Pub Date : 2026-01-27Epub Date: 2025-12-26DOI: 10.1212/WNL.0000000000214448
Ryuzaburo Kochi, Aya Kanno, Hiroshi Uda, Keisuke Hatano, Hidenori Endo, Michael Cools, Robert Rothermel, Aimee F Luat, Eishi Asano
Background and objectives: Since Penfield's era, invasive neurophysiology has laid a lasting foundation for functional neuroscience by elucidating brain regions necessary for speech. Yet, whole-brain studies have not distinguished the millisecond-scale dynamics and specific white matter pathways that support rapid naming in the auditory and visual domains. We developed a whole-brain dynamic causal tractography atlas of speech using intracranial neurophysiologic data.
Methods: This observational study analyzed intracranial EEG during naming tasks in patients with drug-resistant focal epilepsy who underwent epilepsy surgery at Detroit Medical Center, MI. Task-related cortical high-gamma modulations were quantified, and functional coactivation was defined as sustained high-gamma augmentation occurring simultaneously in cortical regions directly connected by a white matter tract. We examined high-gamma modulations and functional coactivation associated with rapid and delayed auditory and picture naming responses. Electrical stimulation tested the causal significance of these dynamics.
Results: A total of 125 patients (5-49 years; 61 female patients) were included. The atlas revealed white matter coactivation intensity patterns at specific 5-millisecond time windows that best aligned with sensorimotor and language symptoms elicited by electrical stimulation. Rapid auditory naming was associated with deactivation of the right rostral middle frontal gyrus and increased coactivation along the left arcuate fasciculus, linked to stimulation-induced receptive and expressive aphasia. By contrast, delayed auditory naming correlated with a late surge in bifrontal coactivation. Rapid picture naming involved early coactivation between cortices connected through the bilateral inferior longitudinal fasciculi-associated with stimulation-induced visual distortions-coinciding with transient co-deactivation of the Broca area. Left-handedness and left-hemispheric epileptogenicity were associated with reduced left-hemispheric dominant high-gamma augmentation in specific regions.
Discussion: These findings delineate dissociable white matter-mediated mechanisms, supporting rapid naming in auditory and visual domains. Reduced inhibitory monitoring by the right dorsolateral prefrontal cortex may facilitate efficient lexical retrieval through left perisylvian pathways during auditory naming, whereas excessive bifrontal interaction may underlie delayed auditory naming. Rapid visual object recognition seems to rely on early occipito-temporal coactivation with minimal Broca area involvement. The resulting atlas provides a resource for trainees studying the network dynamics underlying speech and for presurgical language mapping in patients undergoing cortical or subcortical interventions.
{"title":"Whole-Brain Dynamic Causal Tractography Atlas of Auditory and Visual Speech Networks Derived From Intracranial Neurophysiologic Data.","authors":"Ryuzaburo Kochi, Aya Kanno, Hiroshi Uda, Keisuke Hatano, Hidenori Endo, Michael Cools, Robert Rothermel, Aimee F Luat, Eishi Asano","doi":"10.1212/WNL.0000000000214448","DOIUrl":"10.1212/WNL.0000000000214448","url":null,"abstract":"<p><strong>Background and objectives: </strong>Since Penfield's era, invasive neurophysiology has laid a lasting foundation for functional neuroscience by elucidating brain regions necessary for speech. Yet, whole-brain studies have not distinguished the millisecond-scale dynamics and specific white matter pathways that support rapid naming in the auditory and visual domains. We developed a whole-brain dynamic causal tractography atlas of speech using intracranial neurophysiologic data.</p><p><strong>Methods: </strong>This observational study analyzed intracranial EEG during naming tasks in patients with drug-resistant focal epilepsy who underwent epilepsy surgery at Detroit Medical Center, MI. Task-related cortical high-gamma modulations were quantified, and functional coactivation was defined as sustained high-gamma augmentation occurring simultaneously in cortical regions directly connected by a white matter tract. We examined high-gamma modulations and functional coactivation associated with rapid and delayed auditory and picture naming responses. Electrical stimulation tested the causal significance of these dynamics.</p><p><strong>Results: </strong>A total of 125 patients (5-49 years; 61 female patients) were included. The atlas revealed white matter coactivation intensity patterns at specific 5-millisecond time windows that best aligned with sensorimotor and language symptoms elicited by electrical stimulation. Rapid auditory naming was associated with deactivation of the right rostral middle frontal gyrus and increased coactivation along the left arcuate fasciculus, linked to stimulation-induced receptive and expressive aphasia. By contrast, delayed auditory naming correlated with a late surge in bifrontal coactivation. Rapid picture naming involved early coactivation between cortices connected through the bilateral inferior longitudinal fasciculi-associated with stimulation-induced visual distortions-coinciding with transient co-deactivation of the Broca area. Left-handedness and left-hemispheric epileptogenicity were associated with reduced left-hemispheric dominant high-gamma augmentation in specific regions.</p><p><strong>Discussion: </strong>These findings delineate dissociable white matter-mediated mechanisms, supporting rapid naming in auditory and visual domains. Reduced inhibitory monitoring by the right dorsolateral prefrontal cortex may facilitate efficient lexical retrieval through left perisylvian pathways during auditory naming, whereas excessive bifrontal interaction may underlie delayed auditory naming. Rapid visual object recognition seems to rely on early occipito-temporal coactivation with minimal Broca area involvement. The resulting atlas provides a resource for trainees studying the network dynamics underlying speech and for presurgical language mapping in patients undergoing cortical or subcortical interventions.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 2","pages":"e214448"},"PeriodicalIF":8.5,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12746732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843871","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}
BACKGROUND AND OBJECTIVESTwinkle, encoded by the TWNK gene, is a mitochondrial DNA helicase that unwinds the double helix of DNA during replication, playing a pivotal role in mitochondrial function. Twinkle-related disorders encompass a variety of genetic disorders characterized by mitochondrial dysfunction. Although several phenotypes have been described, the full clinical and molecular spectrum remains poorly defined. The aim of this study was to characterize the phenotypic and genotypic variability among multinational patients diagnosed with Twinkle-related disorders.METHODSA retrospective cohort study was conducted in patients with Twinkle-related disorders at several specialized centers in Italy, France, Germany, Spain, Denmark, Hungary, and the United States, establishing the Twinkle-Related Disorders International Consortium for Trial Readiness (TReDIC). Data were collected from medical records, including clinical features, age at onset, disease progression, and results from genetic testing. Phenotypic categories included infantile-onset cerebellar ataxia, parkinsonism, primary mitochondrial myopathy (PMM), multisystem involvement, asymptomatic carriers, undetermined phenotypes, and other phenotypes. All patients' diagnoses were confirmed by genetic analysis, and their genetic variants were noted. Outcomes included prevalence of phenotypes, symptom chronology, and mutational patterns.RESULTSThe study included a total of 189 patients (116 female), with a mean age at symptom onset of 40.3 years. At the time of analysis, 70.4% were alive. PMM was the predominant syndrome (85.2%), and most common features were progressive external ophthalmoplegia (84.7%) and skeletal myopathy (55.6%), followed by hearing loss (17.5%) and psychiatric symptoms (15.3%). Most patients (76.8%) presented with neuromuscular symptoms, with fewer showing CNS (19.6%) or multiorgan (3.6%) features at onset; by more than 8 years from onset, these proportions shifted to 54.4%, 23.3%, and 23.3%, respectively. A total of 73 TWNK variants (16 novel) were found, mostly missense, clustered in functionally critical regions.DISCUSSIONThis large multinational cohort analysis advances our understanding of Twinkle-related disorders by identifying mutational hotspots with clinical relevance and illustrating the broad phenotypic spectrum and progression patterns. In the context of such rare diseases, the formation of international collaborations, such as TReDIC, can enhance our understanding and support the design of upcoming clinical trials.
{"title":"Clinical and Genotypic Spectrum of Twinkle-Related Disorders: Insights From a Multinational Cohort Study.","authors":"Piervito Lopriore,Zeynep Ünlütürk,Thomas Klopstock,Amel Karaa,Cecile Rouzier,Cristina Domínguez-González,Costanza Lamperti,Michelangelo Mancuso, ,Giulia Cecchi,Vincenzo Montano,Gabriele Siciliano,Valeria Nicoletta,Mariantonietta Maioli,Guido Primiano,Serenella Servidei,Chiara La Morgia,Valerio Carelli,Maria Lucia Valentino,Leonardo Caporali,Ignazio Giuseppe Arena,Olimpia Musumeci,Diego Lopergolo,Alessandro Malandrini,Gian Nicola Gallus,Massimiliano Filosto,Luca Bello,Elena Pegoraro,Giacomo Pietro Comi,Francesca Magri,Dario Ronchi,Alessio Di Fonzo,Marco Percetti,Matteo Azzimonti,Boriana Büchner,Holger Prokisch,Laura Bermejo-Guerrero,Vincent Procaccio,Pauline Gaignard,Andoni Echaniz-Laguna,Manuel Schiff,Agnès Rötig,Annick Toutain,Véronique Paquis-Flucklinger,Godelieve Morel,Stéphanie Robin,Aleksandra Nadaj-Pakleza,Jean-Baptiste Chanson,Annabelle Chaussenot,Samira Ait-El-Mkadem Saadi,Aurélien Trimouille,Christine Tranchant,Emmanuelle Salort-Campana,Eric Bieth,Sabrina Sacconi,Fanny Duval,Juan Luis Restrepo Vera,Maria Judit Molnar,John Vissing,Richard Haas,Austin Larson,Gregory M Enns,Sumit Parikh,Amy Goldstein,Michio Hirano","doi":"10.1212/wnl.0000000000214401","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214401","url":null,"abstract":"BACKGROUND AND OBJECTIVESTwinkle, encoded by the TWNK gene, is a mitochondrial DNA helicase that unwinds the double helix of DNA during replication, playing a pivotal role in mitochondrial function. Twinkle-related disorders encompass a variety of genetic disorders characterized by mitochondrial dysfunction. Although several phenotypes have been described, the full clinical and molecular spectrum remains poorly defined. The aim of this study was to characterize the phenotypic and genotypic variability among multinational patients diagnosed with Twinkle-related disorders.METHODSA retrospective cohort study was conducted in patients with Twinkle-related disorders at several specialized centers in Italy, France, Germany, Spain, Denmark, Hungary, and the United States, establishing the Twinkle-Related Disorders International Consortium for Trial Readiness (TReDIC). Data were collected from medical records, including clinical features, age at onset, disease progression, and results from genetic testing. Phenotypic categories included infantile-onset cerebellar ataxia, parkinsonism, primary mitochondrial myopathy (PMM), multisystem involvement, asymptomatic carriers, undetermined phenotypes, and other phenotypes. All patients' diagnoses were confirmed by genetic analysis, and their genetic variants were noted. Outcomes included prevalence of phenotypes, symptom chronology, and mutational patterns.RESULTSThe study included a total of 189 patients (116 female), with a mean age at symptom onset of 40.3 years. At the time of analysis, 70.4% were alive. PMM was the predominant syndrome (85.2%), and most common features were progressive external ophthalmoplegia (84.7%) and skeletal myopathy (55.6%), followed by hearing loss (17.5%) and psychiatric symptoms (15.3%). Most patients (76.8%) presented with neuromuscular symptoms, with fewer showing CNS (19.6%) or multiorgan (3.6%) features at onset; by more than 8 years from onset, these proportions shifted to 54.4%, 23.3%, and 23.3%, respectively. A total of 73 TWNK variants (16 novel) were found, mostly missense, clustered in functionally critical regions.DISCUSSIONThis large multinational cohort analysis advances our understanding of Twinkle-related disorders by identifying mutational hotspots with clinical relevance and illustrating the broad phenotypic spectrum and progression patterns. In the context of such rare diseases, the formation of international collaborations, such as TReDIC, can enhance our understanding and support the design of upcoming clinical trials.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"30 1","pages":"e214401"},"PeriodicalIF":9.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971798","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}
Pub Date : 2026-01-15DOI: 10.1212/wnl.0000000000214693
Himanshu Verma,Laura Danielson
{"title":"Improvement in Nerve Size on Ultrasound After IV IG in a Multifactorial Chronic Inflammatory Neuropathy (P10-11.032).","authors":"Himanshu Verma,Laura Danielson","doi":"10.1212/wnl.0000000000214693","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214693","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"56 1","pages":"e214693"},"PeriodicalIF":9.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971801","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}
Pub Date : 2026-01-15DOI: 10.1212/wnl.0000000000214676
Marcelo Houat de Brito,Marcos C B Oliveira,Aline Sgnolf Ayres,Sonia M D Brucki
{"title":"Teaching NeuroImage: Tracing a 15-Year Trajectory of Radiation-Induced Leukoencephalopathy to Dementia.","authors":"Marcelo Houat de Brito,Marcos C B Oliveira,Aline Sgnolf Ayres,Sonia M D Brucki","doi":"10.1212/wnl.0000000000214676","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214676","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"34 1","pages":"e214676"},"PeriodicalIF":9.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971800","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}
Pub Date : 2026-01-14DOI: 10.1212/wnl.0000000000214530
Nabila Wali,Abris D Mumcuoglu,Sophie A Van Den Berg,Anne Van Der Meij,Ayesha Sajjad,Mirjam Rachel Heldner,Christina C Marti,Petra Cimflova,Sara Magdalena Pilgram-Pastor,Marcel Arnold,Susanne Wegener,Hakim Baazaoui,Corinne Inauen,Christoph Globas,Annika Nordanstig,Patrik Michel,Georg Kägi,Christoph Riegler,Christian H Nolte,Regina Von Rennenberg,Sami Curtze,Miranda Nybondas,Nicolas Martinez-Majander,Andrea Zini,Stefano Forlivesi,Matteo Paolucci,João Pedro Marto,Miguel Serôdio,Inês Carmo E Pinto,Alessandro Pezzini,Carlo W Cereda,Guido Bigliardi,Gabriele Vandelli,Visnja Padjen,Tamara Svabic-Medjedovic,Issa Metanis,Ronen R Leker,R M Van den Berg-Vos,Stefan T Engelter,Henrik Gensicke,Paul J Nederkoorn,
BACKGROUND AND OBJECTIVESCurrent international guidelines recommend blood pressure (BP) thresholds for patients eligible for endovascular thrombectomy (EVT). Previous studies have suggested that both low and high admission BPs are associated with poor functional outcome after EVT. However, the association between admission BP and outcomes after EVT remains poorly understood.The aim of this study was to investigate the relationship between admission systolic BP (SBP) and outcomes in patients treated with EVT and to assess whether this association is modified by IV thrombolysis (IVT) treatment and recanalization status.METHODSIn this observational, international, multicenter cohort study, we used data from the EVA-TRISP registry. Consecutive patients treated with EVT with available admission SBP were included. The primary outcome was 90-day functional outcome. Secondary outcomes included 90-day mortality, 24-hour NIH Stroke Scale (NIHSS), successful recanalization, and symptomatic intracranial hemorrhage (sICH). We used multivariable regression to study the relation between admission SBP and outcomes and to assess effect modification by IVT treatment and recanalization status.RESULTSWe included 10.963 EVT patients. At baseline, the mean age was 72.8 years (SD 13.5), 50.2% were female and the median NIHSS at presentation was 15 (interquartile range 9-19). The association between admission SBP and functional outcome, mortality, and 24-hour NIHSS score was U-shaped, and the nadir was around 150 mm Hg. Below 150 mm Hg, every 10 mm Hg decrease in SBP was associated with higher odds of poor functional outcome (adjusted odds ratio (aOR) 1.07 [95% CI 1.02-1.11]) and mortality (aOR 1.17 [1.12-1.23]). Above 150 mm Hg, every 10 mm Hg increase in SBP was associated with higher odds of poor functional outcome (aOR 1.05 [1.01-1.08]), mortality (aOR 1.04 [1.01-1.09]), and higher 24-hour NIHSS score (β-coefficient 0.28 [0.17-0.40]). We found a positive linear relationship between admission SBP and sICH (1.04 [1.01-1.08]). IVT treatment modified the association between admission SBP and outcomes after EVT. In 5544 EVT-only treated patients, there was no longer a clear association between higher admission SBP values and worse outcome.DISCISSIONLower and higher admission SBP was associated with worse outcomes in the complete cohort. In EVT-only patients, this association was less evident, suggesting that high admission BP alone should not always delay or preclude treatment with EVT in otherwise eligible patients.
背景和目的当前国际指南推荐适合血管内血栓切除术（EVT）患者的血压（BP）阈值。先前的研究表明，低和高的入院bp与EVT后不良的功能预后相关。然而，入院时血压与EVT后预后之间的关系仍然知之甚少。本研究的目的是探讨EVT患者入院收缩压（SBP）与预后之间的关系，并评估这种关联是否会因静脉溶栓（IVT）治疗和再通状态而改变。方法在这项观察性、国际性、多中心队列研究中，我们使用了EVA-TRISP登记处的数据。纳入连续接受EVT治疗且入院收缩压可用的患者。主要终点为90天功能终点。次要结局包括90天死亡率、24小时NIH卒中量表（NIHSS）、成功再通和症状性颅内出血（sICH）。我们采用多变量回归研究入院收缩压与预后的关系，并评估IVT治疗的效果改善和再通状态。结果纳入EVT患者10.963例。基线时，平均年龄为72.8岁（标准差13.5），50.2%为女性，就诊时NIHSS中位数为15（四分位数范围9-19）。入院时收缩压与功能结局、死亡率和24小时NIHSS评分之间呈u形相关，最低点在150 mm Hg左右。低于150 mm Hg时，收缩压每降低10 mm Hg，功能结局不良的几率就会增加（调整比值比（aOR） 1.07 [95% CI 1.02-1.11]）和死亡率（aOR 1.17[1.12-1.23]）。在150毫米汞柱以上，收缩压每升高10毫米汞柱，功能不良预后的几率（aOR 1.05[1.01-1.08]）、死亡率（aOR 1.04[1.01-1.09]）和24小时NIHSS评分（β-系数0.28[0.17-0.40]）均较高。我们发现入院收缩压与sICH呈正线性关系（1.04[1.01-1.08]）。IVT治疗改变了入院收缩压与EVT后预后之间的关系。在5544例仅接受evt治疗的患者中，入院时较高的收缩压值与较差的预后之间不再有明确的关联。结论：在整个队列中，低收缩压和高收缩压与较差的预后相关。在只有EVT的患者中，这种关联不太明显，这表明仅高入院血压不应总是延迟或排除EVT治疗。
{"title":"Admission Systolic Blood Pressure and Outcomes After Endovascular Thrombectomy: An International EVA-TRISP Cohort Study.","authors":"Nabila Wali,Abris D Mumcuoglu,Sophie A Van Den Berg,Anne Van Der Meij,Ayesha Sajjad,Mirjam Rachel Heldner,Christina C Marti,Petra Cimflova,Sara Magdalena Pilgram-Pastor,Marcel Arnold,Susanne Wegener,Hakim Baazaoui,Corinne Inauen,Christoph Globas,Annika Nordanstig,Patrik Michel,Georg Kägi,Christoph Riegler,Christian H Nolte,Regina Von Rennenberg,Sami Curtze,Miranda Nybondas,Nicolas Martinez-Majander,Andrea Zini,Stefano Forlivesi,Matteo Paolucci,João Pedro Marto,Miguel Serôdio,Inês Carmo E Pinto,Alessandro Pezzini,Carlo W Cereda,Guido Bigliardi,Gabriele Vandelli,Visnja Padjen,Tamara Svabic-Medjedovic,Issa Metanis,Ronen R Leker,R M Van den Berg-Vos,Stefan T Engelter,Henrik Gensicke,Paul J Nederkoorn, ","doi":"10.1212/wnl.0000000000214530","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214530","url":null,"abstract":"BACKGROUND AND OBJECTIVESCurrent international guidelines recommend blood pressure (BP) thresholds for patients eligible for endovascular thrombectomy (EVT). Previous studies have suggested that both low and high admission BPs are associated with poor functional outcome after EVT. However, the association between admission BP and outcomes after EVT remains poorly understood.The aim of this study was to investigate the relationship between admission systolic BP (SBP) and outcomes in patients treated with EVT and to assess whether this association is modified by IV thrombolysis (IVT) treatment and recanalization status.METHODSIn this observational, international, multicenter cohort study, we used data from the EVA-TRISP registry. Consecutive patients treated with EVT with available admission SBP were included. The primary outcome was 90-day functional outcome. Secondary outcomes included 90-day mortality, 24-hour NIH Stroke Scale (NIHSS), successful recanalization, and symptomatic intracranial hemorrhage (sICH). We used multivariable regression to study the relation between admission SBP and outcomes and to assess effect modification by IVT treatment and recanalization status.RESULTSWe included 10.963 EVT patients. At baseline, the mean age was 72.8 years (SD 13.5), 50.2% were female and the median NIHSS at presentation was 15 (interquartile range 9-19). The association between admission SBP and functional outcome, mortality, and 24-hour NIHSS score was U-shaped, and the nadir was around 150 mm Hg. Below 150 mm Hg, every 10 mm Hg decrease in SBP was associated with higher odds of poor functional outcome (adjusted odds ratio (aOR) 1.07 [95% CI 1.02-1.11]) and mortality (aOR 1.17 [1.12-1.23]). Above 150 mm Hg, every 10 mm Hg increase in SBP was associated with higher odds of poor functional outcome (aOR 1.05 [1.01-1.08]), mortality (aOR 1.04 [1.01-1.09]), and higher 24-hour NIHSS score (β-coefficient 0.28 [0.17-0.40]). We found a positive linear relationship between admission SBP and sICH (1.04 [1.01-1.08]). IVT treatment modified the association between admission SBP and outcomes after EVT. In 5544 EVT-only treated patients, there was no longer a clear association between higher admission SBP values and worse outcome.DISCISSIONLower and higher admission SBP was associated with worse outcomes in the complete cohort. In EVT-only patients, this association was less evident, suggesting that high admission BP alone should not always delay or preclude treatment with EVT in otherwise eligible patients.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"8 1","pages":"e214530"},"PeriodicalIF":9.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971802","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}
Pub Date : 2026-01-14DOI: 10.1212/wnl.0000000000214639
Yi Li
{"title":"Valproate Teratogenicity: A Paradigm of Network-Based Pharmacogenomics.","authors":"Yi Li","doi":"10.1212/wnl.0000000000214639","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214639","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"58 1","pages":"e214639"},"PeriodicalIF":9.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971823","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}
Pub Date : 2026-01-14DOI: 10.1212/wnl.0000000000214572
Lachlan Cribb,Margarita Moreno-Betancur,Matthew Paul Pase,Rory Wolfe,Carlene Britt,Zhen Zhou,Raj C Shah,Gary Rance,Kerry M Sheets,Trevor T-J Chong,Robyn L Woods,Anne M Murray,Alice Owen,Joanne Ryan
BACKGROUND AND OBJECTIVESHearing loss is a risk factor of cognitive decline and dementia. We sought to investigate the effect of hearing aid (HA) use on cognition and dementia risk in older adults with hearing impairment.METHODSWe emulated a target trial using data from Australian participants of the ASPirin in Reducing Events in the Elderly study. In the target trial, eligible participants were dementia-free, had moderate hearing impairment, and had no previous HA use. The treatment strategies were "use HAs" and "do not use HAs." Outcomes included overall cognition, dementia (DSM-IV criteria), and cognitive impairment (cognitive decline or dementia). The emulation used new HA prescription and frequency-of-use data measured by questionnaire, as well as cognition data from semiannual assessments over 7 years. Self-reported hearing problems were used as a proxy for moderate hearing impairment. Using the parametric g-formula, we estimated observational analogs of the intention-to-treat effect, using HA prescription to emulate allocation. Analyses for cognition outcomes were restricted to survivors. Multiple imputation was used for missing covariate and cognitive outcome data. We also emulated a second target trial with treatment strategies of (1) never, (2) rarely/sometimes, and (3) often/always use HAs.RESULTSAcross imputed data sets, a median of 2,777 eligible individuals were included, with a median of 664 receiving a new HA prescription. The mean age was 75 years, and 48% were female. The estimated 7-year mean overall cognition scores among survivors were similar under HA prescription and no HA prescription (mean difference 0.03 SDs; 95% CI -0.14 to 0.21). The estimated 7-year risk of dementia was 5.0% under HA prescription and 7.5% under no HA prescription (risk ratio [RR] 0.67; 95% CI 0.37-0.97), and that of cognitive impairment was 36.1% under HA prescription and 42.4% under no HA prescription (RR 0.85; 95% CI 0.70-1.00). The risks of dementia and cognitive impairment were inversely associated with the frequency of HA use.DISCUSSIONWe found that HA use in older people with hearing impairment may reduce dementia risk, although differences in age-related cognitive change were insubstantial. We cannot rule out residual confounding as an explanation for our findings. Long-term randomized trials of HAs for dementia risk are justified.CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that the use of hearing aids did not change overall cognitive scores in people 70 years and older with moderate hearing impairment as compared to those who used hearing aids.
背景与目的听力损失是认知能力下降和痴呆的危险因素。我们试图调查助听器（HA）使用对听力障碍老年人认知和痴呆风险的影响。方法：我们模拟了一项目标试验，使用的数据来自澳大利亚的阿司匹林在减少老年人事件研究中的参与者。在目标试验中，符合条件的参与者无痴呆，有中度听力障碍，以前没有使用过HA。治疗策略为“使用HAs”和“不使用HAs”。结果包括整体认知、痴呆（DSM-IV标准）和认知障碍（认知衰退或痴呆）。模拟使用了新的HA处方和问卷调查的使用频率数据，以及7年半年度评估的认知数据。自我报告的听力问题被用作中度听力障碍的替代指标。使用参数g公式，我们估计意向治疗效果的观察性类似物，使用HA处方模拟分配。对认知结果的分析仅限于幸存者。对缺失的协变量数据和认知结果数据进行多重输入。我们还模拟了第二个目标试验，其治疗策略为(1)从不，(2)很少/有时，(3)经常/总是使用HAs。结果：在估算的数据集中，中位数为2777名符合条件的个体，中位数为664名接受了新的HA处方。平均年龄为75岁，48%为女性。估计幸存者的7年平均总体认知评分在HA处方组和未处方组相似（平均差异0.03 SDs; 95% CI -0.14至0.21）。服用HA组患者的7年痴呆风险为5.0%，未服用HA组患者的7年痴呆风险为7.5%（风险比[RR] 0.67; 95% CI 0.37-0.97）；服用HA组患者的7年认知障碍风险为36.1%，未服用HA组患者的7年认知障碍风险为42.4% （RR 0.85; 95% CI 0.70-1.00）。痴呆和认知障碍的风险与HA的使用频率呈负相关。讨论：我们发现，老年听力障碍患者使用HA可降低痴呆风险，尽管与年龄相关的认知变化差异不大。我们不能排除残留混淆作为我们发现的解释。长期随机试验证明ha对痴呆风险的影响是合理的。证据分类：本研究提供的III级证据表明，与使用助听器的人相比，使用助听器不会改变70岁及以上中度听力障碍患者的总体认知评分。
{"title":"Treating Hearing Loss With Hearing Aids for the Prevention of Cognitive Decline and Dementia.","authors":"Lachlan Cribb,Margarita Moreno-Betancur,Matthew Paul Pase,Rory Wolfe,Carlene Britt,Zhen Zhou,Raj C Shah,Gary Rance,Kerry M Sheets,Trevor T-J Chong,Robyn L Woods,Anne M Murray,Alice Owen,Joanne Ryan","doi":"10.1212/wnl.0000000000214572","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214572","url":null,"abstract":"BACKGROUND AND OBJECTIVESHearing loss is a risk factor of cognitive decline and dementia. We sought to investigate the effect of hearing aid (HA) use on cognition and dementia risk in older adults with hearing impairment.METHODSWe emulated a target trial using data from Australian participants of the ASPirin in Reducing Events in the Elderly study. In the target trial, eligible participants were dementia-free, had moderate hearing impairment, and had no previous HA use. The treatment strategies were \"use HAs\" and \"do not use HAs.\" Outcomes included overall cognition, dementia (DSM-IV criteria), and cognitive impairment (cognitive decline or dementia). The emulation used new HA prescription and frequency-of-use data measured by questionnaire, as well as cognition data from semiannual assessments over 7 years. Self-reported hearing problems were used as a proxy for moderate hearing impairment. Using the parametric g-formula, we estimated observational analogs of the intention-to-treat effect, using HA prescription to emulate allocation. Analyses for cognition outcomes were restricted to survivors. Multiple imputation was used for missing covariate and cognitive outcome data. We also emulated a second target trial with treatment strategies of (1) never, (2) rarely/sometimes, and (3) often/always use HAs.RESULTSAcross imputed data sets, a median of 2,777 eligible individuals were included, with a median of 664 receiving a new HA prescription. The mean age was 75 years, and 48% were female. The estimated 7-year mean overall cognition scores among survivors were similar under HA prescription and no HA prescription (mean difference 0.03 SDs; 95% CI -0.14 to 0.21). The estimated 7-year risk of dementia was 5.0% under HA prescription and 7.5% under no HA prescription (risk ratio [RR] 0.67; 95% CI 0.37-0.97), and that of cognitive impairment was 36.1% under HA prescription and 42.4% under no HA prescription (RR 0.85; 95% CI 0.70-1.00). The risks of dementia and cognitive impairment were inversely associated with the frequency of HA use.DISCUSSIONWe found that HA use in older people with hearing impairment may reduce dementia risk, although differences in age-related cognitive change were insubstantial. We cannot rule out residual confounding as an explanation for our findings. Long-term randomized trials of HAs for dementia risk are justified.CLASSIFICATION OF EVIDENCEThis study provides Class III evidence that the use of hearing aids did not change overall cognitive scores in people 70 years and older with moderate hearing impairment as compared to those who used hearing aids.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"177 1","pages":"e214572"},"PeriodicalIF":9.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971825","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}
Pub Date : 2026-01-14DOI: 10.1212/wnl.0000000000214660
Mina A Jacob,Frank-Erik de Leeuw
{"title":"Blood Pressure Before Endovascular Thrombectomy: \"Don't Drop It\".","authors":"Mina A Jacob,Frank-Erik de Leeuw","doi":"10.1212/wnl.0000000000214660","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214660","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"60 1","pages":"e214660"},"PeriodicalIF":9.9,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971850","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}
Pub Date : 2026-01-13DOI: 10.1212/wnl.0000000000214618
Eduardo Benarroch
Mitochondrial dysfunction is a key pathogenic component of neurodegenerative disorders. Mitochondrial stress, created by accumulation of misfolded proteins, reactive oxygen species, and other mechanisms, triggers signals that promote changes in protein translation and gene transcription aimed at protecting and restoring mitochondrial function and maintaining cellular homeostasis. These quality control responses are the integrated stress response and the mitochondrial unfolded protein response. When triggered by mild mitochondrial stress, these adaptive responses promote mitohormesis, which enhances cell survival and lifespan. The exchange of information between mitochondria allows mitochondrial stress in specific tissues to initiate beneficial adaptations affecting mitochondrial populations in remote tissues and organs. Experimental and human observational studies indicate that approaches to trigger mitohormesis, such as physical exercise, have beneficial effects in neurodegenerative disorders.
{"title":"What Are the Roles of Mitochondrial Stress Responses and Mitohormesis in Neurodegenerative Disorders?","authors":"Eduardo Benarroch","doi":"10.1212/wnl.0000000000214618","DOIUrl":"https://doi.org/10.1212/wnl.0000000000214618","url":null,"abstract":"Mitochondrial dysfunction is a key pathogenic component of neurodegenerative disorders. Mitochondrial stress, created by accumulation of misfolded proteins, reactive oxygen species, and other mechanisms, triggers signals that promote changes in protein translation and gene transcription aimed at protecting and restoring mitochondrial function and maintaining cellular homeostasis. These quality control responses are the integrated stress response and the mitochondrial unfolded protein response. When triggered by mild mitochondrial stress, these adaptive responses promote mitohormesis, which enhances cell survival and lifespan. The exchange of information between mitochondria allows mitochondrial stress in specific tissues to initiate beneficial adaptations affecting mitochondrial populations in remote tissues and organs. Experimental and human observational studies indicate that approaches to trigger mitohormesis, such as physical exercise, have beneficial effects in neurodegenerative disorders.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"96 1","pages":"e214618"},"PeriodicalIF":9.9,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961505","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}
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