Background: The semantic variant of primary progressive aphasia (svPPA) is a form of dementia, mainly featuring language impairment, for which the extent of white matter (WM) damage is less described than its associated grey matter (GM) atrophy. Our study aimed to characterise the extent of this damage using a sensitive and unbiased approach. Methods: We conducted a between-group study comparing 10 patients with a clinical diagnosis of svPPA, recruited between 2011 and 2014 at a tertiary reference centre, with 9 cognitively healthy, age-matched controls. From diffusion tensor imaging (DTI) data, we extracted fractional anisotropy (FA) values using a tract-based spatial statistics approach. We further obtained GM volumetric data using the Freesurfer automated segmentation tool. We compared both groups using non-parametric Wilcoxon rank-sum tests, correcting for multiple comparisons. Results: Demographic data showed that patients and controls were comparable. As expected, clinical data showed lower results in svPPA than controls on cognitive screening tests. Tractography showed impaired diffusion in svPPA patients, with FA mostly decreased in the longitudinal, uncinate, cingulum and external capsule fasciculi. Volumetric data show significant atrophy in svPPA patients, mostly in the left entorhinal, amygdala, inferior temporal, middle temporal, superior temporal and temporal pole cortices, and bilateral fusiform gyri. Conclusions: This syndrome appears to be associated not only with GM but also significant WM degeneration. Thus, DTI could play a role in the differential diagnosis of atypical dementia by specifying WM damage specific to svPPA.

Introduction: White matter hyperintensities (WMHs) were commonly seen in brain magnetic resonance imaging (MRI) of the elderly. Many studies found that WMHs were associated with cognitive decline and dementia. However, the association between WMHs in different brain regions and cognitive decline remains debated. Methods: We explored the association of the severity of WMHs and cognitive decline in 115 non-demented elderly (≥50 years old) sampled from the Wuliqiao Community located in urban area of Shanghai. MRI scans were done during 2009–2011 at the beginning of the study. Severity of WMHs in different brain regions was scored by Improved Scheltens Scale and Cholinergic Pathways Hyperintensities Scale (CHIPS). Cognitive function was evaluated by Mini-Mental State Examination (MMSE) every 2 to 4 years during 2009–2018. Results: After adjusting for confounding factors including age, gender, education level, smoking status, alcohol consumption, depression, hypertension, diabetes, hyperlipidemia, brain infarcts, brain atrophy, apoE4 status, and baseline MMSE score, periventricular and subcortical WMH lesions as well as WMHs in cholinergic pathways were significantly associated with annual MMSE decline ( p < 0.05), in which the severity of periventricular WMHs predicted a faster MMSE decline (–0.187 points/year, 95% confidence interval: –0.349, –0.026, p = 0.024). Conclusions: The severity of WMHs at baseline was associated with cognitive decline in the non-demented elderly over time. Interventions on WMH lesions may offer some benefits for cognitive deterioration.

Background: Advances in multiple sclerosis (MS) disease modifying therapy (DMT) have increased laboratory monitoring requirements. Our goal was to survey existing practices and perceptions of risk in laboratory monitoring throughout Canada and assess whether opportunities to improve patient care and safety exist. Methods: A web-based survey assessing prescriber demographics, current infrastructure, and concerns for lab monitoring was sent to the Canadian Network of MS Clinics (CNMSC) listserv, inviting MS clinicians across the country to participate. Results: Respondents included 32/65 CNMSC-affiliated neurologists (49%), 6 registered nurses (RN), 2 nurse practitioners (NP), and 2 non-neurologist physicians from 8/10 provinces. For some questions, analysis was limited to 34 DMT-prescribing clinicians only. Despite broad implementation of electronic medical records (25/34, 74%), many prescribers (15/34, 44%) still receive laboratory results in paper form. In terms of lab monitoring infrastructure, we noted regional variability in the employment of nursing to monitor patient compliance with required laboratory monitoring. There is also a gap in laboratory surveillance, as less than 5% of respondents reported regularly reviewing results on weekends. Providers’ length of practice and volume of MS patients were not associated with different perception of DMT laboratory monitoring risk. Conclusions: This nation-wide survey showed variability in infrastructure used in laboratory monitoring and regional variation in nursing involvement. Providers’ level of concern for laboratory monitoring for DMTs did not vary by years of experience or volume of MS patients followed, suggesting that improved systems, rather than education, could ameliorate perceptions of risk.

Background: Continuous EEG monitoring, in the form of amplitude-integrated (aEEG) or conventional EEG (cEEG), is used in the neonatal intensive care unit (NICU) to detect subclinical central nervous system pathologies, inform management, and prognosticate neurodevelopmental outcomes. To learn more about provider attitudes and current practices in Canada, we evaluated neurologist and neonatologist opinions regarding NICU EEG monitoring. Methods: A 15-item electronic questionnaire was distributed to 114 pediatric neurologists and 176 neonatologists working across 25 sites. Results: The survey was completed by 87 of 290 physicians. Continuous EEG monitoring is utilized by 97% of pediatric neurologists and 92% of neonatologists. Neurologists and neonatologists differ in their EEG monitoring preferences. For seizure detection and diagnosis of encephalopathy, significantly more neonatologists favor aEEG alone or in combination with cEEG, whereas most neurologists prefer cEEG (p = 0.047, 0.001). There is a significant difference in the perceived gaps in monitoring patients with cEEG between neonatologists (13% would monitor more) and neurologists (41% would monitor more) (p = 0.007). Half of all respondents (53%) reported that they would be interested in attending an education session on neonatal EEG monitoring. Conclusions: Canadian neurologists and neonatologists do not agree on the best monitoring approach for critically ill neonates. Furthermore, neonatologists perceive a smaller cEEG monitoring gap as compared with neurologists. However, many participants from both specialties would like to increase long-term EEG monitoring in the NICU setting. Facilitating access to EEG monitoring and enhancing education may help to address these needs.

Introduction: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Background: Post-craniotomy pain can be severe and is often undermanaged. Opioids can interfere with neurological monitoring and are associated with adverse effects. This systematic review aimed to identify measures of opioid-free analgesia and compare their effectiveness with opioid analgesia for post-craniotomy pain in patients with supratentorial tumors. Methods: EMBASE, MEDLINE, and Cochrane databases were searched from their inception to February 14, 2017, for randomized controlled trials (RCTs) evaluating opioid versus non-opioid analgesia post-supratentorial craniotomy. Two reviewers independently carried out study selection and data extraction. Risk of bias assessment was performed using the Cochrane Collaboration’s tool. Outcomes were pain control (changes to pain scores or use of rescue analgesia) and adverse effects. Considering the number of studies and heterogeneity, a narrative synthesis was done without pooling and results were summarized using tables. Non-opioids were assessed for the potential to be equivalent to opioid-based analgesics for pain relief and adverse effects. Results: Of 467 RCTs, 4 met our inclusion criteria (n = 186 patients). Patients with scalp blocks (2 RCTs) had less post-operative nausea and vomiting (PONV), but scalp block was not superior to morphine for analgesia. Acetaminophen (1 RCT) was less likely to induce PONV but provided inadequate pain relief compared to morphine and sufentanil. Dexmedetomidine (1 RCT) was not superior to remifentanil for analgesia although it delayed time to rescue analgesia. Conclusions: Limited evidence suggests that scalp blocks and dexmedetomidine have the potential to eliminate the need for opioid analgesia. Multimodal analgesia should be considered as significant opioid-sparing effects have been shown.

Introduction: Controversy exists in antiepileptic drug (AED) prophylaxis prescribing in patients with aneurysmal subarachnoid hemorrhage (SAH). We undertook the Use of Antiepileptic Drugs in Aneurysmal Subarachnoid Hemorrhage (ALIBI) study to identify factors associated with prescribing practices. Methods: A retrospective chart review of all consecutive patients requiring Level 1 care with aneurysmal SAH admitted between 2012 and 2014 to the intensive care unit at Toronto Western Hospital, Ontario, Canada, was conducted. Data were collected on clinical and imaging characteristics. Primary and secondary outcomes were AED prophylaxis and clinical seizure activity during hospitalization. Data were compared using chi-square or Mann–Whitney U-tests. Those variables found to be significant, or trending toward significance, on univariate analysis were fitted to multivariate regression. Results: Sixty-eight patients were included. Mean age was 62 ± 12.2, and 42.6% of patients were male. Of these, 21 patients (30.9%) received AED prophylactically, while 18 (26.5%) had reported seizures at some point during hospitalization. Female gender and presence of midline shift (MLS) were significantly associated or approached significance with AED prophylaxis in univariate analysis (p = 0.036 and p = 0.062, respectively). In multivariate analysis, only MLS was an independent predictor (odds ratio 5.09, p = 0.04). Conclusion: The presence of MLS was an independent predictor of seizure activity in patients with aneurysmal SAH. AED prophylaxis prescribing patterns seemed arbitrary and was not informed by identifiable clinical factors or true risk factors for seizure. A current lack of evidence guiding AED prescribing practice highlights the need for larger studies in this patient population.

Background: Cervical spondylotic myelopathy (CSM) is the leading cause of spinal cord impairment. In a public healthcare system, wait times to see spine specialists and eventually access surgical treatment for CSM can be substantial. The goals of this study were to determine consultation wait times (CWT) and surgical wait times (SWT), and identify predictors of wait time length. Methods: Consecutive patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) prospective and observational CSM study from March 2015 to July 2017 were included. A data-splitting technique was used to develop and internally validate multivariable models of potential predictors. Results: A CSORN query returned 264 CSM patients for CWT. The median was 46 days. There were 31% mild, 35% moderate, and 33% severe CSM. There was a statistically significant difference in median CWT between moderate and severe groups; 207 patients underwent surgical treatment. Median SWT was 42 days. There was a statistically significant difference in SWT between mild/moderate and severe groups. Short symptom duration, less pain, lower BMI, and lower physical component score of SF-12 were predictive of shorter CWT. Only baseline pain and medication duration were predictive of SWT. Both CWT and SWT were shorter compared to a concurrent cohort of lumbar stenosis patients (p <0.001). Conclusions: Patients with shorter duration (either symptoms or medication) and less neck pain waited less to see a spine specialist in Canada and to undergo surgical treatment. This study highlights some of the obstacles to overcome in expedited care for this patient population.

Background: As with other specialties, Royal College of Physicians and Surgeons of Canada (RCPSC) trainees in Neurosurgery have anecdotally had challenges securing full-time employment. This study presents the employment status, research pursuits, and fellowship choices of neurosurgery trainees in Canadian programs. Methods: RCPSC neurosurgery trainees (n = 143) who began their residency training between 1998 and 2008 were included in this study. Associations between year of residency completion, research pursuits, and fellowship choice with career outcomes were determined by Fisher’s exact test (p < 0.05, statistical significance). Results: In 2015, 60% and 26% of neurosurgery trainees had permanent positions in Canada and the USA, respectively. Underemployment, defined as locum and clinical associate positions, pursuit of multiple unrelated fellowships, unemployment, and career change to non-surgical career, was 12% in 2015. The proportion of neurosurgery trainees who had been underemployed at some point within 5 years since residency completion was 20%. Pursuit of in-folded research (MSc, PhD, or non-degree research greater than 1 year) was significantly associated with obtaining full employment (94% vs. 73%, p = 0.011). However, fellowship training was not significantly associated with obtaining full employment (78% vs. 75%, p = 1.000). Conclusions: Underemployment in neurosurgery has become a significant issue in Canada for various reasons. Pursuit of in-folded research, but not fellowship training, was associated with obtaining full employment.

Background and Objectives: Federal and provincial governments in Canada are promoting provincial legislation to prevent and manage sport-related concussions (SRCs). The objective of this research was to determine the incidence of concussions in high school sport, the knowledge of the signs, symptoms, and consequences of SRC, and how likely student athletes are to report a concussion. Methods: A cross-sectional survey of athletes (N = 225) from multiple sports in five high schools in one Manitoba school division was conducted. Results: Participants in this study were well aware of the signs, symptoms, and consequences of SRC. Cognitive and emotional symptoms were the least recognized consequences. SRC is prevalent in high schools in both males and females across all sports. Of the 225 respondents, 35.3% reported having sustained an SRC. Less than half (45.5%) reported their concussion. Athletes purposely chose not to report a concussion in games (38.4%) and practices (33.8%). Two major barriers to reporting were feeling embarrassed (3.4/7) and finding it difficult (3.5/7) to report. There was, however, strong agreement (Mean 5.91/7, SD 0.09) when asked if they intend to report a concussion should they experience one in the future. Conclusions: The results suggest that high school athletes would benefit from more SRC education. Coaches and team medical staff must be trained to be vigilant for the mechanism, signs, and symptoms of injury in both game and practice situations. This study will also inform the implementation of pending legislation in Manitoba and perhaps other provinces in Canada.

Natalizumab is an efficacious disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS), often limited by risk of progressive multifocal leukoencephalopathy. We describe the clinical course of RRMS patients switched from natalizumab to another DMT. We identified all RRMS patients treated with natalizumab ≥3 months with JC virus antibody positivity who switched to another DMT. Overall, 84 individuals switched DMT with 57 (68%) beginning fingolimod. On fingolimod, survival without a relapse was 74% (55.8–85.6%) at 36 months and survival without disease progression was 78% (62.6–87.6%) at 36 months. In conclusion, fingolimod is an effective therapy post-natalizumab.

We report three brothers born to consanguineous parents of Syrian descent, with a homozygous novel c.324G>A (p.W108*) mutation in PTRH2 that encodes peptidyl-tRNA hydrolase 2, causing infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We describe the core clinical features of postnatal microcephaly, motor and language delay with regression, ataxia, and hearing loss. Additional features include epileptic seizures, pancreatic insufficiency, and peripheral neuropathy. Clinical phenotyping enabled a targeted approach to the investigation and identification of a novel homozygous nonsense mutation in PTRH2, c.324G>A (p.W108*). We compare our patients with those recently described and review the current literature for IMNEPD.

Community stroke rehabilitation (CSR) is an effective program for survivors to recover at home supported by a multidisciplinary team. A home-based, specialized CSR program was delivered in Windsor, Ontario, to stroke patients who faced barriers to accessing outpatient services following inpatient rehabilitation. Preliminary results show program patients made significant functional improvements from baseline to program discharge. A subgroup analysis revealed that, after adjusting for age and resource intensity, moderate to severe stroke patients made greater functional gains compared to mild stroke patients. The individualized focus of CSR delivered in the home provides an effective model of rehabilitation for continued stroke care in the community.