Background: Ancillary testing assist in the diagnosis of brain death. While traditionally, lack of blood flow (BF) in the intracranial arteries constitutes conclusive evidence that the brain is dead, there is apparent discrepancy between the BF, and sufficient cerebral perfusion; In 15% of patients with confirmed clinical diagnosis of brain death, BF is still preserved. In these patients, cerebral perfusion is significantly impaired suggesting that cerebral perfusion rather than BF more accurately assesses brain function. We aim to present a history of brain death, its pathophysiology, and ancillary tests utilized for its diagnosis- specifically CT Perfusion studies. Methods: A literature search using titles and key terms was conducted for articles containing brain death ancillary testing diagnosis, and CTP as primary focus. Results: Across selected studies, CTP diagnosed brain death with 100% positive predictive value, as none of the patients were proven not-dead on follow-up. The early prediction of mortality outcome in these patients with proven high mortality rate may help decisions for withdrawal of life support. It may also facilitate procurement of organs for transplants. Conclusions: Although clinical assessment is the gold standard method of brain death determination, CTP has shown promising results that could alter our current clinical approach.

Background: Responses to invasive neuromodulation therapy for chronic pain are highly variable after several months of sustained treatment, with some experiencing a complete loss of therapeutic effect. We sought to assess whether functional neuroimaging can provide a biomarker for treatment success and whether these biomarkers offer value in predicting treatment response. Methods: We searched Ovid MEDLINE and EMBASE from 1967 to 2022, including prospective studies correlating functional neuroimaging signatures with treatment response after surgical implantation. Results: After considering 355 studies for initial review, 22 studies were included. While there was significant heterogeneity in experimental design, preliminary findings suggest that differential regional cortical activation profiles and signatures can be employed to differentiate good from poor therapeutic responders. Three studies correlated pre-operative functional imaging with treatment effects post-implantation. For example, baseline activation patterns of specific brain regions on functional imaging modalities such as 11C-diprenorphrine PET and Tc-99m-SPECT significantly correlated with therapeutic response to motor cortex stimulation, and spinal cord stimulation (SCS), respectively. Conclusions: The included studies demonstrate the potential for functional imaging to predict the likelihood of successful neuromodulation treatment. The concept is relatively unexplored in the literature and could benefit from more studies with larger sample sizes to confirm clinical utility.

Background: Effectiveness of “palliative resections” of a dominant epileptogenic focus in adults with multifocal intractable epilepsy confirmed on intracranial EEG has rarely been reported. Methods: We retrospectively reviewed our database to identify patients who underwent focal resection after confirmation of multiple seizure foci on intracranial EEG. Results of presurgical investigations, intracranial EEG, procedures, complications and outcome were collected. Results: A total of 17 patients underwent palliative resection (8 left, 9 right). Preoperative MRI revealed malformations of cortical development in 6 patients, and MTS in 6 patients. Intracranial stereo EEG revealed 8 bilateral and 9 unilateral multifocal epileptogenic foci. Surgical procedures included anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy in 4 patients, ATL plus additional cortical resection in 7 patients, and extratemporal resection in 6 patients. One patient had dysphasia post ATL and a second patient had worsened cognitive dysfunction post extended frontal lobectomy. Favorable seizure outcome (Engel class I and II) was achieved in 10 patients (58.8%). Pathology revealed focal cortical dysplasia in 6 patients and hippocampal sclerosis in 5 patients. Conclusions: Palliative resection of a dominant epileptogenic focus confirmed by intracranial EEG is effective in carefully selected adult cases of intractable epilepsy, particularly in patients with lesional epilepsy.

Background: In Parkinson’s disease, deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) produces comparable motor benefits. Although both increases the risk of cognition and verbal fluency (VF) decline, the risk is greater following STN-DBS. The consequences of stimulating these different sites on brain network activity is unknown. We use functional magnetic resonance imaging (fMRI) during in vivo stimulation to investigate differences between STN-DBS and GPi-DBS and correlate with change in VF. Methods: Left-sided, stimulation-cycling block-design fMRI was acquired at 3-Tesla in 51 STN-DBS and 15 GPi-DBS following routine clinical programming. Blood oxygen level-dependent (BOLD) response to stimulation was compared between groups. Phonemic VF was assessed pre- and postoperatively. Results: Voxel-wise t-test between STN-DBS and GPi-DBS BOLD response maps revealed areas of significant difference (p<0.001) in the left frontal operculum and the left caudate head. Stimulation BOLD response appears to show slight inverse correlation with postoperative VF decline. The trend is reversed at the left frontal operculum in STN-DBS compared to GPi-DBS. Conclusions: Decline in VF in PD-DBS seems associated with the stimulation BOLD response at the left frontal operculum and the left caudate head. The effect differs depending on stimulation site, suggesting differing effects on brain network activity.

Background: Neuromodulation unit placement can provide efficacious control of many neurological conditions. They are high risk for infection with a historic infection rate as high as 10%. Treatment of infection requires surgical removal and a long course of systemic antibiotics. <font size=”1”> </font>At our center, one surgeon uses antibacterial envelopes with all implanted neuromodulation devices. Methods: We conducted a retrospective cohort study of consecutive implantable pulse generator (IPG) and intrathecal pump unit implantation with an antibacterial envelope at our center. This cohort was then compared to a historical cohort of consecutive patients undergoing IPG or pump placement or revision prior to the use of the envelopes. Results: IPG: There were 18 (11.9%) class I infections in the pre-envelope cohort compared with 5 (2.1%) in the post-envelope cohort. The absolute risk reduction (ARR) with the use of antibacterial envelopes was 9.85% (95% confidence interval (CI) 4.3-15.4%, p<0.01).

Pump: There were 6 (14.6%) class I infections in the pre-envelope cohort compared with 1 (1.7%) in the post-envelope cohort. The ARR with the use of antibacterial envelopes was 12.9% (95% confidence interval 1.6-24.3, p<0.05). Conclusions: Based on our results, we recommend usage of antibacterial envelopes to reduce infection rates in neuromodulation surgery. Further study is needed.

Background: Radiofrequency rhizotomy is a commonly used percutaneous technique for treatment of trigeminal neuralgia especially in cases not eligible for microvascular decompression. This technique is usually performed with the patient under conscious sedation. We devised a method for performance of this technique under general anesthetic with neurophysiology monitoring. Methods: The patient is put under general anaesthetic and EMG monitoring is set up. Needles are placed in temporalis muscle, masseter and mylohyoid or anterior belly of digastric. Resting activityis monitored. Rhizotomy is then performed under fluoroscopic guidance, with monitoring of EMG potentials pre- and post-lesioning, with specific attention paid to presence of an abnormal electrophysiologic reflex. Results: A total of 38 procedures were performed in 23 patients. Of these, 15 were revision procedures. Patients had improvement from BNI pain scale 3.8 ±0.8 to 1.3 ±1.5, and had a reduction in number of medications from 1.9 ±1.0 to 0.8 ±0.9. Survey results indicate greater practitioner satisfaction with this technique. Conclusions: Radiofrequency rhizotomy can be performed under GA with IONM guidance with good results. We present a novel method for EMG-based monitoring. Further study is required to validate this technique.

Background: Steroids are widely used in medicine because of their anti-inflammatory and immunosuppressive properties; however, they have numerous adverse effects. In neuro-oncology, dexamethasone is the first-line treatment for vasogenic edema caused by malignant brain tumours. This retrospective chart review investigated the risks and benefits of perioperative steroids in the surgical treatment of malignant brain tumours. Methods: All patients (age ≥ 18 years) who underwent a craniotomy for the treatment of a malignant brain tumour at Windsor Regional Hospital between 2012 and 2020 were assessed for eligibility for this retrospective study. Baseline patient characteristics, cumulative perioperative steroid dose, and postoperative outcomes were recorded from electronic medical records (n = 362). Statistical analysis was performed using SPSS. Results: Patients who received a higher cumulative perioperative steroid dose (≥ 80 mg) had a significantly higher rate of postoperative complications compared to those who received a lower dose. These included wound dehiscence, postoperative brain edema on imaging, unplanned return to the operating room, and readmission within 30 days. Conclusions: Steroids are important medications in neuro-oncology, but they are not without potential complications. The findings of this study highlight the need for careful consideration when using steroids in patients undergoing surgical treatment of a malignant brain tumour.

Background: High grade gliomas (HGG) are diffusely infiltrative brain tumours with dismal prognosis. Recent studies from our lab have demonstrated that glioma cells form synapses with surrounding neurons, and proliferate in response to neuronal input. How these neuron-glioma networks develop, and are influenced by experience, is currently unknown. We aimed to develop a novel imaging tool to study neuron-glioma cell interactions in freely behaving animals. Methods: Several patient-derived HGG cell lines were transfected to express the green calcium indicator GCaMP6s. These cells were xenografted into the premotor cortex of mice, along with a virus expressing the red calcium indicator jRGECO1a under a neuron-specific synapsin promotor to allow dual-color imaging of neurons and glioma cells. The Inscopix mini-microscope system was implanted into the cortex to allow real-time live calcium imaging in freely behaving animals. Results: Several HGG cell lines effectively expressed the GCaMP6s calcium indicator. In vivo, we were successfully able to image both neurons and glioma cells simultaneously in freely behaving mice in real time. Conclusions: The Inscopix system has been modified for studying cancer cells for the first time. This technology will be used to study how pharmacological agents and neuronal experience shape neuron-glioma circuit dynamics, to develop new therapeutic strategies for HGG.

Background: Meningiomas are the most common intracranial tumor, graded from 1 (benign) to 3 (malignant). The aim of this study was to identify clinical features associated with overall survival (OS), progression-free survival (PFS) and functional status for malignant meningiomas. Methods: Demographic, clinical and histopathological data from grade 3 intracranial meningioma cases were identified in the clinical databases from seven sites in North America and Europe from 1991-2022. Summary statistics and Kaplan-Meier OS and PFS curves were generated. Results: We identified 108 patients, with a median age 65 years (IQR: 52, 72) and 53.7% were female. Median OS was 109 months (95% CIs: 88, 227), and 5-year OS rate was 65% (95% CIs: 56, 76). Median PFS was 38 months (95% CIs: 24, 56) and 5-year PFS rate was 37% (95% CIs: 28, 49). OS and PFS were significantly lower in patients aged ≥65 years. Median preoperative KPS score was 80 (IQR: 70, 90), postoperatively KPS was 90 (IQR: 70, 98) and 1-year follow-up KPS was 70 (IQR: 50, 80). Conclusions: This study provides robust survival, recurrence and functional data for grade 3 meningiomas in North America and Europe over a 30-year period.

Background: Due to high risk of recurrence and complications associated with microsurgical resection or aspiration of enlarging cystic sellar lesions, stereotactic intracavitary irradiation with 90Yttrium (90Yt) has been proposed as an alternative to mitigate these challenges. Long-term efficacy data for this procedure is lacking. Methods: We conducted a Health Canada approved, single-centre, prospective cohort study to assess the effect of 90Yt therapy on cyst volume, visual field (VF) testing and endocrine function. All patients underwent right frontal stereotactic insertion of 90Yt colloid (200 Gy cyst wall). Results: 22 patients [mean age = 63.5 (± 15.4) years] received 90Yt therapy. Mean follow-up was 52 (5-113) months. Cysts included: craniopharyngioma (86%), Rathke’s cleft cyst (9%) and cystic prolactinoma (5%). Mean cyst volume reduction was 77% at 12-months (5.2 ± 4.5 cc to 1.2 ± 1.5 cc; p = 0.002). Rate of pre- and post-op hormonal dysfunction was 59% and 68%, respectively (p = 0.50). Pre-operative VF deficits were found in 68% of patients, of which 32% normalized and 36% remained stable (p = 0.180). Worsened vision was detected in 9% of patients post-operatively. Conclusions: 90Yttrium therapy significantly reduces sellar cyst size without having a deleterious effect on vision and endocrine function.

Background: Intracranial intratumoural abscesses are rare occurrences typically treated with antibiotics and possible surgical resection. This study describes a meningioma-associated abscess and a review of the literature. Methods: Medical records and investigations were reviewed. A literature search of PubMed was completed. Results: A 56-year-old male presented with septic shock and dysuria. Urine culture isolated E. Coli, and he was treated with Ertapenem prior to discharge. A CT scan was ordered during hospitalization for unrelenting headaches, revealing a meningioma. Conservative management with follow-up as an outpatient was decided. However, he returned within two weeks with a fever and progressive left-sided weakness. A right frontal craniotomy for tumour resection was performed, and culture of necrotic-appearing tissue within the tumour revealed E. Coli. He was treated with Meropenem for six weeks, and at follow-up, the patient was asymptomatic. Our scoping review illustrated that 18 meningioma-associated abscesses have been reported in the literature since the first report in 1994. Conclusions: This case highlights the hematogenous spread of a urinary infection, resulting in an intratumoural abscess. Review of the literature indicated that, similarly, 39% of cases had recent or concurrant urinary tract infections. Future studies should seek to determine conclusive guidelines for diagnosing intratumoural abscesses.

Background: 5-Aminolevulinic acid (5-ALA) is a prodrug used to selectively illuminate high-grade glioma (HGG) tissue intra-operatively, shown to nearly double complete resection rates in a 2006 multicentre, phase III clinical trial. Here, we review the history of the 2020 approval of 5-ALA in Canada and present some of the first preliminary results on resection rates, survival analysis, and adverse effects from a single Canadian center. Methods: We enrolled 76 patients (median age 61 years, 42 male) with suspected HGG amenable to surgical resection between June 2020 and January 2023. Gross total resection was defined by the absence of enhancing lesions on postoperative MRI. We compared the survival distributions of confirmed HGG cases with complete vs. incomplete resection using a log-rank test and Kaplan-Meier statistic. Results: 52 patients were confirmed as having a HGG based on a pathological diagnosis. In 32 of these patients (60.3%) a gross total resection was achieved. 82.76% were still alive at 180 and 270 days, and 72.73% at 360 days. 47.8% had a survival of 600 or more days. Conclusions: 5-ALA fluorescence-guided surgery resulted in high complete resection rates, and improved overall survival comparable to the literature with no notable adverse side effects.

Background: Since its approval by Health Canada in 2020, several neurosurgical centres across Canada have used 5-ALA, an oral drug that assists with surgical resection of malignant gliomas by causing tumour cells to fluoresce under the microscope. The study’s objective is to prospectively evaluate the extent of resection (EOR) and clinical outcomes in 5-ALA-guided surgery at HSN compared to historical controls. Methods: A retrospective analysis was performed of patients with malignant gliomas having undergone surgery at HSN from 2011 to December 2020, assessing the EOR (contrast-enhanced tumour on post-operative CT/MRI), progression-free survival (PFS), overall survival (OS). Results: 235 patients underwent surgery for malignant glioma including 51 newly-diagnosed patients felt to be surgically resectable and with post-operative imaging. 25/51 (49%) had no residual tumour. The median PFS and OS were 7.1 and 11.5 months respectively. To date, 3 patients have successfully undergone 5-ALA-guided surgery with complete resection of contrast-enhancing tumour and no new focal neurological deficit post-operatively. Conclusions: We continue to recruit and follow prospectively patients having undergone 5-ALA-guided resection of malignant gliomas at HSN. Patients living in Northern Ontario may derive significant benefits from the use of 5-ALA-guided surgery, particularly since other technologies, such as intraoperative MRI and ultrasound, are costly and not available.

Background: Meningiomas can lead to significant morbidity and mortality and have recurrence potential despite their benign classification. The precise location of the recurrence has not been delineated. The objective of this study was to determine any spatial clustering of recurrence for surgically treated Grade 1 meningiomas. Methods: Patients diagnosed with Grade 1 meningiomas and treated with surgical resection with recurrence were reviewed. Patient demographics, presentation, extent of resection, time to recurrence, and location were established by medical records. Outcomes were the time to recurrence and location relative to the original surgical bed. Results: Among the 42 cases that met the study inclusion criteria, 12 were male and 30 were female. The mean age at treatment was 49.7 years, and the mean years until recurrence was 5.2 years. 33 (68.8%) tumours recurred locally, 12 (25.0%) recurred at the periphery (<1cm of the surgical bed), and 3 (6.3%) recurred distal to the resection site. Conclusions: A sizeable portion of cases may benefit from therapy directed beyond the resection margin. It may be more successful to prevent recurrence in these patients by performing a more aggressive resection of the dural attachment surrounding the tumour and/or focusing adjuvant therapy on the area surrounding the resection cavity.

Background: The relationship between glioblastoma extent of surgical resection (EoR) and survival is well documented.1-3 The advent of 5-aminolevulinic acid (5-ALA), a tissue selective fluorophore, has led to increased rates of gross total tumour resection.4-6 Since 5-ALA received approval for use in Canada in 2020, no Canadian centres have examined its impact on rates of complete resection (CR) for newly diagnosed high grade glioma (HGG) patients. Methods: This study evaluates the difference in EoR class7, for newly diagnosed HGG. Fifty-one consecutive patients underwent awake craniotomy with white light illumination (WLS) while 45 consecutive HGG patients were operated with fluorescence guidance (FGS). Analysis of EoR class was blinded and performed by 2 independent reviewers with a third adjudicator available for discrepancies. Residual tumour volumes were quantified by segmentation of postoperative 1mm slice MRI. Results: The FGS group was found to have: 80% complete resection (CR), 11% near-total resection (NTR), and 9% subtotal resection (STR). This compared favourably to the WLS respective rates of 67%, 6%, and 28%. Conclusions: For awake craniotomy protocol, the odds of complete resection were higher in the FGS group, compared to the WLS group (OR = 2; 95% CI 1.06, 2.93).

Background: To localize cortical speech areas, methods such as fMRI are commonly used, but the Wada test can also determine whether a region is critical to the particular task. We report a case of a left-handed patient with a left frontal tumour in whom fMRI language paradigms produced both left and right Broca’s and Wernicke’s areas. Methods: All imaging used a 3 Tesla Siemens Skyra scanner. The patient performed five speech tasks: word reading, picture naming, semantic questions, pseudohomophone reading, and word generation. All preprocessing and statistical analyses for functional images were performed using Brain Voyager QX. Results: The fMRI results revealed right hemisphere dominance for language processing. A Wada test was performed in order to confirm whether the regions in the left hemisphere were critical to speech. The patient experienced speech arrest during the Wada test, thus confirming that despite bilateral speech activation, the left hemisphere speech regions are required for speech production. Conclusions: This case emphasizes the importance of preoperative fMRI in assessing the location of eloquent cortices adjacent to a tumour and the Wada test is still warranted for examining necessity of left hemisphere language regions when fMRI fails to show clear left-lateralization.

Background: Disruption of white matter (WM) tracts is common in traumatic injury to the brain and spinal cord. However, imaging techniques for prognostication and monitoring of recovery are lacking. Myelin Water Imaging (MWI) is a validated MRI based method of quantifying myelin volume and represents a potential tool for application in a clinical environment. Methods: 12 healthy, right-handed participants completed a two-week visuomotor maze training program with MRI scans at baseline and endpoint. The task was designed to be difficult for the non-dominant hand and easy for the dominant, allowing for an inbuilt control. Diffusion Tensor Imaging (DTI) along with MWI data were collected at both timepoints using a 3T MRI. Results: Performance metrics confirmed task performance increased only in the non-dominant hand, and a corresponding endpoint>baseline comparison showed significant increases in the MWF (p<0.05) and DTI indices (p<0.05) in the right corticospinal tract (CST), and no significant change in the left CST. Conclusions: This preclinical validation shows MWI is capable of quantitatively tracking WM changes over the course of weeks in humans. MWI’s clinical utility lies in its ability to assess WM changes over short time periods, as monitoring changes in tissue integrity will assist in guiding treatment decisions after critical injury.

Background: Studies of deep brain stimulation (DBS) require accurate electrode localization and image registration. We used anatomical fiducials to investigate localization and registration errors in patients who underwent subthalamic nucleus (STN) DBS for Parkinson’s disease (PD). Methods: We conducted a retrospective analysis of patients who underwent bilateral STN DBS for PD. Pre and post operative MRI scans were non-linearly normalized to a standard template (MNI152NLin2009bAsym). Four raters localized DBS electrodes (Lead-DBS), the anterior commissure (AC) and posterior commissure (PC). Errors between rater localizations were calculated (fiducial localization error; FLE). We transformed AC and PC coordinates from template to patient space to calculate the fiducial registration error (FRE)Results: Ninety-nine patients were analyzed, with a median FLE of 0.76mm, 0.74mm, 0.71mm and 0.66mm for the right electrode, left electrode, AC and PC respectively (no significant difference, Wilcoxon sign rank). The median FRE was 1.59mm for AC and 1.21mm for PC, significantly higher than FLE at those coordinates (Wilcoxon sign rank, p<0.001). Conclusions: Raters can accurately localize DBS electrodes, AC and PC from clinical images with sub-millimetric accuracy. Higher FREs at AC and PC suggested registration errors may contribute more than localization errors to electrode uncertainty in a common space.

Background: The competency-based medical education (CBME) model has been recently implemented in spinal neurosurgical and orthopedic residencies. This model is grounded on entrustable professional activities (EPAs) that allow the assessment of clinical milestones. Integrating quantitative metrics to evaluate procedural competencies could refine the assessment’s scope. This survey, administered to program directors (PDs), aims to evaluate the current state and anticipated needs for quantitative evaluation to develop innovative assessment techniques. Methods: We surveyed 32 PDs of neurosurgical (N=14) and orthopedics (N=16) programs with a spine service via RedCap. We collected information on the programs’ characteristics. We inquired about existing assessment methods and the perceived values of developing quantitative metrics to assess spinal technical competencies using thirteen questions. Results: The response rate was 53%. All programs use EPAs to assess procedural competencies through direct observation in the operation room. One surgical program employed quantitative metrics for examination. Four PD valued the profitability of quantitative evaluation methods in a clinical or simulatory context. Conclusions: The use of quantitative metrics to assess spinal surgical competencies in Canadian neurosurgical and orthopedic residency programs is seldom. Despite its underutilization, PDs acknowledge the potential for quantitation to improve the accuracy and reliability of CBME assessments in both simulated and clinical settings.

Background: Cerebrovascular reactivity has been identified as an important contributor to secondary injury following moderate to severe traumatic brain injury (TBI). “Gold-standard” intracranial pressure (ICP) based indies of cerebrovascular reactivity are limited by their invasive nature poor spatial resolution. Near infrared spectroscopy (NIRS) based indices of cerebrovascular reactivity are minimally invasive and have improved spatial resolution. In this study, classical machine-learning algorithms are leveraged to better characterize the relationship between these indices. Methods: High-resolution physiologic data was collected in a cohort of adult moderate to severe TBI patients. From this data both ICP and NIRS based indices of cerebrovascular reactivity were derived. Utilizing Agglomerative Hierarchical Clustering (AHC) and Principal Component Analysis, the relationship between these indices in higher dimensional physiologic space was examined. Results: A total of 83 patients with 314,395 minutes of unique and complete physiologic data was obtained. Through AHC and PCA there was higher order clustering between NIRS and ICP based indices, separate from other physiologic parameters. Conclusions: NIRS and ICP based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. NIRS based indices of cerebrovascular reactivity may be a viable alternative to ICP based indices.