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Deep brain stimulation (DBS) represents an important treatment modality for movement disorders and other circuitopathies. Despite their miniaturization and increasing sophistication, DBS systems share a common set of components of which the implantable pulse generator (IPG) is the core power supply and programmable element. Here we provide an overview of key hardware and software specifications of commercially available IPG systems such as rechargeability, MRI compatibility, electrode configuration, pulse delivery, IPG case architecture, and local field potential sensing. We present evidence-based approaches to mitigate hardware complications, of which infection represents the most important factor. Strategies correlating positively with decreased complications include antibiotic impregnation and co-administration and other surgical considerations during IPG implantation such as the use of tack-up sutures and smaller profile devices.Strategies aimed at maximizing battery longevity include patient-related elements such as reliability of IPG recharging or consistency of nightly device shutoff, and device-specific such as parameter delivery, choice of lead configuration, implantation location, and careful selection of electrode materials to minimize impedance mismatch. Finally, experimental DBS systems such as ultrasound, magnetoelectric nanoparticles, and near-infrared that use extracorporeal powered neuromodulation strategies are described as potential future directions for minimally invasive treatment.

Status dystonicus (SD) is a poorly known neurological emergency requiring urgent interventions, including deep brain stimulation (DBS) targeting the globus pallidus interna (GPi). The sensing capabilities of DBS electrodes provide an opportunity to study the pathophysiology of SD. Here, we study local field potentials (LFPs) from GPi-DBS electrodes implanted in a cohort of 10 children longitudinally during SD, recovery and relapse (recording range 11-1155 days). During SD, we report an increase in the periodic component of the power spectrum within the beta-band along with increases in burst amplitude compared to recordings in non-SD states. Furthermore, relapsed SD is characterized by a return of excessive beta signatures. Beta-specific LFP power is also significantly associated with worse quality-of-life scores (PedsQL, R 2  = 0.695). We identify circadian pallidal beta-band periodicity in one participant with chronic narrowband beta-power recordings over months, with significant increase in power during SD. These rare recordings in children with SD point to excessive pallidal beta-band activity as a biomarker of SD. Our findings further suggest that SD is a distinct state with important implications for understanding dystonia pathophysiology, tracking dystonia states from intracranial activity and potential adaptive DBS treatments. This study identifies status dystonicus as a distinct brain state characterized by excessive beta-band activity with implications for the diagnosis and treatment of this poorly known neurological emergency

Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient’s predominant symptoms.

Working memory (WM) deficits are pervasive co-morbidities of epilepsy. Although the pathophysiological mechanisms underpinning these impairments remain elusive, it is thought that WM depends on oscillatory interactions within and between nodes of large-scale functional networks. These include the hippocampus and default mode network as well as the prefrontal cortex and frontoparietal central executive network. Here, we review the functional roles of neural oscillations in subserving WM and the putative mechanisms by which epilepsy disrupts normative activity, leading to aberrant oscillatory signatures. We highlight the particular role of interictal epileptic activity, including interictal epileptiform discharges and high frequency oscillations (HFOs) in WM deficits. We also discuss the translational opportunities presented by greater understanding of the oscillatory basis of WM function and dysfunction in epilepsy, including potential targets for neuromodulation.

Advances in intracranial electroencephalography (iEEG) and neurophysiology have enabled the study of previously inaccessible brain regions with high fidelity temporal and spatial resolution. Studies of iEEG have revealed a rich neural code subserving healthy brain function and which fails in disease states. Machine learning (ML), a form of artificial intelligence, is a modern tool that may be able to better decode complex neural signals and enhance interpretation of these data. To date, a number of publications have applied ML to iEEG, but clinician awareness of these techniques and their relevance to neurosurgery, has been limited. The present work presents a review of existing applications of ML techniques in iEEG data, discusses the relative merits and limitations of the various approaches, and examines potential avenues for clinical translation in neurosurgery. One-hundred-seven articles examining artificial intelligence applications to iEEG were identified from 3 databases. Clinical applications of ML from these articles were categorized into 4 domains: i) seizure analysis, ii) motor tasks, iii) cognitive assessment, and iv) sleep staging. The review revealed that supervised algorithms were most commonly used across studies and often leveraged publicly available timeseries datasets. We conclude with recommendations for future work and potential clinical applications.

Diffuse intrinsic pontine glioma (DIPG) is a brain cancer with a median survival of only 1 year. Lack of molecular characterization of this tumor impedes the development of novel therapies. Membrane protein B7-H3, aka CD276, involved in interactions with host defenses in certain cancers, has been shown to be over-expressed in the majority of malignant neuroectodermal tumors including adult high-grade glioma. Targeting B7-H3 with a monoclonal antibody has demonstrated safety and efficacy in the salvage treatment of stage IV childhood neuroblastoma, another neuroectodermal tumor. It thus stands to reason that B7-H3 might serve as a therapeutic target in DIPG. B7-H3 immunoreactivity was determined in DIPG and non-diffuse brainstem glioma specimens with immunohistochemistry. In addition, B7-H3 mRNA expression was evaluated with microarrays in another set of specimens. All of the nine (100 %) DIPG specimens were shown to be B7-H3 immunoreactive. In the non-diffuse brainstem glioma group, none of the eight WHO grade I specimens showed B7-H3 immunoreactivity and nine of the 24 WHO grade II specimens (37.5 %) showed B7-H3 immunoreactivity. The association between histological grade and B7-H3 immunoreactivity was statistically highly significant. B7-H3 mRNA expression was also significantly higher in DIPG samples than in normal brain and juvenile pilocytic astrocytoma (WHO grade I) specimens. In summary, B7-H3 is over-expressed in DIPG. Given the need for novel treatment in this disease, antibody-based immunotherapy against B7-H3 in DIPG warrants further investigation.

An estimated two billion people worldwide lack adequate access to surgical care. To address this humanitarian emergency, an increasing number of international surgical partnerships are emerging between developed and low- and middle-income countries (LMICs). At present, there are no clear indicators that may be used to assess the effectiveness of such initiatives. We conducted an international qualitative study of 31 surgeons from developed and LMICs involved in international partnerships across a variety of subspecialties. Thematic analysis and grounded theory were applied in order to develop a practical framework that may be applied to monitor and evaluate global surgical initiatives. Several themes emerged from the study: (i) there is a large unmet need to establish and maintain prospective databases in LMICs to inform the monitoring and evaluation of international surgical partnerships; (ii) assessment of initiatives must occur longitudinally over the span of several years; (ii) the domains of assessment are contextual and encompass cultural, institutional and regional factors; and (iv) evaluation strategies should explore broader impact within the community and country. Based on thematic analysis within the domains of inputs, outputs and outcomes, a framework for the monitoring and evaluation of international surgical initiatives, the Framework for the Assessment of InteRNational Surgical Success (FAIRNeSS) is proposed. In response to the increasing number of surgical partnerships between developed and LMICs, we propose a framework to monitor and evaluate international surgical initiatives.

IntroductionSelf-injurious behaviour (SIB) consists of persistent, repetitive movements that can result in serious injury without suicidal intent. These behaviours are prevalent among children with neurodevelopmental disorders, including profound autism. Although many individuals benefit from currently available therapies, some exhibit treatment-refractory SIB that necessitates ongoing use of personal protective equipment and restraint, presumably due to stronger neurobiological drivers. We recently completed a phase I, open-label clinical trial demonstrating the safety, feasibility and preliminary efficacy of bilateral deep brain stimulation targeting the nucleus accumbens (NAc-DBS) in children with profound autism and severe, refractory SIB. The objective of the proposed study is to characterise the effectiveness of NAc-DBS in treating severe, refractory SIB in this unique and vulnerable population.Methods and analysisA single-centre, randomised double-blinded, crossover trial is proposed. Informed by the results of our pilot study, 25 subjects with autism spectrum disorder and severe, refractory SIB will undergo bilateral NAc-DBS. Following a 4-week recovery period, participants will be randomised to either group A (stimulation ON then OFF) or group B (stimulation OFF then ON). Each block will last 12 weeks, separated by a 2-week washout period. Following completion of the second block, all participants will enter a 6-month open-label phase with stimulation ON. The primary outcome is the difference in the Repetitive Behaviour Scale–Revised total score, between DBS-ON and DBS-OFF conditions. Secondary outcomes include measures of quality of life, caregiver burden, daily logs of SIB events and direct observation of SIB under structured analogues.Ethics and disseminationThe proposed trial has been approved by the institutional Research Ethics Board (1000081171). Trial results will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberNCT06529380

To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery. Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions. We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion. One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes. To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable. Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2-8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1-24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4-7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8-13.5, p = 0.002) were associated with a good postoperative seizure outcome. Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.

A recent national policy decision in the UK to fund selective dorsal rhizotomy (SDR) for cerebral palsy has focused attention on this procedure, which remains underused in Canada. The UK decision was based on a recently published commissioned multicentre prospective open-label trial of SDR that showed the procedure to be associated with significant increases in gross motor function and quality of life for children with moderate cerebral palsy. In Canada, access to SDR for children with this disorder remains variable and limited, with many provinces not performing this procedure and others capping funding or restricting indications. Many Canadian families have traveled south of the border at their own expense and risk to access SDR, which has attracted considerable media attention. Here, Davidson advocates for better and more equitable access to this treatment in Canada.