Selected Conference Proceedings
7th Annual Student Neurology Symposium

Student Neurology Symposium
Published online: 19 June 2020



Message from the Student Neurology Symposium Organizing Committee

Selected abstracts from the research presentations of the 7th Student Neurology Symposium, which took place virtually on June 6th, 2020. This annual event is organized by medical students from the four faculties of medicine in Quebec and the University of Ottawa, and was hosted by McGill University this year. The Student Neurology Symposium is the largest event of its kind in the province of Quebec and introduces medical students to the world of neurology, notably with presentations from renowned neurologists, neurosurgeons, and neuroscientists. Special thanks to the presenters, judges, and Shriya Deshmukh, MD-PhD student at McGill University, who made the presentation of these research projects possible.




Actinomycin D: Past Antibiotic, Modern Anticancer agent and future Myotonic Dystrophy Type 1 Therapy?

David Ripsman, Karen Chiang, Pei Wang, Rob Macgregor, Christopher Pearson

Introduction: Myotonic dystrophy type 1 (DM1) is a rare, progressive, fatal degenerative neuromuscular disease. This disease is driven by a CTG trinucleotide repeat (TNR) expansion on chromosome 19. Healthy individuals have short repeats (<35 repeats), while affected individuals have longer repeats (>50 repeats), which are unstable and expand through aberrant mismatch repair (MMR) processing of slipped-out CTG DNA structures. The expanded CTG TNRs produce toxic RNA, which damages muscle cells. Actinomycin D (ActD) has been shown to bind CTG repeats and reduce transcription of the toxic RNA. ActD’s binding to the CTG repeat may also inhibit repair and promote contractions in vivo.

Objective: To determine if ActD can selectively inhibit key steps in MMR.

Methods: ActD binding to CAG, CTG and DNA without repeats was measured by circular dichroism (CD). The effect of ActD on MMR protein binding to a CTG slip-out substrate was explored. ActD inhibition of DNA synthesis through CAG, CTG or no repeats was compared. ActD’s inhibitory effect on repair of a CTG slip-out and a GT mismatch in cell extracts was assessed.

Results: CD analysis showed ActD preferentially binds CTG repeats over CAG or no repeats. ActD inhibited MMR repair protein binding to CTG slip-out DNA, DNA synthesis through a CTG repeat tract and MMR of CTG slip-outs.

Conclusion: ActD can directly bind to selective DNA and prevent mismatch repair, suggesting ActD may reduce the length of the pathogenic DM1 repeat in addition to reducing the level of toxic RNA in DM1.


Corresponding author: David Ripsman, drips036@uottawa.ca




Towards quantitative measures of tremor in the clinical setting: Validation of a standardized, accelerometer-based method in essential tremor patients

Etienne Gauthier-Lafreniere, Dr. Meshal Aljassar, Dr. Abbas Sadikot

Despite having been described as early as 1874, little advancement has been made in the quantitative evaluation of tremor in clinical practice. Since many motor disorders lack disease modifying treatments, qualitative measures or simple scales have been used in order to simplify care. However, this justification falls short considering the vast amounts of data required for clinical trials as well as the substantial limitations of inter-user variability and integer-based scales. With advancements in treatment options, the need for reproducible tremor measurements is increasing, particularly in prognostication, surgical lesion optimization and medication titration. Multiple quantitative methods are present is academia. However, none have been adapted for clinical measurements. In the present study, the use of accelerometer watches is presented as an accessible and reproducible method of tremor characterization. A standardized measurement protocol capturing most tremor patterns is presented, and an analysis toolbox is described and made available. The method is validated by following 10 essential tremor patients undergoing MRI-guided focused ultrasound surgery over a 6-month period. A reliable extraction of tremor characteristics, namely the acceleration power spectrum, peak frequency, and total power of tremor is achieved. These data are shown to demonstrate long term suppression of tremor in all patients. Additionally, they are compared to Clinical Rating Scale for Tremor (CRST) assessments in the same patients, yielding significant correlation (R=0.78) when plotting the postural CRST scales to total power of tremor. The findings of this study are used to discuss advantages of accelerometer watches over traditional scales such as the CRST.


Corresponding author: Etienne Gauthier-Lafreniere, etienne.gauthier-lafreniere@mail.mcgill.ca




The effects of adolescent stress on schizophrenia

Selina Dong, Dr. N. Rajakumar

The etiology of schizophrenia can be understood through the “two-hit” model. The first “hit,” or insult creates a predisposition by disrupting early neurodevelopment. This increases one’s vulnerability to a second insult later in life, which could increase the likelihood of schizophrenia manifestation. The second insult may occur at any time during development; however, adolescence merits attention as schizophrenia symptoms often manifest during and after this time. This study aimed to understand how psychological stress during adolescence affects schizophrenia manifestation when in the presence of a predisposition. We hypothesized that exposure to non-traumatic, mild psychological stressors during adolescence in the presence of a predisposition contributes to abnormalities that are reminiscent of schizophrenia. Male and female Sprague-Dawley rats received bilateral injections of either nerve growth factor (NGF) or saline (control) into the developing medial prefrontal cortex. NGF animal models have been previously established to be a putative model of schizophrenia. Rats were repeatedly exposed to mild, non-traumatic psychological stressors during their adolescence (PND 26–40) and their behaviours were studied during adulthood (after PND 70). Results showed that adolescent stress did not significantly affect sensory gating in predisposed animals, while it appeared to show sex-specific effects in the control animals. In addition, adolescent stress significantly enhanced dopamine sensitivity, but only in female NGF animals. Overall, predisposed animals exposed to adolescent stress did demonstrate some abnormalities that were reminiscent of schizophrenia, albeit through a sex-specific manner.


Corresponding author: Selina Dong, selina.dong@uottawa.ca




Volumetric Extent of Resection of Pituitary Macroadenomas in Saskatchewan

Jasleen Saini, Matt Wright, Kyle Moulton, Luke Hnenny

Based on our population, 1160 SK residents would be expected to have clinically relevant pituitary adenomas. Macroadenomas are histologically benign lesions. However, because of their location near the optic nerves, they can have profound effects on patients. Transsphenoidal surgery is the treatment of choice in patients with visual field defects because this treatment leads to immediate decompression of the optic apparatus. We hypothesize that the rates of gross total resection (GTR) and volumetric extent of resection (VEOR) for patients undergoing transsphenoidal resection of pituitary macroadenomas in SK between 2008 and 2015 will be similar to those published in a recent multicenter prospective cohort trial (TRANSSPHER). Patient information such as age, gender, date of surgery, and availability of 6-month post-operative MRI scan was recorded. Volumetric measurements of pituitary macroadenomas on pre- and postoperative MRI scans was performed using GE Healthcare Filmer followed by calculation of the VEOR. The GTR rates in the SK group were less than those from a recent large multicenter prospective cohort trial (TRANSSPHER) in both microscopic (39.1% vs 80%) and endoscopic (14.3% vs 83.7%) groups. The VEOR in the SK group was lower than the VEOR from TRANSSPHER in both microscopic (68.5% vs 98.1%) and endoscopic (71% vs 97.6%) groups. SK rates of GTR and VEOR do seem to be less than published results. The difference in GTR between the microscopic and endoscopic groups in SK likely relates to a low number of endoscopic cases, and the relative novelty of the technique over the study time period.


Corresponding author: Jasleen Saini, jasleen.saini@usask.ca




Safety and Efficacy of Surgical Treatment of Non-Tumoral Refractory Insular Epilepsy: A Systematic Review

Anne Bouthillier1, Aliya Szpindel1, Farhan A. Mirza2,3
1McGill University, Faculty of Medicine, Montreal, Quebec, Canada
2The Montreal Neurological Institute (MNI), Department of Neurosurgery, McGill University, Montreal, Quebec, Canada
3Kentucky Neuroscience Institute (KNI), Department of Neurosurgery, University of Kentucky, Lexington, KY, USA

Introduction: Insular epilepsy is a rare and possibly under-recognized source of refractory focal epilepsy. Often in failed temporal or frontal resections, insular involvement may be the culprit. This systematic review presents a thorough analysis of all published series on surgical management of purely non-tumoral insular epilepsy.

Methods: PubMed search was conducted with the terms: Insular epilepsy (532), Insular epilepsy surgery (260), Surgical treatment of insular epilepsy (177), Refractory insular epilepsy (86), Surgery for refractory insular epilepsy (58), Opercular resection for epilepsy (29). All English language studies describing surgical treatment of non-tumoral insular epilepsy, with minimum three patients and one-year follow-up were identified. Studies with duplicated patients were combined or the most recent study from the same group was included.

Results: Studies: Twenty-one studies met our inclusion criteria. Fifteen studies (six exclusively pediatric) described open microsurgical methods. Six of these were from the same group. One study each on gamma knife radiosurgery (GKRS), responsive neurostimulation (RNS), radiofrequency-thermocoagulation (RF-TC), bipolar electrocoagulation on functional cortex (BCFC), and two on laser interstitial thermal therapy (LITT) were identified. Two studies described both LITT and open resection. Patients: 218 patients [132 Open (59.6%), 86 minimally invasive surgery (MIS) (40.3%): 3 GKRS, 36 LITT, 19 RF-TC, 20 BCFC, 8 RNS] were included. Treatments: 133 open resections, 3 GKRS treatments, 8 RNS, 36 LITT ablations, 19 RF-TC, and 20 BCFC. Outcomes: Engle Class I was achieved in 80 (60.6%) in the Open group and 44 (51.1%) in the MIS group. Neurological complications: Open group, 61 temporary (45.9%) and 15 permanent (11.3%) complications were noted. MIS group, 28 (32.6%) temporary and 3 permanent (3.5%) complications were noted.

Conclusion: Surgical treatment of insular epilepsy, via microsurgery or minimally invasive lesioning methods, is effective and has acceptable transient neurological complication rates. Open resection appears to have better seizure control rates but longer follow up will be required for minimally invasive methods to gauge the difference.


Corresponding author: Anne Bouthillier, anne.bouthillier@mail.mcgill.ca




Safety of Intrathecal Administration of Gadolinium-based Contrast Agents – A Systematic Review and Meta-analysis

Mihilkumar Patel BHSc, Almohannad Atyani BHSc, Jean-Paul Salameh MSc, Matthew McInnes MD FRCPC, Santanu Chakraborty MD FRCPC

Introduction: Visualizing complex CSF pathology involved in spontaneous intracranial hypotension (SIH), nasoethmoid CSF fistulas, CSF rhinorrhea, and otorrhea require the use of MRI with intrathecally administered Gadolinium-based Contrast Agents (GBCAs) in order to plan further management. While the adverse effects and overall safety of intravenous GBCA administration in humans has been well explored, very few studies have explored the safety profile of intrathecal administration of GBCA.

Methods: A systematic literature search was conducted in MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) using MeSH and keyword variations on GBCAs and intrathecal injections. Data extraction from included studies focused on rates and types of adverse events after intrathecal GBCA use. Meta-regression and two-tailed t-test was used to pool the data and to evaluate the relationship between GBCA dose and presence of serious vs. non-serious adverse events.

Results: 53 studies with a combined total of 1036 patients were included for analysis. The overall rate of adverse events after intrathecal administration of GBCA was 13% (CI: 9.3-18%). Meta-analysis revealed moderate heterogeneity (I2=62%). Serious adverse event rates could not be determined via meta-analysis; they were reported in 10 studies and were primarily neurological in nature, with two cases of coma, one resulting in death. Serious adverse events were associated with significantly higher GBCA doses when compared with non-serious adverse events (µD=4.5 mmol; CI: 2.3-6.6; p = 0.008).

Conclusion: Overall, intrathecal administration of GBCAs at doses greater than 1.0 mmol are associated with serious neurotoxic complications at doses as low as 2.0 mmol.


Corresponding author: Mihilkumar Patel, mpate122@uottawa.ca




Effet de l’âge sur la proprioception du membre supérieur évaluée avec un exosquelette et un système de réalité virtuelle

Dominique Chabot, Andréanne Blanchette, Anne Deblock-Bellamy

Introduction: Comme plusieurs sens, la proprioception peut subir un déclin avec l’âge. La dégradation des récepteurs sensoriels et le ralentissement de la conduction nerveuse sont des changements neurophysiologiques qui pourraient affecter la proprioception. Le but de cette étude quantitative est de comparer les seuils de discrimination de la proprioception du coude de trois groupes d’âge différents.

Méthode: Pour mesurer la position du coude, le KINARM Exosqueleton Lab a été utilisé. Les participants devaient se présenter à 2 séances d’évaluation. Le bras dominant était caché et amené passivement à une position finale. Une représentation virtuelle d’un bras apparaissait ensuite sur un écran. Le participant devait dire comment il percevait son bras. L’activité musculaire du biceps et du triceps des participants étaient monitorés avec un EMG. Le seuil de discrimination était extrait d’une courbe sigmoïde mettant en relation le pourcentage de bonnes réponses avec les différences angulaires. Les participants étaient divisés en 3 groupes. Les moyennes du seuil de discrimination des groupes étaient comparées à l’aide d’une ANOVA.

Résultats: 55 participants âgés de 18 à 80 ans ont été recrutés. Le premier groupe (30 jeunes adultes, moy : 24,5 ans) a obtenu une moyenne de 5,9°. Le deuxième groupe (6 adultes, moy :41,8 ans) a obtenu une moyenne de 7,8°. Finalement, le dernier groupe (23 adultes, moy : 63,8 ans) a obtenu une moyenne de 6,4°. L’ANOVA à 1 facteur est non significatif (F=2,394; p=0,101).

Conclusion: Ces premiers résultats montrent qu’il n’y a pas de différence entre les moyennes du seuil de discrimination de proprioception du coude des différents groupes d’âge. Cela pourrait être expliqué par deux données extrêmes dans le 3e groupe. Plus de recrutement serait nécessaire pour les participants de ce groupe.


Auteur correspondant: Dominique Chabot, dominique.chabot.3@ulaval.ca




Evaluation of Mutant Alleles of Engrailed and Invected in Drosophila Melanogaster Models of Parkinson Disease

Sheldon V. Smith, Brian B. Staveley

Parkinson Disease (PD) is a neurodegenerative disorder, resulting in a gradual decline in voluntary movement, where lifespan remains stable. Drosophila melanogaster offer comparable gene sequences to those targeted in PD; among them are two transcription factors, engrailed (en) and invected (inv). Wild-type homozygous allele Oregon-R (en+, inv+) was compared to heterozygous mutants of en1, en4, en7, en54, en58, invW, inv30 and Df (2R) enE invE. Nine climbing and aging studies were executed from crosses with w1118 (en+, inv+) as the maternal genotype. Independent-samples t-tests were conducted to compare the percent survival (in days). No significant differences were observed between the experimental groups and the control group. A mixed Analysis of Variance was conducted to compare climbing behaviour over time (in weeks) for all nine groups. Both main effects (group, time) and the interaction (group x time) were significant. Post hoc Fisher’s Least Significant Difference tests revealed a significant difference between the control group and en1, en4, en54, invW and Df (2R) enE invE groups. These results support the hypothesis that mutations of en, inv or both will result in a PD phenotype and consequent decreased motor function of D. melanogaster PD models, with or without a significant decrease in lifespan.


Corresponding author: Sheldon V. Smith, svs653@mun.ca





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