impairments, and poor long-term outcomes. These conditions are typically refractory to currently available medical therapies, prompting recent exploration of neuromodulation treatments such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), which aim to modulate epileptic networks spanning cortical and subcortical regions. These advances have occurred alongside an improved understanding of syndrome-specific and interictal epileptiform discharge/seizure-specific brain networks. By targeting key nodes within these networks, DBS and RNS hold promise for influencing seizures and associated cognitive and behavioral comorbidities. Initial experiences with centromedian (CM) thalamic DBS for Lennox-Gastaut syndrome (LGS) have shown modest efficacy across multiple seizure types. Reports also indicate the application of DBS and RNS across various genetic and structural etiologies commonly associated with DEEs, with mixed success. Although DBS and RNS are increasingly used in LGS and other DEEs, their mixed efficacy highlights a knowledge gap in understanding why some patients with LGS do not respond and which neuromodulation approach is most effective for other DEEs. To address these issues, this review first discusses recent neuroimaging studies showing similarities and differences in the epileptic brain networks underlying various DEEs, revealing the common involvement of the thalamus and the default-mode network (DMN) across multiple DEEs. We then examine thalamic DBS for LGS to illustrate how such network insights may be used to optimize neuromodulation. Although network-based neuromodulation is still in its infancy, the LGS model may serve as a framework for other DEEs, where optimal treatment necessitates consideration of the underlying epileptic networks. Lastly, the review suggests future research directions, including individualized connectivity assessment and biomarker identification through collaborative efforts, which may enhance the therapeutic potential of neuromodulation for individuals living with DEEs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To provide consensus-based recommendations for use of vagus nerve stimulation (VNS) therapy in the management of pediatric epilepsy., Methods: Delphi methodology with two rounds of online survey was used to build consensus. A steering committee developed 43 statements related to pediatric epilepsy and the use of VNS therapy, which were evaluated by a panel of 12 neurologists/neurosurgeons with expertise in pediatric epilepsy, who graded their agreement with each statement on a scale of 1 ("I do not agree at all") to 5 ("I strongly agree"). For each statement, consensus was established if ≥70% of the agreement scores were 4 or 5 and <30% were 1 or 2 in the final survey., Results: Twenty-four statements regarding the need for seizure reduction in pediatric epilepsy, the recommended treatment algorithm, the benefits and safety of VNS therapy, management of side effects of VNS therapy, patient selection for VNS therapy, and the use, dosing, and titration of VNS therapy achieved consensus. VNS and other neuromodulation therapies should be considered for pediatric patients with drug-resistant epilepsy who are not candidates for resective surgery, or who do not remain seizure free after resective surgery. When VNS therapy is initiated, the target dose range should be achieved via the fastest and safest titration schedule for each patient. Scheduled programming can be helpful in dose titration., Conclusion: The expert consensus statements represent the panelists' collective opinion on the best practice use of VNS therapy to optimize outcomes in the management of pediatric epilepsy., Competing Interests: Declaration of competing interest James W. Wheless is a consultant for BioMarin, Epiwatch, Neurelis, Neuro Event Labs, Jazz, and Takeda; has received research funding from LivaNova, Jazz, Neurelis, Neuro Event Labs, Shainberg Foundation, SKLSI, TSC Alliance, and UCB; and serves on the speaker's bureau for BioMarin, Jazz, Neurelis, SKLSI, and UCB. Jeffrey S. Raskin is a clinical advisory board member for Synergia, a consultant for Blackrock Neurotech, Iota, and Brainlab, and President of SMERF, Inc 501(c)(3). Anthony L. Fine has no financial interests to disclose. Kelly Knupp has consulted for UCB, Stoke, Encoded, Epygenix, Longboard and Biocodex; has received research funding from Eisai, Stoke, and UCB; and serves on a Data and Safety Monitoring Board for Jazz and Epygenix. John Schreiber is a clinical advisory board member for Stoke Therapeutics and Longboard Pharmacueticals; a consultant for Denali Therapeutics and Neurocrine; receives research funding to his institution from UCB, Neurocrine, and Stoke Therapeutics; and serves on the speaker bureau for UCB and Marinus. Adam P. Ostendorf receives research funding from NINDS and the Nationwide Children's Hospital Foundation. Gregory W. Albert has no financial interests to disclose. Eric H. Kossoff has received consultant fees from LivaNova (not for this study), Simply Good Foods, Nutricia, Vitaflo, Cerecin, and Bloom Science. He is on the data safety monitoring board for a study from NeuroPace. Joseph R. Madsen is a consultant and scientific advisory board member for BioNaut Laboratories and Anuncia Medical. Prakash Kotagal is a consultant for Biocodex, Inc., LivaNova PLC, SK Life Sciences, and Takeda Pharmaceuticals. Adam L. Numis has no financial interests to disclose. Nisha Gadgil has no financial interests to disclose. Deborah L. Holder is a speaker for LivaNova. Elizabeth A. Thiele is a consultant for Jazz, UCB, Biocodex, LivaNova, Pyros, SKLS, Stoke Therapeutics, Takeda, Marinus, and Nobelpharma. She has received research funding from Jazz, UCB, and Biocodex. George M. Ibrahim has received research funding and consulting fees from LivaNova (not for this study). He also receives consulting and advisory fees from Medtronic Inc and Synergia Inc., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Self-injurious behavior (SIB) can occur in the setting of many neurologic disorders that are amenable to deep brain stimulation (DBS). Although certain brain targets are believed to be particularly effective for SIB, improvements in the primary neurologic condition may also reduce co-occurring SIB. We performed a systematic review and meta-analysis of individual participant data to characterize the effects of DBS across various neurologic disorders and brain targets on comorbid SIB., Materials and Methods: A systematic review of all available literature on DBS in treating disorders with co-occurring SIB was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Individual participant data were extracted and standardized mean differences (SMDs) in metrics of SIB severity and/or frequency were calculated for meta-analysis. Demographic variables and adverse events were also collated., Results: Data from 59 patients, identified from 24 articles, with comorbid SIB who underwent DBS for various indications were extracted. The primary neurologic diagnoses included Tourette syndrome (n = 40), dystonia (n = 7), epilepsy (n = 5), acquired brain injury (n = 3), dyskinesia (n = 2), and obsessive-compulsive disorder (n = 2). Overall, DBS was highly effective in treating comorbid SIB (Mean SMD = -2.4, p < 0.0001) across primary disorders and intracranial targets. Patients with dystonia and DBS targeting the posterior hypothalamus had relatively less success at mitigating comorbid SIB., Conclusions: In patients with comorbid SIB, DBS to treat the primary neurologic condition may also mitigate SIB. Although several targets are emerging for the treatment of severe SIB, this work suggests that DBS targeting the primary neurologic condition should be first considered in comorbid SIB., Competing Interests: Conflict of Interest Alfonso Fasano received honoraria and research funding from Medtronic and receives consulting fees from Medtronic, Abbvie, Boston Scientific, Brainlab, and Ipsen. Carolina Gorodetsky received honoraria from Medtronic. George M. Ibrahim receives investigator-initiated grant funding, speaking and consulting fees from LivaNova Inc, consulting fees from Synergia Inc, and consulting fees from Medtronic. The remaining authors report no conflict of interest., (Copyright © 2024 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Outcomes following vagus nerve stimulation (VNS) improve over years after implantation in children with drug-resistant epilepsy. The added value of deep brain stimulation (DBS) instead of continued VNS optimization is unknown. In a prospective, non-blinded, randomized patient preference trial of 18 children (aged 8-17 years) who did not respond to VNS after at least 1 year, add-on DBS resulted in greater seizure reduction compared with an additional year of VNS optimization (51.9% vs. 12.3%, p = 0.047). Add-on DBS also resulted in less bothersome seizures (p = 0.03), but no change in quality of life. DBS may be considered earlier for childhood epilepsy after non-response to VNS. ANN NEUROL 2024;96:405-411., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts., Objective: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery., Methods: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized., Results: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery., Conclusions: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A detailed, unbiased perspective of the inter-relations among medical fields could help students make informed decisions on their future career plans. Using a data-driven approach, the inter-relations among different medical fields were decomposed and clustered based on the similarity of their working environments.Publicly available, aggregate databases were merged into a single rich dataset containing demographic, working environment and remuneration information for physicians across Canada. These data were collected from the Canadian Institute for Health Information, the Canadian Medical Association, and the Institute for Clinical Evaluative Sciences, primarily from 2018 to 2019. The merged dataset includes 25 unique medical specialties, each with 36 indicator variables. Latent Profile Analysis (LPA) was used to group specialties into distinct clusters based on relatedness.The 25 medical specialties were decomposed into seven clusters (latent variables) that were chosen based on the Bayesian Information Criterion. The Kruskal-Wallis test identified eight indicator variables that significantly differed between the seven profiles. These variables included income, work settings and payment styles. Variables that did not significantly vary between profiles included demographics, professional satisfaction, and work-life balance satisfaction.The 25 analyzed medical specialties were grouped in an unsupervised manner into seven profiles via LPA. These profiles correspond to expected and meaningful groups of specialties that share a common theme and set of indicator variables (e.g. procedurally-focused, clinic-based practice). These profiles can help aspiring physicians narrow down and guide specialty choice., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Functional hemispherectomy is an effective surgical intervention for select patients with drug-resistant epilepsy. The last several decades have seen dramatic evolutions in preoperative evaluation, surgical techniques, and postoperative care. Here, the authors present a retrospective review of the medical records of 146 children who underwent hemispherectomy between 1987 and 2022 at The Hospital for Sick Children, providing a unique overview of the evolution of the procedure and patient outcomes over 35 years., Methods: The medical records of all children who underwent hemispherectomy at The Hospital for Sick Children between 1987 and 2022 were reviewed. Demographic information, preoperative clinical features, short-term and long-term seizure outcomes, and details regarding postoperative complications were recorded., Results: The seizure outcomes of 146 children were analyzed. There were 68 females and 78 males with a mean age of 5.08 years, 123 of whom demonstrated seizure freedom (Engel class IA) in the short-term postoperative follow-up period and 89 in the long term. The effectiveness of hemispherectomy in achieving long-term seizure control has improved over time (β = 0.06, p < 0.001). Factors associated with overall seizure freedom included younger age at the time of hemispherectomy and stroke as the etiology of seizures, as well as complete disconnection during the first surgery. Additionally, the etiologies of epilepsy for which hemispherectomy is performed have expanded over time, while complication rates have remained unchanged., Conclusions: Hemispherectomy is an increasingly effective treatment for certain cases of drug-resistant epilepsy. The etiologies of epilepsy for which hemispherectomy is performed are broadening, with no change in its safety profile. Seizure outcomes are better when the etiology of epilepsy is an ischemic injury, and the most common complication after the procedure is hydrocephalus. These findings reinforce the ongoing use of hemispherectomy as a safe and effective treatment option for certain individuals with drug-resistant epilepsy, support its application to a broader range of etiologies, and highlight areas of future investigation.

Research on the mental health of university staff during the COVID-19 pandemic has uncovered a high prevalence of probable anxiety, depression, and post-traumatic stress disorder among academic and non-academic staff in many parts of the world. This study aimed to assess the prevalence of anxiety, depressive symptoms, and resilience among a sample of faculty and staff members working in the Higher College of Technology campuses in the UAE. From September to November 2021, a cross-sectional study was carried out using an online survey. The Generalized Anxiety Disorder 7-item scale, The Patient Health Questionnaire (9-items), and the Connor-Davidson Resilience Scale were used to assess anxiety, depression, and resilience. The impact of COVID-19 was assessed using a designated list of questions. The results demonstrated that the COVID-19 pandemic had impacted the mental health of the studied sample of university workers, with almost 16% of the participants having moderate-to-severe depression and anxiety symptoms. This study highlighted significant differences in the participants' depressive and anxiety symptoms due to sociodemographic differences. Depression and anxiety symptoms were most prevalent among females, those of UAE nationality, and never-married workers, with females scoring 5.81 on the PHQ-9 compared to only 4.10 in males, p = 0.004 *. UAE-national participants had significantly higher mean PHQ-9 scores than their non-national counterparts (6.37 ± 5.49 SD versus 4.77 ± 5.1 SD, respectively, p = 0.040 *). Overall, the total mean scores of all participants were below the assumed cut-off threshold of having a high resilience level (29.51 ± 7.53 SD). The results showed a significant difference in severe depression symptoms as a result of the impact of COVID-19. These results could imply that the COVID-19 pandemic might have augmented negative mental health impacts on this sample of university workers. This study highlighted some areas where the responsible authorities can intervene to further protect and enhance the mental health of university workers, particularly after the COVID-19 pandemic.

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Dystonia is among the most common pediatric movement disorders and can manifest with a range of debilitating symptoms, including sleep disruptions. The duration and quality of sleep are strongly associated with quality of life in these individuals and could serve as biomarkers of dystonia severity and the efficacy of interventions such as deep brain stimulation (DBS). Thus, this study investigated sleep duration and its relationship to disease severity and DBS response in pediatric dystonia., Methods: Actigraphs (wearable three-axis accelerometers) were used to record multiday sleep data in 22 children with dystonia, including 6 patients before and after DBS implantation, and age- and sex- matched healthy controls. Data were preprocessed, and metrics of sleep duration and quality were extracted. Repeated-measures statistical analyses were used., Results: Children with dystonia slept less than typically developing children (p = 0.009), and shorter sleep duration showed trending correlation with worse dystonia severity (r = -0.421, p = 0.073). Of 4 patients who underwent DBS and had good-quality data, 1 demonstrated significantly improved sleep (p < 0.001) postoperatively. Reduction in dystonia severity strongly correlated with increased sleep duration after DBS implantation (r = -0.965, p = 0.035)., Conclusions: Sleep disturbances are an underrecognized marker of pediatric dystonia severity, as well as the effectiveness of interventions such as DBS. They can serve as objective biomarkers of disease burden and symptom progression after treatment.

Background: Refractory (RSE) and super-refractory status epilepticus (SRSE) are serious neurological conditions requiring aggressive management. Beyond anesthetic agents, there is a lack of evidence guiding management in these patients. This systematic review and individual participant data meta-analysis (IPDMA) seeks to evaluate and compare the currently available surgical techniques for the acute treatment of RSE and SRSE., Methods: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data (PRISMA-IPD). Only patients who underwent surgery while in RSE and SRSE were included. Descriptive statistics were used to compare various subgroups. Multivariable logistic regression models were constructed to identify predictors of status epilepticus (SE) cessation, long-term overall seizure freedom, and favorable functional outcome (i.e., modified Rankin score of 0-2) at last follow-up., Results: A total of 87 studies including 161 participants were included. Resective surgery tended to achieve better SE cessation rate (93.9%) compared to non-resective techniques (83.9%), but this did not reach significance ( p  = 0.071). Resective techniques were also more likely to achieve seizure freedom (69.1% vs. 34.4%, p  = <0.0001). Older age at SE (OR = 1.384[1.046-1.832], p  = 0.023) was associated with increased likelihood of SE cessation, while longer duration of SE (OR = 0.603[0.362-1.003], p  = 0.051) and new-onset seizures (OR = 0.244[0.069-0.860], p  = 0.028) were associated with lower likelihood of SE cessation, but this did not reach significance for SE duration. Only shorter duration of SE prior to surgery (OR = 1.675[1.168-2.404], p   = 0.0060) and immediate termination of SE (OR = 3.736 [1.323-10.548], p  = 0.014) were independently associated with long-term seizure status. Rates of favorable functional outcomes (mRS of 0-2) were comparable between resective (44.4%) and non-resective (44.1%) techniques, and no independent predictors of outcome were identified., Conclusion: Our findings suggest that emergency neurosurgery may be a safe and effective alternative in patients with RSE/SRSE and may be considered earlier during the disease course. However, the current literature is limited exclusively to small case series and case reports with high risk of publication bias. Larger clinical trials assessing long-term seizure and functional outcomes are warranted to establish robust management guidelines., Competing Interests: AF serves on the board for Pediatric Epilepsy Surgery Alliance. GI serves on the advisory board of Synergia Medical. AW is a consultant for Monteris and serves on the advisory board of Synergia Medical. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor SS declared a shared affiliation with the author NS at the time of review., (Copyright © 2024 Niazi, Han, Stamm, Shlobin, Korman, Hoang, Kielian, Du Pont-Thibodeau, Ducharme Crevier, Major, Nguyen, Bouthillier, Ibrahim, Fallah, Hadjinicolaou and Weil.)

Background: Cerebellar mutism syndrome (CMS) is a common and debilitating complication of posterior fossa tumor surgery in children. Affected children exhibit communication and social impairments that overlap phenomenologically with subsets of deficits exhibited by children with Autism spectrum disorder (ASD). Although both CMS and ASD are thought to involve disrupted cerebro-cerebellar circuitry, they are considered independent conditions due to an incomplete understanding of their shared neural substrates., Methods: In this study, we analyzed postoperative cerebellar lesions from 90 children undergoing posterior fossa resection of medulloblastoma, 30 of whom developed CMS. Lesion locations were mapped to a standard atlas, and the networks functionally connected to each lesion were computed in normative adult and pediatric datasets. Generalizability to ASD was assessed using an independent cohort of children with ASD and matched controls (n = 427)., Results: Lesions in children who developed CMS involved the vermis and inferomedial cerebellar lobules. They engaged large-scale cerebellothalamocortical circuits with a preponderance for the prefrontal and parietal cortices in the pediatric and adult connectomes, respectively. Moreover, with increasing connectomic age, CMS-associated lesions demonstrated stronger connectivity to the midbrain/red nuclei, thalami and inferior parietal lobules and weaker connectivity to the prefrontal cortex. Importantly, the CMS-associated lesion network was independently reproduced in ASD and correlated with communication and social deficits, but not repetitive behaviors., Conclusions: Our findings indicate that CMS-associated lesions may result in an ASD-like network disturbance that occurs during sensitive windows of brain development. A common network disturbance between CMS and ASD may inform improved treatment strategies for affected children., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: In this study, we examined the utility of simultaneous scalp and stereotactic intracranial electroencephalography (SSIEEG) in epilepsy patients. Although SSIEEG offers valuable insights into epilepsy and cognitive function, its routine use is uncommon. Challenges include interpreting post-craniotomy scalp EEG due to surgically implanted electrodes., New Method: We describe our methodology for conducting SSIEEG recordings. To simulate the potential impact on EEG interpretation, we computed the leadfield of scalp electrodes with and without burrholes using Finite Element Analysis to compare the resulting sensitivity volume and waveforms of simulated intracranial signals between skulls with and without burrholes., Results: The presence of burr holes in the skull layer of the leadfield models did not discernibly modify simulated waveforms or scalp EEG topology. Using realistic SEEG burr hole diameter, the difference in the average leadfield of scalp electrodes was 0.12% relative to the effect of switching two nearby electrodes, characterized by the cosine similarity difference. No patients experienced adverse events related to SSIEEG., Comparison With Existing Methods: Although there is increasing acceptance and interest in SSIEEG, few studies have characterized the technical feasibility. Here, we demonstrate through modelling that scalp recordings from SSIEEG are comparable to that through an intact skull., Conclusion: The placement and simultaneous acquisition of scalp EEG during invasive monitoring through stereotactically inserted EEG electrodes is routinely performed at the Hospital for Sick Children. Scalp EEG recordings may assist with clinical interpretation. Burr holes in the skull layer did not discernibly alter EEG waveforms or topology., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: George M Ibrahim reports financial support was provided by Canadian Institutes of Health Research. Simeon Wong reports financial support was provided by Canadian Institutes of Health Research. George M Ibrahim reports a relationship with LivaNova Plc that includes: funding grants, speaking and lecture fees, and travel reimbursement., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The epilepsy monitoring unit (EMU) is a complex and dynamic operational environment, where the cognitive and behavioural consequences of medical and environmental changes often go unnoticed. The psychomotor vigilance task (PVT) has been used to detect changes in cognition and behaviour in numerous contexts, including among astronauts on spaceflight missions, pilots, and commercial drivers. Here, we piloted serial point-of-care administration of the PVT in children undergoing invasive monitoring in the EMU. Seven children completed the PVT throughout their hospital admission and their performance was associated with daily seizure counts, interictal epileptiform discharges, number of antiseizure medications (ASMs) administered, and sleep quality metrics. Using mixed-effects models, we found that PVT reaction time and accuracy were adversely affected by greater number of ASMs and interictal epileptiform activity. We show that serial point-of-care PVT is simple and feasible in the EMU and may enable greater understanding of individual patient responses to medical and environmental alterations, inform clinical decision-making, and support quality-improvement and research initiatives., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors whose names are listed above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Novel deep brain stimulation devices can record local field potentials (LFPs), which represent the synchronous synaptic activity of neuronal populations. The clinical relevance of LFPs in patients with dystonia remains unclear., Objectives: We sought to determine whether chronic LFPs recorded from the globus pallidus internus (GPi) were associated with symptoms of dystonia in children., Materials and Methods: Ten patients with heterogeneous forms of dystonia (genetic and acquired) were implanted with neurostimulators that recorded LFP spectral snapshots. Spectra were compared across parent-reported asymptomatic and symptomatic periods, with daily narrowband data superimposed in 24 one-hour bins., Results: Spectral power increased during periods of registered dystonic symptoms: mean increase = 102%, CI: (76.7, 132). Circadian rhythms within the LFP narrowband time series correlated with dystonic symptoms: for delta/theta-waves, correlation = 0.33, CI: (0.18, 0.47) and for alpha waves, correlation = 0.27, CI: (0.14, 0.40)., Conclusions: LFP spectra recorded in the GPi indicate a circadian pattern and are associated with the manifestation of dystonic symptoms., Competing Interests: Conflict of interest Carolina Gorodetsky reports a relationship with Medtronic, Inc that includes consulting or advisory and speaking and lecture fees. George M. Ibrahim reports a relationship with LivaNova that includes board membership and consulting or advisory. Alfonso Fasano reports a relationship with Medtronic, Inc, Abbott, and Boston Scientific that includes consulting or advisory and speaking and lecture fees. Lior M. Elkaim is an employee of Neuralink. The remaining authors report no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Epilepsy is a common and debilitating neurological disorder, and approximately one-third of affected individuals have ongoing seizures despite appropriate trials of two anti-seizure medications. This population with drug-resistant epilepsy (DRE) may benefit from neurostimulation approaches, such as vagus nerve stimulation (VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS). In some patient populations, these techniques are FDA-approved for treating DRE. VNS is used as adjuvant therapy for children and adults. Acting via the vagus afferent network, VNS modulates thalamocortical circuits, reducing seizures in approximately 50 ​% of patients. RNS uses an adaptive (closed-loop) system that records intracranial EEG patterns to activate the stimulation at the appropriate time, being particularly well-suited to treat seizures arising within eloquent cortex. For DBS, the most promising therapeutic targets are the anterior and centromedian nuclei of the thalamus, with anterior nucleus DBS being used for treating focal and secondarily generalized forms of DRE and centromedian nucleus DBS being applied for treating generalized epilepsies such as Lennox-Gastaut syndrome. Here, we discuss the indications, advantages and limitations of VNS, DBS and RNS in treating DRE and summarize the spatial distribution of neuroimaging observations related to epilepsy and stimulation using NeuroQuery and NeuroSynth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Stereoelectroencephalography (sEEG) is increasingly utilized for localization of seizure foci, functional mapping, and neurocognitive research due to its ability to target deep and difficult to reach anatomical locations and to study in vivo brain function with a high signal-to-noise ratio. The research potential of sEEG is constrained by the need for accurate localization of the implanted electrodes in a common template space for group analyses., Methods: We present an algorithm to automate the grouping of sEEG electrodes by trajectories, labelled by target and insertion point. This algorithm forms the core of a pipeline that fully automates the entire process of electrode localization in standard space, using raw CT and MRI images to produce atlas labelled MNI coordinates., Results: Across 196 trajectories from 20 patients, the pipeline successfully processed 190 trajectories with localizations within 0.25±0.55 mm of the manual annotation by two reviewers. Six electrode trajectories were not directly identified due to metal artifacts and locations were interpolated based on the first and last contact location and the number of contacts in that electrode as listed in the surgical record., Conclusion: We introduce our algorithm and pipeline for automatically localizing, grouping, and classifying sEEG electrodes from raw CT and MRI. Our algorithm adds to existing pipelines and toolboxes for electrode localization by automating the manual step of marking and grouping electrodes, thereby expedites the analyses of sEEG data, particularly in large datasets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: George M Ibrahim reports financial support was provided by Canadian Institutes of Health Research. Simeon Wong reports financial support was provided by Canadian Institutes of Health Research. George M Ibrahim reports a relationship with Medtronic Inc, Synergia Inc and LivaNova Plc that includes: funding grants, speaking and lecture fees, and travel reimbursement., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Importance: Early-life exposure to painful procedures has been associated with altered brain maturation and neurodevelopmental outcomes in preterm infants, although sex-specific differences are largely unknown., Objective: To examine sex-specific associations among early-life pain exposure, alterations in neonatal structural connectivity, and 18-month neurodevelopment in preterm infants., Design, Setting, and Participants: This prospective cohort study recruited 193 very preterm infants from April 1, 2015, to April 1, 2019, across 2 tertiary neonatal intensive care units in Toronto, Canada. Structural connectivity data were available for 150 infants; neurodevelopmental outcomes were available for 123 infants. Data were analyzed from January 1, 2022, to December 31, 2023., Exposure: Pain was quantified in the initial weeks after birth as the total number of invasive procedures., Main Outcome and Measure: Infants underwent early-life and/or term-equivalent-age magnetic resonance imaging with diffusion tensor imaging to quantify structural connectivity using graph theory measures and regional connection strength. Eighteen-month neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Stratifying by sex, generalized estimating equations were used to assess whether pain exposure modified the maturation of structural connectivity using an interaction term (early-life pain exposure × postmenstrual age [PMA] at scan). Generalized estimating equations were used to assess associations between structural connectivity and neurodevelopmental outcomes, adjusting for extreme prematurity and maternal education., Results: A total of 150 infants (80 [53%] male; median [IQR] gestational age at birth, 27.1 [25.4-29.0] weeks) with structural connectivity data were analyzed. Sex-specific associations were found between early-life pain and neonatal brain connectivity in female infants only, with greater early-life pain exposure associated with slower maturation in global efficiency (pain × PMA at scan interaction P = .002) and local efficiency (pain × PMA at scan interaction P = .005). In the full cohort, greater pain exposure was associated with lower global efficiency (coefficient, -0.46; 95% CI, -0.78, to -0.15; P = .004) and local efficiency (coefficient, -0.57; 95% CI, -1.04 to -0.10; P = .02) and regional connection strength. Local efficiency (coefficient, 0.003; 95% CI, 0.001-0.004; P = .005) and regional connection strength in the striatum were associated with cognitive outcomes., Conclusions and Relevance: In this cohort study of very preterm infants, greater exposure to early-life pain was associated with altered maturation of neonatal structural connectivity, particularly in female infants. Alterations in structural connectivity were associated with neurodevelopmental outcomes, with potential regional specificities.

Objective: Spasticity is a form of muscle hypertonia secondary to various diseases, including traumatic brain injury, spinal cord injury, cerebral palsy, and multiple sclerosis. Medical treatments are available; however, these often result in insufficient clinical response. This review evaluates the role of epidural spinal cord stimulation (SCS) in the treatment of spasticity and associated functional outcomes., Methods: A systematic review of the literature was performed using the Embase, CENTRAL, and MEDLINE databases. We included studies that used epidural SCS to treat spasticity. Studies investigating functional electric stimulation, transcutaneous SCS, and animal models of spasticity were excluded. We also excluded studies that used SCS to treat other symptoms such as pain., Results: Thirty-four studies were included in the final analysis. The pooled rate of subjective improvement in spasticity was 78% (95% confidence interval, 64%-91%; I 2  = 77%), 40% (95% confidence interval, 7%-73%; I 2  = 88%) for increased H-reflex threshold or decreased Hoffman reflex/muscle response wave ratio, and 73% (65%-80%; I 2  = 50%) for improved ambulation. Patients with spinal causes had better outcomes compared with patients with cerebral causes. Up to 10% of patients experienced complications including infections and hardware malfunction., Conclusions: Our review of the literature suggests that SCS may be a safe and useful tool for the management of spasticity; however, there is significant heterogeneity among studies. The quality of studies is also low. Further studies are needed to fully evaluate the usefulness of this technology, including various stimulation paradigms across different causes of spasticity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study reports our center's initial experience with the use of low-frequency stimulation in provoking stimulation-induced seizures (SIS) in children with drug-resistant epilepsy undergoing stereo-EEG evaluations., Methods: This retrospective study enrolled children aged 2 to 18 years with drug-resistant focal epilepsy who underwent stereo-EEG evaluation and extraoperative direct electrical cortical stimulation to elicit seizures. The low-frequency stimulation parameters consisted of biphasic square waveforms at frequency of 1 Hz, pulse width 1 millisecond, current 1 to 3 mA, and train duration of 20 seconds. Various epilepsy-related, imaging, neurophysiology, and surgery-related variables were collected and summarized., Results: Fourteen children (mean age 13 years; 57.1% girls) were included, 10 of whom had unilateral stereo-EEG coverage. Cortical stimulation for provoking seizures was performed after a median of 5 days after electrode implantation. The median number of electrode-contacts stimulated per patient was 42. Four patients (28.6%) experienced habitual SIS (all extratemporal). The etiology in three patients was focal cortical dysplasia. Interictal high-frequency oscillations at electrode-contacts provoking SIS were observed in three cases (75%). Two of these individuals (50%) had class 1 International League Against Epilepsy seizure outcome at last follow-up, after the resection of the brain regions generating SIS., Conclusions: Low-frequency (1-Hz) stimulation could provoke habitual SIS in nearly one-fourth of children with focal epilepsy undergoing stereo-EEG monitoring. This study provides a limited pediatric experience with the low-frequency cortical stimulation and SIS., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Objective: Extent of resection (EOR) is the most important modifiable prognostic variable for pediatric patients with posterior fossa ependymoma. An understanding of primary and recurrent ependymoma complications is essential to inform clinical decision-making for providers, patients, and families. In this study, the authors characterize postsurgical complications following resection of primary and recurrent pediatric posterior fossa ependymoma in a molecularly defined cohort., Methods: The authors conducted a 20-year retrospective single-center review of pediatric patients undergoing resection of posterior fossa ependymoma at the Hospital for Sick Children in Toronto, Canada. Complications were dichotomized into major and minor groups; EOR was compared across complication categories. The association between complication occurrence with length of stay (LOS) and mortality was also assessed using multivariable regressions., Results: There were 60 patients with primary resection included, 41 (68%) of whom were alive at the time of data collection. Gross-total resection was achieved in 33 (58%) of 57 patients at primary resection. There were no 30-day mortality events following primary and recurrent ependymoma resection. Following primary resection, 6 patients (10%) had posterior fossa syndrome (PFS) and 36 (60%) developed cranial neuropathies, 56% of which recovered within 1 year. One patient (1.7%) required a tracheostomy and 9 patients (15%) required gastrostomy tubes. There were 14 ventriculoperitoneal shunts (23%) inserted for postoperative hydrocephalus. Among recurrent cases, there were 48 recurrent resections performed in 24 patients. Complications included new cranial neuropathy in 10 patients (21%), of which 5 neuropathies resolved within 1 year. There were no cases of PFS following resection of recurrent ependymoma. Gastrostomy tube insertion was required in 3 patients (6.3%), and 1 patient (2.0%) required a tracheostomy. Given the differences in the location of tumor recurrence, a direct comparison between primary and recurrent resection complications was not feasible. Following multivariate analysis adjusting for sex, age, molecular status, and EOR, occurrence of major complications was found to be associated with prolonged LOS but not mortality., Conclusions: These results detail the spectrum of postsurgical morbidity following primary and recurrent posterior fossa ependymoma resection. The crude complication rate following resection of infratentorial recurrent ependymoma was lower than that of primary ependymoma, although a statistical comparison revealed no significant differences between the groups. These results should serve to inform providers of the morbidity profile following surgical management of posterior fossa ependymoma and inform perioperative counseling of patients and their families.

The last several decades have seen a shift in understanding many neurological disorders as abnormalities in brain networks rather than specific brain regions. This conceptual revolution, coupled with advancements in computing capabilities and resources, has enabled a wealth of research on delineating and treating aberrant brain networks. One approach to network neuroscience, graph theory, involves modeling network topologies as mathematical graphs and computing various metrics that describe its characteristics. Using graph theory, researchers have derived new insights into the pathophysiology of many neuropsychiatric disorders and even developed treatments targeted at restoring network disturbances. In this chapter, we provide an overview of the principles of graph theory and how to implement it, specific applications of graph theory within clinical neurosurgery, and a discussion on the advantages and limitations of these approaches., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background and Objectives: Gelastic seizures due to hypothalamic hamartomas (HH) are challenging to treat, in part due to an incomplete understanding of seizure propagation pathways. Although magnetic resonance imaging-guided laser interstitial thermal therapy (MRgLITT) is a promising intervention to disconnect HH from ictal propagation networks, the optimal site of ablation to achieve seizure freedom is not known. In this study, we investigated intraoperative post-ablation changes in resting-state functional connectivity to identify large-scale networks associated with successful disconnection of HH., Methods: Children who underwent MRgLITT for HH at two institutions were consecutively recruited and followed for a minimum of one year. Seizure freedom was defined as Engel score of 1A at the last available follow-up. Immediate pre- and post- ablation resting-state functional MRI scans were acquired while maintaining a constant depth of general anesthetic. Multivariable generalized linear models were used to identify intraoperative changes in large-scale connectivity associated with seizure outcomes., Results: Twelve patients underwent MRgLITT for HH, five of whom were seizure-free at their last follow-up. Intraprocedural changes in thalamocortical circuitry involving the anterior cingulate cortex were associated with seizure-freedom. Children who were seizure-free demonstrated an increase and decrease in connectivity to the pregenual and dorsal anterior cingulate cortices, respectively. In addition, children who became seizure-free demonstrated increased thalamic connectivity to the periaqueductal gray immediately following MRgLITT., Discussion: Successful disconnection of HH is associated with intraoperative, large-scale changes in thalamocortical connectivity. These changes provide novel insights into the large-scale basis of gelastic seizures and may represent intraoperative biomarkers of treatment success., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy., Methods: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/)., Results: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%., Significance: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Intracranial neuromodulation is an evolving therapy for patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) is now available as a therapy for patients with DRE and focal-onset seizures in select health care systems; however, there remains a substantial need of efficacy data before DBS can be more widely adopted into routine clinical practice. This review and commentary focuses on a particular shifting paradigm: DBS as a therapy for children with generalized-onset seizures., Competing Interests: Disclosure R.J. Piper has nothing to disclose. G.M. Ibrahim has received research funding as well as consulting and advisory fees from LivaNova, United Kingdom. M.M. Tisdall has received honoraria from Medtronic, sponsorship from Renishaw, and research funding from the Oakgrove Foundation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS., Methods: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks., Results: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality., Significance: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: MR-guided laser interstitial thermal therapy (MRgLITT) is associated with lower seizure-free outcome but better safety profile compared to open surgery. However, the predictors of seizure freedom following MRgLITT remain uncertain. This study aimed to use machine learning to predict seizure-free outcome following MRgLITT and to identify important predictors of seizure freedom in children with drug-resistant epilepsy., Methods: This multicenter study included children treated with MRgLITT for drug-resistant epilepsy at 13 epilepsy centers. The authors used clinical data, diagnostic investigations, and ablation features to predict seizure-free outcome at 1 year post-MRgLITT. Patients from 12 centers formed the training cohort, and patients in the remaining center formed the testing cohort. Five machine learning algorithms were developed on the training data by using 10-fold cross-validation, and model performance was measured on the testing cohort. The models were developed and tested on the complete feature set. Subsequently, 3 feature selection methods were used to identify important predictors. The authors then assessed performance of the parsimonious models based on these important variables., Results: This study included 268 patients who underwent MRgLITT, of whom 44.4% had achieved seizure freedom at 1 year post-MRgLITT. A gradient-boosting machine algorithm using the complete feature set yielded the highest area under the curve (AUC) on the testing set (AUC 0.67 [95% CI 0.50-0.82], sensitivity 0.71 [95% CI 0.47-0.88], and specificity 0.66 [95% CI 0.50-0.81]). Logistic regression, random forest, support vector machine, and neural network yielded lower AUCs (0.58-0.63) compared to the gradient-boosting machine but the findings were not statistically significant (all p > 0.05). The 3 feature selection methods identified video-EEG concordance, lesion size, preoperative seizure frequency, and number of antiseizure medications as good prognostic features for predicting seizure freedom. The parsimonious models based on important features identified by univariate feature selection slightly improved model performance compared to the complete feature set., Conclusions: Understanding the predictors of seizure freedom after MRgLITT will assist with prognostication.

Purpose: Hippocampal Sclerosis (HS) may co-exist with temporal or extratemporal lesions (dual pathology) in children and is usually ipsilateral to the radiological lesion. Here were report three cases with extensive hemispheric cortical malformation and drug resistant epilepsy who had persistent seizures after functional hemispherectomy (FH) and developed contralateral HS after the surgery., Methods: This retrospective study enrolled children who underwent FH and developed contralateral HS after surgery. Their clinical, EEG, radiological and pathological data were reviewed and summarized., Results: Ninety-five children underwent FH during the study period; Three cases (3.2%) were eligible. They all had unilateral extensive hemispheric cortical malformation who underwent FH between 3 and 5 months of age with no clinical, EEG or radiological suggestion for involvement of contralateral hemisphere prior to FH. All three patients had persisting seizures after FH. Contralateral HS was detected between 2.2 to 3.7 years after FH in all three cases. Two of the patients showed pathogenic variants in GATOR1 pathway genes., Conclusions: The genesis of contralateral HS in the reported patients remains unexplained. The presence and distribution of "second-hit" somatic mutations may play an important role in governing the seizure outcomes of epilepsy surgery in patients with apparently unilateral malformations of cortical development., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to disclose., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Cognitive flexibility encompasses the ability to efficiently shift focus and forms a critical component of goal-directed attention. The neural substrates of this process are incompletely understood in part due to difficulties in sampling the involved circuitry. We leverage stereotactic intracranial recordings to directly resolve local-field potentials from otherwise inaccessible structures to study moment-to-moment attentional activity in children with epilepsy performing a flexible attentional task. On an individual subject level, we employed deep learning to decode neural features predictive of task performance indexed by single-trial reaction time. These models were subsequently aggregated across participants to identify predictive brain regions based on AAL atlas and FIND functional network parcellations. Through this approach, we show that fluctuations in beta (12-30 Hz) and gamma (30-80 Hz) power reflective of increased top-down attentional control and local neuronal processing within relevant large-scale networks can accurately predict single-trial task performance. We next performed connectomic profiling of these highly predictive nodes to examine task-related engagement of distributed functional networks, revealing exclusive recruitment of the dorsal default mode network during shifts in attention. The identification of distinct substreams within the default mode system supports a key role for this network in cognitive flexibility and attention in children. Furthermore, convergence of our results onto consistent functional networks despite significant inter-subject variability in electrode implantations supports a broader role for deep learning applied to intracranial electrodes in the study of human attention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: In this study, the authors aimed to quantify the frequency of in-hospital major adverse events (AEs) in a multicenter cohort of pediatric patients with spinal cord injury (SCI) managed at North American trauma centers. They also sought to identify patient and injury factors associated with the occurrence of major and immobility-related AEs., Methods: Data derived from the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) were used to identify a cohort of pediatric patients (age < 19 years) with traumatic SCI. The authors identified individuals with major and immobility-related AEs following injury. They used mixed-effects multivariable logistic regression to identify clinical variables associated with AEs after injury. This analytical approach allowed them to account for similarities in care delivery between patients managed in the same trauma settings during the study period while also adjusting for patient-level confounders. The adjusted impact of AEs on in-hospital mortality and length of stay (LOS) were also assessed through further multivariable regression analysis. Additional subgroup analyses were performed to reduce bias associated with competing risks and explore the age-specific risk factor associations with AEs., Results: A total of 1853 pediatric patients who sustained either cervical or thoracic SCI were managed at ACS TQIP trauma centers between 2017 and 2020. The most frequently encountered AE types were pressure ulcer, unplanned intubation, cardiac arrest requiring cardiopulmonary resuscitation, and ventilator-associated pneumonia. The crude rate of major in-hospital and immobility-related AEs significantly differed between subgroups, with higher proportions of AEs in complete injuries compared with incomplete injuries. The adjusted risk for major AE following injury was significantly elevated for cervical complete SCI, patients with severe concomitant abdominal injuries, and for those presenting with depressed Glasgow Coma Scale scores less than 13. These same risk factors were associated with major AEs in children older than 8 years but were not significant for younger children (age ≤ 8 years). Complication occurrence was not associated with difference in risk-adjusted mortality (OR 0.72, 95% CI 0.45-1.14), but did increase LOS by 2.2 days (95% CI 1.4-2.7 days)., Conclusions: The authors outlined the prevalence of in-hospital AEs in a large multicenter cohort of North American pediatric SCI patients. Important risk factors predisposing this population to AEs include cervical complete injuries, simultaneous abdominal trauma, and Glasgow Coma Scale scores < 13 at presentation. Postinjury complications impacted health resource utilization by increased LOS but did not affect postinjury mortality. These findings have important implications for pediatric SCI providers and future care quality benchmarking.

Objective: We sought to better understand the workflow, outcomes, and complications of deep brain stimulation (DBS) for pediatric status dystonicus (SD). We present a systematic review, alongside a multicenter case series of pediatric patients with SD treated with DBS., Methods: We collected individual data regarding treatment, stimulation parameters, and dystonia severity for a multicenter case series (n = 8) and all previously published cases (n = 77). Data for case series were used to create probabilistic voxelwise maps of stimulated tissue associated with dystonia improvement., Results: In our institutional series, DBS was implanted a mean of 25 days after SD onset. Programming began a mean of 1.6 days after surgery. All 8 patients in our case series and 73 of 74 reported patients in the systematic review had resolution of their SD with DBS, most within 2 to 4 weeks of surgery. Mean follow-up for patients in the case series was 16 months. DBS target for all patients in the case series and 68 of 77 in our systematic review was the globus pallidus pars interna (GPi). In our case series, stimulation of the posterior-ventrolateral GPi was associated with improved dystonia. Mean dystonia improvement was 32% and 51% in our institutional series and systematic review, respectively. Mortality was 4% in the review, which is lower than reported for treatment with pharmacotherapy alone (10-12.5%)., Interpretation: DBS is a feasible intervention with potential to reverse refractory pediatric SD and improve survival. More work is needed to increase awareness of DBS in this setting, so that it can be implemented in a timely manner. ANN NEUROL 2023., (© 2023 American Neurological Association.)

A spinal cord injury (SCI) can be a devastating condition in children, with profound implications for their overall health and quality of life. In this review, we aim to provide a concise overview of the key aspects associated with SCIs in the pediatric population. Firstly, we discuss the etiology and epidemiology of SCIs in children, highlighting the diverse range of causes. We explore the unique anatomical and physiological characteristics of the developing spinal cord that contribute to the specific challenges faced by pediatric patients. Next, we delve into the clinical presentation and diagnostic methods, emphasizing the importance of prompt and accurate diagnosis to facilitate appropriate interventions. Furthermore, we approach the multidisciplinary management of pediatric SCIs, encompassing acute medical care, surgical interventions, and ongoing supportive therapies. Finally, we explore emerging research as well as innovative therapies in the field, and we emphasize the need for continued advancements in understanding and treating SCIs in children to improve their functional independence and overall quality of life.

Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a popular minimally invasive alternative to open resective surgery for drug-resistant epilepsy (DRE). We sought to perform a systematic review and individual participant data meta-analysis to identify independent predictors of seizure outcome and complications following MRgLITT for DRE. Eleven databases were searched from January 1, 2010 to February 6, 2021 using the terms "MR-guided ablation therapy" and "epilepsy". Multivariable mixed-effects Cox and logistic regression identified predictors of time to seizure recurrence, seizure freedom, operative complications, and postoperative neurological deficits. From 8705 citations, 46 studies reporting on 450 MRgLITT DRE patients (mean age = 29.5 ± 18.1 years, 49.6% female) were included. Median postoperative seizure freedom and follow-up duration were 15.5 and 19.0 months, respectively. Overall, 240 (57.8%) of 415 patients (excluding palliative corpus callosotomy) were seizure-free at last follow-up. Generalized seizure semiology (hazard ratio [HR] = 1.78, p = .020) and nonlesional magnetic resonance imaging (MRI) findings (HR = 1.50, p = .032) independently predicted shorter time to seizure recurrence. Cerebral cavernous malformation (CCM; odds ratio [OR] = 7.97, p < .001) and mesial temporal sclerosis/atrophy (MTS/A; OR = 2.21, p = .011) were independently associated with greater odds of seizure freedom at last follow-up. Operative complications occurred in 28 (8.5%) of 330 patients and were independently associated with extratemporal ablations (OR = 5.40, p = .012) and nonlesional MRI studies (OR = 3.25, p = .017). Postoperative neurological deficits were observed in 53 (15.1%) of 352 patients and were independently predicted by hypothalamic hamartoma etiology (OR = 5.93, p = .006) and invasive electroencephalographic monitoring (OR = 4.83, p = .003). Overall, MRgLITT is particularly effective in treating patients with well-circumscribed lesional DRE, such as CCM and MTS/A, but less effective in nonlesional cases or lesional cases with a more diffuse epileptogenic network associated with generalized seizures. This study identifies independent predictors of seizure freedom and complications following MRgLITT that may help further guide patient selection., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Craniopharyngiomas with a predominant cystic component are often seen in children and can be treated with an Ommaya reservoir for aspiration and/or intracystic therapy. In some cases, cannulation of the cyst can be challenging via a stereotactic or transventricular endoscopic approach due to its size and proximity to critical structures. In such cases, a novel placement technique for Ommaya reservoirs via a lateral supraorbital incision and supraorbital minicraniotomy has been used., Methods: The authors conducted a retrospective chart review of all children undergoing supraorbital Ommaya reservoir insertion from January 1, 2000, to December 31, 2022, at the Hospital for Sick Children, Toronto. The technique involves a lateral supraorbital incision and a 3 × 4-cm supraorbital craniotomy, with identification and fenestration of the cyst under the microscope and insertion of the catheter. The authors assessed baseline characteristics and clinical parameters of surgical treatment and outcome. Descriptive statistics were conducted. A review of the literature was performed to identify other studies describing a similar placement technique., Results: A total of 5 patients with cystic craniopharyngioma were included (3 male, 60%) with a mean age of 10.20 ± 5.72 years. The mean preoperative cyst size was 11.6 ± 3.7 cm3, and none of the patients suffered from hydrocephalus. All patients suffered from temporary postoperative diabetes insipidus, but no new permanent endocrine deficits were caused by the surgery. Cosmetic results were satisfactory., Conclusions: This is the first report of lateral supraorbital minicraniotomy for Ommaya reservoir placement. This is an effective and safe approach in patients with cystic craniopharyngiomas, which cause local mass effect but are not amenable to traditional Ommaya reservoir placement stereotactically or endoscopically.

Rapid advances in neurotechnology and neurosurgery are positioned to revolutionize care for patients suffering from debilitating neurological and psychiatric disease. Enthusiasm for the adoption of these technologies is tempered by ethical dilemmas regarding resource allocation, provision of care, communication with patients and other providers, and other potential pitfalls. In the present work, we discuss bioethical implications of novel neurotechnologies for medical practice. In particular, we examine the implications of neurotechnological advancement through the lens of professional communication. Emerging challenges within this domain are presented in the context of physician interactions with four key partners: (i) patients; (ii) other physicians; (iii) industry; and (iv) society-at-large. Anticipated issues as well as mitigation strategies are discussed as they relate to communication with these stakeholders.

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fiber tracts and functionally connected with brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network., Competing Interests: FG, JG, GE, AB, AL, AL, CT, WC, RM, EF, JB, PG, PA, HY, GI, NL, AL, CH No competing interests declared, (© 2023, Gouveia, Germann et al.)

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (β ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (β ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function., (© 2023 International League Against Epilepsy.)

Objective: A recent U.S. study reported that the number of epilepsy surgeries has remained stable or declined in recent years despite an increase in pre-surgical evaluation. This study aimed to evaluate trends in pre-surgical evaluation and epilepsy surgery from 2001 to 2019 and to determine whether these trends have changed in the later period (2014-2019) compared to earlier period (2001-2013)., Methods: This study evaluated trends in pre-surgical evaluation and epilepsy surgery at a tertiary pediatric epilepsy center. Children with drug resistant epilepsy who were evaluated for surgery were included. Clinical data, reasons for not undergoing surgery, and surgical characteristics of surgery patients were collected. Overall trends and trends in later period compared to earlier period for pre-surgical evaluation and epilepsy surgery were assessed., Results: There were 1151 children who were evaluated for epilepsy surgery and 546 underwent surgery. There was an upward trend in pre-surgical evaluation in the earlier period (rate ratio [RR]=1.04 (95%CI:1.02-1.07), p<0.001) and the trajectory of presurgical evaluation in the later period was not significantly different to the earlier period (RR=1.00 [95%CI:0.95-1.06], p = 0.88). Among the reasons for not undergoing surgery, failure to localize the seizures occurred more frequently in later period than earlier period (22.6% vs. 17.1% respectively, p = 0.024). For number of surgeries, there was an upward trend between 2001 and 2013 (RR=1.08 [95%CI:1.05-1.11], p<0.001), and a decreasing trend in the later period compared to earlier period (RR=0.91 [95%CI:0.84-0.99], p = 0.029)., Conclusion: Despite an increasing trend in pre-surgical evaluation, there was a decreasing trend in the number of epilepsy surgery in the later period as there was a larger proportion of patients in whom the seizures could not be localized. Trends in presurgical evaluation and epilepsy surgery will continue to evolve with introduction of technologies such as stereo-EEG and minimally invasive laser therapy., Competing Interests: Declaration of Competing Interest No disclosures relevant to the manuscript., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the epidemiologic profile of microbial keratitis in Alexandria- Egypt, with special emphasis on risk factors, visual outcome and microbiological results., Methods: This retrospective study reviewed files of patients treated for microbial keratitis during a period of 5 years at Alexandria Ophthalmology Hospital Cornea Clinic, Alexandria- Egypt, between February 2017 and June 2022. The patients were evaluated for the risk factors e.g., trauma, eyelid disorders, co-morbidities, and contact lens use. They were also evaluated for their clinical picture, the identified microorganisms, visual outcomes, and complications. Non-microbial keratitis and incomplete files were excluded from the study., Results: A total of 284 patients were diagnosed as microbial keratitis in our study. Viral keratitis was the most common cause of microbial keratitis (n = 118 (41.55%)), followed by bacterial keratitis (n = 77 (27.11%)), mixed keratitis (n = 51 (17.96%)), acanthamoeba keratitis (n = 22 (7.75%)) and the least cause was fungal keratitis (n = 16 (5.63%)). Trauma was the most common risk factor for microbial keratitis (29.2%). Fungal keratitis had a statistically significant association with trauma (p < 0.001), while the use of contact lenses had a statistically significant association with Acanthamoeba keratitis (p < 0.001). The percentage of culture-positive results in our study was 76.8%. Gram-positive bacteria were the most frequently isolated bacterial isolate (n = 25 (36.2%)), while filamentous fungi were the most frequently isolated fungi (n = 13(18.8%)). After treatment, there was a significant increase in the mean visual acuity among all groups; it was significantly higher in Acanthamoeba keratitis group with a mean difference of 0.262 ± 0.161 (p = 0.003)., Conclusion: Viral keratitis followed by bacterial keratitis were the most frequent etiologic agents causing microbial keratitis found in our study. Although trauma was the most frequent risk factor for microbial keratitis, contact lens wear was found an important preventable risk factor for microbial keratitis in young patients. Performing culture properly whenever indicated before starting antimicrobial treatment increased the cultures' positive results., (© 2023. The Author(s).)

Objective: The antiseizure effects of vagus nerve stimulation (VNS) are thought to be mediated by the modulation of afferent thalamocortical circuitry. Cross-frequency phase-amplitude coupling (PAC) is a mechanism of hierarchical network coordination across multiple spatiotemporal scales. In this study, we leverage local field potential (LFP) recordings from the centromedian (CM) (n = 3) and anterior (ATN) (n = 2) nuclei in five patients with tandem thalamic deep brain stimulation and VNS to study neurophysiological changes in the thalamus in response to VNS., Materials and Methods: Bipolar LFP data were recorded from contact pairs spanning target nuclei in VNS "on" and "off" states., Results: Active VNS was associated with increased PAC between theta, alpha, and beta phase and gamma amplitude in CM (q < 0.05). Within the ATN, PAC changes also were observed, although these were less robust. In both nuclei, active VNS also modulated interhemispheric bithalamic functional connectivity., Conclusions: We report that VNS is associated with enhanced PAC and coordinated interhemispheric interactions within and between thalamic nuclei, respectively. These findings advance understanding of putative neurophysiological effects of acute VNS and contextualize previous animal and human studies showing distributed cortical synchronization after VNS., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)