Annals of Clinical and Translational Neurology最新文献

{"title":"Histopathological Evidence of Neurodegenerative Pathology in Epilepsy: A Systematic Review","authors":"Syeda Amrah Hashmi,&nbsp;Aleksander Luniewski,&nbsp;Vanessa Smith,&nbsp;Matthew McCord,&nbsp;Jaideep Kapur,&nbsp;Mark Quigg,&nbsp;Catherine Joshua,&nbsp;Ifrah Zawar","doi":"10.1002/acn3.70486","DOIUrl":"10.1002/acn3.70486","url":null,"abstract":"<p>Epilepsy affects &gt; 50 million people worldwide and is associated with a disproportionate burden of cognitive impairment. Emerging evidence suggests that neurodegenerative proteinopathies, particularly hyperphosphorylated tau (p-tau) and amyloid-β (Aβ), may contribute to cognitive dysfunction in people with epilepsy (PWE), even in the absence of dementia. However, the prevalence, distribution, and clinical significance of these proteins in epilepsy remain unclear. We conducted a systematic review of neuropathological studies examining neurodegenerative pathology in PWE without primary neurodegenerative disease. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42024612990). A search of PubMed/MEDLINE, Ovid MEDLINE, Ovid Embase, and the Cochrane was performed from database inception to 7/8/2024. Eligible studies included human observational studies, case series, and post-mortem or surgical pathology assessing p-tau, amyloid, TDP-43, or related proteinopathies in PWE. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Forty-two studies met the inclusion criteria. Most studies involved drug-resistant temporal lobe epilepsy (TLE) with hippocampal sclerosis. P-Tau was the most consistently reported finding, identified across multiple epilepsy types with a prevalence ranging from 3%–95%. Amyloid was detected less consistently but occurred in both temporal and extratemporal epilepsies. Several studies reported associations between p-tau burden and seizure frequency, epilepsy duration, and cognitive impairment, particularly in mesial TLE, although findings were heterogeneous. Neurodegenerative pathology, especially p-tau, is frequently observed in epilepsy and may represent a biological link between seizures, hyperexcitability, and cognition. These findings suggest that epilepsy may intersect with neurodegenerative mechanisms and underscore the need for studies integrating neuropathology, biomarkers, and cognitive outcomes.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1530-1542"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Prospective Study of Individuals at Risk of Multiple Sclerosis Informs the Design of Primary Prevention Studies","authors":"Amy W. Laitinen,&nbsp;Ceren Tozlu,&nbsp;Tina Roostaei,&nbsp;Fatoumata Diallo,&nbsp;Kaho Onomichi,&nbsp;Jiyeon Son,&nbsp;Zongqi Xia,&nbsp;Philip L. De Jager","doi":"10.1002/acn3.70340","DOIUrl":"10.1002/acn3.70340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In multiple sclerosis, the optimal time for deploying a therapeutic intervention is before the central nervous system is damaged; given the success of trials treating the earliest stage of MS, the radiologically isolated syndrome, developing primary prevention strategies is an important next challenge. To inform this question, we examined the conversion of asymptomatic family members to a diagnosis of MS among Genes and Environment in Multiple Sclerosis (GEMS) project participants. We also evaluated an updated Genetic and Environmental risk score (GERS) and interest in participation in primary prevention trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GEMS is a nationwide prospective study of first-degree relatives of persons with MS; we analyzed data from seven surveys completed over 11 years. 1903 participants completed all questionnaires at study entry. Biological samples were collected in a subset of participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among these 1903 first degree relatives, 141 participants had MS at the time of enrollment; 18 participants converted to MS; and 1744 participants did not acquire an MS diagnosis during 8526 person-years of observation. The GERS was significantly higher among participants who had MS at the initial survey than those who did not have an MS diagnosis. The incidence rate of MS was estimated as 211 cases with a 95% confidence interval of 113 to 308 cases per 100,000 first-degree family members per year, which is 100 times greater than the reported incidence of sporadic MS. 48% of the asymptomatic participants were willing to participate in a prevention trial, while 75% expressed willingness when presented with a scenario assuming an elevated risk (20%) of developing MS based on genetic tests performed with blood samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Primary prevention trials in MS are urgently needed. Our findings support the feasibility for such studies and inform the design of future primary prevention trials in individuals at risk for MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT01353547</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1591-1601"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review and Meta-Analysis of the Recurrence of Autoimmune Encephalitis","authors":"Shangkai Bai,&nbsp;Sen Zhang,&nbsp;Haipei Zhang,&nbsp;Yating Zhang,&nbsp;Junhong Guo,&nbsp;Xiaoyan Yang","doi":"10.1002/acn3.70348","DOIUrl":"10.1002/acn3.70348","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Autoimmune encephalitis (AE) is a disease with a potential for recurrence, and patients receive immunotherapy to prevent it. However, there is no consensus on the duration of immunotherapy. This study aimed to determine the recurrence rate and identify the risk factors for AE to provide guidance on the duration of immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive search of the Embase, Web of Science, Cochrane, and PubMed databases was conducted from database inception until January 18, 2025, to identify clinical studies and observational studies reporting the recurrence of AE. Data on recurrence rates across different AE subtypes, age groups, treatments, and follow-up durations were aggregated. A generalized linear model was employed for regression and multivariate regression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 7892 publications initially identified, 39 observational studies were ultimately included. The overall recurrence rate of AE was 0.162 (95% CI, 0.121–0.207). The recurrence rate for anti-NMDAR encephalitis was 0.148 (95% CI, 0.108–0.193) and significantly decreased after teratoma removal. Second-line treatment decreased the AE recurrence rate. Multivariate regression analysis indicated that having anti-LGI1 encephalitis, age, and shorter delayed treatment duration were risk factors for recurrence. After 1 year of follow-up, the recurrence rate did not increase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Based on the findings, we recommend proactive second-line immunotherapy for patients with AE to reduce recurrence rates, particularly for those with anti-LGI1 encephalitis and adult individuals. Immunotherapy maintenance over 1 year may not be required.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1638-1652"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDG-PET Associations With Disease Severity and Outcomes in NMDA-Receptor IgG Autoimmune Encephalitis","authors":"Jonathan K. Lee,&nbsp;Jeffrey Lambe,&nbsp;Scott Johnson,&nbsp;Akua Abrah,&nbsp;Jennifer Bullen,&nbsp;Jeffrey A. Cohen,&nbsp;Tatchaporn Ongphichetmetha,&nbsp;Amy Kunchok","doi":"10.1002/acn3.70343","DOIUrl":"10.1002/acn3.70343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with <i>N</i>-methyl-D-aspartate (NMDA) receptor-immunoglobulin G (IgG) autoimmune encephalitis (NMDAR-IgG AE) demonstrate occipital lobe hypometabolism on baseline brain fluorodeoxyglucose-positron emission tomography (bFDG-PET). The goal of this study was to determine whether there is an association between bFDG-PET findings, disease severity, and clinical outcomes in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective analysis included adult patients with NMDAR-IgG AE who underwent bFDG-PET within 3 months of symptom onset. Qualitative and quantitative assessments of bFDG-PET findings were performed. Spearman's correlation analysis was used to evaluate potential associations between bFDG-PET findings and clinical severity at diagnosis and at 1 year using modified Rankin Scale (mRS) and Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Sixteen patients (13 women, 3 men; median age, 29.0 years) were included in the analysis. The median time between symptom onset and bFDG-PET was 5 weeks (interquartile range: 3–8). All patients received immunosuppressive therapy. Qualitative and quantitative assessments demonstrated the highest correlation between occipital lobe hypometabolism and clinical severity at diagnosis (Quantitative: mRS: −0.65 [95% confidence interval (CI): −0.87, −0.22]; CASE: –0.68 [95% CI: −0.88, −0.28]). At 1 year (<i>n</i> = 12), quantitative baseline occipital lobe hypometabolism was correlated with higher mRS scores (−0.71 [95% CI: −0.91, −0.23]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with NMDAR-IgG AE, occipital lobe hypometabolism on baseline bFDG-PET is correlated with mRS and CASE scores at the time of diagnosis and mRS scores 1 year later, suggesting that bFDG-PET findings correlate with disease severity and longitudinal outcomes. However, studies with larger patient populations are needed to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1581-1590"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Location-Specific Hematoma Volume Predicts Early Neurological Deterioration in Supratentorial ICH","authors":"Zuoqiao Li,&nbsp;Guilin Meng,&nbsp;Zijie Wang,&nbsp;Xiao Hu,&nbsp;Jing Cheng,&nbsp;Chu Chen,&nbsp;Tiannan Yang,&nbsp;Jiaxin Luo,&nbsp;Zizhen Meng,&nbsp;Xueyun Liu,&nbsp;Qi Li","doi":"10.1002/acn3.70351","DOIUrl":"10.1002/acn3.70351","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Early neurological deterioration (END) adversely affects outcomes in patients with intracerebral hemorrhage (ICH). This study aimed to determine the location-specific hematoma volumes for END in supratentorial ICH patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analyzed supratentorial ICH patients presenting from two prospective cohorts. END was defined as a ≥ 4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score or a ≥ 2-point decrease in the Glasgow Coma Scale score within 24 h of admission. The training cohort was used to determine location-specific hematoma volume cutoffs for END and to develop the location-specific hematoma volume for early neurological deterioration (LIVED) score. Internal validation used 30% of the cohort, with external validation in a separate cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1199 patients with supratentorial ICH were included, divided into training (<i>n</i> = 633), internal validation (<i>n</i> = 272), and external validation (<i>n</i> = 294) cohorts. Hematoma volume thresholds for END were 21 mL for basal ganglia, 12 mL for thalamus, and 32 mL for lobar hemorrhages. Multivariable logistic regression identified location-specific hematoma volume, right-sided ICH, prior ischemic stroke, and NIHSS score as independent predictors, forming the LIVED score (range 0–5 points). The LIVED score showed superior predictive performance for END compared with established ICH scores, with the highest area under the curve (AUC) across cohorts. Additionally, it exhibited strong discrimination for 3-month outcomes, including functional independence, poor outcomes, and mortality, with AUCs &gt; 0.70 in all cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Location-specific hematoma volume thresholds independently predicted END, and the LIVED score demonstrated reliable performance for risk stratification in supratentorial ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1653-1661"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy-Associated Variants of a Single SCN1A Codon Exhibit Divergent Functional Properties","authors":"Lanie N. Liebovitz,&nbsp;Christopher H. Thompson,&nbsp;Linda C. Laux,&nbsp;Alfred L. George Jr.","doi":"10.1002/acn3.70344","DOIUrl":"10.1002/acn3.70344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Pathogenic variants in <i>SCN1A</i>, which encodes the voltage-gated sodium channel Na_V1.1, are associated with multiple epilepsy syndromes exhibiting a range of clinical severity. <i>SCN1A</i> variants are reported in different syndromes, including Dravet syndrome, which is associated with loss-of-function, whereas neonatal/infantile-onset developmental and epileptic encephalopathy (DEE) is associated with gain-of-function. Strategies to predict <i>SCN1A</i> variant pathogenicity and dysfunction have been proposed but are limited by available training data. We investigated the functional properties of four epilepsy-associated <i>SCN1A</i> variants affecting the same codon and sought to correlate channel dysfunction with phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Whole-cell manual patch-clamp recording was performed on heterologously expressed Na_V1.1 variants. Structural modeling of Na_V1.1 variant proteins was conducted using AlphaFold 3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We describe an individual with early infantile-onset DEE associated with <i>SCN1A</i>-I1347T, and identified three additional cases from the literature or ClinVar with distinct variations of the same codon (I1347N, I1347V, I1347F). Functional studies demonstrated mixed function properties for I1347T, I1347V, and I1347F, but complete loss-of-function for I1347N. Structural models suggest important interactions between isoleucine-1347 and the sixth transmembrane helices of domains 3 and 4 that are disrupted most significantly with asparagine replacement at this position (I1347N).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Pathogenic variants in <i>SCN1A</i> involving the same codon can produce divergent functional effects. Our findings suggest that predicting specific functional effects of <i>SCN1A</i> variants should not rely heavily on position in the protein.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1628-1637"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 57-Year-Old Male With Behavioral Variant Frontotemporal Dementia and MATR3 and NOS3 Mutations","authors":"Feifei Lin,&nbsp;Saie Huang","doi":"10.1002/acn3.70459","DOIUrl":"10.1002/acn3.70459","url":null,"abstract":"<p>This report presents a case of behavioral variant frontotemporal dementia caused by mutations in the MATR3 and NOS3 genes, aiming to analyze its clinical manifestations and genetic characteristics. For a case presenting with personality changes and gait abnormalities as the initial symptoms, this study conducted a comprehensive analysis of its clinical manifestations, neuropsychological assessments, cerebrospinal fluid biomarkers, head imaging changes, and genetic test results. It also discussed the possible causes based on the literature. Its main manifestations include personality changes, gait disorders, and a decline in executive functions. 18F-FDG PET shows decreased FDG metabolism in both bilateral frontal lobes, temporal lobes, and anterior cingulate gyrus, accompanied by corresponding brain atrophy, and no abnormal deposition of Aβ in both cerebral hemispheres. The related gene detection indicates mutations in the MATR3 gene (NM_018834.6: intron 11: c.1778 + 3A &gt; G) and NOS3 gene (NM_000603.5: exon 20: c.2435C &gt; A). There is no report of the coexistence of these two genes. The clinical diagnosis is behavioral variant frontotemporal dementia(bvFTD). The conclusion is that the mutations in MATR3 and NOS3 are likely to be associated with the pathological process of frontotemporal dementia by altering the structure and function of the encoded proteins. The identification of these variations provides new candidate gene combinations for the genetic variation spectrum of frontotemporal dementia, which should be regarded as hypothetical generative observation results. The clinical significance of these results needs to be further verified.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1726-1732"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Intermittent Theta-Burst Stimulation for Prolonged Disorders of Consciousness: A Prospective, Randomized, Controlled Trial","authors":"Chuan Xu,&nbsp;Jun Hu,&nbsp;Qianqian Wu,&nbsp;Min Wu,&nbsp;Yamei Yu,&nbsp;Hangcheng Li,&nbsp;Jian Gao,&nbsp;Jingqi Li,&nbsp;Nai Ding,&nbsp;Jie Yu,&nbsp;Benyan Luo","doi":"10.1002/acn3.70342","DOIUrl":"10.1002/acn3.70342","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Emerging evidence suggests that low-frequency neural oscillations are dynamically regulated by consciousness levels, with the recovery of low cortical activity potentially serving as a neurophysiological substrate for conscious emergence. Targeted enhancement of these low-frequency rhythms in patients with disorders of consciousness (DoC) may constitute a promising neuromodulation strategy to facilitate consciousness recovery in severe brain injury.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study systematically examined the neurophysiological effects of intermittent theta-burst stimulation (iTBS), specifically its potential to enhance low-frequency cortical activity and promote consciousness recovery in patients with DoC. Through multimodal neural assessments, we aimed to elucidate the mechanistic relationship between iTBS-induced neural oscillation modulation and behavioral manifestations of consciousness improvement.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This prospective cohort study enrolled 30 patients with DoC, of whom 18 completed the full intervention protocol. Two-way repeated-measures analysis of variance revealed significant group × time interaction effects on the Coma Recovery Scale-Revised (CRS-R) scores, &lt;i&gt;F&lt;/i&gt;(1, 16) = 6.543, &lt;i&gt;p&lt;/i&gt; = 0.021. Post hoc simple effects analysis demonstrated significant temporal improvement in the active transcranial magnetic stimulation (TMS) group, &lt;i&gt;F&lt;/i&gt;(1, 16) = 36.463, &lt;i&gt;p&lt;/i&gt; &lt; 0.001, with mean CRS-R scores increased from 9.300 ± 1.320 at baseline to 11.700 ± 1.409 post-intervention (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Conversely, sham stimulation revealed statistically nonsignificant changes (9.845 ± 1.476 versus 10.750 ± 1.575, &lt;i&gt;p&lt;/i&gt; = 0.067). Neurophysiological assessments revealed emerging neurophysiological changes in the iTBS group, including enhanced resting-state low-frequency oscillations (delta: 21.642% increase, &lt;i&gt;p&lt;/i&gt; = 0.449; theta: 6.800% increase, &lt;i&gt;p&lt;/i&gt; = 0.789) and augmented auditory-evoked responses (phrase-level 22.917% increase, &lt;i&gt;p&lt;/i&gt; = 0.280; syllable-level: 22.963% increase, &lt;i&gt;p&lt;/i&gt; = 0.504), suggesting potential neural plasticity mechanisms that require further validation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Collectively, this study established iTBS targeting the left dorsolateral prefrontal cortex as a clinically effective and well-tolerated neuromodulation approach for consciousness rehabilitation in patients with DoC, with therapeutic effects mediated by iTBS-induced enhancement of thalamocortical","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1619-1627"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-CD19 CAR T Cells in Autoimmune Encephalitis: Inflammation Controlled, Neurodegeneration Unchecked?","authors":"Dimitrios Mougiakakos,&nbsp;Marwa Al-Dubai,&nbsp;Denise Walther,&nbsp;Dominic Borie,&nbsp;Jan D. Lünemann,&nbsp;Marc Pawlitzki,&nbsp;Sven G. Meuth,&nbsp;Solveig Henneicke,&nbsp;Stefan Vielhaber,&nbsp;Stefanie Schreiber","doi":"10.1002/acn3.70414","DOIUrl":"10.1002/acn3.70414","url":null,"abstract":"<p>Just recently, successful chimeric antigen receptor (CAR) T cell therapy was reported in the first patient with refractory, anti-diacylglycerol lipase alpha (DAGLA) antibody-mediated autoimmune encephalitis, achieving partial clinical remission. We now provide extended follow-up demonstrating a stable, relapse-free clinical course and persistent suppression of autoantibodies. However, the patient exhibited progressive neurodegeneration despite sustained control of B cell-mediated inflammation. This dissociation between immune quiescence and structural decline highlights that CAR T cell therapy, while highly effective in extinguishing inflammation, may not be sufficient to prevent or reverse ongoing neuronal damage in disorders characterized by both inflammation and neurodegeneration.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1697-1701"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vestibular Patient Journey: Insights From Vestibular Disorders Association (VeDA) Registry","authors":"Ali Rafati,&nbsp;Sami I. Nassar,&nbsp;Shaun A. Nguyen,&nbsp;Patricia L. Gerend,&nbsp;Michael C. Schubert,&nbsp;Michael T. Teixido,&nbsp;Frederick A. Godley,&nbsp;Joel A. Goebel,&nbsp;Cynthia A. Ryan,&nbsp;Habib G. Rizk,&nbsp;Amir Kheradmand","doi":"10.1002/acn3.70334","DOIUrl":"10.1002/acn3.70334","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Vestibular symptoms impose a high burden of disability. Understanding real-world diagnostic and treatment pathways can identify care gaps and guide interventions. We aimed to characterize symptom profiles, diagnostic trends, provider involvement, and treatment patterns in vestibular disorders. We also examined whether these real-world pathways align with expected clinical features in vestibular diagnoses.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Data from the Vestibular Disorders Association (VeDA) patient registry from March 21, 2023, to January 29, 2024 was analyzed, focusing on vestibular diagnoses, symptom patterns, care pathways, treatments, and diagnostic predictors.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of 172 respondents (75.6% female), 66.3% reported multiple vestibular diagnoses (mean 1.8) and 18.9% reported inability to work. The most prevalent diagnoses were vestibular migraine (VM, 50.6%), benign paroxysmal positional vertigo (BPPV, 36.0%), Meniere's disease (26.9%), persistent postural-perceptual dizziness (PPPD, 20.9%), and vestibular neuritis (VN, 21.6%). VM overlapped with BPPV (44.8%), PPPD (31.0%), and Meniere's disease (27.6%). Patients consulted an average of ~15 providers, underscoring the combined effects of participation bias, diagnostic overlap, and fragmented care pathways characteristic of vestibular conditions. Symptoms, triggers, functional impact, provider involvement, and treatments were broadly similar across diagnoses. Logistic regressions revealed that VM was associated with frequent headaches, spontaneous vertigo, and frequent nausea/vomiting (ORs 24.70, 21.07, 5.58; &lt;i&gt;p&lt;/i&gt; = 0.003, 0.02, 0.036), Meniere's with dietary improvement (OR 38.00; &lt;i&gt;p&lt;/i&gt; = 0.016), PPPD with VM overlap and visual-induced vertigo (ORs 6.83, 0.02; &lt;i&gt;p&lt;/i&gt; = 0.03, 0.02), and VN with the lowest frequency of autonomic symptoms (OR 0.00006; &lt;i&gt;p&lt;/i&gt; = 0.005).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Interpretation&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The findings reveal a complex clinical landscape of vestibular disorders marked by multiple diagnoses and barriers to effective care. Overlapping symptom profiles across disorders further complicate diagnostic accuracy. Although regression analysis confirmed diagnosis-specific features, neither provider involvement nor treatments aligned consistently with diagnoses, highlighting fragmented care pathways. These findings call for clearer diagnostic pathways, enhanced provider training, and coordinated multidisciplinary care to improve diagnostic accuracy and treatment for vestibular","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"13 8","pages":"1602-1618"},"PeriodicalIF":3.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146217944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}