Annals of Neurology最新文献

{"title":"Automated and Interpretable Detection of Hippocampal Sclerosis in Temporal Lobe Epilepsy: AID-HS.","authors":"Mathilde Ripart, Jordan DeKraker, Maria H Eriksson, Rory J Piper, Siby Gopinath, Harilal Parasuram, Jiajie Mo, Marcus Likeman, Georgian Ciobotaru, Philip Sequeiros-Peggs, Khalid Hamandi, Hua Xie, Nathan T Cohen, Ting-Yu Su, Ryuzaburo Kochi, Irene Wang, Gonzalo M Rojas-Costa, Marcelo Gálvez, Costanza Parodi, Antonella Riva, Felice D'Arco, Kshitij Mankad, Chris A Clark, Adrián Valls Carbó, Rafael Toledano, Peter Taylor, Antonio Napolitano, Maria Camilla Rossi-Espagnet, Anna Willard, Benjamin Sinclair, Joshua Pepper, Stefano Seri, Orrin Devinsky, Heath R Pardoe, Gavin P Winston, John S Duncan, Clarissa L Yasuda, Lucas Scárdua-Silva, Lennart Walger, Theodor Rüber, Ali R Khan, Torsten Baldeweg, Sophie Adler, Konrad Wagstyl","doi":"10.1002/ana.27089","DOIUrl":"10.1002/ana.27089","url":null,"abstract":"<p><strong>Objective: </strong>Hippocampal sclerosis (HS), the most common pathology associated with temporal lobe epilepsy (TLE), is not always visible on magnetic resonance imaging (MRI), causing surgical delays and reduced postsurgical seizure-freedom. We developed an open-source software to characterize and localize HS to aid the presurgical evaluation of children and adults with suspected TLE.</p><p><strong>Methods: </strong>We included a multicenter cohort of 365 participants (154 HS; 90 disease controls; 121 healthy controls). HippUnfold was used to extract morphological surface-based features and volumes of the hippocampus from T1-weighted MRI scans. We characterized pathological hippocampi in patients by comparing them to normative growth charts and analyzing within-subject feature asymmetries. Feature asymmetry scores were used to train a logistic regression classifier to detect and lateralize HS. The classifier was validated on an independent multicenter cohort of 275 patients with HS and 161 healthy and disease controls.</p><p><strong>Results: </strong>HS was characterized by decreased volume, thickness, and gyrification alongside increased mean and intrinsic curvature. The classifier detected 90.1% of unilateral HS patients and lateralized lesions in 97.4%. In patients with MRI-negative histopathologically-confirmed HS, the classifier detected 79.2% (19/24) and lateralized 91.7% (22/24). The model achieved similar performances on the independent cohort, demonstrating its ability to generalize to new data. Individual patient reports contextualize a patient's hippocampal features in relation to normative growth trajectories, visualise feature asymmetries, and report classifier predictions.</p><p><strong>Interpretation: </strong>Automated and Interpretable Detection of Hippocampal Sclerosis (AID-HS) is an open-source pipeline for detecting and lateralizing HS and outputting clinically-relevant reports. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Constructs Underlie Patient-Reported and Performance-Rated Outcomes after Stroke.","authors":"Julie A DiCarlo, Abhishek Jaywant, Perman Gochyyev, Anna K Bonkhoff, Richard Hardstone, Kimberly S Erler, Jessica Ranford, Alison Cloutier, Nathan Ward, Kelly L Sloane, Lee H Schwamm, Steven C Cramer, David J Lin","doi":"10.1002/ana.27129","DOIUrl":"https://doi.org/10.1002/ana.27129","url":null,"abstract":"<p><strong>Objective: </strong>Patient-reported outcome measures (PROMs), which capture patients' perspectives on the consequences of health and disease, are widely used in neurological care and research. However, it is unclear how PROMs relate to performance-rated impairments. Sociodemographic factors are known to affect PROMs. Direct damage to brain regions critical for self-awareness (i.e., parietal regions and the salience/ventral-attention network) may also impair self-report outcomes. This study examined the relationship between PROMs and performance-based measures in stroke survivors with arm motor impairments. We hypothesized that PROMs would be distinct from performance-based outcomes, influenced by sociodemographic factors, and linked to damage in brain circuits involved in self-perception.</p><p><strong>Methods: </strong>We longitudinally assessed 54 stroke survivors using patient-reported and performance-rated measures at 4 timepoints. We used factor analysis to reveal the outcome battery's factorial structure. Linear regression examined the association between classes of measures and sociodemographics. Voxel-lesion-symptom-mapping, region-of-interest-based analysis, and voxel-lesion-network-mapping investigated the relationship between classes of outcomes and stroke-related injury.</p><p><strong>Results: </strong>Performance-based and patient-reported measures formed distinct factors, consistent across recovery phases. Higher education (β1 = 0.36, p = 0.02) and income adequacy (β2 = 0.48, p = 0.05) were associated with patient-reported, but not performance-rated outcomes. Greater parietal lobe injury, irrespective of hemisphere, was associated with worse patient-reported outcomes; greater corticospinal tract injury related to worse performance-rated outcomes. Lesions with greater functional connectivity to the salience/ventral-attention network were associated with worse patient-reported outcomes (r = -0.35, p = 0.009).</p><p><strong>Interpretation: </strong>Our findings reveal important differences between performance-rated and patient-reported outcomes, each with specific associated factors and anatomy post-stroke. Incorporating sociodemographic and neuroanatomic characteristics into neurorehabilitation strategies may inform and optimize patient outcomes. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annals of Neurology: Volume 96, Number 6, December 2024","authors":"","doi":"10.1002/ana.26708","DOIUrl":"https://doi.org/10.1002/ana.26708","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 6","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinematic Rendering of Pure Arterial Malformations.","authors":"Linggen Dong, Ming Lv","doi":"10.1002/ana.27134","DOIUrl":"https://doi.org/10.1002/ana.27134","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Goal-Directed Rehabilitation Versus Standard Care for Individuals with Hereditary Cerebellar Ataxia: A Multicenter, Single-Blind, Randomized Controlled Superiority Trial.","authors":"Sarah C Milne, Melissa Roberts, Shannon Williams, Jillian Chua, Alison C Grootendorst, Genevieve Agostinelli, Anneke C Grobler, Hannah L Ross, Amy Robinson, Kristen Grove, Gabrielle Modderman, Annabel Price, Megan Thomson, Libby Massey, Christina Liang, Kishore R Kumar, Kim Dalziel, Joshua Burns, Carolyn M Sue, Pubudu N Pathirana, Malcolm Horne, Nikki Gelfard, Helen Curd, David Szmulewicz, Louise A Corben, Martin B Delatycki","doi":"10.1002/ana.27130","DOIUrl":"https://doi.org/10.1002/ana.27130","url":null,"abstract":"<p><strong>Objective: </strong>Rehabilitation is thought to reduce ataxia severity in individuals with hereditary cerebellar ataxia (HCA). This multicenter, randomized controlled superiority trial aimed to examine the efficacy of a 30-week goal-directed rehabilitation program compared with 30 weeks of standard care on function, ataxia, health-related quality of life, and balance in individuals with an HCA.</p><p><strong>Methods: </strong>Individuals with an autosomal dominant or recessive ataxia (aged ≥15 years) were enrolled at 5 sites in Australia. Participants were randomized (1:1) to receive rehabilitation (6 weeks of outpatient physiotherapy followed by a 24-week home exercise program) (n = 39) or continued their usual activity (n = 37). The primary outcome measure was the motor domain of the Functional Independence Measure (mFIM) at 7 weeks. Secondary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the SF-36v2, assessed at 7, 18, and 30 weeks. Outcome assessors were blinded to treatment allocation.</p><p><strong>Results: </strong>Seventy-one participants (rehabilitation, 37; standard-care, 34) were included in the intention-to-treat analysis. At 7 weeks, mFIM (mean difference 2.26, 95% confidence interval [CI]: 0.26 to 4.26, p = 0.028) and SARA (-1.21, 95% CI: -2.32 to -0.11, p = 0.032) scores improved after rehabilitation compared with standard care. Compared with standard care, rehabilitation improved SARA scores at 30 weeks (mean difference -1.51, 95% CI: -2.76 to -0.27, p = 0.017), but not mFIM scores (1.74, 95% CI: -0.32 to 3.81, p = 0.098). Frequent adverse events in both groups were fatigue, pain, and falls.</p><p><strong>Interpretation: </strong>Goal-directed rehabilitation improved function at 7 weeks, with improvement in ataxia and health-related quality of life maintained at 30 weeks in individuals with HCA, beyond that of standard care. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annals of Neurology: Volume 96, Number S33, November 2024","authors":"","doi":"10.1002/ana.27085","DOIUrl":"https://doi.org/10.1002/ana.27085","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S33","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"53rd Child Neurology Society Annual Meeting","authors":"","doi":"10.1002/ana.27080","DOIUrl":"10.1002/ana.27080","url":null,"abstract":"&lt;p&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;Abatkun, M.  199&lt;/p&gt;&lt;p&gt;Abdelmoity, A.  PL2-5&lt;/p&gt;&lt;p&gt;Abdelmoity, L.  316&lt;/p&gt;&lt;p&gt;Abdullahi, S.  92&lt;/p&gt;&lt;p&gt;Abe, K.  41&lt;/p&gt;&lt;p&gt;Abend, N.  PL2-3&lt;/p&gt;&lt;p&gt;Abera, S.  64&lt;/p&gt;&lt;p&gt;Abler, V.  87&lt;/p&gt;&lt;p&gt;Aboulsaoud, P.  79&lt;/p&gt;&lt;p&gt;Abreu, N.  280&lt;/p&gt;&lt;p&gt;Abushanab, E.  241&lt;/p&gt;&lt;p&gt;Acosta, M.  GAT1-2, 222&lt;/p&gt;&lt;p&gt;Adams, D.  222&lt;/p&gt;&lt;p&gt;Adams, H.  76&lt;/p&gt;&lt;p&gt;Adams, S.  241&lt;/p&gt;&lt;p&gt;Adanene, A.  199&lt;/p&gt;&lt;p&gt;Adeniyi-Jones, S.  85&lt;/p&gt;&lt;p&gt;Aduru, C.  285&lt;/p&gt;&lt;p&gt;Agarwal, R.  53&lt;/p&gt;&lt;p&gt;Agarwal, S.  156&lt;/p&gt;&lt;p&gt;Aggarwal, M.  170&lt;/p&gt;&lt;p&gt;Aghai, Z.  85&lt;/p&gt;&lt;p&gt;Agner, S.  187&lt;/p&gt;&lt;p&gt;Aguilar, S.  GAT2-1&lt;/p&gt;&lt;p&gt;Ahmadi, S.  23&lt;/p&gt;&lt;p&gt;Ahmed, A.  232&lt;/p&gt;&lt;p&gt;Ahmed, M.  7&lt;/p&gt;&lt;p&gt;Ahn, S.-H.  131&lt;/p&gt;&lt;p&gt;Ahsan, N.  248&lt;/p&gt;&lt;p&gt;Ailion, A.  98&lt;/p&gt;&lt;p&gt;Aimetti, A.  9, 205&lt;/p&gt;&lt;p&gt;Aitken, A.  235&lt;/p&gt;&lt;p&gt;Aiuti, A.  GAT1-1&lt;/p&gt;&lt;p&gt;Al Nimir, H.  89&lt;/p&gt;&lt;p&gt;Al Shouli, R.  329&lt;/p&gt;&lt;p&gt;Albazron, F.  51&lt;/p&gt;&lt;p&gt;Albor, L.  54, 107, 120&lt;/p&gt;&lt;p&gt;Alcaraz, W.  240&lt;/p&gt;&lt;p&gt;Aldana, P.  32&lt;/p&gt;&lt;p&gt;Aldinger, K.  30&lt;/p&gt;&lt;p&gt;Alecu, J.  PL1-3, 145&lt;/p&gt;&lt;p&gt;Alfano, L.  280&lt;/p&gt;&lt;p&gt;Algee, S.  107&lt;/p&gt;&lt;p&gt;Alhadid, K.  196&lt;/p&gt;&lt;p&gt;Ali, E.  125&lt;/p&gt;&lt;p&gt;Alleman, K.  8&lt;/p&gt;&lt;p&gt;Allen, S.  207&lt;/p&gt;&lt;p&gt;Allhusen, V.  185&lt;/p&gt;&lt;p&gt;Allison, T.  307&lt;/p&gt;&lt;p&gt;Almashnu, S.  GAT2-4&lt;/p&gt;&lt;p&gt;Alosi, S.  235&lt;/p&gt;&lt;p&gt;Alsayouf, H.  6&lt;/p&gt;&lt;p&gt;Al-Yahia, M.  128&lt;/p&gt;&lt;p&gt;Amin, H.  35&lt;/p&gt;&lt;p&gt;Amin, S.  9&lt;/p&gt;&lt;p&gt;Amoah, N.  20&lt;/p&gt;&lt;p&gt;Anand, P.  111&lt;/p&gt;&lt;p&gt;Ananth, A.  242&lt;/p&gt;&lt;p&gt;Andrade-Machado, R.  241&lt;/p&gt;&lt;p&gt;Andrews, A.  20, 153&lt;/p&gt;&lt;p&gt;Andrews, C.  214&lt;/p&gt;&lt;p&gt;Andringa-Seed, R.  221&lt;/p&gt;&lt;p&gt;Angelis, D.  121&lt;/p&gt;&lt;p&gt;Ankar, A.  57&lt;/p&gt;&lt;p&gt;Annesley, C.  117&lt;/p&gt;&lt;p&gt;Anwar, S.  164&lt;/p&gt;&lt;p&gt;Anwar, T.  17, 38, 69, 86, 254&lt;/p&gt;&lt;p&gt;Aquino, P.  PL3-1, 270&lt;/p&gt;&lt;p&gt;Aradhya, S.  GAT2-1, 209&lt;/p&gt;&lt;p&gt;Aras, S.  PL2-5, 279&lt;/p&gt;&lt;p&gt;Aravamuthan, B.  75&lt;/p&gt;&lt;p&gt;Arellano, J.  191, 286, 319&lt;/p&gt;&lt;p&gt;Arias, J.  169&lt;/p&gt;&lt;p&gt;Arkalgud, A.  269&lt;/p&gt;&lt;p&gt;Armstrong, D.  281&lt;/p&gt;&lt;p&gt;Aronin, N.  207&lt;/p&gt;&lt;p&gt;Arroyave-Wessel, M.  221&lt;/p&gt;&lt;p&gt;Arroyo, M.  127&lt;/p&gt;&lt;p&gt;Asarnow, R.  49&lt;/p&gt;&lt;p&gt;Aschbacher-Smith, L.  93&lt;/p&gt;&lt;p&gt;Asmar, Y.  26, 154&lt;/p&gt;&lt;p&gt;Astorga, G.  201&lt;/p&gt;&lt;p&gt;Atkinson, S.  81, 102&lt;/p&gt;&lt;p&gt;Au, J.  126&lt;/p&gt;&lt;p&gt;Augustine, E.  268&lt;/p&gt;&lt;p&gt;Austin, C.  295&lt;/p&gt;&lt;p&gt;Autio, K.  137&lt;/p&gt;&lt;p&gt;Auvin, S.  118, 219, 228&lt;/p&gt;&lt;p&gt;Avula, S.  292&lt;/p&gt;&lt;p&gt;Aykanat, A.  167&lt;/p&gt;&lt;p&gt;Bach, A.  PL2-7&lt;/p&gt;&lt;p&gt;Bacon, G.  243&lt;/p&gt;&lt;p&gt;Bacon, K.  168&lt;/p&gt;&lt;p&gt;Bacus, P.  15&lt;/p&gt;&lt;p&gt;Badh, R.  64&lt;/p&gt;&lt;p&gt;Bae, G.  8&lt;/p&gt;&lt;p&gt;Baiandurova, A.  298&lt;/p&gt;&lt;p&gt;Bailey, K.  208&lt;/p&gt;&lt;p&gt;Baim, A.  PL1-5&lt;/p&gt;&lt;p&gt;Bain, J.  183&lt;/p&gt;&lt;p&gt;Bajikar, S.  PL2-5&lt;/p&gt;&lt;p&gt;Baker, F.  PL1-7&lt;/p&gt;&lt;p&gt;Baker, M.  157&lt;/p&gt;&lt;p&gt;Bakulski, K.  16&lt;/p&gt;&lt;p&gt;Balamurugan, C.  42&lt;/p&gt;&lt;p&gt;Balasubramaniam, S.  85&lt;/p&gt;&lt;p&gt;Baldoli, C.  GAT1-1&lt;/p&gt;&lt;p&gt;Ballance, E.  3&lt;/p&gt;&lt;p&gt;Ballou, E.  253&lt;/p&gt;&lt;p&gt;Balls-Berry, J.  252&lt;/p&gt;&lt;p&gt;Banerjee, A.  PL2-4&lt;/p&gt;&lt;p&gt;Bansal, S.  84&lt;/p&gt;&lt;p&gt;Banwell, B.  PL2-7, PL3-4&lt;/p&gt;&lt;p&gt;Barber, J.  20, 66&lt;/p&gt;&lt;p&gt;Barisano, G.  PL1-7, 49&lt;/p&gt;&lt;p&gt;Barnfather, A.  GAT2-3&lt;/p&gt;&lt;p&gt;Baronio, D.  122&lt;/p&gt;&lt;p&gt;Barrett, E.  20&lt;/p&gt;&lt;p&gt;Barry, D.  231&lt;/p&gt;&lt;p&gt;Barry, M.  246, 266&lt;/p&gt;&lt;p&gt;Barsh, G.  312&lt;/p&gt;&lt;p&gt;Bartscherer, A.  48&lt;/p&gt;&lt;p&gt;Bass, N.  241&lt;/p&gt;&lt;p&gt;Bassan, H.  GAT2-4&lt;/p&gt;&lt;p&gt;Batschelett, M.  93&lt;/p&gt;&lt;p&gt;Batt","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S33","pages":"S1-S162"},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of Glutamate Uptake as Novel Antiseizure Approach: Preclinical Proof of Concept.","authors":"Krzysztof Kamiński, Katarzyna Socała, Michał Abram, Marcin Jakubiec, Katelyn L Reeb, Rhea Temmermand, Mirosław Zagaja, Maciej Maj, Magdalena Kolasa, Agata Faron-Górecka, Marta Andres-Mach, Aleksandra Szewczyk, Mustafa Q Hameed, Andréia C K Fontana, Alexander Rotenberg, Rafał M Kamiński","doi":"10.1002/ana.27124","DOIUrl":"https://doi.org/10.1002/ana.27124","url":null,"abstract":"<p><strong>Objective: </strong>Excitotoxicity is a common hallmark of epilepsy and other neurological diseases associated with elevated extracellular glutamate levels. Thus, here, we studied the protective effects of (R)-AS-1, a positive allosteric modulator (PAM) of glutamate uptake in epilepsy models.</p><p><strong>Methods: </strong>(R)-AS-1 was evaluated in a range of acute and chronic seizure models, while its adverse effect profile was assessed in a panel of standard tests in rodents. The effect of (R)-AS-1 on glutamate uptake was assessed in COS-7 cells expressing the transporter. WAY 213613, a selective competitive EAAT2 inhibitor, was used to probe the reversal of the enhanced glutamate uptake in the same transporter expression system. Confocal microscopy and Western blotting analyses were used to study a potential influence of (R)-AS-1 on GLT-1 expression in mice.</p><p><strong>Results: </strong>(R)-AS-1 showed robust protection in a panel of animal models of seizures and epilepsy, including the maximal electroshock- and 6 Hz-induced seizures, corneal kindling, mesial temporal lobe epilepsy, lamotrigine-resistant amygdala kindling, as well as seizures induced by pilocarpine or Theiler's murine encephalomyelitis virus. Importantly, (R)-AS-1 displayed a favorable adverse effect profile in the rotarod, the minimal motor impairment, and the Irwin tests. (R)-AS-1 enhanced glutamate uptake in vitro and this effect was abolished by WAY 213613, while no influence on GLT-1 expression in vivo was observed after repeated treatment.</p><p><strong>Interpretation: </strong>Collectively, our results show that (R)-AS-1 has favorable tolerability and provides robust preclinical efficacy against seizures. Thus, allosteric enhancement of EAAT2 function could offer a novel therapeutic strategy for treatment of epilepsy and potentially other neurological disorders associated with glutamate excitotoxicity. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – TOC","authors":"","doi":"10.1002/ana.27086","DOIUrl":"https://doi.org/10.1002/ana.27086","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"96 S33","pages":"i-iii"},"PeriodicalIF":8.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Reperfusion and Procedural Characteristics with Endovascular Thrombectomy Outcomes in Large Core Stroke: Sub-Analysis from the SELECT2 Trial.","authors":"Ameer E Hassan, Michael G Abraham, Spiros Blackburn, Muhammad S Hussain, Santiago Ortega-Gutierrez, Michael Chen, Yin C Hu, Deep K Pujara, Nabeel A Herial, Jenny P Tsai, Ronald F Budzik, Nathan W Manning, Osman Kozak, Ricardo A Hanel, Amin N Aghaebrahim, Chirag D Gandhi, Fawaz Al-Mufti, Andrew Cheung, Bernard Yan, Peter Mitchell, Jordi Blasco, Luis San Román Manzanera, Nirav Vora, Daniel Gibson, Adam Wallace, Daniel Sahlein, Lucas Elijovich, Juan F Arenillas, Teddy Y Wu, Pere Cardona Portela, Natalia Pérez de la Ossa, Joanna D Schaafsma, William J Hicks, Dennis J Cordato, Navdeep Sangha, Steven Warach, Timothy J Kleinig, Faris Shaker, Hannah Johns, Wondwossen Tekle, Mark J Dannenbaum, Koji Ebersole, Gabor Toth, Michael Gooch, Abdulnasser Alhajeri, Krishna Amuluru, Abhishek Ray, Jan-Karl Burkhardt, Mohammad A Abdulrazzak, David P Rosenbaum-Halevi, Haris Kamal, Kelsey R Duncan, Clark W Sitton, Leonid Churilov, Vitor Mendes Pereira, Jeffrey Sunshine, Thanh N Nguyen, Johanna T Fifi, Edgar A Samaniego, Adam Arthur, Stavropoula Tjoumakaris, Pascal Jabbour, Stephen M Davis, Lawrence Wechsler, Nicholas Bambakidis, Scott E Kasner, James C Grotta, Michael D Hill, Bruce C Campbell, Marc Ribo, Amrou Sarraj","doi":"10.1002/ana.27104","DOIUrl":"https://doi.org/10.1002/ana.27104","url":null,"abstract":"<p><p>Endovascular thrombectomy (EVT) was shown to be safe and efficacious in patients with large core stroke in multiple randomized controlled trials. However, the impact of reperfusion and other procedural metrics on EVT outcomes in this population has not been well-characterized.</p><p><strong>Methods: </strong>From the SELECT2 trial, we evaluated the association between reperfusion status, first-pass effect (near-complete or complete reperfusion [extended thrombolysis in cerebral infarction (eTICI) 2c-3] in 1 pass), procedure time and primary technique (aspiration vs stent-retriever) with functional outcomes in patients receiving EVT across ASPECTS (3 vs 4 vs 5) and core estimate strata (<70 vs ≥70ml, <100 vs ≥100ml, and <150 vs ≥150ml).</p><p><strong>Results: </strong>Of 180 patients who received thrombectomy, 144 (80%) achieved successful reperfusion (eTICI 2b-3) and demonstrated better clinical outcomes (adjusted generalized odds ratios [aGenOR]: 1.48, 95% confidence interval [CI]: 1.01-2.15), compared with unsuccessful reperfusion. Results were consistent across ASPECTS and core estimate strata. Additionally, complete or near-complete reperfusion (eTICI 2c-3) was associated with better functional outcome (aGenOR: 1.99, 95% CI: 1.33-2.97) in patients achieving successful reperfusion. Functional outcome point estimates favored those with first-pass-effect (42 of 167 (25%), aGenOR: 1.46, 95% CI: 0.96-2.24). Longer procedure time was associated with worse modified Rankin scale (mRS) distribution (aGenOR: 0.92, 95% CI: 0.87-0.96, p-value = 0.001 for 10 minutes increment). Aspiration-first technique was used in 43 of 154 (25%) patients and was not associated with higher reperfusion (88% vs 78%, p = 0.18) or better functional outcome (aGenOR: 0.74, 95% CI: 0.50-1.10) as compared with stent-retriever first.</p><p><strong>Interpretation: </strong>Successful reperfusion resulted in improved clinical outcomes in large core patients across baseline ischemic core strata. Near complete or complete reperfusion was further associated with better outcomes, whereas prolonged procedures were associated with worse outcomes. Results were consistent regardless of the technique used. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}