Background: Stroke is a rare neurological disease in children, with an annual incidence of 2 - 13/100,000 children per year. Pediatric stroke is associated with significant morbidity and mortality lasting many decades. Diagnosis of pediatric stroke is challenging and often delayed, limiting options for acute intervention, and the pharmacological and mechanical recanalization strategies that have revolutionized adult stroke remain undefined in children. Clinicians are left to draw conclusions from other retrospective cohort studies or case reports and extrapolate adult guidelines to the pediatric population. The TIPS trial eligibility criteria are often used in clinical practice, despite not being validated for this purpose. We present here the case of a healthy 14 year old male who was treated with intravenous tissue plasminogen activator (IV tPA) for a presumed arterial ischemic stroke without large vessel occlusion on neuroimaging. Methods: Retrospective chart review Results: Not applicable Conclusions: Following the administration of IV tPA, the patient made a full recovery. While we do not recommend the routine use of IV tPA for treatment of presumed large vessel or small vessel in children, we suggest that the decision to proceed with IV tPA be considered on a case-by-case basis.

Background: Genetically-determined leukoencephalopathies comprise a rare group of inherited white matter disorders. The vast majority are associated with a progressive disease course and early death. This study seeks to determine the clinical and demographic correlates of stress in parents of leukodystrophy patients, for future clinical guidance. Methods: A cross-sectional study including 36 families was performed. Children aged 1 month to 12 years with a diagnosed leukodystrophy or genetically-determined leukoencephalopathy were included. 31 mothers and 24 fathers completed the Parental Stress Index, 4th edition (PSI-4). One demographic questionnaire was completed per family. Clinical data was gathered within 6 months of the questionnaires. Statistical analysis was performed with total stress (TS) scores as the primary outcome. Results: Mothers and fathers had comparable TS scores. No clinical or demographic factors predicted the father’s TS score. Greater ambulatory impairment, using the GMFCS scale, correlated to lower TS scores in the mother. Conclusions: The progressive nature of these conditions makes it such that anticipating a child’s inability to walk may cause more stress for mothers than a child’s actual inability to ambulate. The inability of all other variables to predict total stress highlights a need for individualized approaches when addressing stress in these families.

Background: Fetal alcohol spectrum disorder (FASD) is used to describe the spectrum of birth defects due to prenatal alcohol exposure; these include craniofacial abnormalities and intellectual disabilities. The prevalence of FASD is estimated at 1 in 100. Diagnostic criteria include distinct facial features, neurodevelopmental deficits and confirmation of alcohol use during pregnancy. Unfortunately, often criteria are missed or absent. No biochemical marker is available for screening and diagnosis of FASD that is easy, accurate and cost-effective. Methods: Five children are being recruited from both the FASD clinic at the Glenrose Rehabilitation Hospital and the Healthy Infants and Children’s Clinical Research Program (HICUPP) registry. The levels of exhaled nasal NO will be measured and compared between the two groups. Metabolomics analysis on urine samples targeting metabolites of the NO pathway, along with other urinary metabolites is being performed. Bioinformatic statistical tools will be applied to determine whether measured metabolite profiles can provide distinct signatures between healthy children and children with FASD. Results: This project is ongoing. Conclusions: We hope to correlate NO levels with FASD, illustrating the relationship between NO, ciliopathies and development of FASD. As well, we hope to determine whether urinary metabolites may yield diagnostic markers of FASD.

Background: Pediatric neurology referral wait times are increasing, often leading to emergency department (ED) utilization. On average 5% of ED patients present with neurological symptoms and 35% of ED neurological diagnoses are revised after specialist review. A Stollery Rapid Access Neurology (RAN) clinic was created to decrease wait time, and initiate an efficient referral process. Methods: The RAN clinic ran weekly from March 2018 until February 2019. This was a prospective study approved by the University of Alberta ethics board. Inclusion criteria were met. Information was collected for diagnosis, along with confidential patient satisfaction surveys. Results: Seventy-five patients were referred, 49% from the ED. Wait time averaged 6 weeks. The most frequent referral reason was seizures, with 60% of referring diagnosis being correct. Prior to RAN appointment, 61% of patients presented to the ED, whereas only 0.1% returned in the following 3 months. Neurology follow up was required in 81% of patients. Overall satisfaction was ranked 9.6/10. Conclusions: The RAN clinic created an effective urgent triage method. Neurologist review revised 40% of diagnoses. This ongoing study reveals that a RAN clinic can reduce visits to the ED following appointment and initiate appropriate follow up. Future evaluation in cost effectiveness and telehealth appointments are required.

Background: Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is an increase in intracranial pressure due to unknown etiology. Presentation in infancy is extremely rare. Little is known about infantile IIH and age-specific treatment guidelines are lacking. Methods: Patient data was obtained from medical records at the Children’s Hospital of Eastern Ontario. A literature review of infantile IIH was performed. Results: A previously healthy 9-month-old boy presented with irritability, decreased appetite, and a bulging fontanelle. CT head imaging and cerebrospinal fluid studies revealed normal results. Symptoms transiently resolved after a lumbar puncture, but 11 days later, his fontanelle bulged again. A second lumbar puncture revealed an elevated opening pressure of 35 cm H2O and led to a diagnosis of IIH in accordance with the modified Dandy Criteria. Treatment with acetazolamide at a dose of 25 mg/kg/day was initiated and the patient remained symptom-free for 6 weeks, followed by another relapse. His acetazolamide was increased to 38 mg/kg/day, with no further relapses to date. Conclusions: A diagnosis of IIH is challenging in infants, since the patients cannot yet verbalize typical IIH-related symptoms, and papilledema is difficult to assess. If undetected and untreated, IIH may result in permanent visual deficits.

Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

Background: Down syndrome (DS) is the most common genetic cause of intellectual disability.Although progress in managing co-morbidities has improved life expectancy, no therapeutic options have showed to significantly improve intellectual deficiencies.The current focus of the pharmacological treatment of DS is on the improvement of the cognitive impairment that is probably due to neurodevelopmental alterations,neurotransmitter alterations and neurodegeneration,and is also targeted to the overexpression of selected genes on HSA21. Methods: We review the clinical trials of the last 5 years focusing on the cognitive improvement of children with DS. Results: We report the results of therapeutic trials concerning selective negative allosteric regulators of the GABAAa5 receptor, NMDA antagonists, Kinase inhibitors of DYRK1A, folinic acid and thyroid hormone supplementation, activators of serotonergic and cholinergic system. Conclusions: The incomplete understanding of individual phenotypic variability, natural history, lack of biomarkers, no adapted neuropsychological tests, placebo effect, epigenetic effect have limited our capacity to succeed, even when promising drugs are tested.We need new tools and models will allow a better understanding of the pathophysiology. We also need to create more sensitive and realistic outcome mesures to quantify disease and therapeutic efficacy. The association of different therapeutic agents (epidrugs included) with cognitive stimulation could be a future strategy.

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.