Background: 4H leukodystrophy is a genetic disorder typically characterized by hypomyelination, hypodontia and hypogonatotropic hypogonadism. Previously reported patients had considerable cognitive and motor deficits. We present a pair of siblings with a less severe phenotype. Methods: Patient data was obtained from medical records from the Children’s Hospital of Eastern Ontario. Results: The first patient was diagnosed with 4H leukodystrophy at the age of 21 years after genetic testing revealed a POLR3B mutation with a homozygous V523E variant. She has hypomyelination on MRI and a history of optic neuritis, as well as intermittent sensory and motor symptoms in the context of a diagnosis of multiple sclerosis. She has no clinical manifestations of 4H leukodystrophy. The patient is now 26 years old and has only mild neurological deficits. Her younger brother was diagnosed with 4H leukodystrophy at the age of 18 years and found to have the same genetic mutation as his sister. He has a history of seizures and mild learning disabilities. He is now 23 years old with no typical symptoms of 4H leukodystrophy. Conclusions: 4H leukodystrophy is usually associated with a severe, disabling phenotype and a poor prognosis. Our patients illustrate that a much milder phenotype exists.

Background: Legalization of recreational cannabis in Canada has increased the presence of cannabis in the public mind. There are online parent advocacy groups which are already calling for the use of cannabinoids in pediatric developmental and behavioural conditions such as Autism Spectrum Disorder (ASD). We set out to perform a rapid review of existing literature regarding use of cannabinoid products in the treatment of the behavioural domains of ASD. Methods: Key search terms were identified in collaboration with a medical librarian and combined into standardized search filters. A total of 55 articles were identified, of which only two included primary data regarding the use of cannabinoids to control behavioural symptoms of ASD in pediatric populations. Results: Both studies found significant reductions in the behavioural measures examined - which included inappropriate speech, irritability, stereotyped behaviours and self injurious behaviours - after treatment with Cannabinoids. Conclusions: The minimal existing evidence indicates the use of cannabinoid products may be useful in improving behavioural difficulties in children with ASD. However, there is a complete lack of well powered, rigorous studies. Further studies with larger cohorts are needed before any recommendations can be confidently made for or against the use of cannabinoids in this population.

Background: Seizures are rare in REM sleep. To our knowledge, the effects of different sleep stages in anti-NMDA encephalitis have not been studied. Methods: Case report. Results: 32 year-old healthy female presented with acute fluctuating level of consciousness with episodic impulsivity, disorientation, and emotional outbursts following 3 days of headache. Her temperature was 37.8°C and she was started on ceftriaxone, vancomycin, and acyclovir. CSF only showed a total nuclear cell count of 182 and pleocytosis. MRI revealed increased T2 hyperintense right lateral temporal and parietal cortical thickening. EEG revealed right frontotemporal seizures with left sided rhythmic jerking, and an extreme delta brush pattern. Interestingly, seizures and extreme delta brush disappeared in REM sleep. After HSV PCR was negative, she was immunosuppressed with corticosteroids, IVIG, rituximab, and cyclophosphamide, given the extreme delta brush pattern. Repeat CSF analysis eventually yielded highly positive anti-NMDA antibodies. Ten weeks later, she became seizure free. Conclusions: For the first time, we report REM sleep in a case of anti-NMDA encephalitis during which there was absence of extreme delta brush and ictal EEG patterns. This observation may provide insight into the ongoing debate over whether extreme delta brush is an ictal EEG pattern.

Background: Reported incidence of critical illness neuropathy (CIN) in burn patients is between 7-41%. Methods: Retrospective review including patients admitted to quaternary ICU for burn injuries between 2010-16. Variables include demographics, burn and neurologic characteristics, EMG reports, and measurements of illness severity. Patients with and without neuropathies were compared. Results: Of 147 patients admitted to ICU, thirteen had EMG studies and eight met CIN criteria. Five had electrophysiological CIN evidence, three had clinical diagnosis. Six EMGs focused on upper limb injuries only, insufficient to diagnose CIN. One patient was diagnosed with critical illness myopathy and nine had superimposed focal mononeuropathies or plexopathy. CIN patients had a mean of larger burns (TBSA 63% vs 21%), more operations (8 vs 2) and escharotomies performed (63% vs 12%), longer ICU admissions (23 vs 9 days), longer ventilation (28 vs 8 days), higher revised Baux score (101 vs 76) and initial APACHE II scores (21 vs 15) than those without. Conclusions: CIN was identified in 5.4% of burn patients admitted to ICU, lower than previously reported in literature, and associated with higher illness severity. CIN may be under recognized if not screened for. Unit examinations should include screening neurological measures and indicated EMGs to evaluate for CIN.

Background: Surveillance by serial magnetic resonance imaging (MRI) is important in the management of diffuse low-grade gliomas (LGGs). Radiological interpretations of LGG scans, however, are typically qualitative and difficult to use clinically. Methods: We retrospectively compared radiological interpretations of LGG growth/stability to volume change measured by manual segmentation. Tumour diameter was measured to evaluate methods for assessing glioma progression, including RECIST criteria, Macdonald/RANO criteria, and mean tumour diameter/ellipsoid method. Results: Tumours evaluated as stable by radiologists grew a median 5.1 mL (11.1%) relative to the comparison scan. Those evaluated as having grown increased by 13.3 mL (23.7%). Diameter-based measurements corresponded well but tended to overestimate segmented volumes, and overestimation error increased with tumour size. Agreement with segmented volume improved from a mean difference of 17.6 to 4.5 to 3.9 mm for diameter and from 104.0 to 25.3 to 15.9 mL for volume with measurements in one, two, and three dimensions. Conclusions: Given evidence that LGG volume and growth are prognostic factors, lesions should be accurately measured. Current radiological reporting workflows fail to appreciate and communicate the true expansion of LGGs. Volumetric analysis remains the gold standard for growth assessment, but diametric measurements in three dimensions may be an acceptable alternative.

Background: Utilization of endovascular procedures in the perioperative management of patients undergoing transsphenoidal surgery is uncommon but plays a critical role in preventing and treating potentially life-threatening vascular complications. Methods: We performed a retrospective review of all patients over a 10-year period who underwent transsphenoidal surgery at two tertiary-care institutions and identified all pre-operative and post-operative endovascular procedures performed. Results: 18 perioperative endovascular procedures were performed including 9 pre- and 9 post-operative. Pre-operative procedures included balloon-test occlusion (n=4), aneurysm coiling (n=4), and parent artery occlusion (n=1). One aneurysm coiling was complicated by coil migration requiring coil retrieval with a snare device and one balloon-test occlusion was complicated by pituitary apoplexy. Pituitary apoplexy following balloon-test occlusion has not been reported and the potential pathophysiology is reviewed. Post-operative procedures included embolization for epistaxis (n=2) and embolization with or without parent artery sacrifice for carotid and anterior cerebral artery vascular injury (n=7). Arterial vascular injury was managed with coil embolization and/or with detachable balloons. Review of anatomical features predisposing to vascular injury are discussed. Conclusions: Patients undergoing transsphenoidal surgery should be managed with a multidisciplinary team ensuring that endovascular treatment options are made available during the perioperative period.

Background: Asymmetric motor symptoms are typical in Parkinson’s disease (PD), with potential implications on disease course. Imaging modalities have demonstrated asymmetry, including thinning of motor-related cortex in the contralateral hemisphere of symptomatic side. The objective is to assess correlation between lateralized symptoms and Diffusion Tensor Imaging (DTI) characteristics of pyramidal tract. Methods: 34 PD patients and 30 controls were evaluated. Disease dominance was assessed using UDPRS III. DTI was performed with 60-directional 3Tesla MRI protocol. A 1cm3 subcortical region of interest was positioned underneath motor cortex. Primary outcome was the difference in fibers between disease-dominant and non disease-dominant cortex. Results: There was a significantly higher number of fibers in the hemisphere corresponding to disease dominance (p=0.0031). The same was true for seed number (p=0.0032) and fractional anisotropy (p=0.0427). Based on 23 patients operated on, the threshold for stimulation-induced side effects on the left side was inversely correlated with number of fibers in left ROI (Spearman -0.497, p=0.0158). Conclusions: Based on current literature we expected a reduction of fibers in the contralateral hemisphere to symptom dominant side. Surprisingly, DTI analysis showed an inverse correlation. The underlying pathophysiology remains unclear with the possibility of a compensatory mechanism or compacting of fibers underneath a shrinking motor cortex.

Background: Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultra-high frequency (UHF) spinal cord stimulation at 10kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. Methods: We studied the effects of conventional (130Hz) and UHF stimulation in five patients with Parkinson’s disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. Results: Motor performance improved in all six patients with UHF DBS. 10kHz stimulation at amplitudes ≥3.0mA appeared to be as effective as 130Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, p=0.110, N=90 trials). Interestingly, 10kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130Hz stimulation. Conclusions: Our results indicate that DBS at 10kHz produces clinical benefits while possibly reducing stimulation-induced adverse effects in patients with movement disorders.

Background: Central neurocytoma’s are typically located in the lateral ventricles and are optimally treated with surgical resection. Surgical entry into the ventricles are associated with a number of complications, including subdural hygroma and shunt-dependent hydrocephalus. Methods: We report a patient who developed acute bilateral uncal herniation from progessively enlarging subdural hygromas following intraventricular tumour resection. Results: A 60-year-old female underwent minimally invasive transcortical transventricular resection of an intraventricular CN. The patient’s postoperative course was complicated by repeated presentations to the emergency department due to persistent and intractable nausea and headaches, without focal neurological deficits. Imaging demonstrated small bilateral subdural hygromas. The patient eventually presented with acute deterioration in her level of consciousness with clinical and radiologic evidence of bilateral uncal herniation, requiring urgent insertion of a subdural drain to treat elevated intracranial pressure (ICP). After insertion of a ventriculoperitoneal shunt, the patient was discharged in stable condition and is currently followed by the multi-disciplinary neuro-oncology team. Conclusions: Bilateral subdural hygroma could mask underlying external hydrocephalus post transventricular surgeries. Patients who are symptomatic from bilateral subdural hygromas after transventricular resection of tumors should be carefully monitored for radiographic or clinical progression, in order to avoid acute deterioration caused by elevated ICP.

Background: Endoscopic endonasal trans-sphenoidal surgery (EETS) is a commonly used approach for the surgical treatment of primary pituitary adenomas. The role of this approach in patients with recurrent disease remains unclear. Here we review a high-volume institutional experience with repeat EETS for recurrent pituitary adenomas and compare outcomes against primary surgeries. Methods: A retrospective chart review of patients who underwent EETS at Toronto Western Hospital from 2008-2016 for pituitary adenomas was completed. Baseline patient characteristics and surgical outcomes were recorded for each surgery. Primary and repeat operations were compared for analysis using Fisher’s exact test and t-test where appropriate. Results: 347 primary and 48 repeat surgery patients were identified. The median follow-up was 3.6 years (range 0-10.6 years). Rates of GTR, optic decompression, endocrinopathy cure, and visual improvement in repeat EETS were 44%, 21%, 22%, and 21%, respectively. While these rates are lower when compared to primary surgeries (75% p<0.001, 58% p<0.001, 75% p=0.01, 37% and p=0.04), they demonstrate that desirable outcomes are still achievable after EETS for recurrent disease. Conclusions: These results from a quaternary-care centre suggest that repeat EETS is a viable option that is safe and effective at improving the visual and endocrine status in select patients with recurrent pituitary disease.

Background: Although previous research has suggested that patients with incidentally discovered low-grade gliomas (iLGG) who undergo surgery prior to the appearance of symptoms have improved outcomes compared to those who are symptomatic, an ideal approach to managing iLGG is not well-established. The purpose of this systematic review is to identify all cases of iLGG in the literature and characterize the effect of the timing of surgery on survival. Methods: We searched EMBASE, MEDLINE, and PubMed for articles related to iLGG. After duplicates were removed, the articles were then screened based on strict inclusion and exclusion criteria. Results: We retrieved 24/1377 unique articles with a total of 175 patients who underwent surgery for iLGG prior to symptoms appearing. The average age was 29.1yrs (range 1-62) and the mean follow-up period was 56 months (range 1-234months). Unfortunately, only 6/24 articles reported progression-free survival (average 32.4months) and only 1/24 reported 10-year survival. Conclusions: The articles we identified favored an early intervention for iLGG, however, there was a considerable lack of long-term follow-up and survival data to justify such a claim. Further studies need to be performed with adequate follow-up data in order to determine the optimal timing of surgical intervention for these patients.

Background: The Endoscopic endonasal approach (EEA) has become increasingly popular in the treatment of suprasellar meningiomas, which often cause visual symptoms due to compression of the anterior optic apparatus. Methods: We performed a retrospective chart review on patients who underwent EEA optic nerve decompression and resection of suprasellar meningiomas between January 1st 2005 and December 1st 2018 at McMaster University. Results: The mean age of our patients was 59.8 years. We treated 9 male and 23 female patients, with a mean follow up of 6.29 years. 23 patients (71.9%) presented with visual symptoms, with a mean duration of 8.65 months. In our patient cohort, 95.5% had stable or improved visual acuity postoperatively. Less than six months of visual decline was more likely to be associated with postoperative improvement of visual acuity, with an odds ratio (OR) of 0.0222 (95% CI: 0.0017–0.289, p<0.05); as well as visual field (OR:0.0625; 95% CI, 0.0042–0.915, p<0.05). Additionally, the absence of RAPD was associated with improved postoperative visual acuity (OR: 0.0675; 95% CI, 0.0354–0.706, p<0.05). Conclusions: Endoscopic endonasal approach can achieve good visual outcome in patients harboring suprasellar meningiomas. Symptom duration of less than six months and absence of RAPD were positive predictor of postoperative visual outcome.

Background: Surgical managment of eloquent lesions in the brain require a multidisciplinary approach. Radiographic imaging, such as magnetic resosnance, can provide details of “normal” anatomy however are limited when lesions can distort/displace due to mass effect or neuroplasticity. Functional MRI (fMRI) has limitations due to patient dependent actions can often be limited due oncological or vascular lesions but known to still be near or involving “eloquent” cortex. Navigated transcranial magnetic stimulation (nTMS) provides the physician with the ability to accurately (~2mm error) stimulate cortex of the brain, in a clinical setting, and to understand function of areas of motor and language and incorporate this information into the surgical theatre. Methods: We will present a personal expierience of complex oncological and vascular cases to illustrate how nTMS can assist in the determination of surgical approaches and educating patients of potential morbidities. Will also review potential research opportunities that nTMS provides. Details of Phase 2 clinical trial of nTMS for improving neuro-cognitive outcomes will be discussed. Results: Case ilustrations will be provided. Preliminary results of Phase 2 clinical study will be discussed. Conclusions: Navigated TMS provides another tool in the armamentarium of neurosurgeons to better manage and approach complex and eloquent lesions in the brain.

Background: Gross total resection of pediatric posterior fossa tumors is paramount towards improving progression-free survival.

Fluorescein accumulates in tumoral tissue, where the blood-brain barrier is disrupted. It can therefore potentially aid in differentiating tumoral versus normal tissue. We aimed to evaluate the efficacy of fluorescent-guidance (using fluorescein) towards the resection of a pediatric cerebellar tumor, as the index case at our institution using this technique. Methods: 5 mg/kg of IV fluorescein sodium was injected upon induction of general anesthesia. During tumor resection, a yellow 560-nm filter (Kinevo microscope, Zeiss) was employed for fluorescent-guidance. The extent of resection was assessed via post-operative MRI. Results: There were no adverse side effects experienced by the patient. Tumoral material was clearly visualized under the yellow 560-nm filter, allowing for satisfactory gross total resection of the lesion (confirmed on post-operative MRI). Preliminary pathology was consistent with medulloblastoma. Conclusions: Fluorescent-guided resection of pediatric posterior fossa tumors appears to be a safe and useful adjunct for gross total resection of these lesions. To the best of our knowledge, this is the first reported case in Canada wherein IV fluorescein was used under a yellow 560-nm filter for resection of a posterior fossa medulloblastoma in a child.

Background: Postoperative follow-up of non-functioning pituitary adenomas (NFAs) occasionally detects residual or recurrent disease. Subsequent treatment options range from continued follow-up, to re-resection or radiotherapy. To better understand current practice patterns on this topic, we surveyed neurosurgeons and radiation oncologists in Canada. Methods: Skull-base neurosurgeons and radiation oncologists across Canada were invited to complete a 25-item online questionnaire. Summary statistics were computed and 2-tailed t-tests were performed to assess significance. Results: 33 participants returned completed questionnaires: neurosurgeons (n=20, 61%) and radiation oncologists (ROs; n=13, 39%). When treating giant (>3cm) tumours, 92% of neurosurgeons in practice for less than 15 years use an endoscopic approach, as compared to only 57% of neurosurgeons in practice for 15 years or more. Additionally, younger neurosurgeons have a greater tendency to advocate for stereotactic radiosurgery (SRS) or re-resection (54% and 38%, respectively), as compared to older surgeons who show a higher propensity (29%) to advocate for observation. The presence of cavernous sinus extension appears to encourage neurosurgeons (40%) to offer radiotherapy sooner, as compared to 62% of ROs. Conclusions: Our results identify both variations and commonalities in practice amongst Canadian neurosurgeons. Approaches deviate in the setting of residual tumors based on years of practice.

Background: It is well understood that gliomas require vast supply of energy to proliferate, invade and spread. We wished to identify novel biomarkers by comparing normal brain and plasma to high and low grade gliomas using newer techniques in laser ionization mass spectroscopy - precision metabolomics and lipidomics. Methods: Single center IRB approved tissue bank of “normal” brain and plasma (n=6) and IDH wild-type GBM tissue and plamsa (n=29), IDH mutant GBM tissue and plamsa (n=6), Low grade glioma (n=4) tissue and plamsa were analyzed for over 2000 endogenous metbolites and complex lipids. Unbiased clustering and Random Forest plots and pathway analysis were performed with appropriate statsitical analysis (significance p < 0.05). Results: IDH mutant GBM had higher levels of 2-HG, however, plasma 2-HG did not reflect IDH genotype. Changes in glucose and fatty acid utilization were observed in IDH WT and mutant gliomas compared to normal brain tissue. Lipidomics of plasma and tissue of normal and gliomas did not reveal a biomarker reaching statistical significance. Conclusions: We will continue to investigate if plasma and tissue biomarkers including hypotaurine, methionine, branched chain amino acid catabolites and pregnonolone can be used to predict tumor progression, response to treatment and clinical outcomes.

Background: The Novalis Certification Program is dedicated to providing a comprehensive and independent assessment of safety and quality in stereotactic radiosurgery (SRS). Methods: The program includes an independent review of SRS program structure, adequacy of personnel resources and training, appropriateness and use of technology, program quality management, patient-specific quality assurance and equipment quality control. Centres applying for Novalis Certification complete a self-study prior to a one-day visit by reviewers. Reviewers generate a descriptive 77-point report which is voted on by a multidisciplinary expert panel. Outcomes of reviews include mandatory requirements and optional recommendations, with the former requiring resolution prior to award of Certification. Sites undergo recertification every 4 years. Results: To date, 42 institutions have received Novalis Certification. A further 140 certification applications are pending. Two sites have been recertified, with 4 more in process this year. Analysis of review outcomes identified improved documentation of procedures as a frequent requirement, while frequent recommendations pertain to equipment/systems QA procedures and effective use of checklists/time outs. Conclusions: Novalis Certification is a unique, expanding peer review program assessing safety and quality in SRS and recognizing a high caliber of practice internationally. The standards-based approach highlights outstanding requirements and provides recommendations to enhance both new and established programs.

Background: Molecular signatures are being increasing used to classify central nervous system (CNS) tumors with incorporation into World Health Organization (WHO) classifications. A recently published genome-wide DNA methylation-based CNS tumor classifier assisted in diagnostically challenging cases. However its impact on patient care has not been reported, limiting translation to other centres. Methods: All 55 challenging CNS tumour diagnoses over three years underwent DNA methylation profiling. Tumor classification along with copy number variant (CNV) plot results were integrated with histopathological findings to determine final diagnoses and corresponding clinical impact was assessed. Results: After methylation profiling 46/55 (84%) received clinically relevant diagnostic changes, 30 (55%) with a new diagnosis or resolved differential diagnosis and 16 (29%) with clinically important molecular diagnostic or subtyping changes. WHO grade changed in 15 (27%), with two-thirds upgraded. Nine new IDH mutations in gliomas, four new molecular subtypes in medulloblastomas/ependymomas, and three false positive 1p/19q codeletions were identified. Patient care was directly changed by methylation profiling in 7/47 (15%) followed-up cases to avoid unnecessary treatment in three, insufficient treatment in three, and medically assisted death in one. Conclusions: This real-world use of methylation-based CNS tumor classification substantially impacts patient care for diagnostically challenging tumors and also avoids misdiagnosis-related uncessary resource use.

Background: Meningiomas are the most commonly occurring benign intracranial tumors. When presenting with peritumoral brain edema (PTBE), surgical treatment can lead to patient morbidity. This retrospective case series aims to describe the conservative medical management of moderate to large meningiomas with large PTBE. Methods: Patients with suspected meningiomas greater than 2.0cm and edema index greater than 2.0 were identified by screening 3345 MRI scans between 2012-2017. Imaging analysis included MR imaging features of suspected meningiomas and clinical data was gathered from the electronic patient record (patient age, sex, patient symptoms, follow-up duration, and follow-up symptoms). Results: We report on 31 patients who received conservative medical management. Presenting complaints included headache, seizure, weakness; many presented asymptomatically. The average follow-up time was 3.96 years. At the final follow-up appointment, 19 (61%) patients were asymptomatic. Among symptomatic patients, seizures were the most common complaint. There was no mortality reported in our cohort and the average tumor progression was 7.04cm3/year. Conclusions: In this retrospective report of meningioma patients with high edema index, we found that most patients remained asymptomatic or had stable symptoms after at least 1-yr follow up after medical treatment. This study provides insight around the surgical decision-making for meningiomas with large spread of edema.

Background: The Endoscopic endonasal approach (EEA) has been gaining popularity in the past decade as an alternative to traditional transcranial and transorbital approaches. We have performed orbital apex decompression for a variety of pathological entities. Methods: We performed a retrospective chart review on patients who underwent EEA orbital apex decompression between January 1st 2010 and December 1st 2018 at McMaster University. Results: Eight patients underwent endoscopic endonasal orbital decompression at our center, including five male patients and three female patients. The mean age of our patients was 50.1 years. The different pathologies we treated included nasopharyngeal carcinoma, hemangioma, fibrous dysplasia, IgG4 disease, inverted papilloma, angioleiomyoma, and neuroendocrine paraganglioma. Five patients presented with visual symptoms. Postoperatively, one of these five patients improved to baseline, three had stable vision, another one had progressive visual decline despite surgical intervention. Conclusions: Endoscopic endonasal approach can be used as an alternative to decompress orbital apex pathologies in selected patients.