Neurology最新文献

{"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":"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":"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}

{"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":"Teaching NeuroImage: Use of Intraoperative Indocyanine Green Angiography to Demonstrate Multiple Spinal Dural Arteriovenous Fistulas.","authors":"Xiaodong Niu, Si Cai, Jin Li","doi":"10.1212/WNL.0000000000213452","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213452","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213452"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605907","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":"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":"To Kill Time: A Bold Step Toward Simplifying Multiple Sclerosis Diagnosis.","authors":"Angela Vidal-Jordana, Daniel Ontaneda","doi":"10.1212/WNL.0000000000213416","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213416","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213416"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557424","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: Domestic Violence and Abuse in People Living With Multiple Sclerosis.","authors":"Aravind Ganesh, Steven L Galetta","doi":"10.1212/WNL.0000000000213407","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213407","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213407"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573568","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":"Genotype-Phenotype Landscape of <i>NALCN</i> and <i>UNC80</i>-Related Disorders.","authors":"Paloma Parra-Díaz, Arnaud Monteil, Daniel Calame, Nawale Hadouiri, Luca Soliani, Egidio Spinelli, Elena Jabbour Caron, Klaus Dieterich, Amy Kritzer, Kacie Riley, Jose M Serratosa Fernández, Jeremy A Tanner, Hélène Tevissen, Christel Thauvin, Rafael Vera-Medialdea, Stephan M Waltz, Álvaro Beltrán-Corbellini, Irene García Morales, Irene Sánchez-Miranda Román, Rafael Toledano, Adrián Valls-Carbó, Antonio Gil-Nagel","doi":"10.1212/WNL.0000000000213429","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213429","url":null,"abstract":"<p><strong>Background and objectives: </strong>The NALCN channelosome regulates the resting membrane potential through sodium leak currents, influencing cellular excitability. Genetic variants in <i>NALCN</i> and <i>UNC80</i>, a subunit of the NALCN channelosome, cause ultra-rare and severe neurodevelopmental disorders. Autosomal dominant congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD) syndrome is associated with gain-of-function (GOF) variants in <i>NALCN</i>. Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) 1 syndrome is associated with biallelic variants in <i>NALCN</i> and IHPRF 2 syndrome with biallelic variants in <i>UNC80</i>, both resulting in a loss-of-function (LOF). This study aims to expand the phenotypes associated with these syndromes, exploring potential genotype-phenotype associations.</p><p><strong>Methods: </strong>This is a cross-sectional study including patients with pathogenic or likely pathogenic variants in <i>NALCN</i> and <i>UNC80</i>. Phenotypes were evaluated through a structured interview, questionnaires, and review of medical records. Associations between variants, clinical features, and syndromes were analyzed.</p><p><strong>Results: </strong>Fifty-one patients were included (34 with CLIFAHDD, 9 with IHPRF 1, 8 with IHPRF 2; 3 months-27 years; 37.3% female). All exhibited neurodevelopmental delay, more severe in patients with LOF variants (<i>p</i> = 0.019). Neurodevelopmental regression was observed in 29.4% of patients with CLIFAHDD syndrome, associated with the onset of ataxia (70%). Patients with CLIFAHDD had more severe respiratory symptoms at birth (11.7% orotracheal intubation). Distal arthrogryposis (76.5%), episodic ataxia (41.2% of ambulatory patients), and paroxysmal dystonia (11.7%) were exclusively diagnosed in patients with CLIFAHDD. Patients with LOF variants presented more frequently with failure to thrive (88.2%, <i>p</i> = 0.001), central sleep apnea (CSA, 64.7%, <i>p</i> < 0.001), and epilepsy (70.6%, <i>p</i> < 0.001). Epilepsy was associated with more severe cognitive delays (<i>p</i> = 0.016) and was refractory in 58.8% of patients. Earlier seizure onset was associated with refractory epilepsy (<i>p</i> = 0.014). Patients with CLIFAHDD and premature death, epilepsy, or paroxysmal dystonia carried variants within NALCN pore domains.</p><p><strong>Discussion: </strong>This study provides an in-depth clinical characterization of <i>NALCN</i>-related and <i>UNC80</i>-related disorders. Distal arthrogryposis, episodic ataxia, and paroxysmal dystonia were diagnosed in patients with CLIFAHDD while failure to thrive, CSA, and epilepsy were associated with LOF variants. We suggest potential genotype-phenotype associations, formulating hypotheses for validation in future studies with larger cohorts.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213429"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573574","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":"Estimating Final Infarct on Baseline CT Perfusion: Tissue, Time, or Both?","authors":"Marie L Luby, José G Merino, Lawrence L Latour","doi":"10.1212/WNL.0000000000213539","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213539","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 7","pages":"e213539"},"PeriodicalIF":7.7,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605873","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}