bluuebunny/crossref_metadata_2025 huggingface dataset:
E.3 fMRI correlates of symptom-specific improvement in STN deep brain stimulation
Authors: Santyr B , Loh A , Germann J , Boutet A , Ajala A , Qiu J , Abbass M , Fasano A , Lozano A
Published: May 2024

Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal symptoms of Parkinson’s disease (PD). However, the therapeutic mechanisms are incompletely understood. By leveraging patient-specific brain responses to DBS using functional magnetic resonance imaging (fMRI) acquired during stimulation, we identify and validate symptom-specific networks associated with clinical improvement. Methods: Forty PD patients with STN-DBS were enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. The four cardinal motor outcomes of PD were chosen a priori and measured using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRSIII): axial instability, tremor, rigidity, bradykinesia. Stimulation-dependent changes in blood oxygen level-dependent (BOLD) signal were correlated with each symptom. Results: The relationship between BOLD response and outcomes revealed significant networks of clinical response (p<0.001). Using BOLD responses from the network hubs, each symptom-specific model was significantly predictive of actual improvement: axial instability (R2=0.38, p=0.000026), bradykinesia (R2=0.29, p=0.00033), rigidity (R2=0.40, p=0.000013), tremor (R2=0.26, p=0.00073). Conclusions: Using patient-specific imaging, we provide evidence of an association between DBS-evoked fMRI response and individual symptom improvement. Brain networks associated with clinical improvement were different depending on the PD symptom examined, suggesting the presence of symptom-specific networks of efficacy which may allow personalization of DBS therapy.
E.5 Designing a paradigm for post endovascular therapy imaging
Authors: Gargan C , Jay C , Thompson L , Roberts DE , Bhalla T , Bender MT , Schartz DA , Mattingly TK
Published: May 2024

Background: There is no guideline for imaging post endovascular therapy (EVT). MRI is considered superior to noncontrast CT for assessment of final infarct volume and to distinguish contrast from hemorrhage. We sought to align the post EVT imaging practices with those after intravenous thrombolysis Methods: We reviewed the EMR records for all EVT patients from Jan 1, 2019 to Dec 31, 2021. We assessed quantity of CT within 24h of EVT, quantity of MRIs performed, and indications listed. We then undertook an educational program targeting stakeholders. The objective was to transition to MRI at 24h for imaging post EVT. Exceptions included neurologic change, need for antiplatelet infusion, or intraoperative complications. Results: Post intervention, a significant reduction in CT within 24h (-28%, P=0.01) and increase in MRIs (+42%, P<0.00). CT within 24h per patient dropped by 50% (1.12 pre vs 0.57 post). Radiation dose per patient dropped by 49%. Average imaging costs increased by 17%, and the number of transfers off unit for imaging increased by 11%. Good functional outcome dropped from 44% preintervention to 34% postintervention (P=0.06). Conclusions: This represents the first systematic evaluation of post EVT imaging in a single center. We demonstrate successful behavior changes for post EVT imaging.
F.1 Oscillatory network markers of subcallosal cingulate deep brain stimulation for depression
Authors: Harmsen IE , Scherer M , Samuel N , Elias GJ , Germann J , Boutet A , Giacobbe P , Rowland NC , Milosevic L , Lozano AM
Published: May 2024

Background: Identifying functional biomarkers related to treatment success can aid in optimizing therapy and provide a better understanding of the neural mechanisms of treatment-resistant depression (TRD) and subcallosal cingulate deep brain stimulation (SCC-DBS). Methods: Magnetoencephalography data were obtained from 16 individuals with SCC-DBS for TRD and 25 healthy subjects. We identified region-specific oscillatory modulations that both (i) discriminate individuals with TRD (SCC-DBS OFF) from healthy controls and (ii) discriminate responders from non-responders (SCC-DBS ON). The effects of stimulation intensity and frequency were also explored. Results: Discriminative regions that differentiated responders from non-responders based on modulations of increased alpha (8-12 Hz) and decreased gamma (32-116 Hz) power included nodes of the default mode, central executive, and somatomotor networks, Broca’s area, and lingual gyrus. Furthermore, low stimulation frequency had stronger effects on oscillatory modulation. Conclusions: The identified functional biomarkers implicate modulations of TRD-related activity in brain regions involved in emotional control/processing, motor control, and interactions between speech, vision, and memory – all implicated in depression. These electrophysiological biomarkers have the potential to be used as functional proxies for therapy optimization. Additional stimulation parameter analyses revealed that oscillatory modulations are strengthened by increasing stimulation intensity or reducing frequency, which may benefit SCC-DBS non-responders.
F.5 A neurotransmitter-dependent mechanism of ependymal cell activation: Insights into a novel therapeutic target for spinal cord injury
Authors: Hachem LD , Moradi H , Balbinot G , Mothe AJ , Lu W , Valiante T , Tator CH , Fehlings MG
Published: May 2024

Background: The drivers that activate endogenous ependymal-derived neural stem/progenitor cells (epNSPCs) remain unknown. Understanding the mechanisms that govern the biology of these cells is critical in developing a therapeutic strategy to harness their regenerative potential after injury. Methods: FoxJ1-CreER-tdTomato reporter mice were used for epNSPC lineage tracing. A conditional genetic knock-out mouse line of glutamate-subtype AMPA receptor (AMPAR) subunits in epNSPCs was generated. Electrophysiological properties were assessed using single cell patch clamp and slice culture recordings. For in vivo studies, mice underwent cervical SCI. To examine the effect of positive modulation of AMPARs, mice received the ampakine CX546 or vehicle and underwent electrophysiological testing, behavioural assessment and spinal cord extraction. Results: Glutamate excitotoxicity, a hallmark in the pathogenesis of acute SCI, drives epNSPCs activation via AMPARs. Genetic knock-out of AMPARs in epNSPCs inhibits their activation following SCI. Positive pharmacological modulation of AMPARs after SCI enhances the migration and differentiation of epNSPCs, increases neuronal sparing and improves long-term locomotor/forelimb function. SCI decreases the excitability of corticospinal tract projections, which is improved with positive AMPAR modulation. Conclusions: Glutamatergic signaling via AMPARs is an important mediator of epNSPC activation after injury. Pharmacological targeting of this mechanism can be used to enhance endogenous regeneration and improve recovery post-SCI.
P.006 Barriers and risk factors for emergency room visits vs smartphone app use for migraine in Canada and the United States
Authors: Portt A
Published: May 2024

Background: Migraine affects more than 1 billion people, with attacks triggered by a variety of factors. Knowledge of environmental triggers for migraine attacks is limited, and has mostly been studied via emergency room (ER) visits. There are significant barriers and delays for attending ER for migraine treatment, which create challenges for estimating causal links to environmental exposures. We assessed whether smartphone app records may have fewer barriers and reduced lags. Methods: American and Canadian participants completed an online survey about their migraine attacks, smartphone app use, and ER visits. Results: Among 308 participants, barriers to visiting ER were similar in both countries, except for financial concerns in the US. About half of participants who attended ER also recorded the attack in a diary or app. Whereas migraine patients often present to ER 7+ days after onset, records in a smartphone app dataset were created within 2 days of onset. Conclusions: Although not all severe migraine attacks are recorded by smartphone users, smartphone app records may have fewer barriers to creation and shorter time lags compared to ER visit records, making them a rich source of data for research on transient neurologic health outcomes and environmental exposures.
P.010 Safety and efficacy of inebilizumab in AQP4+ NMOSD participants with history of immunosuppression treatment prior to N-MOmentum study
Authors: Paul F , Marignier R , Lindsey JW , Kim H , She D , Cimbora D , Patterson K , Cree B
Published: May 2024

Background: The long-term outcomes of inebilizumab in participants from the N-MOmentum trial with a history of immunosuppressant therapy as compared to those without was evaluated. Methods: N-MOmentum (NCT02200770) was a 28-week randomized phase 2/3 trial of inebilizumab vs placebo, with an optional Open-Label Period (OLP) (>2 years). In this post hoc analysis, AQP4+ participants who received inebilizumab (through the OLP) were grouped by no history of immunosuppression therapy beyond treatment of acute NMOSD attacks (naïve), or prior azathioprine (AZA) and/or mycophenolate mofetil (MMF) therapy. Results: Among participants who received inebilizumab during the study, 94 received prior AZA/MMF and 103 were immunosuppressant naïve. Annualized relapse rate (95%CI) for participants with prior AZA/MMF was 0.11 (0.07, 0.17), compared to 0.08 (0.05, 0.14) for naïve. The hospitalization rate (annualized rate [95% CI]) for prior AZA/MMF was 0.15 (0.08, 0.27), and 0.12 (0.06, 0.22) for naïve. Participants with ≥1 study drug-related-treatment-emergent-adverse-event (TEAE) was 30.9% (29/94) in prior AZA/MMF and 46.6% (48/103) of naïve. Most adverse events were infection-related for both groups; 72.3% (68/94) for prior AZA/MMF and 77.7% (80/94) for naïve. Conclusions: This post hoc analysis evaluating long-term outcomes of inebilizumab in AQP4+ NMOSD participants treated with prior AZA/MMF therapy demonstrated a similar efficacy and safety profile as participants without prior immunosuppressant therapy.
P.014 Intravenous immunoglobulin use for central nervous system disorders in British Columbia: implementation of a provincial screening program
Authors: Beadon K , Uy C , Cross H , Hrazdil C , Percy J , Jiwa N , Schrader D , Beauchamp A , Rosinski K , Carruthers R , Traboulsee A , Shih A , Morrison D , Chapman KM
Published: May 2024

Background: Intravenous Immunoglobulin (IVIg) use for Central Nervous System (CNS) conditions has increased over the last decade. In many CNS disorders, robust evidence for IVIg efficacy is still lacking. Building on the success of the British Columbia (BC) Neuromuscular IVIg utilization initiative, Guidelines for IVIg use in CNS conditions were developed. A provincial screening program was launched in 2023. Methods: For CNS IVIg, requests, diagnosis, dosing, consultation letters and treatment questionnaires were reviewed. Patient management was compared to provincial guidelines. A letter was sent to the ordering physician with the results of the review and treatment recommendations when management differed significantly from guidelines. Review of the first year’s cases was conducted. Results: Over the first 11 months of the program, 79 IVIg renewal requests were reviewed. The most common diagnoses were antibody mediated autoimmune encephalitis, severe drug resistant non-surgical epilepsy and Susac’s syndrome. Recommendations included dose reduction, discontinuation of IVIg, or initiation of alternative therapies for many of the requests. Conclusions: IVIg may be effective in the management of some CNS inflammatory conditions. A physician-led utilization program in BC with targeted education to ordering physicians promotes best practice. Review of year one data will inform a quality improvement cycle to optimize the guidelines.
P.017 Ischemic stroke in young adults: a comparison of outcomes, stroke risk factors and etiologies between males and females
Authors: Correia PN , Poppe AY , Gioia LC , Mendes GN , Alhazmi H , Daneault N , Deschaintre Y , Jacquin G , Odier C , Stapf C , Bereznyakova O
Published: May 2024

Background: The primary aim was to determine if functional outcomes among young adults with stroke differed based on sex. The secondary aim was to identify differences in stroke risk factors and etiologies between females and males. Methods: Retrospective analysis of acute ischemic stroke patients aged 18 to 55 years from a stroke registry between 2018 to 2022. Multivariable logistic regression to analyse if modified Rankin Scale at 3-6 months (mRS, 0-2 versus 3-6) was associated with sex. Results: 315 patients (127 female), median age 48 years (IQR 42-52), median NIHSS 10 (IQR 4-19, median mRS (3-6 months) 2 (IQR 1-3). Following adjustment for vascular risk factors, clinical stroke characteristics, baseline mRS and stroke time metrics no significant difference in mRS (3-6 months) based on sex (p=0.40). Females more frequently had an unknown time of stroke onset (p=0.03). Large-artery atherosclerosis as a stroke etiology (p=0.01), known atrial fibrillation (p=0.03) and drug use (p=0.003) were more frequent in males. Conclusions: Patient-oriented outcomes maybe of interest in future studies as functional mRS outcomes do not differ between young male and female stroke patients. Males had a higher prevalence of large-artery atherosclerosis and risk factors including drug use and atrial fibrillation. These findings could help develop targeted stroke prevention strategies.
P.024 Sex and gender reporting in clinical trials among neurological US Food and Drug Administration approvals
Authors: Cooper-Brown L , Chen J , Chen J , Ebadi A , Wilson L , Xie J , Bernhardt B , Bui E
Published: May 2024

Background: Sex and gender are related but distinct determinants of disease, treatment response, and research reproducibility whose consideration is increasingly required for research funding. Nevertheless, the quality of sex and gender reporting in neurological randomized controlled trials (RCTs) remains unknown. Methods: This ongoing study of RCTs associated with Food and Drug Administration neurological drug approvals aims to determine the frequency of accurate reporting of RCT participants’ sex and gender. Secondary outcomes include changes in reporting over time and RCT design characteristics. Results: Preliminary analysis included 145 RCTs (153,410 participants) associated with 77 medications approved in 1985-2023, most commonly for epilepsy (19%), migraine (16%), and multiple sclerosis (16%). Sixty-six RCTs (45.5%) used sex-related terms appropriately. Nine RCTs (6.2%) reported gender accurately. Fifty-three RCTs (37%) used sex- or gender-related terms interchangeably. There are no statistically significant differences in the proportions of studies reporting sex and/or gender accurately when comparing those published until versus after 2017. No RCT reported sex or gender collection methods, definitions of sex or gender, or including sex or gender minority participants. Conclusions: Preliminary results suggest shortcomings in reporting sex and, especially, gender accurately and inclusively among neurological drug RCTs and no significant improvement thereof in recent years.
P.025 Accuracy of code stroke activations: a tale of two comprehensive stroke centres
Authors: Li E , Khinda M , Yu AY , Vyas MV
Published: May 2024

Background: We evaluated the accuracy of code strokes activations at two comprehensive stroke centres in Toronto, Canada. Methods: We conducted a multi-centre, retrospective cohort study of all adult patients seen as code stroke in emergency rooms (ER) of two comprehensive stroke centres (CSC) in Toronto, Canada between January 1, 2022 and Dec 31, 2022. We included cases where the code stroke was activated in the field by paramedics and where it was activated in the ER by a physician. We reported off-criteria code stroke activations as the proportion of code stroke activations that did not meet all criteria for activation, and described the criteria that were not met. Results: A total of 677 (61.9% paramedic) code strokes were seen at CSC1 and 439 (80.6% paramedic) at CSC2. At CSC1, 21.2% paramedic-activated and 38.6% ER-activated were off-criteria, and at CSC2, 14.2% paramedic-activated and 48.1% ER-activated code stroke were off-criteria. Most of these were due to incorrect assessment of the last seen normal time. Conclusions: One in five code strokes did not meet criteria for activation. Improving the accuracy of paramedic and ER assessment of last seen normal time may be an avenue to reduce off-criteria code stroke activations.
P.027 KNOW BRAIN EMBRACE CARE: A study investigating young adult stroke patients’ knowledge and behaviour around lifestyle
Authors: Ibrahim S , Sivakumar K , Ng S , Ravi A , Singh S , Francis T , Stanimirovic A , Casaubon LK , Singh S , Rosand J , Rac V , Pikula A
Published: May 2024

Background: Stroke incidence is rising among younger adults (≤65yrs). Modifiable and behavioural risk factors are linked to stroke; however, limited understanding of knowledge and behaviour exists around preventative/lifestyle medicine (LSM) among this patient population. Study aim was to assess younger adult stroke patients’ lifestyle knowledge, habits, and barriers. Methods: A cross-sectional design was employed. Data were collected through an online, self-reported survey following a routine stroke prevention clinic visit and analyzed using descriptive and inferential statistics. Results: Sample included 103 participants (56.3% women, 60% white, mean age 47.6, 54.5% prior stroke). Majority (63%) understood current healthy lifestyle recommendations around blood pressure, sleep, and alcohol use, but fewer (<24.3%) around exercise and diet. Almost 70% ate processed food weekly, with emotions and social/family situations influencing eating habits. Interestingly, despite not understanding the current recommendations, >80% exercised moderately (3.5d/wk) with work and family responsibilities as main barriers. Over 50% slept <7hrs/night, had moderate to high stress levels, and implemented different coping strategies (food, TV, video games, and exercise). Majority (82.4%) reported willingness to change habits. Conclusions: Our findings provide valuable insight on young adult stroke patients’ preventative/LSM-related knowledge, habits, and barriers and provide new opportunities for the development of brain care-related initiatives.
P.029 Endovascular therapy for cerebral venous thrombosis: an international survey
Authors: Brakel BA , Rebchuk AD , Ospel J , Heran MK , Goyal M , Hill MD , Miao Z , Chen Y , Sacco S , Yaghi S , Ton M , Thomalla G , Boulouis G , Yamagami H , Campbell BC , Raymond J , Saposnik G , Nguyen TN , Field TS
Published: May 2024

Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.
P.030 Remote ischemic conditioning in acute ischemic stroke and small vessel disease – a feasibility study
Authors: Majeed A , Khan N , Bhangoo G , Kate M , Shuaib A , Buck B , Mushahwar V , Ferguson-Pell M , Sarmiento RJ , Kadangot R
Published: May 2024

Background: We tested the hypothesis that delivering remote ischemic conditioning (RIC) with an adjunct tissue reflectance sensor (TRS) device may be feasible in patients with acute ischemic stroke (AIS) and cerebral small vessel disease (cSVD). Methods: AIS patients with neurological deficits within 7 days of symptom onset were screened for moderate to severe cSVD. Eligible patients were randomized 2:1 to receive intervention RIC or sham RIC (7 days). The primary outcome measure was intervention feasibility. It was assessed as an intervention-related comfort by a 5-point Likert scale during each session (1-very uncomfortable, 5-very comfortable). The secondary outcome measure was assessment of TRS derived dermal blood concentration and blood oxygenation changes during RIC. Results: Forty-seven (32 intervention, 15 sham) patients were enrolled at a median (IQR) 39.7 (25-64) hours after symptom onset, with mean±SD age of 75±12 years, 22 (46.8%) were females and median baseline NIHSS of 5(3-7). The Likert scale was 3.5 (3-4) in the intervention group and 4 (4-5) in the sham group. The TRS derived blood concentration and blood oxygenation changes were proportionate in the intervention arm and absent in the sham arm. Conclusions: RIC treatment with TRS is feasible in patients with AIS+cSVD. The efficacy of RIC needs further assessment.
P.054 Long-term safety and efficacy of zilucoplan in myasthenia gravis: additional interim analyses of RAISE-XT
Authors: Genge A , Howard JF , Freimer M , Hewamadduma C , Hussain Y , Maniaol A , Mantegazza R , Smilowski M , Utsugisawa K , Vu T , Weiss MD , Duda PW , Boroojerdi B , Vanderkelen M , de la Borderie G , Leite MI
Published: May 2024

Background: Zilucoplan, a macrocyclic peptide complement component 5 inhibitor, sustained efficacy for up to 60 weeks of treatment, with a favourable safety profile in patients with acetylcholine receptor autoantibody-positive generalised myasthenia gravis in an interim analysis of RAISE-XT (NCT04225871). We evaluate the safety and efficacy of zilucoplan up to 96 weeks. Methods: RAISE-XT, a Phase 3, multicentre, open-label extension study, included patients who participated in the double-blind Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. Patients self-administered daily subcutaneous zilucoplan 0.3mg/kg injections. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: At data cut-off (11 May 2023), median (range) exposure to zilucoplan was 1.8 (0.11–5.1) years (N=200). TEAEs occurred in 191 (95.5%) patients; the most common TEAE was COVID-19 (n=64; 32.0%). At Week 96, mean (standard error) change in MG-ADL score from double-blind study baseline was –6.33 (0.49) and –7.83 (0.60) for patients who received zilucoplan 0.3mg/kg and placebo in the double-blind studies, respectively. Conclusions: Zilucoplan demonstrated a favourable long-term safety profile. Efficacy was sustained for 96 weeks in patients who had previously received zilucoplan and who switched from placebo.
P.056 Real-world reduction in oral corticosteroid utilization following efgartigimod initiation in patients with generalized myasthenia gravis
Authors: Kassardjian CD , Goyal N , Qi C , Stone J , Gelinas D , Jefferson M , Balaji Suthagar T , Menon RR , Goyal A , Phillips G
Published: May 2024

Background: Reducing oral corticosteroids (OCS) use can alleviate the risk of many adverse events related to long-term OCS use. Here, we evaluate real-world utilization of OCS among patients with generalized myasthenia gravis (gMG) over the first 6 months following efgartigimod initiation. Methods: Patients with gMG using OCS who initiated efgartigimod treatment were identified retrospectively from an open US medical and pharmacy claims database (IQVIA Longitudinal Access and Adjudication Data [LAAD], April 2016-April 2023). Average daily dose (ADD) of OCS was analyzed during the 3-month period preceding efgartigimod initiation, and at 3 and 6 months post-efgartigimod initiation. Results: Of 231 patients assessed, 17 (7.4%), 109 (47.1%), and 105 (45.5%) had baseline OCS ADD of 0–5 mg, 5–20 mg, or >20 mg, respectively. At 3 and 6 months post-efgartigimod, 82 (35%) and 99 (43%) patients, respectively, reduced ADD by ≥5 mg. Proportion of patients with ADD of 0–5 mg increased >3-fold (7% baseline vs. 26% 6 months post-efgartigimod) and proportion of patients with ADD of >20 mg decreased by 35% (45% baseline vs. 29% 6 months post-efgartigimod) following efgartigimod initiation. Conclusions: Approximately 43% of patients were able to decrease steroid use or achieved steroid-free status within 6 months of efgartigimod treatment initiation.
P.064 A case of late onset Pompe Disease presenting in 6th decade
Authors: Opala A
Published: May 2024

Background: Late onset Pompe disease (LOPD), rare autosomal recessive lysosomal storage disease, resulting from mutation in alpha glucosidase enzyme (GAA) can present even in 6th decade of life. Slowly progressive, subtle, limb girdle pattern of weakness (LGPW), with auxiliary features such as ptosis, enlarged tongue, axial rigidity, facial diplegia, variable degree of respiratory weakness is not uncommon. Hypertrophic and electrical cardiac abnormalities are well described in LOPD. Methods: We present a case of 67-year-old male presenting with proximal weakness, subtle ptosis, bilateral quadriceps and shoulder girdle atrophy, and left toe numbness. PMHx: CABG, NSTEMI. Statin use. FMHx: noncontributory. Results: EMG: L5 radiculopathy, with unexpected myopathic units in hip/pelvic/ shoulder girdle muscles with active denervation and muscle irritability. CK, CRP, SPEP, ANA, LFTs, HMG-CoA reductase: normal. GAA enzymatic activity=0.96µmol/L/hr (low), genetics: pathogenic variants in GAA gene: c.-32-13T>G and c.1194+3G>C. ECHO: severe diastolic dysfunction, restrictive left ventricular filling. PFTs: normal. Diagnosed with LOPD, started on therapy. Conclusions: LOPD remains a differential for LGPW especially in older patient population with history of cardiopulmonary features. Age-appropriate conconminant pathologies may confound the diagnostic process.Symptoms may preceed diagnosis for years.GAA enzymatic activity followed by genetic testing remains readily available and can confirm diagnosis, preventing delay of approved therapy.
P.067 Pharmacological prophylaxis for chronic migraine: A systematic review and network meta-analysis of randomized controlled trials
Authors: Khalili M , Liaghatdar A , Mahdian F , Levit T , Moradi S , Hedayati E , Torabiardakani K , Ahmadi F , Khademioore S , Sofi-Mahmudi A , Atkin-Jones T , Patil V , Mirzayeh Fashami F , Mehmandoost S , Sharma S , Fereshtehnejad M , Busse J , Sadeghirad B
Published: May 2024

Background: We performed a network meta-analysis of randomized controlled trials to assess the comparative effectiveness of available pharmacological prophylaxis for migraines. Methods: We searched MEDLINE, EMBASE, Web of Science, Scopus, PsycINFO and Cochrane CENTRAL up to October 2023 for trials that: (1) enrolled adults diagnosed with chronic migraine, and (2) randomized them to any prophylactic medication vs. another medication or placebo. We performed a random-effects frequentist network meta-analysis for patient-important outcomes. Results: We included 193 randomized trials. Compared to placebo, CGRP monoclonal antibodies (mean difference [MD] -1.7, 95%CI: -1.1 to -2.2), injection of botulinum toxin (MD -1.8, 95%CI: -0.7 to -2.9), calcium channel blockers (MD -1.8, 95%CI: -0.5 to -3.0), beta-blockers (MD -1.4, 95%CI: -0.2 to -2.6), and anticonvulsants (MD -1.1, 95%CI: -0.4 to -1.8) were among the most effective treatments in reducing average number of headache days per months. Anticonvulsants (Risk Ratio [RR] 2.3, 95%CI: 1.8 to 3.0), calcium channel blockers (RR 1.8, 95% CI: 1.1 to 3.1), and tricyclic antidepressants (RR 2.3, 95% CI: 1.3 to 3.8) showed the highest risk of discontinuation due to adverse events. Conclusions: Our findings suggest that CGRP inhibitors, botulinum toxin, and beta-blockers may provide the greatest benefit, and tolerability, for reducing the frequency of migraine headaches.
P.075 Anatomy and pathology of the lacrimal apparatus: from the sac to the nasal fossa. what the neuroradiologist should know!
Authors: Ardawi J , Tampieri D
Published: May 2024

Background: The aim of our educational exhibit is to review the anatomy and pathology encountered and often overlooked of the excretory lacrimal apparatus from the lacrimal sac to the nasal fossa. Methods: We will provide an anatomical review of the various structures easily identifiable on CT and MRI and suggestions of the best imaging protocols to be used. Results: The lacrimal apparatus includes the various structures related to the production and flow of tears. In this educational exhibit we will focus on the excretory apparatus from the lacrimal sac to the nasal fossa. We will present various pathologies affecting the excretory lacrimal apparatus with attention to the specific features of each condition to facilitate an appropriate differential diagnosis. We will emphasize specific anatomical/imaging findings to help the diagnosis and propose a standardized reporting system for the Neuroradiologist and useful to the ENT surgeon. Conclusions: This educational exhibit offers a unique opportunity to review the anatomy and pathology of sometimes overlooked or forgotten structures which are however always included in our CT and MRI studies.
P.076 Long-term outcomes of radiofrequency ablation for temporal lobe epilepsy
Authors: Wang R , Parrent AG , Steven DA , Burneo JG , Suller-Marti A , Lau JC
Published: May 2024

Background: Radiofrequency ablation (RFA) is a minimally-invasive procedure that has been used to treat temporal lobe epilepsy (TLE), however its long-term efficacy is unknown. We aim to characterize the long-term outcomes of patients from the original series by Parrent and Blume (1999). Methods: Consecutive patients who underwent stereotactic RFA for TLE were retrospectively reviewed. Demographics, procedural details, and seizure outcomes until last follow-up were abstracted. Seizure-freedom after initial RFA treatment was estimated with Kaplan-Meier analysis. Results: 27 patients underwent RFA from 1994 to 2002. There were 14 female (52%) patients. 24 (89%) had mesial temporal sclerosis. Mean age at time of RFA was 33.1 years (range 12-45 years). 17 (63%) patients underwent left-sided RFA. 15 (56%) patients had further interventions: 4 (15%) underwent only repeat RFA, 1 (4%) had repeat RFA and anterior temporal lobectomy (ATL), and 10 (37%) underwent subsequent ATL only. Mean follow-up was 9.0 years (range 0.5-22.7 years). At last follow-up, 16 (59%) patients were seizure-free: 5 (19%) received one RFA treatment and 11 (41%) underwent additional procedures. Conclusions: Based on the original series describing the technique, stereotactic RFA for TLE is a safe, minimally-invasive procedure. The role of stereotactic RFA in the treatment of TLE remains to be determined.
P.078 fMRI-based deep brain stimulation programming: a blinded, crossover clinical trial
Authors: Santyr B , Ajala A , Alhashyan I , Germann J , Qiu J , Boutet A , Fasano A , Lozano A
Published: May 2024

Background: Success of deep brain stimulation (DBS) in Parkinson’s disease (PD) relies on time-consuming trial-and-error testing of stimulation settings. Here, we prospectively compared an fMRI-based stimulation optimization algorithm with >1 year of standard-of-care (SoC) programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-seven PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed, after an overnight medication washout period, under SoC and fMRI-determined stimulation conditions. A predefined non-inferiority margin was -5 points on the Unified Parkinson’s Disease Rating Scale (UPDRSIII). Results: UPDRSIII improved from 45.3 (SD=14.6) at baseline to 24.9 (SD=10.9) and 24.1 (SD=10.9) during SoC and fMRI-determined stimulation, respectively. The mean difference in scores was 0.8 (SD=8.5; 95% CI -4.5 to 6.2). The non-inferiority margin was not contained within the 95% confidence interval, establishing non-inferiority (p=0.013). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests equivalent outcomes may be achieved in 3 hours of fMRI scanning immediately after surgery compared to SoC requiring 6 or more in-person clinic visits throughout >1 year.
P.084 Early malignant transformation of intracranial epidermoid cysts: a case report and systematic review
Authors: Tsai C , Rebchuk AD , Oh J , Yip S , Fatehi M
Published: May 2024

Background: Intracranial epidermoid cysts (IEC) are benign congenital intracranial lesions that rarely undergo malignant transformation. We report a case of IEC evolving into squamous cell carcinoma (SCC) 1-year post-resection. Further, we conducted a systematic review on cases of early malignant transformations of IECs. Methods: MEDLINE, EMBASE, and Scopus were searched from inception until December 2023 for studies reporting malignant transformations of IECs within 2 years of diagnosis. Results: A 48-year-old female underwent surgical resection of a cerebellopontine angle (CPA) IEC in May 2022. She re-presented in July 2023 with headaches, nausea, vomiting, right facial weakness, and rapid cyst progression. Repeat surgical resection revealed a high-grade SCC. Our systematic review identified 19 (10 females, 9 males) additional IEC cases undergoing malignant transformation within 2 years. The mean age at presentation was 57.6 years, most common location was CPA (n=13, 68.4%) and mean time between IEC to malignant transformation was 10.6 months. Eighteen (94.7%) cases transformed to SCC, of which 2 had leptomeningeal carcinomatosis, and 1 transformed to glioblastoma. Conclusions: While malignant transformations of IECs are rare, regular postoperative follow-up is crucial for early malignancy detection and treatment initiation. Further study is warranted to evaluate factors contributing to accelerated malignant progression of IECs.
P.087 Factors affecting health-related quality of life among adult meningioma patients: a systematic review
Authors: Jonas K , Carpino M , Ahn M , Cusimano M
Published: May 2024

Background: Meningiomas are common brain neoplasms that can significantly influence health-related quality of life (HRQOL), yet the factors influencing HRQOL in adult patients remain unclear. We aimed to bridge this knowledge gap by determining these key factors. Methods: We conducted a systematic review, searching EMBASE, MEDLINE, CINAHL, Scopus, and PsycINFO up to March 2023. We included original, peer-reviewed studies focusing on adult patients (>18 years) with current or past meningioma at any stage of treatment that measured HRQOL or its proxies in relation to tumour-, treatment-, and patient-related factors. Two independent reviewers screened abstracts and full texts, selecting studies with acceptable risk of bias for data extraction and narrative synthesis. Results: Of N=2942 identified studies, N=30 were included. Key factors found to influence HRQOL in adult meningioma patients include surgery, radiotherapy, neurological function, functional status, comorbidities, sleep quality, psychological impairment, age, and employment. Factors related to tumour characteristics yielded inconsistent findings. Heterogeneity and inconsistencies in HRQOL measurement across studies hindered definitive conclusions about the impact of factors on HRQOL. Conclusions: Our review emphasizes the need for standardized, disease-specific HRQOL assessments in meningioma patients. More consistent, large-scale, prospective research is essential to comprehensively understand and improve HRQOL, and thereby ensure tailored care for this population.
P.093 BMI as a predictor of recurrence in high-grade meningioma: A single center retrospective cohort study
Authors: Toyota P , Persad AR , Liu E , Saini J , Zherebitskiy V , Auer R , Hnenny L
Published: May 2024

Background: Elevated BMI has been proposed as a risk factor for the development of meningioma. The relationship between body mass index (BMI) and disease control in high-grade meningioma has not yet been examined. A retrospective cohort study was performed to assess the relationship between high-grade meningioma recurrence and BMI. Methods: This is a retrospective cohort study of patients with Grade 2 or Grade 3 meningioma at a single tertiary care center between 2008 and 2017. We collected clinical data including age, sex, BMI, location, Simpson grade, brain invasion, and radiation treatments. Disease control was monitored on followup MRI scans. We stratified patients by BMI greater than or less than 25. Results: A total of 45 patients were included. Recurrence was observed in 15 patients (33.3%). There were 32 (71.1%) patients with BMI > 25, and 13 (28.9%) patients with normal BMI. Patients with elevated BMI had higher risk of recurrence (p=0.04). Multivariate analysis identified BMI as an independent predictor of recurrence. Conclusions: Our results suggest that overweight patients with a Grade 2 or Grade 3 meningioma are at higher risk of recurrence than patients with normal BMI. The explanation for this association unknown. Further research is suggested to confirm and better characterize this association.
P.096 Hearing preservation and quality of life outcomes in partial labyrinthectomy petrous apicectomy for microsurgical resection of large posterior fossa skullbase tumors
Authors: Kam J , Hounjet C , Makarenko S , Brakel B , Rebchuk A , Castle-Kirszbaum M , Akagami R
Published: May 2024

Background: The Partial Labyrinthectomy Petrous Apicectomy (PLPA) aims to give transpetrosal access whilst preserving hearing for challenging tumors such as petroclival meningioma. There are few studies assessing resection and morbidity and no large studies that document hearing preservation and quality of life (QOL). We present the first large series to do so. Methods: A retrospective review was performed of all PLPA cases between 2005 and 2023 at a tertiary center. Demographics, tumor characteristics, neuromonitoring, hearing and surgical outcomes were collected. QOL was measured with the 36-item short form survey (SF-36). Results: Of 73 PLPAs, data for 56 patients undergoing 57 surgeries was obtained. Petroclival meningioma (57.8%) and epidermoid tumors (21.0%) were common indications . The mean patient age and tumor size were 51.6 years and 44mm. Gross total resection was achieved in 40.3%, near total in 15.8% and subtotal in 43.8% of cases with no perioperative mortality and was not influenced by attempted hearing preservation (p=0.183). Of 39 hearing preservation cases, 27 (69.2%) were preserved, 10 (25.6%) were lost and 2 had unclear outcomes. Conclusions: Improved microsurgery and neuromonitoring during PLPA leads to decreased mortality and morbidity compared to historical cohorts while achieving a high rate of resection, hearing preservation and maintained QOL.
P.097 Glioblastoma treatment, end-of-life resource utilization, and outcomes in Ontario
Authors: Ellenbogen Y , Taslimi S , Alkins R
Published: May 2024

Background: The end-of-life (EoL) phase of care is pivotal for glioblastoma (GBM) patients. While early integration of palliative care has shown benefits in various cancer types, its role in GBM care remains underexplored. This study aims to characterize EoL care patterns in GBM patients, assessing their temporal evolution, regional disparities, and socioeconomic influences. Methods: This is retrospective study of all patients with GBM treated in Ontario between 1994 and 2018 using the ICES data repository. Variables analyzed included patient demographics, comorbidities, palliative care utilization, and aggressive/supportive care components. Results: We identified 9,013 GBM patients within the study period. There was a gradual increase in palliative care utilization over time, accompanied by a decrease in in-hospital deaths. However, the proportion of patients receiving chemotherapy in the last 14 days of life increased. Multivariate logistic regression found socioeconomic status influenced palliative care access and rural patients also had a higher rate of in-hospital deaths, possibly due to limitations in outpatient palliative care services. Conclusions: The findings in this study clarify the status of EoL care for GBM patients within Ontario, and demonstrates key areas for future research, underscoring the need for standardized EoL care practices to enhance the quality of care for GBM patients.
P.102 Integration of Ultrasensitive electroluminescent immunoassay and cell-free DNA methylation analysis for the non-invasive discrimination of adult diffuse gliomas
Authors: Ajisebutu A , Chatanaka M , Patil V , Prassas I , Eleftherios D , Zadeh G
Published: May 2024

Background: Gliomas are highly aggressive brain tumors with nearly universal recurrence rate. Despite this, the ability to accurately predict tumor recurrence relies solely on serial MRI imaging, highlighting the need for prognostic biomarkers. Due to the low accuracies of individual serum markers, we have proposed the use of an integrated, multi-platform approach to biomarker discovery. Methods: A cohort of 107 glioma plasma samples, including 30 pairs, underwent plasma proteomic, consisting of a panel of serum proteins (FABP4, GFAP, NFL, Tau and MMP3,4 &7) quantified through ultrasensitive electrochemiluminescence multiplexed immunoassays, and plasma DNA methylation analysis, captured through cell-free methylated DNA immunoprecipitation and high-throughput sequencing. Results: Unsupervised hierarchal clustering revealed robust separation of primary and recurrent tumors through plasma proteomics, associated with a distinct plasma methylation signature. NFL, Tau and MMP3 levels differed between primary and recurrent samples; pair-wise analysis revealed increased in NFL and Tau concentrations upon recurrence. Tau levels predicted outcome independent of WHO Grade and IDH status. A predictive model created through the integration of the proteomic and methylation signatures revealed an AUC of 0.83. Conclusions: The combination of DNA methylation and plasma proteomics showcases that an integrative approach may improve the ability of these techniques for the serial monitoring of gliomas patients.
P.103 Automated pituitary adenoma segmentation for radiosurgery with deep learning-based model
Authors: Balasubramaniam N , Cerny M , May J , Hamackova L , Novotnyml J , Barucic D , Kybic J , Majovsky M , Hallak H , Liscak R , Netuka D
Published: May 2024

Background: Pituitary adenomas are treated with endoscopic surgery, while stereotactic radiosurgery addresses complex cases. Our study highlights AI’s role in accurate segmentation, improving treatment planning workflow efficiency Methods: In a retrospective study at Na Homolce Hospital (January 2010 to October 2022), SRS for pituitary adenomas was analyzed. Data were split 80:20 for training and validation. Using nnU-net, a medical image segmentation tool, a model predicted precise tumor, optic nerve, and pituitary gland segmentation. Accuracy was evaluated quantitatively with Dice similarity coefficient and qualitatively by human experts. The study explored the impact of tumor volume and hormonal activity status on segmentation accuracy. Results: The study comprised 582 and 146 patients in training and validation sets, respectively. The model achieved Dice similarity coefficients of 83.1% (tumor), 62.9% (normal gland), and 78.0% (optic nerve). Expert assessments deemed 41% directly applicable, 31.5% needing minor adjustments, and 27.4% unsuitable for clinical use. Larger tumor volume and non-functioning adenomas correlated with higher accuracy. Including T2 weighted scans improved DSC for optic nerve and normal gland. Conclusions: The study showcases deep learning’s potential in automating pituitary adenoma segmentation from MRI data, particularly excelling in large, hormonally inactive macroadenomas. Encourages collaborative use with clinicians for improved neurosurgical patient care.
P.104 Prognostic value of NIRS regional oxygen saturation based cerebrovascular reactivity in TBI: a Canadian high resolution traumatic brain injury (CAHR-TBI) cohort study
Authors: Gomez A , Froese L , Griesdale D , Thelin EP , Raj R , van Iperenburg L , Tas J , Aries M , Stein KY , Gallagher C , Bernard F , Kramer AH , Zeiler FA
Published: May 2024

Background: Near-infrared spectroscopy regional cerebral oxygen saturation (rSO2) has gained interest as a raw parameter and as a basis for measuring cerebrovascular reactivity (CVR). This study aimed to identify threshold values of rSO2 and rSO2 based CVR at which outcomes worsened following traumatic brain injury (TBI). Methods: A retrospective multi-institutional cohort study was performed. The cerebral oxygen indices, COx (using rSO2 and cerebral perfusion pressure) as well as COx_a (using rSO2 and arterial blood pressure) were calculated for each patient. 2x2 tables were created grouping patients by alive/dead and favorable/unfavorable outcomes at various thresholds of COx and COx_a as well as rSO2 itself. Chi-square values were calculated to identify the most discriminative significant threshold. Results: In the cohort of 129 patients rSO2 did not have any statistically significant threshold value. For COx and COx_a, an optimal threshold value of 0.2 was identified for both survival and favorable outcomes with values above this associated with worse outcomes. Conclusions: In this study, raw rSO2was found to contain no significant prognostic information. However, rSO2 based indices of CVR, were found to have a uniform threshold of 0.2, above which clinical outcomes worsened. This study lays the groundwork to transition to less invasive means of continuously measuring CVR.
P.107 How often does digital subtraction angiography change management in CT angiogram negative subarachnoid hemorrhages?
Authors: Ong K , Rizzuto M , Dhillon K , Sekhon A , Fatehi M
Published: May 2024

Background: Subarachnoid hemorrhages (SAH) are emergencies that require expedient workup. While Aneurysms and vascular malformations are a common cause, a subset of cases may lack detectable structural causes. If a CT angiogram (CTA) is negative, the more invasive Digital Subtraction Angiogram (DSA) is used for diagnosis. It is unclear how often DSA alters treatment for CTA negative SAHs. Methods: A retrospective review of SAH patients from our institution (Vancouver General Hospital) with a negative CTA with subsequent DSA in the past 25 years. Results: Our preliminary analysis included 233 patients. The median age was 55. 105 (45%) were female, and 128 (55%) were male. The average length of hospitalization was 9.6 days, and 226 (97%) were discharged alive. The median number of CTAs and DSAs administered were 2 and 1 respectively. In 12 (5%) cases, DSA detected an abnormality not seen on CTA, which led to endovascular or open surgery treatment in 5 (2%) cases. 5 DSA procedures led to complications including transient neurologic changes and ischemia. Conclusions: In SAH patients with CTA negative scans, additional DSA testing identified actionable pathology in only a small minority of cases. Clinicians must weigh the benefit of DSAs in these cases.