Transcranial electrical stimulation during functional magnetic resonance imaging in patients with genetic generalized epilepsy: a pilot and feasibility study.

Objective: A third of patients with epilepsy continue to have seizures despite receiving adequate antiseizure medication. Transcranial direct current stimulation (tDCS) might be a viable adjunct treatment option, having been shown to reduce epileptic seizures in patients with focal epilepsy. Evidence for the use of tDCS in genetic generalized epilepsy (GGE) is scarce. We aimed to establish the feasibility of applying tDCS during fMRI in patients with GGE to study the acute neuromodulatory effects of tDCS, particularly on sensorimotor network activity. Methods: Seven healthy controls and three patients with GGE received tDCS with simultaneous fMRI acquisition while watching a movie. Three tDCS conditions were applied: anodal, cathodal and sham. Periods of 60 s without stimulation were applied between each stimulation condition. Changes in sensorimotor cortex connectivity were evaluated by calculating the mean degree centrality across eight nodes of the sensorimotor cortex defined by the Automated Anatomical Labeling atlas (primary motor cortex (precentral left and right), supplementary motor area (left and right), mid-cingulum (left and right), postcentral gyrus (left and right)), across each of the conditions, for each participant. Results: Simultaneous tDCS-fMRI was well tolerated in both healthy controls and patients without adverse effects. Anodal and cathodal stimulation reduced mean degree centrality of the sensorimotor network (Friedman's ANOVA with Dunn's multiple comparisons test; adjusted p = 0.02 and p = 0.03 respectively). Mean degree connectivity of the sensorimotor network during the sham condition was not different to the rest condition (adjusted p = 0.94). Conclusion: Applying tDCS during fMRI was shown to be feasible and safe in a small group of patients with GGE. Anodal and cathodal stimulation caused a significant reduction in network connectivity of the sensorimotor cortex across participants. This initial research supports the feasibility of using fMRI to guide and understand network modulation by tDCS that might facilitate its clinical application in GGE in the future.

Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning - obtained from IQ tests (domains: Full-Scale IQ, Verbal IQ, Performance IQ, Working Memory, and Processing Speed) and tests of academic attainment (Reading, Spelling and Numeracy) - and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery (median age at surgery = 11.9 years, interquartile range = [7.8,15.0]) and neuropsychology assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all p-values ≤ 0.001; e.g., ßFSIQ = -1.9, SEFSIQ = 0.3, pFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27-43% declined by 10 or more points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (Full-Scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all p-values > 0.128). However, children who became seizure-free through surgery showed higher postoperative neuropsychological performance (e.g., rrb-FSIQ = 0.37, p < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g., ßFSIQ = 0.9, SEFSIQ = 0.3, pFSIQ = 0.004). Children who had discontinued antiseizure medication (ASM) treatment at one-year follow-up showed an eight-to-13-point advantage in postoperative Working Memory, Processing Speed, and Numeracy, and greater improvements in Verbal IQ, Working Memory, Reading, and Spelling (all p-values < 0.034) over the postoperative period compared to children who were seizure-free and still receiving ASMs. In conclusion, by providing seizure freedom and the opportunity for ASM cessation, epilepsy surgery may not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible, or potentially prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

Functional brain connectivity in children with focal epilepsy: A systematic review of functional MRI studies.

Epilepsy is increasingly recognised as a brain network disorder and many studies have investigated functional connectivity (FC) in children with epilepsy using functional MRI (fMRI). This systematic review of fMRI studies, published up to November 2023, investigated profiles of FC changes and their clinical relevance in children with focal epilepsy compared to healthy controls. A literature search in PubMed and Web of Science yielded 62 articles. We categorised the results into three groups: 1) differences in correlation-based FC between patients and controls; 2) differences in other FC measures between patients and controls; and 3) associations between FC and disease variables (for example, age of onset), cognitive and seizure outcomes. Studies revealed either increased or decreased FC across multiple brain regions in children with focal epilepsy. However, findings lacked consistency: conflicting FC alterations (decreased and increased FC) co-existed within or between brain regions across all focal epilepsy groups. The studies demonstrated overall that 1) interhemispheric connections often displayed abnormal connectivity and 2) connectivity within and between canonical functional networks was decreased, particularly for the default mode network. Focal epilepsy disrupted FC in children both locally (e.g., seizure-onset zones, or within-brain subnetworks) and globally (e.g., whole-brain network architecture). The wide variety of FC study methodologies limits clinical application of the results. Future research should employ longitudinal designs to understand the evolution of brain networks during the disease course and explore the potential of FC biomarkers for predicting cognitive and postsurgical seizure outcomes.

An embedded intracranial seizure monitor for objective outcome measurements and rhythm identification.

Providing clinicians with objective outcomes of neuromodulation therapy is a key unmet need, especially in emerging areas such as epilepsy and mood disorders. These diseases have episodic behavior and circadian/multidien rhythm characteristics that are difficult to capture in short clinical follow-ups. This work presents preliminary validation evidence for an implantable neuromodulation system with integrated physiological event monitoring, with an initial focus on seizure tracking for epilepsy. The system was developed to address currently unmet requirements for patients undergoing neuromodulation therapy for neurological disorders, specifically the ability to sense physiological data during stimulation and track events with seconds-level granularity. The system incorporates an interactive software tool to enable optimal configuration of the signal processing chain on an embedded implantable device (the Picostim-DyNeuMo Mk-2) including data ingestion from the device loop recorder, event labeling, generation of filter and classification parameters, as well as summary statistics. When the monitor parameters are optimized, the user can wirelessly update the system for chronic event tracking. The simulated performance of the device was assessed using an in silico model with human data to predict the real-time device performance at tracking recorded seizure activity. The in silico performance was then compared against its performance in an in vitro model to capture the full environmental constraints such as sensing during stimulation at the tissue electrode interface. In vitro modeling demonstrated comparable results to the in silico model, providing verification of the software tool and model. This study provides validation evidence of the suitability of the proposed system for tracking longitudinal seizure activity. Given its flexibility, the event monitor can be adapted to track other disorders with episodic and rhythmic symptoms represented by bioelectrical behavior.Clinical relevance-An implantable neuromodulation system is presented that enables chronic tracking of physiological events in disease. This physiological monitor provides the basis for longitudinal assessments of therapy outcomes for patients, such as those with epilepsy where objective identification of patient seizure activity and rhythms might help guide therapy optimization. The system is configurable for other disease states such as Parkinson's disease and mood disorders.

Extent of piriform cortex resection in children with temporal lobe epilepsy.

OBJECTIVE: A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe resection (ATLR) for drug-resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort. METHODS: A retrospective, neuroimaging cohort study of children with TLE who underwent ATLR between 2012 and 2021 was undertaken. The PC, hippocampal and amygdala volumes were measured on the preoperative and postoperative T1-weighted MRI. Using these volumes, the extent of resection per region was compared between the seizure-free and not seizure-free groups. RESULTS: In 50 children (median age 9.5 years) there was no significant difference between the extent of resection of the temporal PC in the seizure-free (median = 50%, n = 33/50) versus not seizure-free (median = 40%, n = 17/50) groups (p = 0.26). In a sub-group of 19 with ipsilateral hippocampal atrophy (quantitatively defined by ipsilateral-to-contralateral asymmetry), the median extent of temporal PC resection was greater in children who were seizure-free (53%) versus those not seizure-free (19%) (p = 0.009). INTERPRETATION: This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom-compatible with an adult series in which 85% of patients had hippocampal sclerosis. In a combined group of children with and without hippocampal atrophy, the extent of PC resection was not associated with seizure outcome, suggesting different epileptogenic networks within this cohort.

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes, patient characteristics, genetic testing, and postsurgical outcomes.

OBJECTIVE: Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. METHODS: We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. RESULTS: A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. SIGNIFICANCE: Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful.

Predicting seizure outcome after epilepsy surgery: Do we need more complex models, larger samples, or better data?

OBJECTIVE: The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using data-driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome. METHODS: We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models-a logistic regression, a multilayer perceptron, and an XGBoost model-to predict 1-year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance. RESULTS: Our logistic regression achieved an accuracy of 72% (95% confidence interval [CI] = 68%-75%, area under the curve [AUC] = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP = 67%-74%, AUCMLP = .70; 95% CIXGBoost own = 68%-75%, AUCXGBoost own = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%-67%, AUC = .62; pLR = .005, pMLP = .01, pXGBoost own = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data-driven feature selection. SIGNIFICANCE: We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.

Endoscopic third ventriculostomy for the management of children with cerebrospinal fluid disorders, ventriculomegaly, and associated Chiari I malformation.

OBJECTIVES: Our objective was to review the outcomes of children with CIM and associated cerebrospinal fluid (CSF) disorders and ventriculomegaly undergoing endoscopic third ventriculostomy (ETV) as a primary intervention. MATERIALS AND METHODS: A retrospective, single-center, observational cohort study was conducted of consecutive children with CIM with associated CSF disorders and ventriculomegaly treated first by ETV between January 2014 and December 2020. RESULTS: Raised intracranial pressure symptoms were the most frequent in ten patients, followed by posterior fossa and syrinx symptoms in three cases. One patient had a later stoma closure and required a shunt insertion. The success rate of the ETV in the cohort was 92% (11/12). There was no surgical mortality in our series. No other complications were reported. The median herniation of the tonsils was not statistically different in the pre vs. post-operative MRI (1.14 vs. 0.94, p=0.1). However, the median Evan's index (0.4 vs. 0.36, p<0.01) and the median diameter of the third ventricle (1.35 vs. 0.76, p<0.01) were statistically different between the two measurements. The preoperative length of the syrinx did not change significantly compared with the postoperative (5 vs. 1; p=0.052); nevertheless, the median transverse diameter of the syrinx did improve significantly after the surgery (0.75 vs. 0.32, p=0.03). CONCLUSIONS: Our study supports ETV's safety and effectiveness for managing children with CSF disorders, ventriculomegaly, and associated CIM.

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic.

BACKGROUND: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. METHODS: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients' location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. RESULTS: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37-5.74) compared to HIC. CONCLUSIONS: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors.

Towards network-guided neuromodulation for epilepsy.

Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.

Delivering Large-Scale Neurosurgical Studies in the UK: The Impact of Trainees.

The UK neurosurgical community has a track record of delivering high-quality, practice-changing clinical research studies, facilitated by a robust clinical research infrastructure and close collaborations between neurosurgical centers. More recently, these large-scale studies have been conceived, developed, and delivered by neurosurgical trainees, working under the umbrella of the British Neurosurgical Trainee Research Collaborative (BNTRC). In this paper, we outline the current landscape of large-scale neurosurgical studies in the UK, focusing on the role of trainees in facilitating this research. Importantly, we focus on our experience of trainee-led studies, including the development of the network, current challenges, and future directions. We believe that a similar model can be applied in different settings and countries, which will drive up the quality of neurosurgical research, ultimately benefiting future neurosurgical patients.

External validation and recalibration of an incidental meningioma prognostic model - IMPACT: protocol for an international multicentre retrospective cohort study.

INTRODUCTION: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model. METHODS AND ANALYSIS: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods. ETHICS AND DISSEMINATION: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media.

Intracranial neuromodulation with deep brain stimulation and responsive neurostimulation in children with drug-resistant epilepsy: a systematic review.

OBJECTIVE: In children with drug-resistant epilepsy (DRE), resective, ablative, and disconnective surgery may not be feasible or may fail. Neuromodulation in the form of deep brain stimulation (DBS) and responsive neurostimulation (RNS) may be viable treatment options, however evidence for their efficacies in children is currently limited. This systematic review aimed to summarize the literature on DBS and RNS for the treatment of DRE in the pediatric population. Specifically, the authors focused on currently available data for reported indications, neuromodulation targets, clinical efficacy, and safety outcomes. METHODS: PRISMA guidelines were followed throughout this systematic review (PROSPERO no. CRD42020180669). Electronic databases, including PubMed, Embase, Cochrane Library, OpenGrey, and CINAHL Plus, were searched from their inception to February 19, 2021. Inclusion criteria were 1) studies with at least 1 pediatric patient (age < 19 years) who underwent DBS and/or RNS for DRE; and 2) retrospective, prospective, randomized, or nonrandomized controlled studies, case series, and case reports. Exclusion criteria were 1) letters, commentaries, conference abstracts, and reviews; and 2) studies without full text available. Risk of bias of the included studies was assessed using the Cochrane ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool. RESULTS: A total of 35 studies were selected that identified 72 and 46 patients who underwent DBS and RNS, respectively (age range 4-18 years). Various epilepsy etiologies and seizure types were described in both cohorts. Overall, 75% of patients had seizure reduction > 50% after DBS (among whom 6 were seizure free) at a median (range) follow-up of 14 (1-100) months. In an exploratory univariate analysis of factors associated with favorable response, the follow-up duration was shorter in those patients with a favorable response (18 vs 33 months, p < 0.05). In the RNS cohort, 73.2% of patients had seizure reduction > 50% after RNS at a median (range) follow-up of 22 (5-39) months. On closer inspection, 83.3% of patients who had > 50% reduction in seizures actually had > 75% reduction, with 4 patients being seizure free. CONCLUSIONS: Overall, both DBS and RNS showed favorable response rates, indicating that both techniques should be considered for pediatric patients with DRE. However, serious risks of overall bias were found in all included studies. Many research needs in this area would be addressed by conducting high-quality clinical trials and establishing an international registry of patients who have undergone pediatric neuromodulation, thereby ensuring robust prospective collection of predictive variables and outcomes.

Neurosurgery activity levels in the United Kingdom and republic of Ireland during the first wave of the covid-19 pandemic - a retrospective cross-sectional cohort study.

The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April-June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 (n = 304) and 2019 (n = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.

Functional Connectivity of the Anterior Nucleus of the Thalamus in Pediatric Focal Epilepsy.

Objective: Whilst stimulation of the anterior nucleus of the thalamus has shown efficacy for reducing seizure frequency in adults, alterations in thalamic connectivity have not been explored in children. We tested the hypotheses that (a) the anterior thalamus has increased functional connectivity in children with focal epilepsy, and (b) this alteration in the connectome is a persistent effect of the disease rather than due to transient epileptiform activity. Methods: Data from 35 children (7-18 years) with focal, drug-resistant epilepsy and 20 healthy children (7-17 years) were analyzed. All subjects underwent functional magnetic resonance imaging (fMRI) whilst resting and were simultaneously monitored with scalp electroencephalography (EEG). The fMRI timeseries were extracted for each Automated Anatomical Labeling brain region and thalamic subregion. Graph theory metrics [degree (DC) and eigenvector (EC) centrality] were used to summarize the connectivity profile of the ipsilateral thalamus, and its thalamic parcellations. The effect of interictal epileptiform discharges (IEDs) captured on EEG was used to determine their effect on DC and EC. Results: DC was significantly higher in the anterior nucleus (p = 0.04) of the thalamus ipsilateral to the epileptogenic zone in children with epilepsy compared to controls. On exploratory analyses, we similarly found a higher DC in the lateral dorsal nucleus (p = 0.02), but not any other thalamic subregion. No differences in EC measures were found between patients and controls. We did not find any significant difference in DC or EC in any thalamic subregion when comparing the results of children with epilepsy before, and after the removal of the effects of IEDs. Conclusions: Our data suggest that the anterior and lateral dorsal nuclei of the thalamus are more highly functionally connected in children with poorly controlled focal epilepsy. We did not detect a convincing change in thalamic connectivity caused by transient epileptiform activity, suggesting that it represents a persistent alteration to network dynamics.

First Report of a Multicenter Prospective Registry of Cranioplasty in the United Kingdom and Ireland.

BACKGROUND: There are many questions that remain unanswered regarding outcomes following cranioplasty including the timing of cranioplasty following craniectomy as well as the material used. OBJECTIVE: To establish and evaluate 30-d outcomes for all cranial reconstruction procedures in the United Kingdom (UK) and Ireland through a prospective multicenter cohort study. METHODS: Patients undergoing cranioplasty insertion or revision between June 1, 2019 and November 30, 2019 in 25 neurosurgical units were included. Data collected include demographics, craniectomy date and indication, cranioplasty material and date, and 30-d outcome. RESULTS: In total, 313 operations were included, consisting of 255 new cranioplasty insertions and 58 revisions. Of the new insertions, the most common indications for craniectomy were traumatic brain injury (n = 110, 43%), cerebral infarct (n = 38, 15%), and aneurysmal subarachnoid hemorrhage (n = 30, 12%). The most common material was titanium (n = 163, 64%). Median time to cranioplasty was 244 d (interquartile range 144-385), with 37 new insertions (15%) within or equal to 90 d. In 30-d follow-up, there were no mortalities. There were 14 readmissions, with 10 patients sustaining a wound infection within 30 d (4%). Of the 58 revisions, the most common reason was due to infection (n = 33, 59%) and skin breakdown (n = 13, 23%). In 41 (71%) cases, the plate was removed during the revision surgery. CONCLUSION: This study is the largest prospective study of cranioplasty representing the first results from the UK Cranial Reconstruction Registry, a first national registry focused on cranioplasty with the potential to address outstanding research questions for this procedure.

CovidNeuroOnc: A UK multicenter, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service.

BACKGROUND: The COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors. METHODS: We performed a multicenter prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. All patients had at least 30-day follow-up data. Descriptive statistical reporting was used. RESULTS: There were 1357 referrals for newly diagnosed or recurrent intracranial tumors across 15 neuro-oncology centers. Of centers with all intracranial tumors, a change in initial management was reported in 8.6% of cases (n = 104/1210). Decisions to change the management plan reduced over time from a peak of 19% referrals at the start of the study to 0% by the end of the study period. Changes in management were reported in 16% (n = 75/466) of cases previously recommended for surgery and 28% of cases previously recommended for chemotherapy (n = 20/72). The reported SARS-CoV-2 infection rate was similar in surgical and non-surgical patients (2.6% vs. 2.4%, P > .9). CONCLUSIONS: Disruption to neuro-oncology services in the UK caused by the COVID-19 pandemic was most marked in the first month, affecting all diagnoses. Patients considered for chemotherapy were most affected. In those recommended surgical treatment this was successfully completed. Longer-term outcome data will evaluate oncological treatments received by these patients and overall survival.

UK Chiari 1 Study: protocol for a prospective, observational, multicentre study.

INTRODUCTION: Chiari 1 malformation (CM1) is a structural abnormality of the hindbrain characterised by the descent of the cerebellar tonsils through the foramen magnum. The management of patients with CM1 remains contentious since there are currently no UK or international guidelines for clinicians. We therefore propose a collaborative, prospective, multicentre study on the investigation, management and outcome of CM1 in the UK: the UK Chiari 1 Study (UKC1S). Our primary objective is to determine the health-related quality of life (HRQoL) in patients with a new diagnosis of CM1 managed either conservatively or surgically at 12 months of follow-up. We also aim to: (A) determine HRQoL 12 months following surgery; (B) measure complications 12 months following surgery; (C) determine the natural history of patients with CM1 treated conservatively without surgery; (D) determine the radiological correlates of presenting symptoms, signs and outcomes; and (E) determine the scope and variation within UK practice in referral patterns, patient pathways, investigations and surgical decisions. METHODS AND ANALYSIS: The UKC1S will be a prospective, multicentre and observational study that will follow the British Neurosurgical Trainee Research Collaborative model of collaborative research. Patients will be recruited after attending their first neurosurgical outpatient clinic appointment. Follow-up data will be collected from all patients at 12 months from baseline regardless of whether they are treated surgically or not. A further 12-month postoperative follow-up timepoint will be added for patients treated with decompressive surgery. The study is expected to last three years. ETHICS AND DISSEMINATION: The UKC1S received a favourable ethical opinion from the East Midlands Leicester South Research Ethics Committee (REC reference: 20/EM/0053; IRAS 269739) and the Health Research Authority. The results of the study will be published in peer-reviewed medical journals, presented at scientific conferences, shared with collaborating sites and shared with participant patients if they so wish.

CSF rhinorrhoea after endonasal intervention to the anterior skull base (CRANIAL): proposal for a prospective multicentre observational cohort study.

BACKGROUND: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. METHODS: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. ETHICS AND DISSEMINATION: Formal institutional ethical board review was not required owing to the nature of the study - this was confirmed with the Health Research Authority, UK. CONCLUSIONS: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.