Successful magnetic resonance-guided focused ultrasound treatment of tremor in patients with a skull density ratio of 0.4 or less.

OBJECTIVE: The use of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor-related disorders and other novel indications has been limited by guidelines advocating treatment of patients with a skull density ratio (SDR) above 0.45 ± 0.05 despite reports of successful outcomes in patients with a low SDR (LSDR). The authors' goal was to retrospectively analyze the sonication strategies, adverse effects, and clinical and imaging outcomes in patients with SDR ≤ 0.4 treated for tremor using MRgFUS. METHODS: Clinical outcomes and adverse effects were assessed at 3 and 12 months after MRgFUS. Outcomes and lesion location, volume, and shape characteristics (elongation and eccentricity) were compared between the SDR groups. RESULTS: A total of 102 consecutive patients were included in the analysis, of whom 39 had SDRs ≤ 0.4. No patient was excluded from treatment because of an LSDR, with the lowest being 0.22. Lesioning temperatures (> 52°C) and therapeutic ablations were achieved in all patients. There were no significant differences in clinical outcome, adverse effects, lesion location, and volume between the high SDR group and the LSDR group. SDR was significantly associated with total energy (rho = -0.459, p < 0.001), heating efficiency (rho = 0.605, p < 0.001), and peak temperature (rho = 0.222, p = 0.025). CONCLUSIONS: The authors' results show that treatment of tremor in patients with an LSDR using MRgFUS is technically possible, leading to a safe and lasting therapeutic effect. Limiting the number of sonications and adjusting the energy and duration to achieve the required temperature early during the treatment are suitable strategies in LSDR patients.

Accelerated Transcranial Ultrasound Neuromodulation in Parkinson's Disease: A Pilot Study.

OBJECTIVE: Low-intensity transcranial focused ultrasound (TUS) is a novel method for neuromodulation. We aimed to study the feasibility of stimulating the bilateral primary motor cortices (M1) with accelerated theta-burst TUS (a-tbTUS) on neurophysiologic and clinical outcomes in Parkinson's disease (PD). METHODS: Patients were randomly assigned to receive active or sham a-tbTUS for the first visit and the alternate condition on the second visit, at least 10 days apart. a-tbTUS was administered in three consecutive sonications at 30-minute intervals. We used an accelerated protocol to produce an additive effect of stimulation. Patients were studied in the OFF-medication state. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) were used to assess motor cortical excitability before and after TUS. Clinical outcomes after a-tbTUS administration were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III. RESULTS: A total of 20 visits were conducted in 10 PD patients. Compared to the baseline, TMS-elicited MEP amplitudes significantly increased following active but not sham sonication (P = 0.0057). MEP amplitudes were also higher following a-tbTUS than sham sonication (P = 0.0064). There were no statistically significant changes in MDS-UPDRS-III scores with active or sham a-tbTUS. CONCLUSIONS: a-tbTUS increases motor cortex excitability and is a feasible non-invasive neuromodulation strategy in PD. Future studies should determine optimal dosing parameters and the durability of neurophysiologic and clinical outcomes in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Trends and disparities in deep brain stimulation utilization in the United States: a Nationwide Inpatient Sample analysis from 1993 to 2017.

Background: Deep brain stimulation (DBS) is an approved treatment option for Parkinson's Disease (PD), essential tremor (ET), dystonia, obsessive-compulsive disorder and epilepsy in the United States. There are disparities in access to DBS, and clear understanding of the contextual factors driving them is important. Previous studies aimed at understanding these factors have been limited by single indications or small cohort sizes. The aim of this study is to provide an updated and comprehensive analysis of DBS utilization for multiple indications to better understand the factors driving disparities in access. Methods: The United States based National Inpatient Sample (NIS) database was utilized to analyze the surgical volume and trends of procedures based on indication, using relevant ICD codes. Predictors of DBS use were analyzed using a logistic regression model. DBS-implanted patients in each indication were compared based on the patient-, hospital-, and outcome-related variables. Findings: Our analysis of 104,356 DBS discharges from 1993 to 2017 revealed that the most frequent indications for DBS were PD (67%), ET (24%), and dystonia (4%). Although the number of DBS procedures has consistently increased over the years, radiofrequency ablation utilization has significantly decreased to only a few patients per year since 2003. Negative predictors for DBS utilization in PD and ET cohorts included age increase and female sex, while African American status was a negative predictor across all cohorts. Significant differences in patient-, hospital-, and outcome-related variables between DBS indications were also determined. Interpretation: Demographic and socioeconomic-based disparities in DBS use are evident. Although racial disparities are present across all indications, other disparities such as age, sex, wealth, and insurance status are only relevant in certain indications. Funding: This work was supported by Alan & Susan Hudson Cornerstone Chair in Neurosurgery at University Health Network.

Investigation of neurophysiologic and functional connectivity changes following glioma resection using magnetoencephalography.

Background: In patients with glioma, clinical manifestations of neural network disruption include behavioral changes, cognitive decline, and seizures. However, the extent of network recovery following surgery remains unclear. The aim of this study was to characterize the neurophysiologic and functional connectivity changes following glioma surgery using magnetoencephalography (MEG). Methods: Ten patients with newly diagnosed intra-axial brain tumors undergoing surgical resection were enrolled in the study and completed at least two MEG recordings (pre-operative and immediate post-operative). An additional post-operative recording 6-8 weeks following surgery was obtained for six patients. Resting-state MEG recordings from 28 healthy controls were used for network-based comparisons. MEG data processing involved artifact suppression, high-pass filtering, and source localization. Functional connectivity between parcellated brain regions was estimated using coherence values from 116 virtual channels. Statistical analysis involved standard parametric tests. Results: Distinct alterations in spectral power following tumor resection were observed, with at least three frequency bands affected across all study subjects. Tumor location-related changes were observed in specific frequency bands unique to each patient. Recovery of regional functional connectivity occurred following glioma resection, as determined by local coherence normalization. Changes in inter-regional functional connectivity were mapped across the brain, with comparable changes in low to mid gamma-associated functional connectivity noted in four patients. Conclusion: Our findings provide a framework for future studies to examine other network changes in glioma patients. We demonstrate an intrinsic capacity for neural network regeneration in the post-operative setting. Further work should be aimed at correlating neurophysiologic changes with individual patients' clinical outcomes.

Spinal Cord Stimulation for Parkinson's Disease: A Systematic Review and Meta-Analysis of Pain and Motor Outcomes.

BACKGROUND: Spinal cord stimulation (SCS) has been investigated as a potential therapeutic option for managing refractory symptoms in patients with Parkinson's disease (PD). OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of SCS in PD. METHOD: A comprehensive literature search was conducted on PubMed and Web of Science to identify SCS studies reporting Unified Parkinson Disease Rating Scale-III (UPDRS-III) or Visual Analogue Scale (VAS) score changes in PD cohorts with at least 3 patients and a follow-up period of at least 1 month. Treatment effect was measured as the mean change in outcome scores and analyzed using an inverse variance random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale and funnel plots. RESULTS: A total of 11 studies comprising 76 patients were included. Nine studies involving 72 patients reported an estimated decrease of 4.43 points (95% confidence interval [CI]: 2.11; 6.75, p < 0.01) in UPDRS-III score, equivalent to a 14% reduction. The axial subscores in 48 patients decreased by 2.35 points (95% CI: 1.26; 3.45, p < 0.01, 20% reduction). The pooled effect size of five studies on back and leg pain VAS scores was calculated as 4.38 (95% CI: 2.67; 6.09, p < 0.001), equivalent to a 59% reduction. CONCLUSIONS: Our analysis suggests that SCS may provide significant motor and pain benefits for patients with PD, although the results should be interpreted with caution due to several potential limitations including study heterogeneity, open-label designs, small sample sizes, and the possibility of publication bias. Further research using larger sample sizes and placebo-/sham-controlled designs is needed to confirm effectiveness.

Current landscape of social media use pertaining to glioblastoma by various stakeholders.

Background: Given the potential for social media to allow widespread public engagement, its role in healthcare, including in cancer care as a support network, is garnering interest. To date, the use of social media in neuro-oncology has not been systematically explored. In the current manuscript, we sought to review Twitter use on glioblastoma among patients, caregivers, providers, researchers, and other stakeholders. Methods: The Twitter application programming interface (API) database was surveyed from inception to May 2022 to identify tweets about glioblastoma. Number of tweet likes, retweets, quotes, and total engagement were noted for each tweet. Geographic location, number of followers, and number of Tweets were noted for users. We also categorized Tweets based on their underlying themes. A natural language processing (NLP) algorithm was used to assign a polarity score, subjectivity score, and analysis label to each Tweet for sentiment analysis. Results: A total of 1690 unique tweets from 1000 accounts were included in our analyses. The frequency of tweets increased from 2013 and peaked in 2018. The most common category among users was MD/researchers (21.6%, n = 216), followed by Media/News (20%, n = 200) and Business (10.7%); patients or caregivers accounted for only 4.7% (n = 47) while medical centers, journals, and foundations accounted for 5.4%, 3.7%, and 2.1%. The most common subjects that Tweets covered included research (54%), followed by personal experience (18.2%) and raising awareness (14%). In terms of sentiment, 43.6% of Tweets were classified as positive, 41.6% as neutral, and 14.9% as negative; a subset analysis of "personal experience" tweets revealed a higher proportion of negative Tweets (31.5%) and less neutral tweets (25%). Only media (ß = 8.4; 95% CI [4.4, 12.4]) and follower count (minimally) predicted higher levels of Tweet engagement. Conclusion: This comprehensive analysis of tweets on glioblastoma found that the academic community are the most common user group on Twitter. Sentiment analysis revealed that most negative tweets are related to personal experience. These analyses provide the basis for further work into supporting and developing the care of patients with glioblastoma.

Parenting and Childbearing in Neurosurgical Residency: Perspectives from the United States and Canada.

BACKGROUND: Despite growing interest in family planning alongside surgical training, significant barriers exist including time constraints, stigma, and lack of paid leave and formal policies. We currently lack a deep understanding of the challenges residents face and how practice cultures may prohibit successful policy enactment. OBJECTIVE: To investigate residents' perspectives surrounding parenting and childbearing during neurosurgical residency in the United States and Canada. METHODS: A cross-sectional, qualitative study methodology was used, including focus groups with neurosurgical residents. Purposive sampling was employed to capture a broad range of perspectives including stage of training, geographical location, and gender. Data collection and analysis occurred in parallel, using a thematic analysis approach. Data collection continued until no new themes relating to the research questions were identified. RESULTS: Notable challenges included lack of formal family leave policies, time constraints, insufficient clinical human resources, physical health concerns, lack of lactation accommodations, and lack of mentorship. A subset of barriers were uncovered that stem specifically from workplace cultures, including gender norms, difficulty in asking for help, concerns for inconveniencing others, and pressures to time parental leave during research blocks. Several positive changes were identified including growing awareness and female representation, and benefits of the dual surgeon-parent identity. CONCLUSION: While parenting during neurosurgery residency is becoming increasingly common, significant practical and cultural barriers persist including a marked absence of formal policies. Culture shifts are essential in ensuring opportunities for life outside of medicine for all residents, irrespective of family status.

Technical and clinical considerations for electroencephalography-based biomarkers for major depressive disorder.

Major depressive disorder (MDD) is a prevalent and debilitating psychiatric disease that leads to substantial loss of quality of life. There has been little progress in developing new MDD therapeutics due to a poor understanding of disease heterogeneity and individuals' responses to treatments. Electroencephalography (EEG) is poised to improve this, owing to the ease of large-scale data collection and the advancement of computational methods to address artifacts. This review summarizes the viability of EEG for developing brain-based biomarkers in MDD. We examine the properties of well-established EEG preprocessing pipelines and consider factors leading to the discovery of sensitive and reliable biomarkers.

Magnetic resonance-guided focused ultrasound for the treatment of tremor.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging treatment for tremor and other movement disorders. An incisionless therapy, it is becoming increasingly common worldwide. However, given MRgFUS' relative novelty, there remain limited data on its benefits and adverse effects. AREAS COVERED: We review the current state of evidence of MRgFUS for tremor, highlight its challenges, and discuss future perspectives. EXPERT OPINION: Essential tremor (ET) has been the major indication for MRgFUS since a milestone randomized controlled trial (RCT) in 2016, with substantial evidence attesting to the efficacy and acceptable safety profile of this treatment. Patients with other tremor etiologies are also being treated with MRgFUS, with studies - including an RCT - suggesting parkinsonian tremor in particular responds well to this intervention. Additionally, targets other than the ventral intermediate nucleus, such as the subthalamic nucleus and internal segment of the globus pallidus, have been reported to improve parkinsonian symptoms beyond tremor, including rigidity and bradykinesia. Although MRgFUS is encumbered by certain unique technical challenges, it nevertheless offers significant advantages compared to alternative neurosurgical interventions for tremor. The fast-growing interest in this treatment modality will likely lead to further scientific and technological advancements that could optimize and expand its therapeutic potential.

Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex.

INTRODUCTION: There is currently a gap in accessibility to neuromodulation tools that can approximate the efficacy and spatial resolution of invasive methods. Low intensity transcranial focused ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation (NIBS) that can penetrate cortical and deep brain structures with more focal stimulation compared to existing NIBS modalities. Theta burst TUS (tbTUS, TUS delivered in a theta burst pattern) is a novel repetitive TUS protocol that can induce durable changes in motor cortex excitability, thereby holding promise as a novel neuromodulation tool with durable effects. OBJECTIVE: The aim of the present study was to elucidate the neurophysiologic effects of tbTUS motor cortical excitability, as well on local and global neural oscillations and network connectivity. METHODS: An 80-s train of active or sham tbTUS was delivered to the left motor cortex in 15 healthy subjects. Motor cortical excitability was investigated through transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) using paired-pulse TMS. Magnetoencephalography (MEG) recordings during resting state and an index finger abduction-adduction task were used to assess oscillatory brain responses and network connectivity. The correlations between the changes in neural oscillations and motor cortical excitability were also evaluated. RESULTS: tbTUS to the motor cortex results in a sustained increase in MEP amplitude and decreased SICI, but no change in ICF. MEG spectral power analysis revealed TUS-mediated desynchronization in alpha and beta spectral power. Significant changes in alpha power were detected within the supplementary motor cortex (Right > Left) and changes in beta power within bilateral supplementary motor cortices, right basal ganglia and parietal regions. Coherence analysis revealed increased local connectivity in motor areas. MEP and SICI changes correlated with both local and inter-regional coherence. CONCLUSION: The findings from this study provide novel insights into the neurophysiologic basis of TUS-mediated neuroplasticity and point to the involvement of regions within the motor network in mediating this sustained response. Future studies may further characterize the durability of TUS-mediated neuroplasticity and its clinical applications as a neuromodulation strategy for neurological and psychiatric disorders.

Identifying the neural network for neuromodulation in epilepsy through connectomics and graphs.

Deep brain stimulation is a treatment option for patients with drug-resistant epilepsy. The precise mechanism of neuromodulation in epilepsy is unknown, and biomarkers are needed for optimizing treatment. The aim of this study was to describe the neural network associated with deep brain stimulation targets for epilepsy and to explore its potential application as a novel biomarker for neuromodulation. Using seed-to-voxel functional connectivity maps, weighted by seizure outcomes, brain areas associated with stimulation were identified in normative resting state functional scans of 1000 individuals. To pinpoint specific regions in the normative epilepsy deep brain stimulation network, we examined overlapping areas of functional connectivity between the anterior thalamic nucleus, centromedian thalamic nucleus, hippocampus and less studied epilepsy deep brain stimulation targets. Graph network analysis was used to describe the relationship between regions in the identified network. Furthermore, we examined the associations of the epilepsy deep brain stimulation network with disease pathophysiology, canonical resting state networks and findings from a systematic review of resting state functional MRI studies in epilepsy deep brain stimulation patients. Cortical nodes identified in the normative epilepsy deep brain stimulation network were in the anterior and posterior cingulate, medial frontal and sensorimotor cortices, frontal operculum and bilateral insulae. Subcortical nodes of the network were in the basal ganglia, mesencephalon, basal forebrain and cerebellum. Anterior thalamic nucleus was identified as a central hub in the network with the highest betweenness and closeness values, while centromedian thalamic nucleus and hippocampus showed average centrality values. The caudate nucleus and mammillothalamic tract also displayed high centrality values. The anterior cingulate cortex was identified as an important cortical hub associated with the effect of deep brain stimulation in epilepsy. The neural network of deep brain stimulation targets shared hubs with known epileptic networks and brain regions involved in seizure propagation and generalization. Two cortical clusters identified in the epilepsy deep brain stimulation network included regions corresponding to resting state networks, mainly the default mode and salience networks. Our results were concordant with findings from a systematic review of resting state functional MRI studies in patients with deep brain stimulation for epilepsy. Our findings suggest that the various epilepsy deep brain stimulation targets share a common cortico-subcortical network, which might in part underpin the antiseizure effects of stimulation. Interindividual differences in this network functional connectivity could potentially be used as biomarkers in selection of patients, stimulation parameters and neuromodulation targets.

Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is gaining traction as a safe and non-invasive technique in human studies. There has been a rapid increase in TUS human studies in recent years, with more than half of studies to date published after 2020. This rapid growth in the relevant body of literature necessitates comprehensive reviews to update clinicians and researchers. OBJECTIVE: The aim of this work is to review human studies with an emphasis on TUS devices, sonication parameters, outcome measures, results, and adverse effects, as well as highlight future directions of investigation. METHODS: A systematic review was conducted by searching the Web of Science and PubMed databases on January 12, 2022. Human studies of TUS were included. RESULTS: A total of 35 studies were identified using focused/unfocused ultrasound devices. A total of 677 subjects belonging to diverse cohorts (i.e., healthy, chronic pain, dementia, epilepsy, traumatic brain injury, depression) were enrolled. The stimulation effects vary in a sonication parameter-dependant fashion. Clinical, neurophysiological, radiological and histological outcome measures were assessed. No severe adverse effects were reported in any of the studies surveyed. Mild symptoms were observed in 3.4% (14/425) of the subjects, including headache, mood deterioration, scalp heating, cognitive problems, neck pain, muscle twitches, anxiety, sleepiness and pruritis. CONCLUSIONS: Although increasingly being used, TUS is still in its early phases. TUS can change short-term brain excitability and connectivity, induce long-term plasticity, and modulate behavior. New techniques should be used to further elucidate its underlying mechanisms and identify its application in novel populations.

Anxiety and depression in patients with intracranial meningioma: a mixed methods analysis.

BACKGROUND: While diagnosis with a high-grade intracranial tumor is known to be associated with increased psychosocial burden, the burdens associated with meningioma are less well described. This study aimed to investigate the mental health burden in patients with meningiomas who have undergone surgical resection or serial observation, so as to identify and enhance awareness of gaps in care. METHODS: The Hospital Anxiety and Depression Scale (HADS) was administered to participants. Fisher's Exact tests were performed to evaluate frequency distributions and t-tests were applied to compare postoperative and non-surgical patients' HADS scores. Semi-structured interviews were completed on a subset of participants. Thematic analysis of interviews identified emerging themes. RESULTS: Thirty patients with intracranial meningiomas met inclusion criteria. The cohort's mean age was 56.01 years and 66.67% were women (n = 20). Fourteen underwent surgery; sixteen were treated conservatively with observation. The average time since diagnosis of the sample was 37.6 months. Prevalence of mild to severe symptoms of anxiety was 28.6% amongst surgical management patients and 50% for active surveillance patients (p = 0.325). The prevalence of mild to severe symptoms of depression was 7.14% amongst surgical management patients and 6.25% for active surveillance patients (p = 0.533). Emerging themes from eight interviews reveal the influence of resilience, uncertainty and time, social support, interactions with medical experts, and difficulties during recovery on mental health. CONCLUSION: The findings from the present study reveal that patients with meningiomas experience a significant mental health burden, illustrating the need for enhanced patient-centred care focusing on mental health.

Clinical outcomes and complications of peripheral nerve field stimulation in the management of refractory trigeminal pain: a systematic review and meta-analysis.

OBJECTIVE: Peripheral nerve field stimulation (PNFS) is a tool in the armamentarium of treatment options for trigeminal pain. The efficacy of this modality in mitigating trigeminal pain remains unclear. The aim of this study was to examine the existing literature on PNFS and elucidate pain score outcomes associated with its use in patients with trigeminal pain. METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA framework. The PubMed, Web of Science, and Scopus databases were queried on June 10, 2020. Studies reporting pain outcomes in more than 5 adult patients treated with PNFS for facial pain were included. The primary outcome of the study was the mean difference in the visual analog scale (VAS) score from the last follow-up to baseline, and it was analyzed by an inverse-variance, random-effect model. The risk of bias was assessed using the Newcastle-Ottawa Scale and a funnel plot. RESULTS: Of the 4597 studies screened for inclusion, 46 relevant full-text articles were assessed for eligibility. Eleven observational cohort studies from the 46 articles were found to be eligible, and reported on a total of 109 patients. In 86% (94/109) of cases, trial stimulation was successful and followed by a permanent system implantation. VAS scores improved by 75% (mean difference 6.32/10 points, 95% CI 5.38-7.27 points) compared to baseline. Seventy-six percent (42/55) of patients became medication free or required lower doses of medications. The complication rate necessitating surgical revision was estimated at 32% per procedure. CONCLUSIONS: These findings support the belief that PNFS provides effective, long-term pain control for trigeminal pain. Statistical heterogeneity was considerable across all studies. Future work should be aimed at conducting double-blind randomized controlled trials to determine the utility of PNFS for treating various forms of trigeminal pain for which limited therapeutic options exist.

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease.

BACKGROUND: Leukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown. CASE PRESENTATION: We present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter. CONCLUSIONS: These findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.

Deep brain stimulation targets in epilepsy: Systematic review and meta-analysis of anterior and centromedian thalamic nuclei and hippocampus.

Deep brain stimulation (DBS) is a neuromodulatory treatment used in patients with drug-resistant epilepsy (DRE). The primary goal of this systematic review and meta-analysis is to describe recent advancements in the field of DBS for epilepsy, to compare the results of published trials, and to clarify the clinical utility of DBS in DRE. A systematic literature search was performed by two independent authors. Forty-four articles were included in the meta-analysis (23 for anterior thalamic nucleus [ANT], 8 for centromedian thalamic nucleus [CMT], and 13 for hippocampus) with a total of 527 patients. The mean seizure reduction after stimulation of the ANT, CMT, and hippocampus in our meta-analysis was 60.8%, 73.4%, and 67.8%, respectively. DBS is an effective and safe therapy in patients with DRE. Based on the results of randomized controlled trials and larger clinical series, the best evidence exists for DBS of the anterior thalamic nucleus. Further randomized trials are required to clarify the role of CMT and hippocampal stimulation. Our analysis suggests more efficient deep brain stimulation of ANT for focal seizures, wider use of CMT for generalized seizures, and hippocampal DBS for temporal lobe seizures. Factors associated with clinical outcome after DBS for epilepsy are electrode location, stimulation parameters, type of epilepsy, and longer time of stimulation. Recent advancements in anatomical targeting, functional neuroimaging, responsive neurostimulation, and sensing of local field potentials could potentially lead to improved outcomes after DBS for epilepsy and reduced sudden, unexpected death of patients with epilepsy. Biomarkers are needed for successful patient selection, targeting of electrodes and optimization of stimulation parameters.

The biology of ependymomas and emerging novel therapies.

Ependymomas are rare central nervous system tumours that can arise in the brain's supratentorial region or posterior fossa, or in the spinal cord. In 1924, Percival Bailey published the first comprehensive study of ependymomas. Since then, and especially over the past 10 years, our understanding of ependymomas has grown exponentially. In this Review, we discuss the evolution in knowledge regarding ependymoma subgroups and the resultant clinical implications. We also discuss key oncogenic and tumour suppressor signalling pathways that regulate tumour growth, the role of epigenetic dysregulation in the biology of ependymomas, and the various biological features of ependymoma tumorigenesis, including cell immortalization, stem cell-like properties, the tumour microenvironment and metastasis. We further review the limitations of current therapies such as relapse, radiation-induced cognitive deficits and chemotherapy resistance. Finally, we highlight next-generation therapies that are actively being explored, including tyrosine kinase inhibitors, telomerase inhibitors, anti-angiogenesis agents and immunotherapy.

Laser interstitial thermal therapy for the treatment of insular lesions: A systematic review.

Background: The surgical treatment of insular lesions has been historically associated with high morbidity. Laser interstitial thermal therapy (LITT) has been increasingly used in the treatment of insular lesions, commonly neoplastic or epileptogenic. Stereotaxis is used to guide laser probes to the insula where real-time magnetic resonance thermometry defines lesion creation. There is an absence of previously published reviews on insular LITT, despite a rapid uptake in use, making further study imperative. Methods: Here we present a systematic review of the PubMed and Scopus databases, examining the reported clinical indications, outcomes, and adverse effects of insular LITT. Results: A review of the literature revealed 10 retrospective studies reporting on 53 patients (43 pediatric and 10 adults) that were treated with insular LITT. 87% of cases were for the treatment of epilepsy, with 89% of patients achieving seizure outcomes of Engle I-III following treatment. The other 13% of cases reported on insular tumors and radiological improvement was seen in all cases following treatment. All but one study reported adverse events following LITT with a rate of 37%. The most common adverse events were transient hemiparesis (29%) and transient aphasia (6%). One patient experienced an intracerebral hemorrhage, which required a decompressive hemicraniectomy, with subsequent full recovery. Conclusion: This systematic review highlights the suitability of LITT for the treatment of both insular seizure foci and insular tumors. Despite the growing use of this technique, prospective studies remain absent in the literature. Future work should directly evaluate the efficacy of LITT with randomized and controlled trials.

A Network-Based Approach to Glioma Surgery: Insights from Functional Neurosurgery.

The evaluation and manipulation of structural and functional networks, which has been integral to advancing functional neurosurgery, is beginning to transcend classical subspecialty boundaries. Notably, its application in neuro-oncologic surgery has stimulated an exciting paradigm shift from the traditional localizationist approach, which is lacking in nuance and optimization. This manuscript reviews the existing literature and explores how structural and functional connectivity analyses have been leveraged to revolutionize and individualize pre-operative tumor evaluation and surgical planning. We describe how this novel approach may improve cognitive and neurologic preservation after surgery and attenuate tumor spread. Furthermore, we demonstrate how connectivity analysis combined with neuromodulation techniques can be employed to induce post-operative neuroplasticity and personalize neurorehabilitation. While the landscape of functional neuro-oncology is still evolving and requires further study to encourage more widespread adoption, this functional approach can transform the practice of neuro-oncologic surgery and improve the care and outcomes of patients with intra-axial tumors.