Background: Intracranial hemorrhage due to sagittal sinus thrombosis is an unusal inital clinical presentation and a series of 3 cases is presented. Methods: A retrospective study of stroke patients seen at the William Osler Health System between 2014 -2016. Results: 1: 43 y.o. female presented with headaches and right hemiparesis. CT and MRI/MRV showed L. parietal intra-cerebral hemorrhage and sagittal and transverse sinus thrombosis. She was treated with IV heparin and subsequent oral Warfarin but developed symptomatic left subdural hematoma which was successfully evacuated. Hypercoagulable workup was negative. Subsequent MRI/MRV showed resolution of her sinus thrombosis and received asparin only since. 2: 45 y.o. male presented with generalized seizure 10 days following a motor vehicle accident. Initial CT showed focal right frontal subarachnoid hemorrhage and subsequent MRI/MRV confirmed extensive sagittal sinus thrombosis. He was treated with IV heparin and subsequent Warfarin without any complications. 3: 32 y.o. male presented with generalized seizure. CT and MRI/MRV confirmed a large right temporal lobe intra-cerebral hemorrhage and extensive right transverse sinus and straight sinus thrombosis. He was successfully treated with IV heparin followed by oral Warfarin. Conclusions: Despite intracranial hemorrhage in patients with cerebral sinus venous thrombosis, they could be managed successfully with anticoagulation therapy and with careful clinical and neuro-imaging monitoring.

Background: Approximately 12-15% of patients with intracranial aneurysms (IA) have affected first-degree relatives, and are considered to have familial intracranial aneurysms (FIA). Individuals with FIA are at higher risk for aneurysm formation and subarachnoid hemorrhage. THSD1 is the only gene to be associated with nonsyndromic FIA at this time. Our study aims to find rare DNA variants that are major risk factors for FIA in our cohort of patients. Methods: To date we have enrolled 37 affected and 31 unaffected people from 16 families. We have done exome or genome sequencing on at least 1 person from each of 12 families. Results: A rare p.(R686W) variant in THSD1 was found in 1/12 families, but did not cosegregate fully with disease. While less attractive as the primary cause of FIA, we cannot rule out the potential modifying effects of THSD1 p.(R686W) in this family. A second candidate, an extracellular matrix gene within a chromosomal region previously implicated by familial mapping studies, contains rare variants in 4/12 of our families. All four variants are predicted to be damaging. Conclusions: Alongside environmental risk factors, individual FIA families may also have complex rare variant contributions to their disease, such as digenic and multi-locus contributions.

Background: Atrial fibrillation (AF) is an important risk factor for ischemic stroke but has no recognized screening method. Wearable devices have the potential to provide near continuous monitoring to detect AF. This systematic review evaluates the current state of software capable of detecting AF using wearable devices. Methods: We conducted a systematic search using PRISMA method of Medline, CENTRAL, PubMed and trial registries up to January 15, 2017. Abstracts and titles were screened, and relevant articles reviewed fully. English articles were selected if reporting on (1) software for AF detection (2) using heart rhythm signal, (3) theoretically applicable to wearable technology. Quality was evaluated with Cochrane GRADE. Results: Of 269 unique abstracts, 54 were identified for full review. 20 studies met inclusion criteria for algorithm accuracy analysis. Sensitivity and specificity ranged from 87.0 - 97.6% and 89.0 - 99.6%, respectively. 4 studies analyzed signal acquired using mobile devices with similar accuracy. Algorithms were potentially portable to wearable devices. Qualitative observations on the state and applicability of technology were made. Conclusions: Software analysing heart rhythm may be accurate for AF screening, but has not been tested on wearable devices. Such technology is promising but may be limited by hardware accuracy and high false positive rates.

Background: In patients with acute stroke, nasogastric (NG) tubes are commonly inserted for feeding when dysphagia is identified, and percutaneous endoscopic gastrostomy (PEG) tubes are placed for severe or persistent dysphagia. However, little is known regarding predictors of PEG insertion. Methods: We used the Ontario stroke registry from 2003-2013 to identify baseline characteristics of all patients with NG or PEG tube insertion after stroke. We used multiple logistic regression with backwards selection to determine variables that were independent predictors of PEG tube insertion during admission. Results: 4002 patients with NG and 1903 patients with PEG were included in the analysis. Independent predictors of PEG were: Age (80+ vs. <60; odds ratio [OR] 1.70), past history of stroke (OR 1.17), higher stroke severity (severe vs. mild stroke; OR 1.37), stroke unit admission (OR 1.46), and dysphagia screening (OR 1.52). Factors associated with reduced odds of PEG insertion were: Prior history of peptic ulcer disease (OR 0.70), prior independence (OR 0.78), dementia (OR 0.76), palliative status (OR 0.49), and thrombolysis (OR 0.66). *All p<0.01 Conclusions: The strongest predictors of PEG were older age, higher stroke severity, stroke unit admission and dysphagia screening. Patients with dementia had reduced odds of PEG. Thrombolysis also reduced odds of PEG and may be protective.

Background: Visuomotor learning can be elicited experimentally by displacing the target of a saccade during the ongoing eye movement. In healthy subjects, the resulting mismatch between expected and experienced visual error after saccade completion elicits a gradual adaptation of saccade amplitude. The goal of this project was to explore the role of cerebro-thalamo-cerebellar circuits in the dynamics of visuomotor learning. Methods: Patient RK is a 38-year-old right hand dominant male who suffered a focal thalamic stroke of the right thalamus, confined to ventral lateral posterior and ventral medial nuclei. We employed a standard saccadic adaptation paradigm and assessed dynamics of visuomotor learning by fitting a simple state-equation to saccade amplitudes towards the ipsi- and contralesional hemifield. Results: While RK was able to adapt saccade amplitudes in both directions, adaptation dynamics were different for leftward versus rightward saccades. Rightward, ipsilesional saccades exhibited a lower learning rate but similar retention of altered saccade metrics, compared to leftward, contralesional saccades. Conclusions: The present study assessed a patient with a focal lesion to the right cerebellar thalamus on a saccade adaptation paradigm. Results demonstrated slower visuomotor learning for saccades into the ipsilesional hemifield, suggesting an important contribution of cerebello-cortical projections mediated by thalamic relays for visuomotor learning.

Background: Earlier studies suggest that age and stroke severity are the main determinants in stroke patient disposition after rehabilitation. We examined these and other variables to determine those that correlated with returning home vs. long-term care (LTC). Methods: Chart review of ischemic stroke patients with initial alpha-FIM scores between 40 and 80 admitted to our Rehabilitation Unit from January 1, 2005 to December 31, 2014. Univariate and multivariate analyses were performed. Results: There were 162 suitable patients. 130 went home and 32 went to LTC. The multivariable analysis showed the following variables favored LTC disposition: age (1.2x increased risk with increased age, P<0.01), residence (17.5x increased risk if not starting at home, P<0.01), right vs. left hemisphere (5.4x greater risk with right hemisphere, p=0.01), bowel continence (10.6x greater risk if not continent, p<0.01), and caregiver (0.05x decreased risk if a caregiver is present, p<0.01). No differences were found for sex, diabetes mellitus, atrial fibrillation, previous stroke, congestive heart failure, COPD, obesity, hemianopsia or financial status. Conclusions: Numerous variables probably affect patient disposition after rehabilitation for acute ischemic stroke.

Background: Canadian Stroke Best Practices recommend early mobilization and engagement in activities after stroke to enhance recovery. StrokeEngine reports the use of music can further promote recovery by harnessing neuroplasticity. Using music to enhance participation in activities after stroke may impact favorably on outcome after stroke. Methods: This descriptive study will be offered to patients admitted on the stroke unit. Based on the music preferences of willing participants and guided by the physiotherapy assessment, music, singing or dance movements will be incorporated into extra-therapeutic activities using specific musical instruments matched to patient ability. The music-enhanced activity program includes at least 3 sessions per week with a trained volunteer and additional sessions with family members for the duration of the hospital stay. Each session will last between 20 and 30 mins. The program will run for six weeks. Results: Data on patient participation in daily therapy and activities on the stroke unit will be presented and compared to a similar group of stroke patients. Changes in patient stroke recovery parameters will be measured and reported on magnitude of change for future work. Conclusions: Innovative ways to enhance patient engagement early after a stroke can optimalize stroke recovery. This project will shed some light on the effects of a music-enhanced intervention

Background: SPH and VGH are the two largest tertiary care centers in BC’s Lower Mainland. Among those served are the low-SES, high-risk population of Vancouver’s Downtown East Side (DTES). We aim to characterize the changing epidemiology of infective endocarditis (IE) in this population from 1995 and 2014. To date, our database is among the world’s largest. Methods: 1337 cases were identified using ICD9/10 codes. A retrospective chart review was conducted to collect demographic data including HIV status, IVDU, neurologic complications and mortality. The cohort was dichotomized into IVDU and non-IVDU, and first (1995-2005) and second (2006-2014) decades. Data analysis was performed using univariate chi-square and t-tests. Results: Age at presentation has increased in the past decade (45 vs 55,p<0.001). Rates of IVDU and HIV have decreased significantly (50.5% vs 44.3%,p<0.001; 21.8% vs 7.9%,p<0.001, respectively). Neurologic complications were less frequent in non-IVDUs (16.5% vs 28.9%,p<0.01). Mortality was greater in those with neurologic complications (RR=2.6 95%CI:2.1-3.3,p<0.001). Patients with neurologic complications were more likely to undergo cardiac surgery (RR=1.6 95%CI:1.3-2.0,p<0.001). Conclusions: Our findings highlight the changing epidemiology of IE. Some discrepancies between our data and the existing literature may be accounted for by Vancouver’s unique DTES population. Further work characterizing this is ongoing.

Background: Dementia is more prevalent in women. Sex differences exist as the disease progresses (e.g. males are more likely to become aggressive). In many medical illnesses (e.g. cardiac disease), there are differences in presentation between men and women. The current study explores sex differences at the patients’ initial presentation to the Rural and Remote Memory Clinic (RRMC). Methods: Patients were referred to the RRMC in Saskatoon, Saskatchewan. Cognitive and demographic data were collected. Questionnaires included cognitive (e.g. Mini-Mental Status Examination) and daily living (e.g. Instrumental Activities of Daily Living) assessments. Results: Three hundred and seventy-five (159 male, 216 female) patients participated. Of these patients, 146 (49 male, 97 female) were diagnosed with Alzheimer’s disease. Males and females presented to the clinic at similar ages. Females were more likely to have a son or daughter caregiver and to live alone. Males were more likely to be currently working and to be a former smoker. No statistically significant differences were found for cognitive assessment scores. Conclusions: Analysis of the initial presentation of patients to the RRMC revealed females and males had similar presentation in measures of cognitive impairment. This may be reassuring for patients and their families knowing their family member, regardless of sex, is receiving equivalent referral to receive care.

Background: With a growing and aging population, the number of individuals with AD and dementias and their associated costs are expected to increase in Canada. Up to now, no national mechanism was in place to monitor the epidemiological burden of AD and dementias. This presentation will showcase the first CCDSS data available on these conditions. Methods: Through the CCDSS, a Federal/Provincial/Territorial partnership, health administrative databases are linked to collect data on chronic conditions. Using selected ICD-9(CM)/ICD-10 codes for AD and dementias, the validated case definition implemented to identify relevant cases aged 65+ is:

1+ hospitalizations; or

3+ physician claims within 2 years, with a 30-day-gap between each claim; or

1+ anti-dementia drug prescriptions.

Prevalence and incidence rates will be presented by 5-year age group, sex, province/territory, and fiscal year. Results: Overall, incidence and prevalence rates were higher in women. The prevalence rate approximately doubled between 5-year age groups and sex differences tended to widen with age. While aged-standardised data show increasing prevalence rates over time, incidence rates fluctuated but suggest a decline since 2009/10. Conclusions: CCDSS data can be used to monitor the burden of AD and dementias in Canada. This information is important for the assessment of prevention actions and the planning of health care resources.

Background: ILI has been in use in Canada since 2011 to treat advanced PD. We review the benefits and complications of ILI for PD in a tertiary movement disorders center in Canada. Methods: Detailed chart review of patients treated with ILI at including motor UPDRS scores, ILI pump and PEG-J tube complications. Patients and caregivers were interviewed at regular clinic follow up about their experience with ILI. Results: 13 patients received ILI [10M, 3F; mean age 65.6 yrs, range (51.8-79.5); PD duration 14.2 yrs, range (9.1-22.0); mean follow-up 1.8 yrs, range (0.2-4.8)]. Patients reported improvement in motor function, decreased dyskinesias and ‘OFF times’ [mean motor UPDRS: pre-ILI 37.1, 1-6months post-ILI 27.5]. Common complications included dislodgement, knotting or blockage of the jejunal tube extension requiring endoscopic re- insertion (29 incidents in 6 patients over 5 yrs). Four patients discontinued Duodopa treatment, for reasons of declining cognition, inability to care for the pump, and/or minimal benefit. Conclusions: ILI is useful for the treatment of advanced PD, in patients that can care for the pump apparatus.

Background: AHEM is a rare form of acute disseminated encephalomyelitis (ADEM) characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome. Methods: A case report and review of literature. Results: A 6-year-old girl known SCD presented an acute demyelinating syndrome (ADS) with diplopia due to unilateral fourth nerve palsy. She received (20mg/kg/day for 5 days) of IVMP (intravenous methylprednisolone). Two weeks after steroid weaning, she presented right hemiplegia. Brain MRI showed a left frontal necrotico-hemorrhagic lesion and new areas of demyelination. She showed signs of herniation and underwent craniotomy. Investigations ruled out vascular and infectious process in both events. The deterioration stopped concomitantly to the initiation of IVMP. She was discharged with a longer oral wean. Later, she was diagnosed with Crohn’s disease and primary sclerosing cholangitis. We considered AHEM as the most plausible diagnosis based on the clinical and radiological presentation, the preceding ADS, the exclusion of other etiologies, and the response to IVMP including resolution of non-necrotic lesions. Similar - but fatal - AHEM has been reported in 2 SCD patients. Conclusions: In any ADS occurring in the context of SCD and/or auto-immune condition, we recommend to slowly wean steroids, and to closely monitor the patient after weaning to quickly treat any recurrence with IVMP.

Background: The Gilenya® Go ProgramTM offers education and support services, including coordination of first dose observation (FDO) and follow-up contact to reinforce monitoring recommendations and compliance in fingolimod-treated relapsing-remitting multiple sclerosis (RRMS) patients. Methods: Data were analyzed for patients enrolled in the Canadian Gilenya® Go ProgramTM from March 2011 to January 2016. The retention to fingolimod therapy, reasons for treatment discontinuation and incidence of adverse events (AEs) during treatment are reported. Results: At data cut-off, 3956 patients had completed FDO; 3201 patients were being actively treated. Mean age at enrolment was 41.0 years; 74.9% patients were female. The overall fingolimod exposure was 7869 patient-years. Most recent previous therapies (n=3746) included interferons (43.3%) and glatiramer acetate (29.6%). Most common reasons for switching to fingolimod (n=3674) was lack of efficacy (31.8%). Retention to therapy at data cut-off was 81.3%. AEs (45.2%) were the most common reason (n=334) for treatment discontinuation and included low lymphocyte count/abnormal hematology values (13.8%), gastrointestinal disturbances (6.9%), and elevated liver enzyme levels (7.8%). Adherence to recommended ophthalmic examination was 92.4%. Conclusions: In real-world clinical practice in Canada, adherence to both fingolimod treatment and monitoring was high. The Gilenya® Go Program™ helps to meet the safety monitoring recommendations for fingolimod-treated RRMS patients.

Background: As therapy for MS has expanded to include multiple immunomodulatory and immunosuppressive therapies, the need to consider patient vaccination status has emerged as a salient issue in the treatment of MS. Unfortunately, there is little research or consensus about how vaccination in these patients should be addressed. Methods: A search of primary literature on the topic of potential pathogens and available vaccinations in immunosuppressed patients was performed. We reviewed the limited available information in the MS, gastroenterology, and rheumatology literature. As well, the current Canadian immunization guide was referred to along with expert opinion from public health nurses and infectious disease specialists. Results: There is currently little consensus about vaccination protocols for patients initiating immunosuppressive therapy. We integrated information from all of our sources to create a preliminary protocol for the vaccination of MS patients prior to initiation of immunosuppressive therapy. Conclusions: More work needs to be done to create standardized vaccination protocols for MS patients who will be undergoing immunosuppressive therapy. We have created a preliminary protocol in conjunction with public health to standardize the vaccinations that MS patients receive. We hope that this will streamline immunization of patients immediately after diagnosis of MS so that initiation of immunosuppressive therapy will not be delayed in the future.

Background: Multiple sclerosis (MS) is a neurological disease which is highly prevalent in Canada. To date limited data exists on the characteristics of this population in Ontario. Methods: A retrospective chart review was conducted of initial patient presentations to a MS clinic in 2011. Initial and follow-up consult notes were reviewed. Patients with a previous MS diagnosis were excluded. Results: 81 patients presented to the clinic for the first time in 2011. 41 were given alternative diagnoses (non-MS). Of the remaining 40 patients (MS group), 9 had clinically or radiologically isolated syndrome and 8 were in a progressive phase of MS. The mean age of presentation was 22 (MS group) and 47 (non-MS group). The most common initial symptom in both groups was a sensory disturbance. The mean initial EDSS in the MS group was 1.75 (0-6.5). In the MS group only 35% were put on disease modifying treatments. The most common reasons for exclusion of treatment were progressive disease phase, clinically or radiologically isolated syndrome, and unclear diagnosis. In the non-MS group, the most common diagnoses were non-specific MRI findings, transverse myelitis and peripheral nerve or muscular diagnoses. Conclusions: This retrospective review has outlined the characteristics of a MS population in Ontario.

Background: MRI criteria are used to support multiple sclerosis diagnosis and evolution. However, normal age-related lesions (ARLs) can be cofounded with MS white matter lesion (MSL). Methods: Two Multiparametric 7T MRI scans 4 motnhs apart from 5 relapsing MS (RMS) patients were analyzed and compared to 5 matched healthy controls (HC) aiming to differentiate MSLs from ARLs. Six-echo GRE, FLAIR and MPRAGE sequences were acquired. Results: Average size of ARLs was 51 mm3 and of MSLs was 69 mm3 (p=0.27). Both have the same general appearance on FLAIR and MPRAGE contrasts, but different contrast on the R2* and QS maps. Inter-visit variation on MPRAGE was significantly higher in MSLs. Inter-visit signal change in the other contrasts (QSM, R2* and FLAIR) was not significant. Conclusions: R2*, QS maps and inter-visit variation using MPRAGE allowed differentiating MSLs from ARLs in 5 RMS with mean long term disease duration. This could improve correct early diagnosis and accurate lesion load accumulation evolution.

Background: Preliminary studies have supported the utility of exercise as a treatment for Charcot-Marie-Tooth disease (CMT) patients. Despite being the most common inherited neuropathy, there remains a paucity of guidelines for CMT management. Methods: A retrospective chart review was performed on 297 CMT patients. Self-reported exercise and strength results from standardized dynamometer testing were obtained from adult patients’ first visits. Values were converted and analyzed based on previously reported age and sex matched normative values. Results: Participants with CMT2 were stronger than CMT1 in hand grip, elbow flexion, and dorsiflexion (p<0.05). CMT1A participants were weaker than those with CMT1B/D. Participants with CMT1 and CMT2 who exercised were statistically significantly stronger in elbow flexion and dorsiflexion than those who did not exercise. Conclusions: These preliminary results suggest that self-directed exercise is associated with greater strength in patients with CMT. Furthermore, they support the evidence that the dysmyelinating process in CMT1 may lead to greater loss of strength compared to the axonal degeneration in CMT2, and that exercise may benefit both subtypes. Self-directed exercise may be a convenient, sustainable, and effective method of improving strength and decreasing disability in these individuals. Future research should explore the type of exercise prescription that best addresses the needs of the CMT population.

Background: Fatigue is frequent and disabling in adults with neuromuscular disorders, but not well characterized in paediatric neuromuscular disorders. Recently, fatigue was reported to be associated with poor health-related quality of life in children with Duchenne muscular dystrophy (DMD). Determinants of fatigue—a modifiable symptom—have not been studied in DMD. Our objective was to explore risk factors for fatigue in children with DMD. Methods: Patients aged 4–17 years identified via the Canadian Neuromuscular Disease Registry received mailed questionnaires. Fatigue was assessed using the PedsQLTM Multidimensional Fatigue Scale (patient- and parent-report). Standardized measures for depressive symptoms, sleep disturbances, functional ability and physical activity were used. Spearman’s correlations and Wilcoxon rank-sum tests were computed. Results: Of 194 eligible patients, 64 have responded to date. DMD patients reported greater fatigue than healthy controls from published data. Depressive symptoms were associated with greater fatigue, by patient-report (ρ=-0.44, P<0.001) and parent-report (ρ=-0.40, P=0.002). Sleep disturbances were associated with greater fatigue, by patient-report (ρ=-0.41, P=0.007) and parent-report (ρ=-0.51, P<0.001). Greater functional ability was associated with less fatigue, by parent-report (ρ=0.30, P=0.02). Physical activity and ambulatory status were not associated with fatigue. Conclusions: Fatigue is a significant issue in DMD. Depressive symptoms and sleep disturbances are associated with fatigue, warranting attention in therapeutic strategies to reduce fatigue.

Background: Mowat-Wilson Syndrome (MWS) is a genetic syndrome (ZEB2, OMIM: 235730) that occurs in 1 in 50000 births. It is characterized by microcephaly, intellectual disability, dysmorphisms (prominent chin, cupped ears, broad nasal bridge) and Hirschsprung’s disease. Although motor delay and hypotonia are common components, a myopathy has not been described in MWS literature. A childhood case with myopathic features prompted further study of this rare disease. Methods: Patients were recruited from the Mowat-Wilson Foundation via email or social media to complete a survey. Results: Thirteen surveys were returned to date. Although 54% of the patients reported motor delay, none of the patients had myopathy investigations. The index patient, presented at 1 year old, with hypotonia and developmental delay. Pregnancy and family history were unremarkable. Investigations revealed high CK levels (range 300 to 500 U/L), EMG confirmed myopathic motor units, and muscle biopsy showed type 1 fibre predominance. Single gene sequencing revealed pathogenic mutations of ZEB2, confirming a diagnosis of MWS. Conclusions: The description of myopathic features expands the spectrum of this rare syndrome and adds to the differential diagnosis of hyperCKemia in early childhood.

Background: Few studies have explored the effects of anti-epileptic drugs (AEDs) on electroencephalograph (EEG) findings during the assessment of seizure management. Although a patient may reach seizure freedom, EEG results may continue to be abnormal. Further information is required to understand the trend of EEG findings during seizure treatment. Methods: This is a retrospective study based on chart reviews. Patients who had epilepsy evaluations at the Royal University Hospital in Saskatoon between January 2012 and December 2015, were selected. The relationships among time of initiating AEDs, EEG findings, and seizure outcome on follow-ups, have been evaluated. Results: 151 patients had first seizure clinic assessments, in which 75 patients had an EEG before starting AEDs. Among the 75 patients, 54 (72%) had abnormal EEGs. From those, 38 (70.3%) patient’s EEGs became normal and 16 (29.7%) patients continued to have abnormal EEGs after the introduction of AEDs. The seizure freedom was 81.5% among those who had normal EEG on follow-up, and 43.7% of those who continued to have abnormal EEGs. Conclusions: Although patients with normal EEGs after starting AEDs may encounter a higher chance of seizure freedom, the seizure free patients with abnormal EEGs indicate that EEG is not completely sufficient in predicting seizure status.