Background: Improving diagnostic and therapeutic tools associated with glioblastoma multiforme (GBM), an aggressive brain tumour, is crucial as average patient survival remains slightly over a year. Challenges include early diagnosis and acquired drug resistance. Improving these challenges notably require a multidisciplinary team and a dedicated brain tumour specimen collection initiative. We hypothesize that implementing such an approach in Moncton would provide significant benefits to GBM patients and researchers in New Brunswick. Methods: A Brain Tumour Tissue Repository was instigated to collect and preserve primary tumour specimens. Storage of circulating samples from patients undergoing temozolomide (TMZ) therapy was also performed. In parallel, molecular leads were investigated in different GBM models to identify therapeutic targets. Results: Collection of 7 primary specimens was accomplished in 2016. Over 15 primary samples are housed in the tumour biorepository to date with circulating samples collected from 3 patients. Additionally, numerous deregulated non-coding RNAs were identified by qRT-PCR in GBM models and shown to be modulated following TMZ treatment warranting further investigation. Conclusions: Overall, these results provide novel therapeutic leads for GBMs and, most importantly, highlight the instigation of a New Brunswick-based brain tumor biorepository which will undoubtedly strengthen brain tumour research in the Maritimes.

Background: The optimal therapeutic approach for adult craniopharyngioma remains controversial. Some advocate for gross total resection (GTR), while others support subtotal resection followed by adjuvant radiotherapy (STR + XRT). Methods: MEDLINE (1946 to July 1st 2016) and EMBASE (1980 to June 30th 2016) were systematically reviewed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. At our institution, from 1975 to 2013, 33 patients were treated with initial surgical resection for adult onset craniopharyngioma. 22 patients were included in the present case series. Results: Eligible studies (n=21) were identified from the literature in addition to a case series of our institutional experience. Three groups were available for analysis: GTR, STR + XRT, and STR. The rates of recurrence were 17 %, 27 % and 45%, respectively. This differs from childhood population. The difference in risk of recurrence after GTR vs. STR + XRT did not reach significance (OR: 0.63, 95% confidence interval: 0.33-1.24, P=0.18). This maybe because of low pooled sample size (n=99) who underwent STR+XRT. Conclusions: This is the first and largest meta-analysis examining rate of recurrence in adult craniopharyngioma. Thus, when safe and feasible, a goal of gross total resection should be favored. Each patient should be considered on a case-by-case basis.

Background: The goal of a brain tumour operation is maximal safe resection. No widely used guidelines for the use of functional magnetic resonance imaging (fMRI) in these patients currently exist. In this study we are trying to determine if and how Canadian neurosurgeons use fMRI in the management of patients with low grade glioma (LGG). Methods: A 15-25 minute survey was created using an online survey tool. In Part One of the study the survey was distributed to neurosurgery consultant and resident staff at the London Health Sciences Centre (LHSC). In Part Two of the study the survey is being distributed to members of the Canadian Neurosurgical Society. The survey consists of two sections - background and case-based decision making. Results: There were six surveys from the LHSC staff. On average respondents indicated that they obtain fMRI for 9% of LGG patients, though 67% indicated that they were comfortable ordering and interpreting fMRI studies. In the case-based section, fMRI data did not tend to affect respondents’ preferred treatment, confidence in their treatment, or their predicted risk of surgical treatment. Conclusions: In this limited survey of LHSC neurosurgical staff there was no regular use of fMRI in LGG patients. We await the results of a national survey of Canadian neurosurgeons.

Background: Diffusion weighted imaging (DWI) has useful diagnostic and predictive value in the assessment of glial tumors. Most studies evaluating the use of DWI in glioblastomas have done so in regions that overlap with abnormal T2/fluid attenuation inversion recovery (FLAIR) signal or contrast enhancement. Isolated DWI abnormalities, which do not overlap with contrast enhancing lesions, are less commonly described. Their relationship with the tumour, and implications for prognosis, are not well understood, though it has been speculated that these lesions may represent infiltrative tumour cells. To our knowledge, this is the first reported case where the presence of infiltrative tumour cells in an area of diffusion restriction has been confirmed via biopsy. Methods: A ring enhancing lesion and isolated DWI hyperintensity from a newly diagnosed patient were biopsied separately. Results: Pathological specimens from both targets were identified as glioblastoma (WHO Grade IV), negative for IDH-1 R132H mutation, with methylated MGMT promoter. Conclusions: In patients with glioblastoma, DWI hyperintensities distant from areas of abnormal T2/FLAIR or contrast enhancement can contain infiltrative tumour cells. The presence of isolated diffusion restriction may be a useful predictor of disease progression and prognosis but further investigation into the nature and behavior of isolated DWI lesions is required.

Background: With the advent of the 2016 WHO classification of tumours, prognostically distinct subclasses of glioma have been revealed. A subset of gliomas which harbor the isocitrate dehydrogenase (IDH) mutation have a survival advantage. 2-Hydroxyglutarate (2-HG) is a byproduct of faulty IDH metabolism in IDH mutants making it an ideal tumour biomarker. Since pre-operative detection of this metabolite using magnetic resonance spectroscopy (MRS) may yield valuable information for the neurosurgeon, we undertook the first Canadian utility study to detect 2-HG via MRS. Methods: We will recruit 150 patients presenting with a newly suspected glioma. All patients will undergo MRS scans for 2-HG pre-operatively and the neuropathologist will determine IDH status post-operatively based on immunohistochemistry and DNA sequencing. Pre-operative detection of 2-HG will be compared to post-operative IDH status. Results: To date, of 34 eligible subjects, 29 have glioma determined by pathology. Seven of these were IDH-mutant positive by pathology, of which 3 were detected by MRS. One glioma positive for 2-HG on MRS turned out to be IDH mutant negative on pathology. Conclusions: Prospective detection of 2-HG via MRS is feasible in the clinical setting. Additional subjects as well as refinement of our MRS protocol may yield higher sensitivity and specificity of this novel and clinically relevant diagnostic tool.

Background: Spontaneous hemorrhage from angiographically occult vascular malformations is not a rare occurrence. We present a case of in-hospital cavernous malformation rupture after initial normal CT. Methods: A 55-year-old female presented with severe headache with onset during activity, and normal neurological examination. Rapid neurological deterioration occurred 60 minutes following the CT scan. The patient was intubated, and repeat CT scan showed significant parafalcine ICH and intrahemispheric SAH. ICU transfer and expectant management led to neurological recovery and discharge to rehabilitation. Results: The patient underwent angiography on initial admission which was negative. A delayed MRI showed the presence of a cavernous malformation. This was followed conservatively with repeat imaging. The malformation remained stable. Conclusions: Our unique case highlights the sudden onset of hemorrhage occurring almost immediately following normal brain imaging. A cavernous malformation was discovered to be the cause, and was observed.

Background: Intracranial mycotic aneurysms are rare forms of vascular abnormalities. They are typically fragile and have high tendency to bleed. Even when they are successfully secured upon intervention, the medical management can be challenging in presence of other non-ruptured aneurysms and concomitant cerebral vasospasm. Methods: A 31 year old female was admitted with right sided large intracerebral hemorrhage due to ruptured mycotic MCA aneurysm. She was also known with severe tricuspid regurgitation from drug abuse. Others aneurysms were also located intracranially and extracranially, including subclavian and renal arteries. Results: The MCA aneurysm was successfully clipped during decompressive craniectomy. The non-ruptured left ACA aneurysm was occluded through endovascular intervention. Due to cardiac condition and presence of other non-secured extarcranial aneurysms, we followed the MNI protocol for treating cerebral vasospsam by milrinone infusion. The treatment was successful for over three weeks until another micro-aneurysm had ruptured which had lead to severe and rapid clinical deterioration, that had lead eventually to death. Conclusions: Intracranial mycotic aneurysms remain challenging. Patients should be selected for surgical clipping versus endovascular intervention based on clinical state and radiological features. We suggest using milrinone over induced hypertension therapy for post-intervention cerebral vasospasm in order to lower the risk for rupturing non-secured aneurysms.

Background: Results of previous studies examining seasonal variation in the incidence of aneurysmal subarachnoid hemorrhage (SAH) are conflicting. The aim of this study is to investigate whether there is a seasonal effect in online search queries for SAH that may reflect an association between meteorological factors and aneurysm rupture. Methods: We utilized the Google Trends data service to analyze the volume of internet queries for SAH on Google’s search engine from January 1, 2004 to November 2016. We used comprehensive search terms and collected data from: USA, Canada, Finland, and Japan, as well as worldwide search volume. Potential seasonal variations in the data were assessed by comparative non-parametric tests and curve-fit regression model. Results: Our analyses revealed that USA had the highest median search scores (115 vs. 86, 46, 46 for Finland, Canada and Japan, respectively). The term “brain aneurysm” was the commonly used search term among countries, followed by “cerebral aneurysm”. There was no evidence of seasonality in any of the countries studied on both univariate tests and regression time-adjusted analysis. Conclusions: There are no seasonal variations in internet search query volume for SAH. Further studies are needed to explore whether online search volumes correlate with the actual incidence of SAH.

Background: Hybrid neurovascular operating rooms offer significant advantages for vascular neurosurgery. In 2008, we installed North America’s first robotic intraoperative rotational 2D/3D angiography unit in a neurosurgery operating room. To date, 200 procedures have been performed. Methods: In selected cases of spinal dural arteriovenous fistula (dAVF)requiring surgical disconnection, intraoperative spinal angiographic roadmapping, angiographic image overlay onto the skin and surgically exposed spine, and laser cross-hair image guidance were utilized to accurately determine the location and trajectory of the draining vein. Results: In four cases of spinal dAVF, a minimally invasive approach was employed, via either single-level (N=2) or two-level (N=1) hemilaminectomy. Techniques used included: angiographic roadmap / image overlay and intraoperative fluoroscopic with laser light guidance. These provided sub-centimeter accuracy in localizing the path of the draining vein. Surgical incision lengths ranged between 4 to 5 cm, with the shortest incision measuring only 4.2 cm. Complete cure was obtained in all cases, with no untoward complications. Conclusions: Hybrid neurovascular operating room technology can facilitate the use of minimally invasive approaches to spinal dural AVF disconnection.

Background: Intracranial aneurysms are relatively common and often incidentally detected. Elective treatment may eliminate the risk of future hemorrhage, but carries risks of permanent deficit or death. Case-control studies have suggested factors predisposing to aneurysm rupture as well as risks of elective aneurysm repair. A clinical tool was recently developed to weigh benefits of repair against treatment risks. We evaluate its performance against real-world clinical decisions made by a cerebrovascular multidisciplinary team (MDT). Methods: Chart review of all patients with unruptured intracranial berry aneurysms (UIA) discussed at cerebrovascular MDT rounds 2008-2015. Management decisions and clinical outcomes were recorded. The Unruptured Intracranial Aneurysm Treatment Score (UIATS) was calculated for each patient (each aneurysm in the case of multiple UIA). Results: We identified 240 patients with a total of 279 aneurysms. UIATS recommended aneurysm repair in 79 cases, conservative management in 88 cases, and was equivocal in 112 cases. Where the UIATS gave a clear decision, that decision was concordant with the MDT decision in 119/167 cases (71%). Discordant decisions often related to the presence of comorbidities. Clinical outcomes did not differ in cases where the recommendations were clearly concordant vs. discordant. Conclusions: The UIATS may provide guidance to non-expert clinicians. It did not outperform the MDT.

Background: Nonconvulsive seizures (NCSz) occur commonly in critically ill patients and are harmful. Diagnosis requires detection with continuous electroencephalography (cEEG) that necessitates frequent interpretation by experts. This is often not possible, and requires large amounts of resources. Screening level interpretation of cEEG by ICU nurses to facilitate timely expert diagnosis may be one solution. Methods: Kern’s approach to curriculum development was utilized to inform creation of a cEEG curriculum for ICU nurses. Results: A needs assessment revealed 80%, 94%, and 100% of nurses lacked comfort in basic seizure/EEG principles, EEG and CDSA interpretation respectively. The most requested method of learning (76%) involved simulation. A spiral curriculum of 15 interactive online tutorials with corresponding practice/simulation modules providing instant feedback was developed. To evaluate curriculum impact, time spent on modules, improvement in nursing knowledge, and diagnostic accuracy will be evaluated using pre and post curriculum tests. Participant satisfaction will be evaluated using electronic surveys. Conclusions: Development of a curriculum to teach ICU nurses basic screening diagnostic skills for NCSz is possible. Moving forward, we hope to refine and validate this learning tool and formally implement its use to help screen for NCSz prior to expert interpretation.

Background: A diagnosis of SCD in childhood confers a 200-fold increase in the risk of arterial ischemic stroke. Blood flow velocity measures provide better identification of ischemic risk compared to angiography. This indicates that steno-occlusive arteriopathy is not the singular causative factor. Cerebrovascular reactivity allows for augmentation of cerebral blood flow when needed. Kosinski et al in 2016 demonstrated a direct correlation between CVR and hematocrit levels in SCD. We report a case where CVR persistently normalized in an SCD patient following bone marrow transplant therapy (BMT). Methods: A nine-month-old SCD patient presented with right AIS. Angiography revealed a bilateral Moya-Moya like arteriopathy. A TCD study was normal while a CVR-MRI study revealed markedly impaired reactivity in the entire anterior circulation. Haemaglobin-S at that time was 20.2 %. BMT was performed at age four due to frequent sickle cell crises. Results: One year post-transplant, CVR had dramatically improved in areas previously shown to have impairment (haemoglobin-S 0%). Neuroimaging five years post-transplant showed no further arteriopathy and persistently normalized CVR. Conclusions: BMT therapy resulted in the arrest of progressive intracranial arteriopathy and persistently restored vascular reserve. SCD might not only produce global hematological effects but also triggers local processes such as endothelial dysfunction and vascular inflammation that impair cerebrovascular function.

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.