Pub Date : 2026-02-24Epub Date: 2026-01-15DOI: 10.1212/WNL.0000000000214455
Patricia Diaz-Galvan, Pablo Franco-Rosado, Jesus Silva-Rodriguez, Sandra Castro-Labrador, Miguel Angel Labrador-Espinosa, Laura Muñoz-Delgado, Michel J Grothe, Pablo Mir
{"title":"Association of Physical Exercise With Structural Brain Changes and Cognitive Decline in Patients With Early Parkinson Disease.","authors":"Patricia Diaz-Galvan, Pablo Franco-Rosado, Jesus Silva-Rodriguez, Sandra Castro-Labrador, Miguel Angel Labrador-Espinosa, Laura Muñoz-Delgado, Michel J Grothe, Pablo Mir","doi":"10.1212/WNL.0000000000214455","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214455","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 4","pages":"e214455"},"PeriodicalIF":8.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985306","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 : 2026-02-24Epub Date: 2026-02-02DOI: 10.1212/WNL.0000000000214638
Jonathan R Crowe
{"title":"Getting Patients With a Large Vessel Occlusion From the Field to Treatment: The Next Frontier.","authors":"Jonathan R Crowe","doi":"10.1212/WNL.0000000000214638","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214638","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 4","pages":"e214638"},"PeriodicalIF":8.5,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106545","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 : 2026-02-10Epub Date: 2025-12-31DOI: 10.1212/WNL.0000000000214468
Ruvarashe Sharara, Heather Rigby
{"title":"Teaching Video NeuroImage: Jaw Closing Dystonia After Years of Excessive Gum Chewing.","authors":"Ruvarashe Sharara, Heather Rigby","doi":"10.1212/WNL.0000000000214468","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214468","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214468"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878647","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 : 2026-02-10Epub Date: 2026-01-08DOI: 10.1212/WNL.0000000000213324
Lina Palaiodimou, Georgios Tsivgoulis
{"title":"Author Response: Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Lina Palaiodimou, Georgios Tsivgoulis","doi":"10.1212/WNL.0000000000213324","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213324","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e213324"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934551","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 : 2026-02-10Epub Date: 2026-01-14DOI: 10.1212/WNL.0000000000214570
Alison Anderson, Piero Perucca, Elena Vianca, Daniel Sandvik, Ana Antonic-Baker, Roland Krause, Dana Jazayeri, Alison Hitchcock, Janet Graham, Marian Todaro, Torbjörn Tomson, Dina Battino, Emilio Perucca, Meritxell Martinez Ferri, Anne Rochtus, Lieven Lagae, Maria Paola Canevini, Elena Zambrelli, Ellenr Campbell, Aleksei Rakitin, Bobby Koeleman, Ingrid E Scheffer, Samuel F Berkovic, Patrick Kwan, Sanjay M Sisodiya, John J Craig, Frank J Vajda, Terence J O'Brien
Background and objectives: Valproate (VPA) use during pregnancy is associated with a wide range of structural birth defects, but not all exposed children are affected and there is evidence for a genetic predisposition. The development of a pharmacogenomic biomarker test that can be used for preconception counseling, allowing access to women unnecessarily denied VPA treatment because of concern about teratogenic risks if they were to become pregnant, is challenged by a poor understanding of how variation in maternal DNA could modify the risk. We hypothesized that genomic variants that affect the binding affinity of transcription factors (TFs), key regulators of gene expression, are integral to VPA-associated teratogenicity and a plausible explanation for both variance in interindividual risk and the wide range of birth defect types.
Methods: We interrogated genomic variants within maternal exomes from women recruited through international epilepsy pregnancy registries and genomics consortia. We applied a network-based approach that contextualized the variant spectra to genes associated with diverse birth defect types, gene burden tests, and evidence from multiple modalities to identify variant-sensitive TFs.
Results: Sixty-six pregnancies were exposed to VPA as monotherapy or polytherapy, leading to 28 cases with birth defects, and 184 were exposed to other antiseizure medications (ASMs), leading to 20 cases with birth defects. The variant burden within genes associated with 32 different birth defect types was higher for those exposed to VPA compared with those exposed to other ASMs (OR 1.73 [95% CI 1.39 to 2.13], p < 0.0001). Variants in a network comprising significant genes from VPA-exposed mothers were predicted to modify the binding affinity of 359 TFs. These variant-sensitive TFs formed a highly connected protein-protein interaction network, among which the acetyltransferase EP300 connected to 41% (147/359) of all proteins. Profiling of coexpression between EP300 and other TFs in an embryonic stem cell (hESC) model showed that VPA exposure alters EP300-TF interactions.
Discussion: These findings suggest that VPA-induced disruption of EP300-related gene regulation is a teratogenic mechanism that is common to heterogeneous birth defect types and sensitive to genetic variation. This has implications for the development of pharmacogenomic risk biomarkers and safer drugs for women of childbearing potential.
背景和目的：妊娠期间丙戊酸钠（VPA）的使用与广泛的结构性出生缺陷有关，但并非所有暴露的儿童都受到影响，有证据表明存在遗传易感。可用于孕前咨询的药物基因组学生物标志物测试的发展，允许由于担心怀孕后致畸风险而不必要地拒绝VPA治疗的妇女，受到对母体DNA变异如何改变风险的了解不足的挑战。我们假设，影响转录因子（转录因子是基因表达的关键调节因子）结合亲和力的基因组变异是vpa相关致畸性的组成部分，也是个体间风险差异和广泛的出生缺陷类型的合理解释。方法：我们询问了通过国际癫痫妊娠登记和基因组学联盟招募的妇女的母体外显子组中的基因组变异。我们采用了一种基于网络的方法，将变异谱与不同出生缺陷类型相关的基因、基因负担测试和来自多种模式的证据联系起来，以识别变异敏感的tf。结果：VPA单药或多药治疗66例，导致出生缺陷28例；其他抗癫痫药物治疗184例，导致出生缺陷20例。与其他asm相比，暴露于VPA的32种不同出生缺陷类型相关基因的变异负担更高（OR 1.73 [95% CI 1.39至2.13],p < 0.0001）。由暴露于vpa的母亲的重要基因组成的网络中的变异预计会改变359个tf的结合亲和力。这些变异敏感tf形成了一个高度连接的蛋白-蛋白相互作用网络，其中乙酰转移酶EP300连接了41%（147/359）的蛋白。胚胎干细胞（hESC）模型中EP300与其他tf的共表达分析表明，VPA暴露改变了EP300- tf的相互作用。讨论：这些发现表明，vpa诱导的ep300相关基因调控的破坏是一种致畸机制，这种机制在异质出生缺陷类型中很常见，并且对遗传变异很敏感。这对开发药物基因组学风险生物标志物和更安全的生育潜力妇女药物具有重要意义。
{"title":"Transcription Factor Binding and Individual Genetic Risk of Valproate Teratogenicity.","authors":"Alison Anderson, Piero Perucca, Elena Vianca, Daniel Sandvik, Ana Antonic-Baker, Roland Krause, Dana Jazayeri, Alison Hitchcock, Janet Graham, Marian Todaro, Torbjörn Tomson, Dina Battino, Emilio Perucca, Meritxell Martinez Ferri, Anne Rochtus, Lieven Lagae, Maria Paola Canevini, Elena Zambrelli, Ellenr Campbell, Aleksei Rakitin, Bobby Koeleman, Ingrid E Scheffer, Samuel F Berkovic, Patrick Kwan, Sanjay M Sisodiya, John J Craig, Frank J Vajda, Terence J O'Brien","doi":"10.1212/WNL.0000000000214570","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214570","url":null,"abstract":"<p><strong>Background and objectives: </strong>Valproate (VPA) use during pregnancy is associated with a wide range of structural birth defects, but not all exposed children are affected and there is evidence for a genetic predisposition. The development of a pharmacogenomic biomarker test that can be used for preconception counseling, allowing access to women unnecessarily denied VPA treatment because of concern about teratogenic risks if they were to become pregnant, is challenged by a poor understanding of how variation in maternal DNA could modify the risk. We hypothesized that genomic variants that affect the binding affinity of transcription factors (TFs), key regulators of gene expression, are integral to VPA-associated teratogenicity and a plausible explanation for both variance in interindividual risk and the wide range of birth defect types.</p><p><strong>Methods: </strong>We interrogated genomic variants within maternal exomes from women recruited through international epilepsy pregnancy registries and genomics consortia. We applied a network-based approach that contextualized the variant spectra to genes associated with diverse birth defect types, gene burden tests, and evidence from multiple modalities to identify variant-sensitive TFs.</p><p><strong>Results: </strong>Sixty-six pregnancies were exposed to VPA as monotherapy or polytherapy, leading to 28 cases with birth defects, and 184 were exposed to other antiseizure medications (ASMs), leading to 20 cases with birth defects. The variant burden within genes associated with 32 different birth defect types was higher for those exposed to VPA compared with those exposed to other ASMs (OR 1.73 [95% CI 1.39 to 2.13], <i>p</i> < 0.0001). Variants in a network comprising significant genes from VPA-exposed mothers were predicted to modify the binding affinity of 359 TFs. These variant-sensitive TFs formed a highly connected protein-protein interaction network, among which the acetyltransferase <i>EP300</i> connected to 41% (147/359) of all proteins. Profiling of coexpression between <i>EP300</i> and other TFs in an embryonic stem cell (hESC) model showed that VPA exposure alters <i>EP300</i>-TF interactions.</p><p><strong>Discussion: </strong>These findings suggest that VPA-induced disruption of <i>EP300-</i>related gene regulation is a teratogenic mechanism that is common to heterogeneous birth defect types and sensitive to genetic variation. This has implications for the development of pharmacogenomic risk biomarkers and safer drugs for women of childbearing potential.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214570"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985226","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 : 2026-02-10Epub Date: 2026-01-08DOI: 10.1212/WNL.0000000000214545
Aravind Ganesh, Steven L Galetta
{"title":"Editors' Note: The Evidence-Based Transition From Alteplase Toward Tenecteplase for Thrombolysis In Acute Ischemic Stroke.","authors":"Aravind Ganesh, Steven L Galetta","doi":"10.1212/WNL.0000000000214545","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214545","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214545"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934531","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 : 2026-02-10Epub Date: 2026-01-08DOI: 10.1212/WNL.0000000000214621
Bradley Ashley Ong, Alise K Carlson
Progressive myelopathy in immunocompromised patients presents a broad differential diagnosis and requires careful localization, imaging interpretation, and correlation with clinical context. A 66-year-old man with human immunodeficiency virus and diabetes mellitus developed vertigo, followed by asymmetric limb weakness beginning in the right leg and later progressing to the left leg, trunk, and upper extremities; gait imbalance with falls; paresthesias; and urinary urgency approximately 3 months after restarting antiretroviral therapy and 4 weeks after receiving a COVID-19 booster shot. Neurologic examination revealed mild symmetric quadriparesis, brisk reflexes, and impaired proprioception in the lower limbs. CSF analysis demonstrated elevated protein, oligoclonal bands, and an elevated immunoglobulin G index. Magnetic resonance imaging demonstrated longitudinally extensive tract-specific spinal cord abnormalities, which resolved spontaneously after several months without immunotherapy. This report illustrates the stepwise approach to myelopathy in immunocompromised patients, emphasizing the differential diagnosis for tract-specific imaging findings, clinical localization, and the role of immune reconstitution in neurologic disease.
{"title":"Clinical Reasoning: Progressive Quadriparesis and Falls in a 66-Year-Old Man With Longstanding Human Immunodeficiency Virus.","authors":"Bradley Ashley Ong, Alise K Carlson","doi":"10.1212/WNL.0000000000214621","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214621","url":null,"abstract":"<p><p>Progressive myelopathy in immunocompromised patients presents a broad differential diagnosis and requires careful localization, imaging interpretation, and correlation with clinical context. A 66-year-old man with human immunodeficiency virus and diabetes mellitus developed vertigo, followed by asymmetric limb weakness beginning in the right leg and later progressing to the left leg, trunk, and upper extremities; gait imbalance with falls; paresthesias; and urinary urgency approximately 3 months after restarting antiretroviral therapy and 4 weeks after receiving a COVID-19 booster shot. Neurologic examination revealed mild symmetric quadriparesis, brisk reflexes, and impaired proprioception in the lower limbs. CSF analysis demonstrated elevated protein, oligoclonal bands, and an elevated immunoglobulin G index. Magnetic resonance imaging demonstrated longitudinally extensive tract-specific spinal cord abnormalities, which resolved spontaneously after several months without immunotherapy. This report illustrates the stepwise approach to myelopathy in immunocompromised patients, emphasizing the differential diagnosis for tract-specific imaging findings, clinical localization, and the role of immune reconstitution in neurologic disease.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214621"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934534","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 : 2026-02-10Epub Date: 2026-01-07DOI: 10.1212/WNL.0000000000214584
Samuel W Terman
{"title":"Heart of the Matter: Calcitonin Gene-Related Peptide Antagonists and Cardiovascular Risk.","authors":"Samuel W Terman","doi":"10.1212/WNL.0000000000214584","DOIUrl":"https://doi.org/10.1212/WNL.0000000000214584","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e214584"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917877","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 : 2026-02-10Epub Date: 2026-01-08DOI: 10.1212/WNL.0000000000210311
Lina Palaiodimou, Georgios Tsivgoulis
{"title":"Author Response: Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Lina Palaiodimou, Georgios Tsivgoulis","doi":"10.1212/WNL.0000000000210311","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210311","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"106 3","pages":"e210311"},"PeriodicalIF":8.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934484","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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