Guidelines recommend Botulinum toxin-A (BoNT-A) after deep brain stimulation (DBS), although the effectiveness of their combined use is uncertain. A chart review of Parkinson’s disease (17) and dystonia (7) patients undergoing 302 injections with IncobotulinumtoxinA before or after DBS was performed. Patients with cervical dystonia received less IncobotulinumtoxinA after DBS (290.7 ± 124.0 vs. 192.4 ± 131.4, p = 0.005) and experienced an increased benefit (4.0 ± 3.4 vs. 8.4 ± 3.6 weeks, p = 0.003). No significant differences were found when comparing the treatment outcomes of 14 patients who received both IncobotulinumtoxinA and OnabotulinumtoxinA after DBS. The use of BoNT-A after DBS is a useful strategy although prospective studies are needed.

Background: People with Parkinson disease (PD) face progressive mobility loss, but medical treatment is dependent on clinical assessment and examination. Regional patient and physician density patterns pose further problems to accessing care. Telehealth may improve access particularly among rural populations, but an approach to this problem should consider patient perspectives. Methods: We surveyed and conducted a focus group for people with PD and their caregivers. Questions assessed perceptions of barriers to neurological care and use of telehealth for PD management. Thematic analysis was performed to classify qualitative data. Results: 18 individuals completed the survey and 7 parties joined the focus group. 52% of participants travel >50km for neurologist appointments (range = 59 to 842km). Perceived barriers include cost and difficulty of travel, wait times, lack of interdisciplinary healthcare and deep brain stimulation outside large cities. 80% of participants (95% C.I. 64-96%) would likely or very likely use telehealth for follow-up neurologist appointments if proven as good as in-office visits. Participants associated telehealth with improved quality of care, improved access to care, and cost savings. Conclusions: This sample of people with PD and their caregivers report willingness to access care via telehealth to reduce perceived cost and travel for specialty care.

Background: We recently demonstrated that late functional improvement between 3-12 months post-stroke occurs in about one-fourth of patients with ischaemic stroke. It is unknown whether this improvement is associated with better long-term clinical or health-economic outcomes. Methods: In a prospective, population-based cohort of 1-year ischaemic stroke survivors (Oxford Vascular Study;2002-2014), we determined changes in functional status (modified Rankin Scale[mRS], Rivermead Mobility Index[RMI], Barthel Index[BI]) from 3-12 months post-stroke. We examined the association of late improvement (by ≥1 mRS grades, ≥1 RMI points, and/or ≥2 BI points) with 5-year mortality, institutionalization (Cox regressions), and health/social-care costs (generalized linear models), adjusted for age/sex/3-month disability/stroke subtype. Results: Among 1,288 1-year survivors, 1,135 had 3-month mRS>0, with 319(28.1%) demonstrating late improvement. 1-year survivors with late mRS improvement had lower 5-year mortality (aHR:0.68,95%CI 0.51-0.91,p=0.009), institutionalization (aHR:0.48,0.33-0.72,p<0.001), and costs (margin -$17,369,-25,271 to -9,469,p<0.001). These associations remained on excluding patients with recurrent strokes during follow-up (e.g. 5-year death/institutionalization aHR:0.59,0.44-0.79,p<0.001) and on examining late improvement per RMI and/or BI (e.g. 5-year death/institutionalization aHR:0.67,0.53-0.84,p=0.001). Conclusions: Late functional improvement post-stroke is associated with lower 5-year mortality, institutionalization, and costs. These findings should motivate patients and clinicians to maximize late recovery and encourage payers to consider access to rehabilitative services for at least 1-year post-stroke.

Background: Penetrating traumatic injuries to the clivus are rare. We describe the case of a 79-year-old man who presented to the emergency room with a butter knife protruding from his left cheek. Imaging showed the blade entering just beneath the left zygoma and transecting the clivus to terminate within the prepontine cistern. The tip of the knife abutted the right anterior inferior cerebellar artery and lower basilar artery. Methods: He was brought to the interventional neuroradiology OR with knife in place, by a combined surgical team of ENT, neurosurgery, and neuroradiology. Under local anaesthetic and intravenous sedation, vascular access to the distal left vertebral artery was obtained and a balloon positioned. Traction was applied to the knife and the knife was successfully removed avoiding any angular or rotational movements. An immediate angiogram showed no evidence of arterial injury. Results: The patient recovered uneventfully and was discharged home with no neurological deficit. Follow-up CT/CTA was performed a month later and confirmed no pseudoaneurysm or other complication. Conclusions: Management of penetrating skull base injuries by a multidisciplinary surgical team is advisable. Vascular imaging is crucial. Positioning of balloons within large vessels close to the penetrating object is recommended to control bleeding that may occur on removal.

Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.

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: The aim of this study was to investigate intraoperative methods to generate patient-specific PMMA bone implants during a craniotomy. The proposed methods combine a cost-efficient, and non-invasive structured light scanner (SLS) as an imaging modality and a prototype printer for rapid generation of implant molds. Methods: This simulation study was performed using retrospective data from three craniotomy patients. The extracted bone flap and the cranial defect were scanned using a SLS, which generates a 3D surface model of an object by projecting a series of light-patterns on it. Prototype printed implant models were generated using two different techniques. The molds were then used to shape PMMA bone implants. These implants were evaluated regarding their accuracy to reconstruct the natural skull anatomy and compared to freehand formed implants. Results: The patient-specific bone implants reconstructed the preoperative anatomy with an average RMS error of 1.37mm (StDev 0.27), compared to an error of 1.5mm (StDev 0.43) for the freehand shaped implants. On average the intraoperative scanning time was 4.7min. The average time to generate and print the implant molds was 204 min. Conclusions: Results of this study have shown great promise for the proposed method to be used for patient-specific bone flap reconstruction during craniotomies.

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: SMA1, a rapidly progressing disease, results in muscle weakness, respiratory failure, hospitalization, and early death. This study highlights the value of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy for SMA1. Methods: Twelve SMA1 patients received a one-time intravenous proposed therapeutic dose of AVXS-101 (CL-101; NCT02122952). Event-free survival (no death/permanent ventilation), pulmonary/nutritional interventions, swallow function, hospitalization rates, CHOP-INTEND, motor milestones, and safety were assessed (2-year follow-up). Results: By study end, all 12 patients survived event-free; 7 did not require non-invasive ventilation; 11 had stable/improved swallowing function (6 exclusively fed by mouth); 11 spoke. On average, patients experienced 1.4 (SD=0.41, range=0–4.8) respiratory hospitalizations/year. The mean proportion of time hospitalized was 4.4% (range=0–18.3%); mean unadjusted rate of hospitalization/year was 2.1 (range=0–7.6), with a mean hospital stay of 6.7 (range=3–12.1) days. CHOP-INTEND increased by 9.8 (SD=3.9) and 15.4 (SD=6.4) points at 1- and 3-months post-treatment. At long-term follow-up, 11 patients sat unassisted, 4 stood with assistance, and 2 walked. Adverse events included elevated serum aminotransferase levels, which were attenuated by prednisolone. Conclusions: AVXS-101 in CL-101 resulted in dramatic survival and motor function improvements. The reduced healthcare utilization in treated infants could decrease cost and alleviate patient, caregiver, and societal burden.

Background: Topiramate is an antiepileptic frequently used in pediatrics with multiple mechanisms of action. This includes carbonic anhydrase inhibition, which has unclear relevance to its antiepileptic effect. Metabolic acidosis, hypocitraturia and nephrolithiasis are known side-effects of carbonic anhydrase inhibition and can limit therapeutic effect. Alkali therapy may normalize acidosis, increase urinary citrate, and reduce nephrolithiasis risk. We hypothesize that provision of sodium bicarbonate supplementation to patients with topiramate-induced acidosis will mitigate these side-effects without worsening seizure frequency or severity. Methods: Pediatric patients on antiepileptic therapy with topiramate are being recruited from outpatient pediatric neurology clinics at McMaster Children’s Hospital. We aim to recruit 20 patients with metabolic acidosis and 20 control patients. Measures include blood gas, electrolytes, urine electrolytes and citrate. Patients with metabolic acidosis will be given daily sodium bicarbonate for one month, followed by repeat bloodwork. Seizure frequency will be prospectively documented in all participants throughout the three-month period. Results: Recruitment is ongoing, and three patients (1 with acidosis) have been recruited thus far. Results will be analyzed with chi-squared and paired T tests. Conclusions: This pilot study is the first to evaluate the safety and efficacy of sodium bicarbonate supplementation in patients receiving topiramate for seizure control.

Background: There are only few studies approaching the prevalence and cause of stroke in children and adults with Down Syndrome (DS). Methods: We did a retrospective study of our cohort of 4962 patients of Jerome Lejeune Institute since 2007. We collected age of stroke, clinical presentation, cause (TOAST classification), treatment and clinical course. Results: We identified 20 patients from 6 to 56 years old .In all cases, it was a stroke of ischemic origin.: 8 children with a prevalence of 0.33%. 4 had a cardio-embolic origin, 3 secondary to Moya-Moya syndrome and one of undetermined origin. 12 adults (21 to 52 years old) with a prevalence of 0.46%.The majority of the causes of these ischemic strokes are indeterminate (9 of 12), Conclusions: We found a low prevalence and an ischemic cause in all cases of stroke, which differs from the general population. For pediatric stroke, the causes are expected thromboembolic in a context of heart disease most often or secondary to a Moya-Moya syndrome. For adult strokes, the average age is younger than that in the general population and the cause is indeterminate in most cases. We must better explore our patients to identify the risk factors in DS population.

Background: In preparation for July 2019 rollout of competency-based design (CBD) in Canadian neurosurgery residency training, the University of Calgary launched a pilot-program of five representative EPAs using the One45 program. Our study objectives were to examine the uptake of CBD with residents and faculty and to quantify CBD implementation barriers. Methods: Phase one of the One45-based CBD pilot-program launched on November 1st, 2018 and ended on January 8th, 2019, after which a questionnaire was sent to each participating resident. The questionnaire examined number of EPAs initiated, measures of favourability, importance, ease of use, and barriers encountered. Results: Results obtained from the survey show 93.8% response rate (15/16 residents). 66.7% of residents feel that CBD is moderately important or higher to their education. Over the 10 study weeks, there were only 8 completed EPAs (expected was 50), five of which were completed by a single resident. Major expressed barriers of implementation of CBD were time involved (50.0%) and technical unfamiliarity with the platform itself (50.0%). Conclusions: This study demonstrates the critical importance of piloting a CBD program prior to official implementation as immediate buy-in was significantly slower than anticipated. Technical and time barriers exist which need to be rectified in advance of July 2019.