Neurology最新文献

{"title":"Author Response: Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.","authors":"Lori C Jordan, R Sky Jones, Michael R Debaun, Andria L Ford","doi":"10.1212/WNL.0000000000209737","DOIUrl":"https://doi.org/10.1212/WNL.0000000000209737","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e209737"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922117","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":"Comparison of Plasma p-tau217 and [¹⁸F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia.","authors":"Kely Monica Quispialaya, Joseph Therriault, Antonio Aliaga, Andrea L Benedet, Nicholas J Ashton, Thomas Karikari, Arthur Cassa Macedo, Nesrine Rahmouni, Cécile Tissot, Jaime Fernandez Arias, Yi-Ting Tina Wang, Lydia Trudel, Seyyed Ali Hosseini, Takashi Matsudaira, Tevy Chan, Tharick Pascoal, Brian Gilfix, Paolo Vitali, Eduardo R Zimmer, Karine Provost, Jean-Paul Soucy, Serge Gauthier, Henrik Zetterberg, Bertrand J Jean-Claude, Kaj Blennow, Pedro Rosa-Neto","doi":"10.1212/WNL.0000000000210211","DOIUrl":"10.1212/WNL.0000000000210211","url":null,"abstract":"<p><strong>Background and objectives: </strong>To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [¹⁸F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments.</p><p><strong>Methods: </strong>We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [¹⁸F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications. To determine whether the [¹⁸F]FDG-PET images were compatible with AD, images were visually rated by 2 nuclear medicine experts. Using a contingency analysis, we evaluated the accuracy of [¹⁸F]FDG-PET scan interpretation and plasma p-tau217 for an AD biomarker profile in CSF and for amyloid-PET positivity.</p><p><strong>Results: </strong>A total of 81 individuals with early onset and/or atypical dementia were included in this study (mean age = 65 years; 48/81 female (59%). Both [¹⁸F]FDG-PET and plasma p-tau217 showed high levels of agreement with reference standard AD biomarkers ([¹⁸F]FDG-PET area under the curve [AUC]: 71%; plasma p-tau217 AUC: 81%). Although both biomarkers had similar specificity for AD [¹⁸F]FDG-PET: 70%, CI: 0.56-0.81; plasma p-tau217: 70%, CI: 0.56-0.81), plasma p-tau217 had higher sensitivity for AD (plasma p-tau217: 97%, CI: 0.85-0.99 vs [¹⁸F]FDG-PET: 73%, CI: 0.57-0.85) (<i>p</i> = 0.01). Overall accuracy was also higher for plasma p-tau217 (AUC = 84%, CI: 0.75-0.93 vs 72%, CI: 0.60-0.83 of [¹⁸F]FDG-PET) (<i>p</i> = 0.02). The same pattern of results was observed when using amyloid-PET as the reference standard.</p><p><strong>Discussion: </strong>Our study provides evidence that plasma p-tau217 has strong discriminative accuracy for AD among patients with early-onset and/or atypical dementia assessed in specialized settings. Future work should replicate these findings in secondary care settings.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e210211"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882451","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":"Effect of IV Thrombolysis With Alteplase in Patients With Vessel Occlusion in the WAKE-UP Trial.","authors":"Ivana Galinovic, Jochen B Fiebach, Florent Boutitie, Bastian Cheng, Tae-Hee Cho, Martin Ebinger, Matthias Endres, Christian Enzinger, Jens Fiehler, Ian Ford, Johannes Gregori, Matthias Günther, Robin Lemmens, Keith W Muir, N Nighoghossian, Pascal Roy, Claus Z Simonsen, Vincent N Thijs, Anke Wouters, Christian Gerloff, Götz Thomalla, Salvador Pedraza","doi":"10.1212/WNL.0000000000209871","DOIUrl":"10.1212/WNL.0000000000209871","url":null,"abstract":"<p><strong>Background and objectives: </strong>Data from randomized trials on the treatment effect of pure thrombolysis in patients with vessel occlusion are lacking. We examined data from a corresponding subsample of patients from the multicenter, randomized, placebo-controlled WAKE-UP trial to determine whether MRI-guided IV thrombolysis with alteplase in unknown-onset ischemic stroke benefits patients presenting with vessel occlusion.</p><p><strong>Methods: </strong>Patients with an acute ischemic lesion visible on MRI diffusion-weighted imaging but no marked parenchymal hyperintensity on fluid-attenuated inversion recovery images were randomized to treatment with IV alteplase or placebo. The primary end point was a favorable outcome defined by a modified Rankin Scale score of 0-1 at 90 days after stroke. We investigated the interaction between vessel status and treatment effect using an unconditional logistic regression model. Treatment effects (adjusted odds ratio [aOR]) and their 95% CI were compared in patients with and without any vessel occlusion (AVO) and large vessel occlusion (LVO).</p><p><strong>Results: </strong>185 patients (mean age 64.5 years, 46% female, median NIH Stroke Scale score 9, median time between last seen well and MRI 10.26 hours) received treatment and presented with an occlusion. 98 (20%) had LVO (defined as occlusion of the internal carotid artery, middle cerebral artery trunk, or combination). A favorable outcome was observed in 30 of 94 patients with AVO (31.9%) in the alteplase group and in 18 of 91 (19.8%) in the placebo group (aOR 2.04, 95% CI 1.00-4.18). In the subgroup of patients with LVO, a favorable outcome was observed in 16 of 53 (30.2%) in the alteplase group and in 7 of 44 (15.9%) in the placebo group (aOR 2.08, 95% CI 0.71-6.10). Treatment with alteplase was associated with higher odds of favorable outcomes with no heterogeneity of treatment effect between patients with AVO and patent vessel (<i>p</i> = 0.56), or between patients with and without LVO (<i>p</i> = 0.69).</p><p><strong>Discussion: </strong>Although the WAKE-UP study was not powered to demonstrate treatment efficacy in patient subpopulations, this subgroup analysis points to a benefit of MRI-guided thrombolysis in patients with unknown-onset ischemic stroke, independent of vessel occlusion.</p><p><strong>Clinical trial registration: </strong>Registered at ClinicalTrials.gov with unique identifier NCT01525290 (clinicaltrials.gov/study/NCT01525290). The study was first posted on February 2, 2012; the first patient was enrolled on September 24, 2012.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that for patients with unknown-onset ischemic stroke with AVO, MRI-guided treatment with IV tissue plasminogen activator improves outcomes.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 2","pages":"e209871"},"PeriodicalIF":7.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869678","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":"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":"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}