Z. Siddiqi, JA Allen, I Basta, C Eggers, J Guptill, K Gwathmey, C. Hewamadduma, E Hofman, Y. Hussain, S Kuwabara, F Leypoldt, J. Lin, M Lipowska, M Lowe, G Lauria Pinter, L Querol, N Suresh, T Chang, A Tse, P Ulrichts, PA van Doorn, B Van Hoorick, R. Yamasaki, RA Lewis
Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.
{"title":"D.1 Efficacy, safety, and tolerability of subcutaneous efgartigimod in chronic inflammatory demyelinating polyneuropathy: results from the ADHERE trial","authors":"Z. Siddiqi, JA Allen, I Basta, C Eggers, J Guptill, K Gwathmey, C. Hewamadduma, E Hofman, Y. Hussain, S Kuwabara, F Leypoldt, J. Lin, M Lipowska, M Lowe, G Lauria Pinter, L Querol, N Suresh, T Chang, A Tse, P Ulrichts, PA van Doorn, B Van Hoorick, R. Yamasaki, RA Lewis","doi":"10.1017/cjn.2024.92","DOIUrl":"https://doi.org/10.1017/cjn.2024.92","url":null,"abstract":"Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"25 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Chepke, K. Cote, K. Pinner, J. Yardley, M. Moline
Background: Improvements in daytime functioning ideally accompany improvements in insomnia. Scores on the Insomnia Severity Index (ISI) daytime-related items were analyzed following treatment with lemborexant (LEM), a dual orexin receptor antagonist, or placebo (PBO), based on baseline severity. Methods: Participants (≥18 y) with insomnia disorder in E2006-G000-303, a 12-month, randomized, double-blind, PBO-controlled study (first 6 months: Treatment Period 1 [TP1]), were randomized to PBO or LEM 5 mg (LEM5) or 10 mg (LEM10) for 6 months. ISI items are rated 0 (no problem) to 4 (very severe problem); daytime-related ISI items have a maximum score of 16. Results: Of 949 participants, 749 (78.9%) completed the ISI at baseline and end of TP1. Baseline daytime ISI total score distributions were similar between groups. More participants with baseline scores of 9-12 and 13-16 shifted to 0-4 with LEM5 (49.7% and 39.1%, respectively) and LEM10 (46.2% and 46.3%) versus PBO (26.6% and 29.6%). Overall shift distributions were significantly different, favoring both LEM groups (P<0.01). LEM was well tolerated. Conclusions: More LEM-treated participants had improved daytime functioning, evidenced by the significantly larger number of participants whose scores moved into lower categories (ie, better sleep) versus PBO-treated participants, demonstrating additional value beyond improved sleep parameters.
{"title":"P.020 Shifts in daytime functioning items on the insomnia severity scale with lemborexant after 6 months of treatment","authors":"C. Chepke, K. Cote, K. Pinner, J. Yardley, M. Moline","doi":"10.1017/cjn.2024.127","DOIUrl":"https://doi.org/10.1017/cjn.2024.127","url":null,"abstract":"Background: Improvements in daytime functioning ideally accompany improvements in insomnia. Scores on the Insomnia Severity Index (ISI) daytime-related items were analyzed following treatment with lemborexant (LEM), a dual orexin receptor antagonist, or placebo (PBO), based on baseline severity. Methods: Participants (≥18 y) with insomnia disorder in E2006-G000-303, a 12-month, randomized, double-blind, PBO-controlled study (first 6 months: Treatment Period 1 [TP1]), were randomized to PBO or LEM 5 mg (LEM5) or 10 mg (LEM10) for 6 months. ISI items are rated 0 (no problem) to 4 (very severe problem); daytime-related ISI items have a maximum score of 16. Results: Of 949 participants, 749 (78.9%) completed the ISI at baseline and end of TP1. Baseline daytime ISI total score distributions were similar between groups. More participants with baseline scores of 9-12 and 13-16 shifted to 0-4 with LEM5 (49.7% and 39.1%, respectively) and LEM10 (46.2% and 46.3%) versus PBO (26.6% and 29.6%). Overall shift distributions were significantly different, favoring both LEM groups (P<0.01). LEM was well tolerated. Conclusions: More LEM-treated participants had improved daytime functioning, evidenced by the significantly larger number of participants whose scores moved into lower categories (ie, better sleep) versus PBO-treated participants, demonstrating additional value beyond improved sleep parameters.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"55 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SS Haile, A Boutet, AZ Wang, H. Son, M Malik, V Pai, M Nasralla, J. Germann, A. Vetkas, F. Khalvati, BB Ertl-Wagner
Background: Interest in artificial intelligence (AI) and machine learning (ML) has been growing in neuroradiology, but there is limited knowledge on how this interest has manifested into research and the field’s trends, challenges, and future directions. Methods: The American Journal of Neuroradiology was queried for original research articles published since inception (Jan. 1, 1980) to Sept. 19, 2022 that contained any of the following key terms: “machine learning”, “artificial intelligence”, or “radiomics”. Articles were screened, categorized into Statistical Modelling (Type 1), AI/ML Development (Type 2), or End-user Application (Type 3) and then bibliometrically analyzed. Results: A total of 124 articles were identified with 85% being non-integration focused (Type 1 n = 41, Type 2 n = 65) and the remaining (n = 18) being Type 3. The total number of articles published grew two-fold in the last five years, with Type 2 articles mainly driving this growth. While most (66%) Type 2 articles were led by a radiologist with 55% possessing a postgraduate degree, a minority of Type 2 articles addressed bias (15%) and explainability (20%). Conclusions: The results of this study highlight areas for improvement but also strengths that stakeholders can consider when promoting the shift towards integrating practical AI/ML solutions in neuroradiology.
{"title":"P.074 Assessing the emergence and evolution of artificial intelligence and machine learning research in neuroradiology","authors":"SS Haile, A Boutet, AZ Wang, H. Son, M Malik, V Pai, M Nasralla, J. Germann, A. Vetkas, F. Khalvati, BB Ertl-Wagner","doi":"10.1017/cjn.2024.180","DOIUrl":"https://doi.org/10.1017/cjn.2024.180","url":null,"abstract":"Background: Interest in artificial intelligence (AI) and machine learning (ML) has been growing in neuroradiology, but there is limited knowledge on how this interest has manifested into research and the field’s trends, challenges, and future directions. Methods: The American Journal of Neuroradiology was queried for original research articles published since inception (Jan. 1, 1980) to Sept. 19, 2022 that contained any of the following key terms: “machine learning”, “artificial intelligence”, or “radiomics”. Articles were screened, categorized into Statistical Modelling (Type 1), AI/ML Development (Type 2), or End-user Application (Type 3) and then bibliometrically analyzed. Results: A total of 124 articles were identified with 85% being non-integration focused (Type 1 n = 41, Type 2 n = 65) and the remaining (n = 18) being Type 3. The total number of articles published grew two-fold in the last five years, with Type 2 articles mainly driving this growth. While most (66%) Type 2 articles were led by a radiologist with 55% possessing a postgraduate degree, a minority of Type 2 articles addressed bias (15%) and explainability (20%). Conclusions: The results of this study highlight areas for improvement but also strengths that stakeholders can consider when promoting the shift towards integrating practical AI/ML solutions in neuroradiology.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"14 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141099744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Genge, J. Howard, M. Freimer, C. Hewamadduma, Y. Hussain, A. Maniaol, R. Mantegazza, M. Śmiłowski, K. Utsugisawa, T. Vu, MD Weiss, PW Duda, B. Boroojerdi, M. Vanderkelen, G. de la Borderie, MI Leite
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.
{"title":"P.054 Long-term safety and efficacy of zilucoplan in myasthenia gravis: additional interim analyses of RAISE-XT","authors":"A. Genge, J. Howard, M. Freimer, C. Hewamadduma, Y. Hussain, A. Maniaol, R. Mantegazza, M. Śmiłowski, K. Utsugisawa, T. Vu, MD Weiss, PW Duda, B. Boroojerdi, M. Vanderkelen, G. de la Borderie, MI Leite","doi":"10.1017/cjn.2024.161","DOIUrl":"https://doi.org/10.1017/cjn.2024.161","url":null,"abstract":"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.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"60 13","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"P.006 Barriers and risk factors for emergency room visits vs smartphone app use for migraine in Canada and the United States","authors":"A. Portt","doi":"10.1017/cjn.2024.114","DOIUrl":"https://doi.org/10.1017/cjn.2024.114","url":null,"abstract":"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.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141098612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ME Yasuda, J Moore, T Nguyen, Y. Alammar, MA Mohd Slim, A. Mastrolonardo, D. Sommer, K. Reddy
Background: Minimally invasive endoscopic techniques via the transorbital approach (ETOA) have emerged as a promising alternative for addressing skull base tumours. This study aims to showcase our institution’s extensive experience with ETOA, detailing the surgical technique employed and presenting comprehensive patient outcomes. Methods: A retrospective analysis was conducted on data from patients who underwent ETOA within the past five years. Results: Over the study period, 24 ETOA procedures were performed on 21 patients, with an average age of 48.92, 13 of whom were women. The superior orbital corridor was utilized in 95.83% of cases, and in 79.17%, ETOA was complemented by a transnasal approach. Spheno-orbital meningioma accounted for the most common surgical indication (33.33%, n=8), all resulting in vision improvement, followed by lateral frontal sinus mucocele (25%, n=6). The median length of stay was one day, and ETOA achieved the procedure goal in 19 patients. Transient V1 numbness was the primary complication (29.17%, n=7), and 20.83% (n=5) necessitated another surgery. Notably, no mortality was associated with this procedure. Conclusions: Our institution’s experience underscores the notable safety and efficacy potential of ETOA, with 19 out of 21 patients exhibiting positive outcomes, obviating the need for revision surgery in most cases.
{"title":"P.141 Endoscopic transorbital approach to the skull base: a single centre experience","authors":"ME Yasuda, J Moore, T Nguyen, Y. Alammar, MA Mohd Slim, A. Mastrolonardo, D. Sommer, K. Reddy","doi":"10.1017/cjn.2024.242","DOIUrl":"https://doi.org/10.1017/cjn.2024.242","url":null,"abstract":"Background: Minimally invasive endoscopic techniques via the transorbital approach (ETOA) have emerged as a promising alternative for addressing skull base tumours. This study aims to showcase our institution’s extensive experience with ETOA, detailing the surgical technique employed and presenting comprehensive patient outcomes. Methods: A retrospective analysis was conducted on data from patients who underwent ETOA within the past five years. Results: Over the study period, 24 ETOA procedures were performed on 21 patients, with an average age of 48.92, 13 of whom were women. The superior orbital corridor was utilized in 95.83% of cases, and in 79.17%, ETOA was complemented by a transnasal approach. Spheno-orbital meningioma accounted for the most common surgical indication (33.33%, n=8), all resulting in vision improvement, followed by lateral frontal sinus mucocele (25%, n=6). The median length of stay was one day, and ETOA achieved the procedure goal in 19 patients. Transient V1 numbness was the primary complication (29.17%, n=7), and 20.83% (n=5) necessitated another surgery. Notably, no mortality was associated with this procedure. Conclusions: Our institution’s experience underscores the notable safety and efficacy potential of ETOA, with 19 out of 21 patients exhibiting positive outcomes, obviating the need for revision surgery in most cases.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141101098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Abbass, B. Corrigan, R. Johnston, R. Gulli, A. Sachs, JC Lau, J. Martinez-Trujillo
Background: The lateral prefrontal cortex (LPFC) is uniquely found in primates and has been associated with contextual learning. This function is thought to be subserved by neurons that are tuned to abstract concepts and the combination of those concepts. LPFC neuron tuning remains to be fully investigated in naturalistic conditions. Methods: Two macaques were trained to perform a context-colour association task while using a joystick to navigate in an X-shaped maze. They were implanted with two 96-channel microelectrode arrays, targeting the LPFC. Mean firing rates were computed and multivariate linear regressions were used to determine tuning. Results: LPFC neurons were tuned to context (12.4%), color position (6.2%), target side (17.2%), and were selective to more than one feature (21.2%). LPFC neurons acquired tuning to task features in an ordered manner, starting with context (130.1±27.4ms), followed by the colour position (296.2±21.4ms) and then target side (493.3±19.3ms). Furthermore, most neurons (54%) changed their tuning over time. Conclusions: We demonstrate that single neurons can encode relevant features embedded in a naturalistic virtual environment. Our results support previous observations that LPFC neurons combine individual features and suggest that these features are also combined temporally. These findings contribute towards understanding the LPFC and have potential practical implications.
{"title":"P.133 Neurons in the lateral prefrontal cortex encode task features during virtual navigation","authors":"M. Abbass, B. Corrigan, R. Johnston, R. Gulli, A. Sachs, JC Lau, J. Martinez-Trujillo","doi":"10.1017/cjn.2024.234","DOIUrl":"https://doi.org/10.1017/cjn.2024.234","url":null,"abstract":"Background: The lateral prefrontal cortex (LPFC) is uniquely found in primates and has been associated with contextual learning. This function is thought to be subserved by neurons that are tuned to abstract concepts and the combination of those concepts. LPFC neuron tuning remains to be fully investigated in naturalistic conditions. Methods: Two macaques were trained to perform a context-colour association task while using a joystick to navigate in an X-shaped maze. They were implanted with two 96-channel microelectrode arrays, targeting the LPFC. Mean firing rates were computed and multivariate linear regressions were used to determine tuning. Results: LPFC neurons were tuned to context (12.4%), color position (6.2%), target side (17.2%), and were selective to more than one feature (21.2%). LPFC neurons acquired tuning to task features in an ordered manner, starting with context (130.1±27.4ms), followed by the colour position (296.2±21.4ms) and then target side (493.3±19.3ms). Furthermore, most neurons (54%) changed their tuning over time. Conclusions: We demonstrate that single neurons can encode relevant features embedded in a naturalistic virtual environment. Our results support previous observations that LPFC neurons combine individual features and suggest that these features are also combined temporally. These findings contribute towards understanding the LPFC and have potential practical implications.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"93 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141101137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PN Correia, A. Poppe, L. Gioia, GN Mendes, H Alhazmi, N. Daneault, Y. Deschaintre, G. Jacquin, C. Odier, C Stapf, O. Bereznyakova
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.
{"title":"P.017 Ischemic stroke in young adults: a comparison of outcomes, stroke risk factors and etiologies between males and females","authors":"PN Correia, A. Poppe, L. Gioia, GN Mendes, H Alhazmi, N. Daneault, Y. Deschaintre, G. Jacquin, C. Odier, C Stapf, O. Bereznyakova","doi":"10.1017/cjn.2024.125","DOIUrl":"https://doi.org/10.1017/cjn.2024.125","url":null,"abstract":"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.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"18 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141100178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Electrophysiological tests such as the tapping test are used to distinguish functional and organic tremors, in which patients with functional tremor commonly show entrainment and amplitude reduction (>50% decrease relative to baseline) of contralateral tremor during tapping. While these features are suggested to be specific to functional tremor, the tapping test in Parkinson’s disease (PD) tremor has not been tested. Methods: We evaluated 18 PD patients (2F, age 64.17±7.30 [mean±SD] years) with rest and postural tremors using surface electromyography and triaxial accelerometry. Patients were recorded while tapping at 1, 3 and 5 Hz with the contralateral arm at rest or outstretched. Tremor amplitude and frequency were calculated using power spectrum analysis from accelerometer recordings. Results: Reduction of rest tremor amplitude was observed in 3/18 patients during 1 and 3 Hz tapping. Reduction was seen in 3/16 and 1/16 patients with postural tremors at 1 and 3 Hz tapping, respectively. Frequency shifts (>1.5 Hz) were observed in 3/18 rest tremors and 6/16 postural tremors. Seven patients exhibited rest and/or postural tremor entrainment during 3 or 5 Hz tapping. Conclusions: Distractibility and entrainment can be found in PD tremor. The tapping test may not reliably distinguish between PD tremor and functional tremor.
{"title":"P.051 Parkinson’s disease tremor can show entrainment and distractibility with tapping test","authors":"NC Sheth, T. Grippe, N. Raies, M. Ding, R Chen","doi":"10.1017/cjn.2024.158","DOIUrl":"https://doi.org/10.1017/cjn.2024.158","url":null,"abstract":"Background: Electrophysiological tests such as the tapping test are used to distinguish functional and organic tremors, in which patients with functional tremor commonly show entrainment and amplitude reduction (>50% decrease relative to baseline) of contralateral tremor during tapping. While these features are suggested to be specific to functional tremor, the tapping test in Parkinson’s disease (PD) tremor has not been tested. Methods: We evaluated 18 PD patients (2F, age 64.17±7.30 [mean±SD] years) with rest and postural tremors using surface electromyography and triaxial accelerometry. Patients were recorded while tapping at 1, 3 and 5 Hz with the contralateral arm at rest or outstretched. Tremor amplitude and frequency were calculated using power spectrum analysis from accelerometer recordings. Results: Reduction of rest tremor amplitude was observed in 3/18 patients during 1 and 3 Hz tapping. Reduction was seen in 3/16 and 1/16 patients with postural tremors at 1 and 3 Hz tapping, respectively. Frequency shifts (>1.5 Hz) were observed in 3/18 rest tremors and 6/16 postural tremors. Seven patients exhibited rest and/or postural tremor entrainment during 3 or 5 Hz tapping. Conclusions: Distractibility and entrainment can be found in PD tremor. The tapping test may not reliably distinguish between PD tremor and functional tremor.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"17 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Adherence to healthy lifestyle behaviours or to prescribed medication requires perseverance with stamina, and this is captured by Grit, a non-cognitive trait defined as perseverance and passion for long-term goals. Despite predicting cognitive decline and physical, emotional, and social functioning, Grit remains poorly understood and its neural substrates are unknown in cognitive aging. Methods: Ninety-five cognitively unimpaired older adults with a family history of Alzheimer’s disease were recruited through the PREVENT-AD longitudinal cohort. Participants completed tests that assess grit and conscientiousness and underwent resting-state functional magnetic resonance imaging (fMRI). Multivariate pattern analyses (MVPA), a rigorous data-driven whole-brain approach, were used to examine if resting-state functional connectivity of connectome-wide voxels were associated with grit scores, controlling for age, sex, APOE ε4 carriership, mean displacement, and conscientiousness. Results: Our analyses identified two large (≥54 voxels) and statistically significant (p<0.01 corrected for family-wise error) clusters in the right ventrolateral prefrontal cortex and the left orbitofrontal cortex underlying grit. Conclusions: Being the first to identify functional neural correlates supporting grit in the aging population while accounting for the variance of conscientiousness, our study provides unique insights into the construct which has important applications in adherence to clinical and empirical neurological interventions as well as in successful aging.
{"title":"A.2 Understanding Grit in healthy older adults at-risk for Alzheimer’s disease","authors":"V. Dhir, CS Walker, R. Spreng, MR Geddes","doi":"10.1017/cjn.2024.75","DOIUrl":"https://doi.org/10.1017/cjn.2024.75","url":null,"abstract":"Background: Adherence to healthy lifestyle behaviours or to prescribed medication requires perseverance with stamina, and this is captured by Grit, a non-cognitive trait defined as perseverance and passion for long-term goals. Despite predicting cognitive decline and physical, emotional, and social functioning, Grit remains poorly understood and its neural substrates are unknown in cognitive aging. Methods: Ninety-five cognitively unimpaired older adults with a family history of Alzheimer’s disease were recruited through the PREVENT-AD longitudinal cohort. Participants completed tests that assess grit and conscientiousness and underwent resting-state functional magnetic resonance imaging (fMRI). Multivariate pattern analyses (MVPA), a rigorous data-driven whole-brain approach, were used to examine if resting-state functional connectivity of connectome-wide voxels were associated with grit scores, controlling for age, sex, APOE ε4 carriership, mean displacement, and conscientiousness. Results: Our analyses identified two large (≥54 voxels) and statistically significant (p<0.01 corrected for family-wise error) clusters in the right ventrolateral prefrontal cortex and the left orbitofrontal cortex underlying grit. Conclusions: Being the first to identify functional neural correlates supporting grit in the aging population while accounting for the variance of conscientiousness, our study provides unique insights into the construct which has important applications in adherence to clinical and empirical neurological interventions as well as in successful aging.","PeriodicalId":9571,"journal":{"name":"Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques","volume":"15 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141102538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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