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.

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.

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.

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.

Surgical Residents at the Forefront of the COVID-19 Pandemic: Perspectives on Redeployment.

The COVID-19 pandemic has led many of us to re-evaluate our approaches to disaster management, reflect on our experiences, and be reminded of the strong resolve for our work. This article details a resident's perspective on redeployment of surgical residents to the COVID-19 frontline setting, using the example of the COVID-19 intensive care unit. Redeployment during a pandemic brings the unique opportunity to collaborate with colleagues on the frontlines and learn alongside one another about the evolving management of this disease. During this ongoing pandemic, it is incumbent upon us as clinicians to work together in a multidisciplinary manner and reflect on ways this pandemic impacts the delivery of patient care.

Stereotactic radiosurgery training patterns across neurosurgical programs: a multi-national survey.

INTRODUCTION: The field of neurosurgery has witnessed a dramatic increase in the use of stereotactic radiosurgery (SRS) as a modality to treat various cranial and spinal pathologies. However, studies have consistently demonstrated disparities in SRS training. Accordingly, the present study represents a cross-sectional analysis of current SRS training and practice patterns. METHODS: An online survey was utilized to collect data from participants. Two-sided t-tests were used in order to compare frequency tables for statistically significant differences between groups. Qualitative analyses were performed by modified thematic analyses, employing open and axial coding. RESULTS: A total of 67 participants completed the online survey (16.4% response rate). The majority of participants were neurosurgery attendings (58.2%), followed by neurosurgery residents (25.4%). The majority of participants reported that resident exposure to SRS was gained primarily through non-SRS focused rotations (52.2%). The survey found that exposure to tumor cases was most frequent, followed by functional, vascular, and spine indications. The majority of participants (49.3%) indicate that residents are not competent or exhibit a low level of competency in SRS at the completion of neurosurgical residency. Qualitative analyses demonstrated that respondents believe SRS is a critical modality in current cranial neurosurgical care and that increased training is needed. CONCLUSIONS: This study provides a multi-national analysis of SRS residency training and practice patterns, and aims to stimulate improvement in SRS in training worldwide. Enhanced resident training in SRS must include wider exposure to vascular, neoplastic, functional and pediatric indications for SRS.

Cross-sectional analysis of women in neurosurgery: a Canadian perspective.

OBJECTIVE: Although the past decades have seen a steady increase of women in medicine in general, women continue to represent a minority of the physician-training staff and workforce in neurosurgery in Canada and worldwide. As such, the aim of this study was to analyze the experiences of women faculty practicing neurosurgery across Canada to better understand and address the factors contributing to this disparity. METHODS: A historical, cross-sectional, and mixed-method analysis of survey responses was performed using survey results obtained from women attending neurosurgeons across Canada. A web-based survey platform was utilized to collect responses. Quantitative analyses were performed on the responses from the study questionnaire, including summary and comparative statistics. Qualitative analyses of free-text responses were performed using axial and open coding. RESULTS: A total of 19 of 31 respondents (61.3%) completed the survey. Positive enabling factors for career success included supportive colleagues and work environment (52.6%); academic accomplishments, including publications and advanced degrees (36.8%); and advanced fellowship training (47.4%). Perceived barriers reported included inequalities with regard to career advancement opportunities (57.8%), conflicting professional and personal interests (57.8%), and lack of mentorship (36.8%). Quantitative analyses demonstrated emerging themes of an increased need for women mentors as well as support and recognition of the contributions to career advancement of personal and family-related factors. CONCLUSIONS: This study represents, to the authors' knowledge, the first analysis of factors influencing career success and satisfaction in women neurosurgeons across Canada. This study highlights several key factors contributing to the low representation of women in neurosurgery and identifies specific actionable items that can be addressed by training programs and institutions. In particular, female mentorship, opportunities for career advancement, and increased recognition and integration of personal and professional roles were highlighted as areas for future intervention. These findings will provide a framework for addressing these factors and improving the recruitment and retention of females in this specialty.

Correction to: Postoperative isolated lower extremity supplementary motor area syndrome: case report and review of the literature.

The original version of this article unfortunately contained an error. The author apologizes for having provided an incorrect name: "Ali Moghadammjou" should be "Ali Moghaddamjou". Given in this article is the correct author name.

Postoperative isolated lower extremity supplementary motor area syndrome: case report and review of the literature.

The supplementary motor area (SMA) syndrome is characterized by transient weakness and akinesia contralateral to the side of the affected hemisphere. The underlying pathology of the syndrome is not fully understood but is thought to be related to lesions in the SMA, residing principally in the mesial superior frontal gyrus (Broadmann's area 6c). Although the SMA syndrome a well-characterized clinical entity, we report herein, to our knowledge, the first case of isolated lower extremity SMA syndrome in the literature. This case highlights the importance of considering this rare clinical entity in the context of new or worsening postoperative neurologic deficits. Moreover, early studies did not support somatotopic organization of the SMA as in the primary motor cortex; emerging evidence suggests that delicate somatotopic representation may underlie distinct presentations like that reported in the present case.

Genetic basis of intracranial aneurysm formation and rupture: clinical implications in the postgenomic era.

OBJECTIVE: Despite the prevalence and impact of intracranial aneurysms (IAs), the molecular basis of their pathogenesis remains largely unknown. Moreover, there is a dearth of clinically validated biomarkers to efficiently screen patients with IAs and prognosticate risk for rupture. The aim of this study was to survey the literature to systematically identify the spectrum of genetic aberrations that have been identified in IA formation and risk of rupture. METHODS: A literature search was performed using the Medical Subject Headings (MeSH) system of databases including PubMed, EMBASE, and Google Scholar. Relevant studies that reported on genetic analyses of IAs, rupture risk, and long-term outcomes were included in the qualitative analysis. RESULTS: A total of 114 studies were reviewed and 65 were included in the qualitative synthesis. There are several well-established mendelian syndromes that confer risk to IAs, with variable frequency. Linkage analyses, genome-wide association studies, candidate gene studies, and exome sequencing identify several recurrent polymorphic variants at candidate loci, and genes associated with the risk of aneurysm formation and rupture, including ANRIL (CDKN2B-AS1, 9p21), ARGHEF17 (11q13), ELN (7q11), SERPINA3 (14q32), and SOX17 (8q11). In addition, polymorphisms in eNOS/NOS3 (7q36) may serve as predictive markers for outcomes following intracranial aneurysm rupture. Genetic aberrations identified to date converge on posited molecular mechanisms involved in vascular remodeling, with strong implications for an associated immune-mediated inflammatory response. CONCLUSIONS: Comprehensive studies of IA formation and rupture have identified candidate risk variants and loci; however, further genome-wide analyses are needed to identify high-confidence genetic aberrations. The literature supports a role for several risk loci in aneurysm formation and rupture with putative candidate genes. A thorough understanding of the genetic basis governing risk of IA development and the resultant aneurysmal subarachnoid hemorrhage may aid in screening, clinical management, and risk stratification of these patients, and it may also enable identification of putative mechanisms for future drug development.

Primary mediastinal paraganglioma associated with a familial variant in the succinate dehydrogenase B subunit gene.

Surgical management is the mainstay of therapy for primary cardiac tumors, yet due to the rarity of these malignancies, their management and workup remains a challenge. Here, we report a unique case of a patient with a primary left ventricular cardiac paraganglioma (PGL) and describe the role of a medical genetics assessment leading to the identification of a rare variant in the SDHB gene to be the causative etiology of this cardiac tumor. Due to decreasing costs and accessibility of molecular genetic analysis, genetic testing may become an emerging diagnostic adjunct in cases of cardiac tumors.

Assessment of TP53 Polymorphisms and MDM2 SNP309 in Premenopausal Breast Cancer Risk.

Germline polymorphic variants in cancer predisposition genes such as TP53 have been shown to impact the risk of premenopausal cancer. Accordingly, the aim of this study was to assess the spectrum of polymorphisms in TP53 and its negative regulatory gene, MDM2 (SNP309:T>G) in patients with premenopausal breast cancer. Our findings in a cohort of 40 female patients demonstrate no significant correlation between the studied polymorphisms and risk of premenopausal breast cancer. Although one polymorphism is found in high frequency in this cohort (rs1800372:A>G, 9.0%), it was not associated with the risk of developing cancer before the age of 35 years in an extended cohort of 1,420 breast cancer cases. Functional studies of the rs1800372:A>G polymorphic allele reveal that it does not affect p53 transactivation function. Further study of variants or mutations in other cancer susceptibility genes is warranted to refine our understanding of the germline contribution to premenopausal breast cancer susceptibility.

Patient Perspectives Regarding Ethics of Spinal Column Stimulators in the Surgical Management of Persistent Postoperative Neuropathic Pain.

OBJECTIVE: The aim of this study is to better understand perspectives of patients with persistent postoperative neuropathic pain (PPNP) and assess perceptions of the ethical issues surrounding their structural spinal surgeon also performing spinal cord stimulation (SCS). METHODS: Semistructured face-to-face interviews with 20 neurosurgical spine patients were conducted. Patients were recruited from the neurosurgery clinics at Toronto Western Hospital and were seen in consultation for PPNP. Interviews were transcribed and subjected to thematic analysis using open and axial coding. RESULTS: The range of the duration of participants' preoperative symptoms varied from one month to more than 20 years, and was primarily back dominant (13/20). The median time since patients most recently underwent spinal surgery was three years. The majority of patients (15/20) do not view their current condition of PPNP as a failure of their initial spine surgeon. The most commonly reported reason for this is that patients trusted their physician and clear communication between the physician and the patient, prior to their surgery, ensured an understanding of the goals of the procedure. Nearly unanimously (19/20), patients did not perceive an ethical problem with a surgeon performing a structurally corrective spinal surgery and subsequently also implanting a SCS device if the same patient that develops medically refractory PPNP. CONCLUSIONS: This is the first clinical qualitative study of values and ethical perceptions of patients with medically refractory PPNP. Our findings provide a framework for understanding the values of patients with PPNP and demonstrate that a strong surgeon-patient relationship can ameliorate concerns surrounding PPNP and SCS implantation.

Clinical and pathological outcomes after resection of intramedullary spinal cord tumors: a single-institution case series.

OBJECTIVE The objective of this study was to identify clinically relevant predictors of progression-free survival and functional outcomes in patients who underwent surgery for intramedullary spinal cord tumors (ISCTs). METHODS An institutional spinal tumor registry and billing records were reviewed to identify adult patients who underwent resection of ISCTs between 1993 and 2014. Extensive data were collected from patient charts and operative notes, including demographic information, extent of resection, tumor pathology, and functional and oncological outcomes. Survival analysis was used to determine important predictors of progression-free survival. Logistic regression analysis was used to evaluate the association between an "optimal" functional outcome on the Frankel or McCormick scale at 1-year follow-up and various clinical and surgical characteristics. RESULTS The consecutive case series consisted of 63 patients (50.79% female) who underwent resection of ISCTs. The mean age of patients was 41.92 ± 14.36 years (range 17.60-75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07-31.11, p = 0.0026) and myxopapillary ependymomas (HR 8.01, 95% CI 1.44-44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23-9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an "optimal" outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89-0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33-17.63, p = 0.017), McCormick score (OR 0.22, 95% CI 0.084-0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012-0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001-0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores. CONCLUSIONS Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status.

Scientific overview: CSCI-CITAC Annual General Meeting and Young Investigators' Forum 2014.

The Canadian Society of Clinician Investigators (CSCI) and Clinical Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) annual general meeting (AGM) was held in Toronto during November 21-24, 2015 for the first time in conjunction with the University of Toronto Clinician-Investigator Program Research Day. The overall theme for this year's meeting was the role of mentorship in career development, with presentations from Dr. Chaim Bell (University of Toronto), Dr. Shurjeel Choudhri (Bayer Healthcare), Dr. Ken Croitoru (University of Toronto), Dr. Astrid Guttman (University of Toronto), Dr. Prabhat Jha (University of Toronto) and Dr. Sheila Singh (McMaster University). The keynote speakers of the 2014 AGM included Dr. Qutayba Hamid, who was presented with the Distinguished Scientist Award, Dr. Ravi Retnakaran, who was presented with the Joe Doupe Award, and Dr. Lorne Babiuk, who was the CSCI-RCPSC Henry Friesen Award winner. The highlight of the conference was, once again, the outstanding scientific presentations from the numerous clinician investigator (CI) trainees from across the country who presented at the Young Investigators' Forum. Their research topics spanned the diverse fields of science and medicine, ranging from basic science to cutting-edge translational research, and their work has been summarized in this review. Over 120 abstracts were presented at this year's meeting. This work was presented during two poster sessions, with the six most outstanding submitted abstracts presented in the form of oral presentations during the President's Forum.

Proteomic analyses of CSF aimed at biomarker development for pediatric brain tumors.

Primary brain tumors cumulatively represent the most common solid tumors of childhood and are the leading cause of cancer related death in this age group. Traditionally, molecular findings and histological analyses from biopsies of resected tumor tissue have been used for diagnosis and classification of these diseases. However, there is a dearth of useful biomarkers that have been validated and clinically implemented for pediatric brain tumors. Notably, diseases of the central nervous system (CNS) can be assayed through analysis of cerebrospinal fluid (CSF) and as such, CSF represents an appropriate medium to obtain liquid biopsies that can be informative for diagnosis, disease classification and risk stratification. Proteomic profiling of pediatric CNS malignancies has identified putative protein markers of disease, yet few effective biomarkers have been clinically validated or implemented. Advances in protein quantification techniques have made it possible to conduct such investigations rapidly and accurately through proteome-wide analyses. This review summarizes the current literature on proteomics in pediatric neuro-oncology and discusses the implications for clinical applications of proteomics research. We also outline strategies for translating effective CSF proteomic studies into clinical applications to optimize the care of this patient population.

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.