Neurology最新文献

{"title":"Association of Cardiovascular Autonomic Failure With Progression and Phenoconversion in Isolated REM Sleep Behavior Disorder.","authors":"Luca Baldelli, Luisa Sambati, Felice Di Laudo, Pietro Guaraldi, Giulia Giannini, Annagrazia Cecere, Giuseppe Loddo, Greta Mainieri, Francesco Mignani, Giorgio Barletta, Pietro Cortelli, Federica Provini, Giovanna Calandra-Buonaura","doi":"10.1212/WNL.0000000000213470","DOIUrl":"10.1212/WNL.0000000000213470","url":null,"abstract":"<p><strong>Background and objectives: </strong>Isolated REM sleep behavior disorder (iRBD) is a prodromal state of α-synucleinopathies, presenting years before overt neurodegenerative disorders. Autonomic nervous system (ANS) involvement, particularly cardiovascular autonomic failure, may indicate progression. However, its role as a (multidimensional) marker for disease progression and phenoconversion remains unclear. This study aimed to investigate whether cardiovascular autonomic failure and symptoms of autonomic dysfunction serve as multidimensional markers in patients with iRBD.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of patients with iRBD (iRBDs) and controls. Participants underwent cardiovascular reflex tests (CRTs) with beat-to-beat monitoring of blood pressure (BP) and ANS symptom assessments at baseline and annually. Primary outcomes were prevalence and progression of cardiovascular autonomic failure and the risk factors of phenoconversion. Longitudinal changes were evaluated through mixed-effects regression, predictors associated with conversion with Cox regression analysis.</p><p><strong>Results: </strong>Sixty-four iRBDs (mean age 68.89 ± 6.75 years, 75% male) and 67 controls (66.57 ± 7.91 years, 68% male) were recruited. At baseline, iRBDs exhibited a prevalent sympathetic cardiovascular dysfunction, with more frequent neurogenic orthostatic hypotension (nOH in 9 iRBDs) and abnormal BP responses to CRTs (pathologic Valsalva maneuver [VM] overshoot in 27 iRBDs). Longitudinal data demonstrated progressive deterioration of sympathetic baroreflex function, with increased prevalence of nOH (7 iRBDs with incident nOH; yearly odds ratio [OR] = 2.44) and deterioration of parasympathetic cardiovagal function. Thirteen patients (20.3%) phenoconverted to α-synucleinopathies. Neurogenic OH (hazard ratio [HR] = 5.05), altered sympathetic baroreflex function (pathologic VM HR = 3.49), and blunted parasympathetic cardiovagal responses (pathologic deep breathing heart rate ratio HR = 3.27) were significant risk factors for phenoconversion; their early appearance 5 years from iRBD onset increased the conversion risk, up to 4-fold. Symptoms of autonomic failure were more prevalent in iRBD and deteriorated over time but failed to predict conversion.</p><p><strong>Discussion: </strong>Progressive deterioration of cardiovascular autonomic function is a feature of iRBDs and affects the risk of phenoconversion. Limitations include the relatively short follow-up period and small number of converters. This study highlights the importance of objective cardiovascular autonomic testing as a multidimensional marker for risk stratification in iRBD.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213470"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670418","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":"What Is the Role of Inner Membrane Metalloproteases in Mitochondrial Quality Control and Disease?","authors":"Eduardo Benarroch","doi":"10.1212/WNL.0000000000213532","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213532","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213532"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784422","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":"Five-Year Changes in 24-Hour Sleep-Wake Activity and Dementia Risk in Oldest Old Women.","authors":"Sasha Milton, Clémence Cavaillès, Sonia Ancoli-Israel, Katie L Stone, Kristine Yaffe, Yue Leng","doi":"10.1212/WNL.0000000000213403","DOIUrl":"10.1212/WNL.0000000000213403","url":null,"abstract":"<p><strong>Background and objectives: </strong>Sleep disruptions are associated with cognitive aging in older adults. However, little is known about longitudinal sleep changes in the oldest old and whether these changes are linked to cognitive impairment. We aimed to determine whether changes in 24-hour multidimensional sleep-wake activity are associated with mild cognitive impairment (MCI) and dementia in oldest old women.</p><p><strong>Methods: </strong>We studied cognitively unimpaired women enrolled in the Study of Osteoporotic Fractures who completed wrist actigraphy twice (baseline and follow-up) and had cognitive status evaluated at follow-up using a neuropsychological battery and adjudication. To identify multidimensional sleep-wake change profiles, we performed hierarchical clustering on principal components on the 5-year changes (median 5.0 [range 3.5-6.3] years) in nighttime sleep (sleep duration, sleep efficiency [SE], and wake after sleep onset [WASO]), napping (duration and frequency), and circadian rest-activity rhythms (RARs; acrophase, amplitude, mesor, and robustness). Using multinomial logistic regression, we evaluated the associations between these profiles-and individual parameter changes-and MCI and dementia risk at follow-up.</p><p><strong>Results: </strong>Of 733 participants (mean age 82.5 ± 2.9 years), 164 (22.4%) developed MCI and 93 (12.7%) developed dementia by the follow-up visit. We identified 3 sleep-wake change profiles: stable sleep (SS; n = 321 [43.8%]) was characterized by stability or small improvements; declining nighttime sleep (n = 256 [34.9%]) showed decreases in nighttime sleep quality and duration, moderate napping increases, and worsening circadian RARs; and increasing sleepiness (IS; n = 156 [21.3%]) exhibited large increases in daytime and nighttime sleep duration and quality, and worsening circadian RARs. After adjustment for age, education, race, body mass index, diabetes, hypertension, myocardial infarction, antidepressant use, and baseline cognition, women with IS had approximately double the risk of dementia (odds ratio 2.21, 95% CI 1.14-4.26) compared with those with SS. SE, WASO, nap duration, and nap frequency were individually associated with dementia. Neither sleep-wake change profiles nor individual parameters were associated with MCI.</p><p><strong>Discussion: </strong>Among community-dwelling women in their 80s, those with increasing 24-hour sleepiness over 5 years had doubled dementia risk during that time. Change in multidimensional 24-hour sleep-wake activity may serve as an early marker or risk factor for dementia in oldest old women.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213403"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664100","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":"Changes to Average Survival of Patients With Amyotrophic Lateral Sclerosis (1995-2018): Results From the Piemonte and Valle d'Aosta Registry.","authors":"Rosario Vasta, Filippo De Mattei, Salvatore Tafaro, Antonio Canosa, Umberto Manera, Maurizio Grassano, Francesca Palumbo, Sara Cabras, Enrico Matteoni, Francesca Di Pede, Grazia Zocco, Giorgio Pellegrino, Emilio Minerva, Daniela Pascariu, Barbara Iazzolino, Stefano Callegaro, Giuseppe Fuda, Paolina Salamone, Fabiola De Marchi, Letizia Mazzini, Cristina Moglia, Andrea Calvo, Adriano Chiò","doi":"10.1212/WNL.0000000000213467","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213467","url":null,"abstract":"<p><strong>Background and objectives: </strong>The average survival of patients with amyotrophic lateral sclerosis (ALS) ranges from 2 to 5 years from symptom onset. However, it remains unclear whether this estimate has improved over time. The objective of this study was to analyze the survival trend of a large population-based cohort of patients with ALS over a 24-year period.</p><p><strong>Methods: </strong>Patients from the Piemonte and Valle d'Aosta registry for ALS (PARALS) were categorized into the first (1995-2002), second (2003-2010), or third (2011-2018) epoch based on their diagnosis date. Survival was defined as the time from diagnosis to death, tracheostomy, or censoring date. A Cox proportional hazard model was developed with diagnosis epoch as the primary variable of interest, adjusted for sex, site of onset, age at onset, diagnostic delay, forced vital capacity at diagnosis, Δbody mass index from onset to diagnosis, noninvasive mechanical ventilation use, gastrostomy use, and site of follow-up. A subset analysis comparing the 2007-2012 and 2013-2018 cohorts was conducted, incorporating riluzole prescription, genetics, and preslope category as additional covariates.</p><p><strong>Results: </strong>A total of 3,134 patients were included, evenly distributed across the 3 epochs (990, 1,023, and 1,121, respectively). The median survival remained stable during the first and second epoch (18.6 months vs 18.3 months) but improved during the third epoch (20.1 months; <i>p</i> = 0.0041), with a hazard ratio (HR) of 0.76 (95% CI 0.67-0.87, <i>p</i> = 0.00003). In the subset analysis, the most recent epoch (2013-2018) showed a continued survival advantage (HR 0.77, 95% CI 0.65-0.90). Of interest, the survival benefit was only evident among intermediate progressors (HR 0.60, 95% CI 0.45-0.80).</p><p><strong>Discussion: </strong>In the PARALS, ALS survival increased over time. In a subset analysis, the beneficial effect of the epoch was only evident among intermediate progressors. The improvement in multidisciplinary care provided by tertiary centers may be one possible explanation for this finding, although further dedicated studies are needed to confirm this hypothesis.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213467"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700995","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":"Associations Between Measures of Structural Racism and Acute Ischemic Stroke Incidence in the United States.","authors":"Sai Polineni, Praneet Polineni, Daniel Santos, David Daniel, Mandip Singh Dhamoon","doi":"10.1212/WNL.0000000000213413","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213413","url":null,"abstract":"<p><strong>Background and objectives: </strong>Racial differences in socioeconomic characteristics are believed to be secondary to structural racism. While socioeconomic factors explain some of the racial disparity in stroke incidence at an individual level, little is known about the association between societal-level structural racism and incidence of acute ischemic stroke (AIS). We aimed to determine whether the geographic racial disparity in stroke incidence across the United States is associated with structural racism.</p><p><strong>Methods: </strong>We performed a national, population-based analysis of 71,078,619 adults (844,406 with incident AIS) aged 65 years and older who were enrolled in Medicare from January 1, 2016, to December 31, 2019. The primary exposure was a composite score calculated from 8 county-level measures of structural racism (segregation indices [delta, dissimilarity, isolation], Gini index, housing discrimination, educational attainment, employment, and income) that account for validated domains of structural racism based on an ecosocial model. The primary outcome was incident AIS. Marginal Cox models with data clustered at the county level were used to estimate the hazard ratio (HR) of AIS incidence, comparing Black individuals with White individuals. Separate marginal Cox models tested associations between each measure of structural racism and AIS incidence, with further testing to screen for interaction with the race variable.</p><p><strong>Results: </strong>The composite structural racism score identified significant geographic variation in structural racism across the United States (mean 0.818, SD 2.874, interquartile range 3.02). Black individuals had a 19% increased hazard of AIS compared with White individuals (HR 1.19, 95% CI 1.14-1.25, <i>p</i> < 0.0001). All constituent measures of structural racism, except for housing discrimination, were associated with AIS incidence independently of race. Each SD increase in the composite structural racism score was associated with an 18% increased incidence in AIS in the total population. This association interacted with race (<i>p</i> = 0.03), with a greater magnitude of association for White (HR 1.19, 95% CI 1.13-1.25, <i>p</i> < 0.0001) vs Black (HR 1.09, 95% CI 1.03-1.16, <i>p</i> = 0.0073) individuals.</p><p><strong>Discussion: </strong>There is significant county-level geographic variation in structural racism across the United States, and increasing levels of structural racism are associated with increased incidence of AIS, regardless of race.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213413"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700856","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":"Teaching Video NeuroImage: Painful Tonic Spasms.","authors":"Yang Zheng, Duong T Chu, Jeremy J Moeller","doi":"10.1212/WNL.0000000000213518","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213518","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213518"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670434","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":"Pearls & Oy-sters: Severe Myotonic Crisis Resembling Malignant Hyperthermia.","authors":"Anil R Wadhwani, Ashna Aggarwal, Steven Loscalzao, Megan L McSherry, Justin L Lockman, John Frederick Brandsema, Jennifer McGuire, Susan Matesanz","doi":"10.1212/WNL.0000000000213497","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213497","url":null,"abstract":"<p><p>Patients with myotonic disorders are at risk for severe generalized muscle contraction, referred to as a \"myotonic crisis.\" For those patients with nondystrophic myotonia (NDM), the most common trigger of a myotonic crisis is exposure to succinylcholine. In this case, a 10-year-old female patient with NDM secondary to an <i>SCN4A</i> pathogenic variant developed a severe myotonic crisis in the setting of an upper respiratory infection and asthma flare treated with a beta-adrenergic agonist (ß-agonist). She presented with generalized rigidity and features of hypermetabolism resembling an anesthetic-related malignant hyperthermia. Management necessitated multidisciplinary collaboration, a complex intubation strategy, and an extended course in the pediatric intensive care unit. We suspected that this crisis was precipitated in part by continuous ß-agonist use during her initial asthma management. Treatments targeting sequential steps of the myocyte activation cascade tempered the contractile apparatus leading to clinical improvement in rigidity.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213497"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700999","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":"Wake-Up Call: The Association Between Sleep Disturbances and Dementia.","authors":"Marino Muxfeldt Bianchin, Eduardo Rigon Zimmer","doi":"10.1212/WNL.0000000000213516","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213516","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213516"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663504","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":"Long-Term Clinical Landscapes of Spinal Hypertrophic Pachymeningitis With Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.","authors":"Akihiro Nakajima, Mariko Hokari, Fumihiro Yanagimura, Etsuji Saji, Hiroshi Shimizu, Yasuko Toyoshima, Kaori Yanagawa, Musashi Arakawa, Akiko Yokoseki, Takahiro Wakasugi, Kouichirou Okamoto, Kei Watanabe, Keitaro Minato, Yutaka Otsu, Yukiko Nozawa, Daisuke Kobayashi, Kazuhiro Sanpei, Hirotoshi Kikuchi, Shunsei Hirohata, Kazuaki Awamori, Aya Nawata, Mitsunori Yamada, Hitoshi Takahashi, Masatoyo Nishizawa, Hironaka Igarashi, Noboru Sato, Akiyoshi Kakita, Osamu Onodera, Izumi Kawachi","doi":"10.1212/WNL.0000000000213420","DOIUrl":"10.1212/WNL.0000000000213420","url":null,"abstract":"<p><strong>Background and objectives: </strong>Spinal hypertrophic pachymeningitis (HP) is an extremely rare disorder characterized by the thickening of the spinal dura mater, which harbors distinct repertoires of immune cells due to the unique partitioning of the arachnoid blood-CSF barrier. The objectives were to identify the pathogenesis and therapeutic strategies for spinal HP.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed the clinical and pathologic profiles of patients with idiopathic/immune-mediated HP including spinal HP.</p><p><strong>Results: </strong>Among 61 patients with idiopathic/immune-mediated HP, all 6 Japanese patients with spinal HP, with a median observation period of 88.8 months, were myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA)-seropositive. The MPO-ANCA⁺ spinal HP cohort had the following characteristics: (1) a predominance of older women; (2) all patients were classified as having microscopic polyangiitis based on the 2022 American College of Rheumatology/European League Against Rheumatism criteria; (3) 83% of patients developed subacute/chronic myelopathy due to extramedullary spinal cord compression; (4) 50% of patients had lesion extension to the epidural compartment and vertebral column; (5) 50% of patients presented with chronic sinusitis, otitis media, or mastoiditis; (6) 33% of patients had involvement of the lower airways or kidneys; (7) a higher disease activity of the nervous system was noted based on the Birmingham Vasculitis Activity Score (BVAS), in contrast to MPO-ANCA⁺ cranial HP; (8) granulomatous inflammation with myofibroblasts, immune cells including granulocytes, and B-cell follicle-like structures were observed in the thickened dura mater; (9) immunotherapies (with or without surgical decompression) were effective in reducing the modified Rankin Scale score and reduced BVAS during the first active insults; (10) combined immunotherapies with glucocorticoids and cyclophosphamide/rituximab helped in reducing relapses in the long term; and (11) surgical decompression, including laminectomy and duraplasty, was necessary for compressive myelopathy. These data suggest that MPO-ANCA⁺ spinal HP shares common features with MPO-ANCA⁺ cranial HP (1, 2, 6, 8, 9, and 10), but also has unique clinical features (3, 4, 5, 7, and 11).</p><p><strong>Discussion: </strong>Our findings highlight the significant pathogenic role of ANCA in spinal HP. MPO-ANCA⁺ spinal HP, as an organ-threatening disease, should be positioned as having unique characteristics, whether limited to the CNS or as part of a generalized form in ANCA-associated vasculitis.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e213420"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11919275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662727","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":"Reader Response: Multipsychiatric Comorbidity in People With Epilepsy Compared With People Without Epilepsy: A Systematic Review and Meta-Analysis.","authors":"Shu Cong, Jun Wang","doi":"10.1212/WNL.0000000000209898","DOIUrl":"https://doi.org/10.1212/WNL.0000000000209898","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 8","pages":"e209898"},"PeriodicalIF":7.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674231","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}