NeurologyPub Date : 2026-11-10Epub Date: 2026-10-16DOI: 10.1212/WNL.0000000000218596
Hilary L Colbeth, Alexander Ivan B Posis, Batool Mahboob Rizvi, Charles S Decarli, M Maria Glymour, Kristen M George, Maria M Corrada, Paola Gilsanz, Rachel A Whitmer
{"title":"Role of <i>APOE</i> ɛ4 and ɛ2 With Longitudinal Cognitive Decline Among Those With Exceptional Longevity: The LifeAfter90 Study.","authors":"Hilary L Colbeth, Alexander Ivan B Posis, Batool Mahboob Rizvi, Charles S Decarli, M Maria Glymour, Kristen M George, Maria M Corrada, Paola Gilsanz, Rachel A Whitmer","doi":"10.1212/WNL.0000000000218596","DOIUrl":"https://doi.org/10.1212/WNL.0000000000218596","url":null,"abstract":"<p><strong>Background and objectives: </strong><i>APOE</i> ɛ4 is the strongest genetic risk factor for late-onset Alzheimer disease, while ɛ2 is associated with decreased risk. However, it is unclear how these genotypes relate to cognitive decline among those aged older than 90+. We examined associations of ɛ4 and ɛ2 with longitudinal change in 3 cognitive domains among individuals aged 90+.</p><p><strong>Methods: </strong>LifeAfter90 is an ongoing longitudinal multiethnic cohort study of those aged 90+. <i>APOE</i> genotyping was conducted using DNA extracted from saliva. Two dichotomous exposures were defined as ɛ4 carriers (ɛ2/ɛ4, ɛ3/ɛ4, or ɛ4/ɛ4 genotypes) vs non-ɛ4-carriers with no ɛ4 allele and ɛ2 carriers (ɛ2/2, ɛ2/3 genotypes) vs non-ɛ2-carriers (ɛ3/ɛ3, ɛ2/ɛ4, ɛ3/ɛ4, or ɛ4/ɛ4). Executive function (EF), semantic memory (SM), and verbal episodic memory (VEM) were measured every 6 months on up to 11 occasions using the Spanish and English Neuropsychological Scales. Time to all-cause mortality was calculated from baseline to death. We fit linear mixed-effects (LME) models and joint models (LME and Cox proportional hazard submodels) to account for the competing risk of death. Models adjusted for age and sex.</p><p><strong>Results: </strong>We evaluated 445 participants (mean age at baseline 93 years, SD 2.31, range 90-104; 59% female). In total, 20% were ɛ4 carriers, 15% were ɛ2 carriers, and 54% died during follow-up. The ethnoracial composition was 21% African American/Black, 22% as Asian, 16% as Hispanic/Latinx, 9% as multiracial/other, and 32% as White. The mean follow-up time was 3.9 years (SD 1.63, range 0.68-6.67). Neither ɛ4 nor ɛ2 carriers averaged substantially greater or lesser mortality hazard than noncarriers. In joint models, ɛ4 carriers had faster decline in EF (β = -0.07, 95% CI -0.12 to -0.02), but similar decline in VEM (β = -0.01, 95% CI -0.08 to 0.05) and SM (β = -0.03; 95% CI -0.08 to 0.02). <i>APOE</i> ɛ2 carriers had similar decline in EF (β = 0.01, 95% CI -0.05 to 0.08) and SM (β = 0.01, 95% CI -0.05 to 0.08) but slower decline in VEM (β = 0.07, 95% CI 0.00-0.15) compared with noncarriers. Longitudinal results were similar for LME and joint models.</p><p><strong>Discussion: </strong>After accounting for the competing risk of death, the negative consequences of ɛ4 on EF decline extend to those with exceptional longevity.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"107 9","pages":"e218596"},"PeriodicalIF":8.9,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207289","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}
NeurologyPub Date : 2026-11-10Epub Date: 2026-10-20DOI: 10.1212/WNL.0000000000218572
Anika Menetrey, Haya S AlFaris, Liali Aljouda, Nicole Martin, Sangeetha Yoganathan, Laura Guilder, Carolina Gorodetsky
{"title":"Child Neurology: Neonatal Management of Tyrosine Hydroxylase Deficiency: How Early Is Early Enough?","authors":"Anika Menetrey, Haya S AlFaris, Liali Aljouda, Nicole Martin, Sangeetha Yoganathan, Laura Guilder, Carolina Gorodetsky","doi":"10.1212/WNL.0000000000218572","DOIUrl":"https://doi.org/10.1212/WNL.0000000000218572","url":null,"abstract":"<p><p>Tyrosine hydroxylase deficiency is a rare, treatable, autosomal recessive disorder of monoamine neurotransmitter biosynthesis that typically presents in infancy or early childhood. Despite potential benefits of presymptomatic treatment with levodopa/carbidopa, prenatal or neonatal diagnosis remains extremely rare. We report 2 preterm neonates from unrelated families, both with known family history of tyrosine hydroxylase deficiency. After early diagnosis, levodopa/carbidopa therapy was initiated during the neonatal period. This proactive approach proved feasible and well tolerated, leading to early normalization of subtle motor abnormalities. These cases highlight the importance of early genetic diagnosis of this rare condition and the feasibility of levodopa/carbidopa treatment in neonates.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"107 9","pages":"e218572"},"PeriodicalIF":8.9,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149228323","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}
NeurologyPub Date : 2026-11-10Epub Date: 2026-10-16DOI: 10.1212/WNL.0000000000218628
Baris Alten, Natalie L Ullman, Giulia Porcari, Kelly L Sloane, Ana G Cristancho, Aaron Rothstein
{"title":"A Primer on <i>COL4A1/COL4A2</i>-Related Cerebral Small Vessel Disease for Neurologists.","authors":"Baris Alten, Natalie L Ullman, Giulia Porcari, Kelly L Sloane, Ana G Cristancho, Aaron Rothstein","doi":"10.1212/WNL.0000000000218628","DOIUrl":"https://doi.org/10.1212/WNL.0000000000218628","url":null,"abstract":"<p><p><i>COL4A1</i> and <i>COL4A2</i> encode type IV collagen, a principal structural component of basement membranes, and pathogenic variants in these genes cause a multisystem small vessel vasculopathy with prominent cerebrovascular involvement. Despite increasing recognition with the expansion of genetic testing, <i>COL4A1/2</i>-related cerebral small vessel disease remains underrecognized in clinical practice, in part due to its striking phenotypic heterogeneity. Presentations span a broad clinical spectrum-from asymptomatic individuals or incidental imaging findings to recurrent ischemic events, intracerebral hemorrhage, and catastrophic perinatal brain injury-and may occur across the lifespan. In this narrative review, we provide a clinically oriented framework for recognizing and managing <i>COL4A1/2</i>-related cerebral small vessel disease. We integrate underlying molecular mechanisms of type IV collagen dysfunction with vascular pathophysiology, highlighting how impaired basement membrane integrity leads to a dual hemorrhagic-ischemic phenotype. We describe characteristic neuroimaging patterns, including microhemorrhages, white matter hyperintensities, lacunes, and dilated perivascular spaces, and emphasize their anatomic distribution and clinical relevance. Given the systemic nature of the disorder, we also review key extracerebral manifestations-including ocular, renal, and musculoskeletal features-that serve as important diagnostic \"red flags.\" We outline practical considerations for clinical care, including indications for genetic testing, initial diagnostic evaluation, and longitudinal management strategies tailored to neurologists. Particular emphasis is placed on individualized decision-making around antithrombotic therapy, hemorrhage risk mitigation, and surveillance for complications such as intracranial aneurysms. Illustrative multigenerational cases are incorporated to demonstrate genotype-phenotype correlation, incomplete penetrance, and common diagnostic pitfalls. By providing a mechanism-informed and clinically actionable synthesis, this review aims to improve recognition, reduce misdiagnosis, and guide management of <i>COL4A1/2</i>-related cerebral small vessel disease.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"107 9","pages":"e218628"},"PeriodicalIF":8.9,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207626","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}
NeurologyPub Date : 2026-11-10Epub Date: 2026-10-16DOI: 10.1212/WNL.0000000000218457
Ahmad Nehme, Romain Schneckenburger, Marguerite Watrin, Jean Bouchart, Marion Boulanger, Julien Cogez, Sophie Guettier, Estelle La Porte, Lucie Laroche, Gwendoline Le Du, Olivier Martinaud, Rémy Morello, Denis Vivien, Emmanuel Touzé
{"title":"Incidence and Post-Stroke Survival in the Normandy Stroke Population-Based Study (2017-2022): Impact of Time-Based Versus Tissue-Based Definitions.","authors":"Ahmad Nehme, Romain Schneckenburger, Marguerite Watrin, Jean Bouchart, Marion Boulanger, Julien Cogez, Sophie Guettier, Estelle La Porte, Lucie Laroche, Gwendoline Le Du, Olivier Martinaud, Rémy Morello, Denis Vivien, Emmanuel Touzé","doi":"10.1212/WNL.0000000000218457","DOIUrl":"https://doi.org/10.1212/WNL.0000000000218457","url":null,"abstract":"<p><strong>Objectives: </strong>The 11th edition of the International Classification of Diseases (ICD-11) incorporates a tissue-based definition of stroke and may alter estimates of incidence and outcomes. We assessed whether transitioning from a time-based to a tissue-based definition introduces age-dependent changes in stroke incidence and post-stroke survival.</p><p><strong>Methods: </strong>The Normandy Stroke Study is a population-based study using multiple overlapping sources to identify stroke cases in Caen-Normandy-Metropole, France. Events occurring between May 15, 2017, and December 31, 2022, were classified using time-based (symptoms ≥24 hours) and tissue-based definitions (symptoms ≥24 hours or <24 hours with neuroimaging evidence of ischemic injury).</p><p><strong>Results: </strong>Among 3,826 first-ever strokes meeting the tissue-based definition, median (IQR) age was 76 (64-85) years, and 1,932 (50.5%) were female. The age-standardized incidence rate of stroke (95% CI) was 161 (156-166) per 100,000 person-years (ESP2013), including 132 (128-137) for ischemic or undetermined stroke, 22 (20-24) for intracerebral hemorrhage, and 7 (6-8) for subarachnoid hemorrhage. Three-year mortality was 36.4% (95% CI 34.9-38.0). Compared with the time-based definition, the tissue-based definition increased stroke incidence by 6.5% and reduced 3-year mortality by 3.9%. The impact of the tissue-based definition on stroke incidence was greater at younger ages (all strokes: younger than 55 years = +8.5%; 55 years or older = +6.0%; ischemic stroke: younger than 55 years = +12.5%; 55 years or older = +7.3%).</p><p><strong>Discussion: </strong>Adoption of a tissue-based definition modestly increased stroke incidence and post-stroke survival, with greater impacts at younger ages. Implementation of ICD-11 may introduce age-related differences in temporal trends, highlighting the importance of consistent definitions in stroke surveillance.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"107 9","pages":"e218457"},"PeriodicalIF":8.9,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207666","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}
NeurologyPub Date : 2026-11-10Epub Date: 2026-10-16DOI: 10.1212/WNL.0000000000218755
Philip S Nash, Gareth Ambler, Jonathan G Best, Duncan Wilson, Houwei Du, Rustam Al-Shahi Salman, Hans Rolf Jäger, Gregory Y H Lip, Martina B Goeldlin, Morin Beyeler, Philipp Bücke, Marwan El-Koussy, Heinrich P Mattle, Leonidas Panos, Dianne H K van Dam-Nolen, Florian Dubost, Jeroen Hendrikse, M Eline Kooi, Werner H Mess, Paul J Nederkoorn, Nicolas Christ, Maximilian Bellut, Sarah Gunkel, Christopher Charles Karayiannis, John Ly, Shaloo Singhal, Lee-Anne Slater, Young Dae Kim, Keon-Joo Lee, Jae-Sung Lim, Hideo Hara, Masashi Nishihara, Jun Tanaka, Masaaki Yoshikawa, Derya Selcuk Demirelli, Zeynep Tanriverdi, Ender Uysal, Shelagh B Coutts, Francesca M Chappell, Stephen Dj Makin, Henry Ka Fung Mak, Kay Cheong Teo, Debbie Y K Wong, Lisa Hert, Marta Kubacka, Philippe A Lyrer, Alexandros A Polymeris, Benjamin Wagner, Annaelle Zietz, Jill Abrigo, Cyrus Cheng, Winnie Cw Chu, Thomas W Leung, David Julian Seiffge, Urs Fischer, Simon Jung, Daniel Bos, Felix Fluri, Thanh G Phan, Velandai K Srikanth, Ji Hoe Heo, Hee-Joon Bae, Yusuke Yakushiji, Dilek Necioglu Orken, Eric E Smith, Joanna M Wardlaw, Gary Kui Kai Lau, Stefan T Engelter, Nils Peters, Yannie O Y Soo, Tae-Jin Song, Robert J Simister, David C Wheeler, David John Werring
{"title":"Association of Enlarged Perivascular Spaces and Total Small Vessel Disease Burden With Kidney Function.","authors":"Philip S Nash, Gareth Ambler, Jonathan G Best, Duncan Wilson, Houwei Du, Rustam Al-Shahi Salman, Hans Rolf Jäger, Gregory Y H Lip, Martina B Goeldlin, Morin Beyeler, Philipp Bücke, Marwan El-Koussy, Heinrich P Mattle, Leonidas Panos, Dianne H K van Dam-Nolen, Florian Dubost, Jeroen Hendrikse, M Eline Kooi, Werner H Mess, Paul J Nederkoorn, Nicolas Christ, Maximilian Bellut, Sarah Gunkel, Christopher Charles Karayiannis, John Ly, Shaloo Singhal, Lee-Anne Slater, Young Dae Kim, Keon-Joo Lee, Jae-Sung Lim, Hideo Hara, Masashi Nishihara, Jun Tanaka, Masaaki Yoshikawa, Derya Selcuk Demirelli, Zeynep Tanriverdi, Ender Uysal, Shelagh B Coutts, Francesca M Chappell, Stephen Dj Makin, Henry Ka Fung Mak, Kay Cheong Teo, Debbie Y K Wong, Lisa Hert, Marta Kubacka, Philippe A Lyrer, Alexandros A Polymeris, Benjamin Wagner, Annaelle Zietz, Jill Abrigo, Cyrus Cheng, Winnie Cw Chu, Thomas W Leung, David Julian Seiffge, Urs Fischer, Simon Jung, Daniel Bos, Felix Fluri, Thanh G Phan, Velandai K Srikanth, Ji Hoe Heo, Hee-Joon Bae, Yusuke Yakushiji, Dilek Necioglu Orken, Eric E Smith, Joanna M Wardlaw, Gary Kui Kai Lau, Stefan T Engelter, Nils Peters, Yannie O Y Soo, Tae-Jin Song, Robert J Simister, David C Wheeler, David John Werring","doi":"10.1212/WNL.0000000000218755","DOIUrl":"https://doi.org/10.1212/WNL.0000000000218755","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"107 9","pages":"e218755"},"PeriodicalIF":8.9,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207669","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}
NeurologyPub Date : 2026-11-10Epub Date: 2026-10-07DOI: 10.1212/WNL.0000000000218518
Serhat V Okar, Ashley A Thommana, Corinne Donnay, Silvina G Horovitz, María Inés Gaitán, Irene Cortese, Govind Nair, Daniel S Reich
{"title":"Portable Ultra-Low-Field MRI in Neurologic Diseases: Current Status and Potential in Clinical Practice, Research, and Trials.","authors":"Serhat V Okar, Ashley A Thommana, Corinne Donnay, Silvina G Horovitz, María Inés Gaitán, Irene Cortese, Govind Nair, Daniel S Reich","doi":"10.1212/WNL.0000000000218518","DOIUrl":"https://doi.org/10.1212/WNL.0000000000218518","url":null,"abstract":"<p><p>Neurologic diseases are highly prevalent, and MRI plays a crucial role in their diagnosis, prognosis, and treatment monitoring. Conventional MRI at high magnetic field strength (≥1.5 tesla) is one of the most widely used modalities in clinical practice and a common outcome measure in clinical trials. Despite its importance and effectiveness, challenges, such as high cost, limited accessibility, and disease-related constraints, can hinder its widespread use. Recent advancements in portable ultra-low-field (<0.1 tesla) MRI technology offer potential solutions by enabling point-of-care brain imaging for neurologic diseases. However, the substantially lower magnetic field strength results in lower signal-to-noise ratio, reduced spatial resolution, and more limited imaging contrast, although ongoing computational approaches aim to mitigate some of these limitations. In this narrative review, we examine current evidence on applications of portable ultra-low-field MRI to neurologic disorders, discussing the technology's utility, limitations, and clinical implications. In addition, we highlight key open research questions and future opportunities for further integration of this emerging technology.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"107 9","pages":"e218518"},"PeriodicalIF":8.9,"publicationDate":"2026-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128261","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
