Neurology最新文献

{"title":"Transdiagnostic Network Localization of Social, Language, and Motor Symptoms in Patients With Frontotemporal Lobar Degeneration.","authors":"Tony X Phan, W Andrew Mullins, Aaron M Tetreault, Kiiya Shibata, Jayden L Lee, Kilian Hett, Ciaran M Considine, R Ryan Darby","doi":"10.1212/WNL.0000000000213514","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213514","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213514"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605883","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":"From Diffusion MRI to Prognosis: How Advanced Imaging Techniques Enhance Stroke Recovery Assessment.","authors":"Mara Cercignani, Marco Bozzali","doi":"10.1212/WNL.0000000000213512","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213512","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213512"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605903","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":"Neurodegeneration and Demyelination in the Multiple Sclerosis Spinal Cord: Clinical, Pathological, and 7T MRI Perspectives.","authors":"Kedar R Mahajan, Danielle Herman, Yufan Zheng, Caroline Androjna, Bhaskar Thoomukuntla, Daniel Ontaneda, Kunio Nakamura, Bruce D Trapp","doi":"10.1212/WNL.0000000000210259","DOIUrl":"10.1212/WNL.0000000000210259","url":null,"abstract":"<p><strong>Background and objectives: </strong>Key findings in people with multiple sclerosis (MS) with progressive motor disability are spinal cord (SC) atrophy signifying irreversible axonal loss and SC demyelinated lesions. This study aimed to identify neurodegenerative changes and assess the clinical impact and pathologic characteristics of SC lesions.</p><p><strong>Methods: </strong>A cross-sectional study was performed using postmortem cervical cord segments from the Cleveland Clinic MS Rapid Autopsy Program. Inclusion included proximity to our center, absence of transmissible infections, and lack of prolonged hypoxia. In situ MRIs were performed before tissue removal and fixation followed by 7T MRI and immunohistochemistry. Quantitative T2* relaxation times were correlated with myelin, axons, and activated microglia/macrophages (major histocompatibility complex II [MHCII]) using Tukey comparison of means and a linear mixed-effects model; T2* was correlated with clinical disease characteristics using Wilcoxon rank sum.</p><p><strong>Results: </strong>The study included 40 MS cases (median age 58, female 55%) and 9 controls (median age 69, female 89%). A T2* threshold reliably discriminated demyelination (accuracy 89.7%, sensitivity 95.5%, and specificity 87.0%). Myelin content (95% CI -0.82 to -0.58, estimate -0.70) was the only significant predictor of T2*. T2* hyperintensities within the segments ranged from 0% to 100% (median 33.6, interquartile range 12.9-64.3) with only 57.1% demyelinated. T2*-hyperintense/myelinated regions had increased T2* relaxation time (19.2 ms, 95% CI 9.97-28.4), reduced myelin content (-8.3%, 95% CI -12.1 to -4.4), increased MHCII (3.6%, 95% CI 0.45-6.7), reduced axonal counts (-349.8, 95% CI -565.4 to -134.1), and increased axonal area (2.0 µm², 95% CI 1.0-3.1) compared with normal-appearing MRI regions. These regions occurred adjacent to T2*-hyperintense/demyelinated lesions (periplaque) or along tracts (tract-based). 7T postmortem T2* hyperintensities were subtle on clinical 1.5T axial T2, and only 43% were detected sagittally. T2*-hyperintense/demyelinated lesions correlated with Expanded Disability Status Scale (EDSS) (rho = 0.61, <i>p</i> < 0.0001) and upper cervical cord area (rho = -0.64, <i>p</i> < 0.0001) while T2*-hyperintense/myelinated regions did not.</p><p><strong>Discussion: </strong>Thresholding 7T T2* postmortem MRI can effectively discriminate demyelinated lesions which correlate with clinical disability and cord atrophy. T2*-hyperintense/myelinated regions exhibit myelin and axonal pathology in periplaque or tract-based distributions suggestive of neurodegeneration. Limitations include sampling of 2-cm of SC across participants making conclusions about proximal and distal pathology difficult.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e210259"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625432","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":"Uncommon Spinal Cord MRI Findings in a Patient With Early-Onset Amyotrophic Lateral Sclerosis: A Case Report.","authors":"Manh-Louis Nguyen, Andrei Haddad, Bruno Law-Ye, Adele Hesters","doi":"10.1212/WNL.0000000000213503","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213503","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213503"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557434","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 Plasma Biomarkers With Longitudinal Atrophy and Microvascular Burden on MRI Across Neurodegenerative and Cerebrovascular Diseases.","authors":"Erlan Sanchez, Gillian T Coughlan, Tim Wilkinson, Joel Ramirez, Saira Saeed Mirza, Andrée-Ann Baril, Allison A Dilliott, Andrew Frank, Anthony E Lang, Ayman Hassan, Bruce G Pollock, Christopher J M Scott, Connie Marras, Corinne E Fischer, Dallas Seitz, Daniela Andriuta, Dar Dowlatshahi, David A Grimes, David F Tang-Wai, Demetrios J Sahlas, Ekaterina A Rogaeva, Elizabeth Finger, John F Robinson, Kubra Tan, Malcolm A Binns, Maria Carmela Tartaglia, Michael J Borrie, Michael J Strong, Miracle Ozzoude, Nuwan D Nanayakkara, Rafaella A Goncalves, Robert Bartha, Robert A Hegele, Sali M K Farhan, Sandra E Black, Sanjeev Kumar, Sean P Symons, Seyyed M H Haddad, Stephen H Pasternak, Stephen R Arnott, Tarek K Rajji, Thomas Steeves, Walter Swardfager, Nicholas J Ashton, Hlin Kvartsberg, Henrik Zetterberg, Douglas P Munoz, Mario Masellis","doi":"10.1212/WNL.0000000000213438","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213438","url":null,"abstract":"<p><strong>Background and objectives: </strong>Plasma biomarkers of Alzheimer disease (AD), neuroinflammation, and neurodegeneration are increasingly being used in clinical trials for diagnosis and monitoring of dementia. However, their association with longitudinal structural brain MRI changes, an important outcome measure across neurodegenerative and cerebrovascular diseases, is less known. We investigated how baseline plasma biomarkers reflect MRI markers of progression over time in patients with neurodegenerative and cerebrovascular diseases.</p><p><strong>Methods: </strong>This longitudinal cohort study included patients from the Ontario Neurodegenerative Disease Research Initiative diagnosed with AD or mild cognitive impairment (AD/MCI), Parkinson disease (PD), frontotemporal dementia spectrum disorders (FTD), or cerebrovascular disease (CVD), followed annually for 2 years. Recruitment took place at specialized university-based dementia, movement disorders, and/or stroke clinics in the province of ON, Canada. MRI outcomes included markers of cerebral atrophy (ventricular CSF and regional gray matter volumes) and of small vessel disease pathology (white matter hyperintensity [WMH], perivascular spaces, and lacunar volumes). Hemorrhagic markers at baseline were also included. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau181 and tau217 (p-tau181, p-tau217), and β-amyloid (Aβ_42/40) were quantified from blood samples collected at baseline using Simoa and used as predictors in linear mixed models adjusted for time (months), age, sex, apolipoprotein E (<i>APOE</i>)-ε4 carrier status, kidney function, vascular risk factors, microtubule-associated protein tau (<i>MAPT</i>) diplotypes, waist-hip circumference ratio, and disease duration.</p><p><strong>Results: </strong>We analyzed 1,240 MRIs from 473 patients (age: 69.2 ± 7.4 [range: 49-87]; 32.8% women). Elevated baseline levels of GFAP, NfL, p-tau181, and p-tau217, and to a lesser extent decreased levels of Aβ_42/40, were significantly associated with more cerebral atrophy and WMH burden at baseline (|<i>B</i>| = 0.02 to 1.69, <i>p</i> = 0.044 to <0.001) and with progression over time (|<i>B</i>| = 0.001 to 0.028, <i>p</i> = 0.049 to <0.001) in the pooled disease-agnostic group. Within disease-specific cohorts, GFAP and NfL were associated with cerebral atrophy and/or small vessel disease copathology in AD/MCI, PD, FTD, or CVD. P-tau181 and p-tau217 were associated with cerebral atrophy and/or small vessel disease copathology in AD/MCI, CVD, PD-MCI, or PD-dementia.</p><p><strong>Discussion: </strong>Selected plasma biomarkers seem useful as prognosis and monitoring tools of longitudinal imaging changes within real-world populations of neurodegenerative and/or cerebrovascular diseases, and provide insight into overlap across diseases in shared pathologic burden.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213438"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597044","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":"Clinical Reasoning: A 56-Year-Old Woman With New-Onset Hoarseness and Dysphagia.","authors":"Michael McAree, Jennifer A Frontera","doi":"10.1212/WNL.0000000000213363","DOIUrl":"10.1212/WNL.0000000000213363","url":null,"abstract":"<p><strong>Statement of the clinical problem addressed by the case: </strong>We report an atypical clinical presentation of a rapidly progressive neurologic emergency that required prompt investigation and treatment of impending respiratory failure. We discuss the differential diagnosis, evaluation, emergency management, and treatment options of patients with atypical variants of this disorder.</p><p><strong>Brief description of case presentation: </strong>A 56-year-old woman with a history of hypothyroidism, anxiety, and depression presented to the emergency department 3 weeks after an upper respiratory and ear infection with cough, pain with sinus palpation, tingling in her fingers bilaterally and right foot, hives, and an episode of blurry vision on awakening. She was discharged home with antibiotics. That evening, she developed rapidly progressing hoarseness and dysphagia and returned to the emergency department. An initial examination and laryngoscopy revealed complete left vocal cord paralysis, consistent with a left cranial nerve X palsy, which prompted a neurologic evaluation. Her examination progressively worsened over the next day requiring mechanical ventilation and ICU admission.</p><p><strong>Summary of the key teaching point in the case: </strong>New-onset bulbar cranial neuropathies should raise concern for neurologic disorders that can be rapidly progressive and result in respiratory failure. Urgent diagnosis and treatment are warranted.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213363"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597092","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 NeuroImage: Peripheral Facial Palsy as the Initial Manifestation of Chronic Invasive Fungal Rhinosinusitis.","authors":"Mingwen Guo, Kun Chio Cheong, Zhaohui Shi, Xifu Wu","doi":"10.1212/WNL.0000000000213435","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213435","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213435"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605904","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":"Infantile TK2 Deficiency Causing Mitochondrial Encephalomyopathy With Migrating Focal Seizures.","authors":"Luca Bergonzini, Sara Carli, Silvia Pelle, Ilaria Pettenuzzo, Silvia Bonetti, Erika Santi, Caterina Visconti, Monica Maffei, Marta Sheremet, Eleonora Lamantea, Andrea Marsala, Olena Klub, Valentina Gentile, Duccio Maria Cordelli, Caterina Garone","doi":"10.1212/WNL.0000000000213373","DOIUrl":"10.1212/WNL.0000000000213373","url":null,"abstract":"<p><strong>Objective: </strong>Recessive variants in the <i>TK2</i> gene cause thymidine kinase 2 deficiency (TK2d) presenting with infantile, childhood, or adult-onset myopathy. CNS involvement is reported in only 25% of the infantile form. Compassionate use of deoxynucleoside substrate enhancement therapy (dC/dT) has been demonstrated safe and effective in TK2d myopathy, but no data are available on the potential efficacy on the human brain disease.</p><p><strong>Methods: </strong>Here, we report for the first time a patient with infantile TK2d epileptic encephalomyopathy enrolled in an early access program with dC/dT treatment (MT1621).</p><p><strong>Results: </strong>At age 3 months, he presented progressive hypotonia, motor regression, failure to thrive, and respiratory failure. At age 8 months, he developed drug-resistant epilepsy with migrating focal seizures. Brain MRI showed progressive atrophy and bilateral subcortical lesions with lactate peak. Exome sequencing revealed 2 novel biallelic heterozygous variants in the <i>TK2</i> gene (c.182G>A, p.Ser61Asn, c.704 T>C, p.Ile235Thr) whose pathogenicity was confirmed with in vitro studies. Early access compassionate use of dC/dT at 400 mg/kg prolonged the survival and stabilized the muscle disease but was not effective on the brain.</p><p><strong>Discussion: </strong>Our report highlights the importance of deep-phenotyping infantile TK2d before dC/dT supplementation to stratify disease severity further and suggests a limited tissue-specific brain efficacy.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213373"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557402","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":"Case of Pure Agraphia in Kana and Romaji Without Sensorimotor Deficits After a Small Infarct of the Posterior Limb of the Internal Capsule.","authors":"Kazuto Katsuse, Akatsuki Kubota, Kazuo Kakinuma, Shoko Ota, Shigenori Kanno, Toshiyuki Kakumoto, Yuichiro Shirota, Masashi Hamada, Tatsushi Toda, Kyoko Suzuki","doi":"10.1212/WNL.0000000000210254","DOIUrl":"10.1212/WNL.0000000000210254","url":null,"abstract":"<p><strong>Objectives: </strong>Infarctions of the posterior limb of the internal capsule (plIC) typically cause contralateral motor deficits. Cases with pure agraphia, writing impairments alone, are rare. We present a case of agraphia as the sole symptom after a small infarction in the anterior portion of the left plIC, which facilitates understanding of the interplay between the subcortical and cortical networks controlling writing.</p><p><strong>Methods: </strong>This study evaluated a 62-year-old right-handed Japanese man presenting with difficulties in typing and writing. In addition to neuropsychological assessments, diffusion tensor tractography and brain perfusion scintigraphy were used to analyze subcortical-cortical network disruptions.</p><p><strong>Results: </strong>Neuropsychological tests revealed selective agraphia in Kana and Romaji, characterized by phonological errors, but intact Kanji writing. Neuroimaging revealed disrupted neural fibers connecting the thalamus to the superior and middle frontal gyri and mild hypoperfusion in the middle frontal cortex.</p><p><strong>Discussion: </strong>Selective impairment of thalamic radiation projecting to the left frontal cortex due to the plIC infarction can result in pure agraphia. Our findings suggest a specific role of the left anterior plIC in writing Kana and Romaji, specifically in sound-to-letter conversion and postorthographic processes. This case underscores the importance of evaluating writing ability in patients with plIC infarctions to avoid overlooking agraphia.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e210254"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11902897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605850","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":"Ictal Hyperperfusion Highlights the Right Mesial Parietal Heading Direction System in Roller Coaster Reflex Epilepsy.","authors":"David N Vaughan, Chris Tailby, Marty Bryant, Alexander Berry-Noronha, John S Archer, Graeme D Jackson","doi":"10.1212/WNL.0000000000213494","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213494","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213494"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597285","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}