Neurology最新文献

{"title":"Association of Menopause With Functional Outcomes and Disease Biomarkers in Women With Multiple Sclerosis.","authors":"Hannah E Silverman, Alan Bostrom, Alyssa N Nylander, Amit Akula, Ann A Lazar, Refujia Gomez, Adam Santaniello, Adam Renschen, Meagan Michaela Harms, Tiffany P Cooper, Robin Lincoln, Shane Poole, Ahmed Abdelhak, Roland G Henry, Jorge Oksenberg, Stephen L Hauser, Bruce Anthony Campbell Cree, Riley Bove","doi":"10.1212/WNL.0000000000210228","DOIUrl":"10.1212/WNL.0000000000210228","url":null,"abstract":"<p><strong>Background and objective: </strong>The impact of menopause on the brain is not well understood. Hormonal changes, including puberty and pregnancy, influence the onset and course of multiple sclerosis (MS). After menopause, a worsening of MS disease trajectory measured on the clinician-rated Expanded Disability Status Scale (EDSS) was reported in some, but not all, studies. Evaluating the association between menopause and more objective measures of CNS injury is warranted. This study sought to assess the trajectory of objective functional outcomes and disease biomarkers in women with MS before and after menopause in a longitudinal prospective observational cohort.</p><p><strong>Methods: </strong>Data were collected prospectively from a longitudinally followed MS cohort, including the performance-based Multiple Sclerosis Functional Composite (MSFC) as the primary functional outcome and the paraclinical marker of neuronal injury serum neurofilament light chain (sNfL) as the primary biomarker outcome. Outcomes were analyzed using segmented linear mixed model regressions adjusted for age, BMI, and tobacco use, with a change in slope at the time of menopause, as the a priori inflection point.</p><p><strong>Results: </strong>One hundred and eighty-four postmenopausal women met inclusion criteria. Participants were followed for a median of 13 years (interquartile range [IQR] = 4, range: 1-17). The median MS duration was 24 years (IQR = 13, range: 3-64), and the median EDSS score was 2.5 (IQR = 2, range: 0-8). The median age at natural menopause was 50 years (IQR = 5, range: 33-60); 17% of participants used any systemic menopausal hormone therapy. Menopause reflected an inflection point in MSFC worsening (slope difference 0.08, 95% CI 0.01, 0.14, <i>p</i> = 0.0163) and increase in serum neurofilament light chain (slope difference -0.95, 95% CI -1.74 to -0.16, <i>p</i> = 0.0194) while the opposite was found for EDSS (slope difference 0.05, 95% CI 0.01-0.09, <i>p =</i> 0.0200). Findings remained significant after adjustment for multiple covariates. When using additional nonlinear regression modeling, similar inflection points were found (within 3 years of the final menstrual period) for sNfL and EDSS but not MSFC.</p><p><strong>Discussion: </strong>The menopausal transition may represent an inflection in accumulation of neuronal injury and functional decline in MS.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210228"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882437","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":"Robert Wartenberg and the Hallervorden Affair, 1953: A Clash Between Medical Ethics and Cold War Politics.","authors":"Lawrence A Zeidman","doi":"10.1212/WNL.0000000000210122","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210122","url":null,"abstract":"<p><p>Robert Wartenberg was an emigrant from Nazi Germany and an iconic pioneer in neurology, describing eponyms and helping to found and nurture the American Academy of Neurology. However, in 1953, ironically, he became embroiled in a controversial event regarding the German neuroscientist and Nazi collaborator Julius Hallervorden. Wartenberg attempted to convince the Dutch delegation to attend the International Neurological Congress in Lisbon from which they had withdrawn in response to Hallervorden's inclusion as a speaker. In addition, he rallied neuroscientists worldwide to help convince the Dutch, largely ignoring and burying their concerns about Hallervorden's ethical transgressions. In numerous letters, Wartenberg wanted to both ignore and exonerate Hallervorden of ethical violations in collecting 700 brains from patients murdered in the Nazi euthanasia program. Wartenberg's unexpected defense of Hallervorden, despite not knowing him professionally, purportedly was to reintegrate German neuroscience to the international community and to create Western \"unity\" against communism. However, Wartenberg's efforts and the lack of international censure against Hallervorden prevented proper attention to the victims' brains that remained in Hallervorden's collection for decades and the use of these brains in scientific publications. Those who stood against Hallervorden have been vindicated by history, but work remains to uncover all brain specimens in German collections. Wartenberg's misguided and shortsighted involvement in this affair serves as a lesson for future generations of neurologists in the consequences of ignoring ethical concerns for expediency and politics.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210122"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869683","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":"Reassuring Insights Into the Effect of COVID-19 on Symptoms and Disability in People With Multiple Sclerosis: Weathering the Storm.","authors":"Alessandro Cagol, Noemi Montobbio","doi":"10.1212/WNL.0000000000210272","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210272","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210272"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882474","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":"Reader Response: Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.","authors":"Calixto Machado","doi":"10.1212/WNL.0000000000209723","DOIUrl":"https://doi.org/10.1212/WNL.0000000000209723","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e209723"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922169","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":"Association of Sleep Spindle Rate With Memory Consolidation in Children With Rolandic Epilepsy.","authors":"Hunki Kwon, Dhinakaran M Chinappen, Elizabeth A Kinard, Skyler K Goodman, Jonathan F Huang, Erin D Berja, Katherine G Walsh, Wen Shi, Dara S Manoach, Mark A Kramer, Catherine J Chu","doi":"10.1212/WNL.0000000000210232","DOIUrl":"10.1212/WNL.0000000000210232","url":null,"abstract":"<p><strong>Background and objectives: </strong>Rolandic epilepsy (RE), the most common childhood focal epilepsy syndrome, is characterized by a transient period of sleep-activated epileptiform activity in the centrotemporal regions and variable cognitive deficits. Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in RE and related sleep-activated epileptic encephalopathies. To further evaluate the association between this electrographic biomarker and cognitive dysfunction in this common disease, we investigate whether children with RE have deficient sleep-dependent memory consolidation and whether impaired memory consolidation is associated with reduced sleep spindles in the centrotemporal regions.</p><p><strong>Methods: </strong>In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using an automated sleep spindle detector validated for use in children with and without epilepsy.</p><p><strong>Results: </strong>Twenty-three children with RE (9 with active disease, 5F, age 6.9-12.8 years; 14 with resolved disease, 8F, age 8.8-17.8 years) and 19 age-matched and sex-matched controls (8F, age 6.9-18.7 years) were enrolled. Children with active epilepsy had decreased memory consolidation compared with control children (<i>p</i> = 0.001, mean percentage reduction 25.7%, 95% CI 10.3%-41.2%) and compared with children with resolved epilepsy (<i>p</i> = 0.007, mean percentage reduction 21.9%, 95% CI 6.2%-37.6%). Children with active epilepsy had decreased sleep spindle rates in the centrotemporal region compared with controls (<i>p</i> = 0.008, mean decrease 2.5 spindles per minute, 95% CI 0.7-4.4 spindles per minute). Spindle rate, but not spike rate or spike-wave index, correlated with sleep-dependent memory consolidation (<i>p</i> = 0.004, mean MST improvement of 3.9%, 95% CI 1.3%-6.4%, for each unit increase in spindles per minute).</p><p><strong>Discussion: </strong>Children with RE have impaired sleep-dependent memory consolidation during the active period of disease that correlates with a deficit in the sleep spindle rate. This finding identifies a noninvasive biomarker to aid diagnosis and a potential etiologic mechanism to guide therapeutic discovery of cognitive dysfunction in RE and related sleep-activated epilepsy syndromes.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210232"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971790","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":"Do You Work Here?","authors":"Danielle Chammas","doi":"10.1212/WNL.0000000000210280","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210280","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210280"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896481","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":"Editors' Note: Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.","authors":"Aravind Ganesh, Steven L Galetta","doi":"10.1212/WNL.0000000000210315","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210315","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210315"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922158","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":"Microenhancement as a Biomarker for Cerebral Microbleed in Inflammatory Cerebral Amyloid Angiopathy: Insights From 3D T1 Black-Blood MR Imaging.","authors":"Ty Shang, Peter V Sguigna, Marco C Pinho, William Moore, Erica Jones, Suriya Subramanian, Parth Upadhyaya, Brendan Kelley, Kimmo J Hatanpaa, Jack Raisanen","doi":"10.1212/WNL.0000000000210258","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210258","url":null,"abstract":"<p><strong>Objectives: </strong>Cerebral microbleeds (cMBs) are common imaging findings in conditions related to cerebral amyloid angiopathy (CAA). Blood-brain barrier (BBB) leakage is considered pivotal in their pathogenesis. This study investigates the potential role of cerebral microenhancement (cME) as an imaging biomarker on 3D T1 black-blood MRI (BB-MRI) for BBB rupture, predicting the formation of cMBs in inflammatory CAA variants.</p><p><strong>Methods: </strong>A retrospective review was conducted on biopsy-confirmed cases of CAA-related inflammation (CAA-ri) and amyloid-beta-related angiitis (ABRA) from the UT Southwestern Medical Center's BB-MRI registry (2014-2022). Subjects underwent 3D T1 BB MRI and susceptibility-weighted imaging. The presence and progression of cMEs and cMBs were assessed.</p><p><strong>Results: </strong>A total of 5 subjects (1 CAA-ri, 4 ABRA) were identified. Frequent cMEs on 3D T1 BB MRI scans preceded cMB formation, particularly in subjects with the <i>ApoE</i> ɛ4/4 genotype experiencing a refractory clinical course. Stable subjects had fewer cMEs and cMBs.</p><p><strong>Discussion: </strong>The presence of cME before cMB suggests their potential as a biomarker for cMB formation. The findings align with the hypothesis that BBB rupture and focal inflammation are critical in cMB pathogenesis. Further validation of 3D T1 BB MRI as an assessment tool for cMB formation in inflammatory CAA based on clinicoradiologic diagnosis and noninflammatory CAA could enhance monitoring and treatment strategies.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210258"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922165","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":"Effects of COVID-19 Infection on Symptom Severity and Disability in Multiple Sclerosis.","authors":"Amber Salter, Samantha Lancia, Gary R Cutter, Robert J Fox, Ruth Ann Marrie","doi":"10.1212/WNL.0000000000210149","DOIUrl":"10.1212/WNL.0000000000210149","url":null,"abstract":"<p><strong>Background and objectives: </strong>Infections, including infection with SARS-CoV-2 (COVID-19), could alter the course of multiple sclerosis (MS). Previous studies assessing the effects of COVID-19 on MS outcomes were small and had discordant findings. The study objective was to evaluate the association of COVID-19 infection with changes in the trajectory of MS symptoms and disability.</p><p><strong>Methods: </strong>We used a controlled interrupted time series (ITS), a quasiexperimental study design using longitudinal data from the North American Research Committee on Multiple Sclerosis Registry. Participants who completed at least 3 surveys before and after their index survey were identified. Exposure of interest was COVID-19 infection based on confirmed diagnosis using an at-home or laboratory test, as reported by the participant. Symptoms were measured using the SymptoMScreen (SMSS), a self-report measure of symptom severity across 12 domains common in MS. Disability was measured using PDDS. Segmented regression was used to compare changes in outcomes over time between cohorts, before and after the exposure (COVID-19 infection).</p><p><strong>Results: </strong>The spring 2023 survey response rate was 67.3%, and 4,787 participants completed the COVID-19 questions. Of those participants, 2,106 (44.0%) reported ever having confirmed COVID-19. The COVID-19 infection cohort included 796 participants with ≥3 surveys both before and after index survey. The uninfected cohort included 1,534 participants (32.0%) who reported never having COVID-19 nor other infections in the previous 6 months, of whom 1,336 had the requisite number of presurveys and postsurveys. After adjusting for participant characteristics, the SMSS score increased nominally over time in the COVID-19 and uninfected cohorts and this change over time did not differ between cohorts either before (0.005, 95% CI -0.025 to 0.035) or after (-0.0002, 95% CI -0.014 to 0.014) COVID-19 infection. The immediate effect of COVID-19 infection on the SMSS total score was minimal within the COVID-19 cohort and did not differ between cohorts (0.41, 95% CI -0.13 to 0.94). Findings were similar for disability.</p><p><strong>Discussion: </strong>Our study using an ITS design found that COVID-19 infection was not associated with immediate changes in symptom severity or disability, nor did it change the trajectories of these outcomes over a median follow-up of 18 months. Although results may not generalize to younger people with MS, these findings enhance our general understanding of the consequences of infection in people with MS.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210149"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882469","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":"Chemotherapy-Related Cognitive Impairment and Changes in Neural Network Dynamics: A Systematic Review.","authors":"Sandra Leskinen, Samir Alsalek, Rosivel Galvez, Favour C Ononogbu-Uche, Harshal A Shah, Morana Vojnic, Randy S D'Amico","doi":"10.1212/WNL.0000000000210130","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210130","url":null,"abstract":"<p><strong>Background and objectives: </strong>This systematic review aims to synthesize the current literature on the association between chemotherapy (CTX) and chemotherapy-related cognitive impairment (CRCI) with functional and structural brain alterations in patients with noncentral nervous system cancers.</p><p><strong>Methods: </strong>A comprehensive search of the PubMed/MEDLINE, Web of Science, and Embase databases was conducted, and results were reported following preferred reporting items for systematic review and meta-analyses guidelines. Data on study design, comparison cohort characteristics, patient demographics, cancer type, CTX agents, neuroimaging methods, structural and functional connectivity (FC) changes, and cognitive/psychological assessments in adult patients were extracted and reported. Study quality was assessed using an adapted version of the Newcastle-Ottawa Scale (NOS) for observational studies. Qualitative synthesis of cognitive and psychological testing outcomes, functional and structural connectivity changes, and their associations with CRCI were performed.</p><p><strong>Results: </strong>From 11,335 records identified, 63 studies analyzing 3,642 patients were included. Study designs included 24 prospective studies, 1 retrospective study, 36 cross-sectional studies, and 2 longitudinal studies. Most studies (75%) focused on patients with breast cancer. Common neuroimaging techniques included functional magnetic resonance imaging and diffusion tensor imaging. Postchemotherapy, many studies reported structural and FC alterations in brain networks such as the default mode, central executive, and dorsal attention networks. Cognitive function was assessed in 56 of the 63 included studies. Of the studies examining specific cognitive domains, 64% reported worsened learning and memory, 56% found impaired processing speed, and 70% identified deficits in attention/working memory in patients after CTX. Of the studies examining associations between connectivity changes and worsened cognitive function, 72% reported significant correlations in postchemotherapy patients. However, most of these studies were of low evidence, while 45% of high evidence-level studies, including prospective cohort studies, did not find significant associations between connectivity alterations and cognitive impairments.</p><p><strong>Discussion: </strong>While there is evidence suggesting CTX affects brain connectivity and neural network dynamics that can lead to cognitive difficulties, the findings are inconsistent. More robust and standardized research is needed to conclusively determine the extent of these effects and to develop targeted interventions for mitigating potential cognitive impairments in patients undergoing systemic treatment.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210130"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971795","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}