Background: Childhood epilepsy has increased in global incidence. Children with epilepsy require immediate healthcare evaluation and monitoring. Waiting times between first seizure onset and pediatric neurology assessment may impact seizure outcome at follow-up. Quality of medical care for children with first seizure onset will be assessed and the impact of pediatric neurology clinic waiting times on seizure outcomes will be determined Methods: This retrospective study, based on chart review, includes patients with first seizure evaluation at the Royal University Hospital in Saskatoon between January 2012 and December 2015. The interim period before first assessment and other factors were studied in relation to seizure outcome on follow-up. Results: 1158 patients were assessed. 378 (32.6%) patients had first seizure clinic assessment. 197 (52%) had epileptic events. 181 (48%) had non-epileptic events. The mean age of patients was 8.8 years. The mean waiting time for assessment by a pediatric neurologist was 4.33 months. The mean duration of follow-up was 20.9 months. At the last seizure assessment, 132 patients were free of seizures and 65 patients had a recurrence of seizures. Conclusions: First seizure assessment is crucial for management of children with epilepsy. Waiting time and other factors may influence seizure outcome, representing opportunities to improve standard medical care.

Background: To promote patient-centred care in epilepsy, it is essential to understand the issues most important to patients. Literature on patient perceptions of epilepsy treatments is sparse. One source of data is online patient support groups. Patients turn to social media for support from other patients and often express viewpoints not shared with healthcare providers. Methods: Using a qualitative content analysis approach, we analyzed major online epilepsy patient support groups. We initially selected a month-long discussion text across these forums, and further threads were sampled with maximum variation until theme saturation was reached. For data coding and analysis, we employed a combination of a priori codes and emergent codes, using NVivo 11 for data analysis. Results: In our preliminary analysis, we identified topics and categorized them into themes: 1) differential perceptions and understandings of epilepsy; (2) understanding treatment options; (3) experiences of physiological and psychological treatment side effects; (4) concerns about healthcare providers’ knowledge and communication regarding treatments. Conclusions: Preliminary results indicate a variety of patient perceptions and understandings of epilepsy and its treatments. Our findings also suggest that patient educational needs should be addressed by incorporating their understanding and concerns. Shared-decision making tools informed by patient perceptions could help healthcare providers better communicate treatment options with patients.

Background: Focal cortical dysplasia (FCD) refers to malformation of cortical development featuring abnormalities of cortical layering, neuronal differentiation and maturation. It is a common cause of medically refractory epilepsy. The coexistence of FCD and low-grade glial neoplasms such as ganglioglioma and dysembryoplastic neuroepithelial tumour is classified by the International League Against Epilepsy as “FCD Type IIIb”. We present a case of FCD Type IIIb associated with low grade oligodendroglioma (WHO grade II) in a seizure free patient. Methods: A 20-year-old male presented with suspected arteriovenous malformation of the right pinna. Imaging revealed an incidental right frontal lobe mass. Surgical resection was performed. Pathologic analysis revealed FCD Type IIIb associated with low grade oligodendroglioma (WHO grade II). Results: The patient recovered uneventfully. Only 4 prior cases of FCD Type IIIb associated with oligodendroglioma have been reported. This is the first reported case of FCD Type IIIb discovered incidentally in a seizure free patient. Conclusions: FCD Type IIIb associated with oligodendroglioma is rare. The mechanism(s) by which glioneuronal neoplasms and perilesional cortical tissue jointly contribute to epileptogenicity have not been clearly defined. There may be a reduced risk of seizures with oligodendroglioma rather than tumors with a neuronal component.

Background: Morphometry and connectivity studies targeting the thalamus have revealed specific patterns of atrophy and deafferentiation in patients with temporal lobe epilepsy (TLE). We used probabilistic tractography to investigate thalamic connectivity with respect to duration of epilepsy and surgical outcomes in TLE. Methods: Patients (N=20) with drug-resistant TLE (10 short duration (<15 years), 10 long duration (>15 years)) were scanned with multi-parametric 3T MRI and compared with 34 healthy controls. The Harvard-Oxford atlas was modified to create 14 target regions in the temporal lobes. Probabilistic tractography (FSL) was used to delineate thalamic sub-regions most connected to each target. The volume, mean T1, T2, FA and MD of each thalamic sub-region was quantified. Surgical success was quantified using Engel outcome scores. Results: Significant decreases in thalamic connected volumes to the hippocampus in patients with longer duration of TLE were revealed. Likewise, when stratified based on surgical success, significant differences in diffusion metrics to the hippocampus, parahippocampal gyrus, and temporal neocortex were found. Significant differences did not withstand false discovery rate (FDR) correction. Conclusions: These findings suggest ongoing connectivity changes dependent on epilepsy duration and promote further investigation into the use of thalamic connectivity data as biomarkers for predicting surgical outcomes in TLE patients.

Background: The KCNT1 gene encodes subunits of the Na+-activated K+ channel, widely expressed in the CNS. Mutations of this gene have been implicated in Malignant Migrating Partial Seizures of Infancy (MMPSI). This early-onset epileptic encephalopathy represents a challenge due to pharmacoresistance. The channel-specific mutation represents the potential for targeted pharmacotherapy. Quinidine is a partial antagonist of the KCNT1 encoded channel; patients with MMPSI have been reported to have responded to doses ranging 34.4/kg/d - 60mg/kg/d. We present a case of MMPSI with a KCNTI mutation (c.G1283A:p.R428Q) trialled on quinidine. Methods: Following ineffective trials of 6 anti-seizure medications, this patient was trialled on oral quinidine. This patient was titrated up to a dose of 52mg/kg/d. Twenty-four hour EEG monitoring prior to quinidine therapy, and at target dose were compared. Results: Prior to initiation of quinidine, this patient experienced 22 electrographic seizures over 24 hours. At target dose, this patient experienced greater than 70 seizures over 24 hours. Conclusions: Quinidine has previously been reported to be effective in patients with MMPSI with the same and different mutations. We report the second case of a patient with MMPSI and KCNT1 mutation R428Q with poor clinical response to quinidine.

Background: A significant part of the developmental delay (DD) population has epilepsy (26-70%) and live in an institution. These patients tend to have atypical presentation of epileptic seizures with higher risk of misdiagnosis. Distinguishing their ictal events from paroxysmal behaviors can be challenging.There often is a lack of description of the spells or inadequate history from the caregivers or the patients. These patients often have drug resistant epilepsy requiring polypharmacy with increased risk of morbidity and mortality. The aim of this study was to determine usefulness of Epilepsy Monitoring Unit (EMU) in diagnosis and management of these patients. Methods: This is a retrospective observational study of the patients with epilepsy and DD living in institutions that were admitted to the EMU. Results: Four patients met the inclusion criteria for this study. The mean age was 45(29-71), 3/4 (N=3) were male and 3/4 had focal epilepsy. All patients had mood disorders and 2 were taking antipsychotic medication. The mean admission-time was 6,25 days

(2-15) and there was a correlation with the events and seizures in 2/4 of the patients and the rest had a combination of behavioural-changes and seizures. Conclusions: EMU admission can provide an accurate diagnosis of spells in patients with DD and epilepsy, and improve their quality of life.

Background: Perampanel (PER) is a new anti-seizure medication that inhibits the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) class of glutamate receptors. It is available in Canada for children since 2014. It is important for physicians to be aware of the efficacy and tolerability of drugs in the post-marketing phase. Methods: We did a retrospective review of our experience with PER at BC Children’s Hospital. Patients on PER were identified. Clinical data, including demographics, efficacy, tolerability, adverse effects (AE) and retention rates were obtained by review of clinical records. Results: Of 24 patients pediatric patients prescribed PER, 21 (87%) had focal and three had symptomatic generalized epilepsy. Ten (42%) had greater than 50% reduction in seizures. In fifteen patients, (63%) PER was discontinued due to AE or poor response. Twelve (50%) had behavioral AE and eight (33%) had non-behavioral AE. PER was effective, at lower doses than required for adults. One third experienced serious AE. One patient experienced oculogyric crisis, not previously reported with PER. AE were not associated with high doses and were reversible. Possible risk factors for behavioral AE include behavioral problems with other medications and pre-existing behavioral co-morbidities. Conclusions: It is important for clinicians to be aware of and counsel patients about serious AE, particularly behavioral, when prescribing PER.

Background: Hemimegalencephaly (HME) is a hamartomatous malformation of one cerebral hemisphere, resulting in refractory epilepsy, intellectual disability, and autistic features. Hemispherectomy is the definitive treatment, but there is risk of high morbidity and mortality, especially when done in early infancy. Various preclinical studies have shown that dysregulation of the mTOR pathway has an integral role in the development of various epilepsy syndromes, including tuberous sclerosis complex (TSC), focal cortical dysplasia and HME. Recently, mTOR inhibitors were proven to be effective in treating seizures in TSC. Methods: We present a case of a 6 day old female with refractory epilepsy despite the trial of 9 anti-seizure medications and the ketogenic diet. As the patient was awaiting epilepsy surgery, an mTOR inhibitor, rapamycin was initiated. Results: After 1 week of the initiation, she had over a 50% reduction in seizures. At two weeks, the parents felt that for the first time, she was making developmental gains. She also appeared brighter and more interactive. Due to her response to treatment, her hemispherectomy was deferred to when she is older, so there will be a decreased risk of complications from the surgery. Conclusions: This case exemplifies how mTOR inhibitors should be considered as a treatment option for patients with HME and refractory epilepsy.

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.