Annals of Neurology最新文献

{"title":"Outcomes of Intra-Arterial Tenecteplase after Endovascular Reperfusion for Acute Ischemic Stroke Due to Cardioembolism and Non-Cardioembolism: A Secondary Analysis of the POST-TNK Trial","authors":"Miao Chai MD,&nbsp;Qin Zhang MD,&nbsp;Xuexiao Zhao MD,&nbsp;Chawen Ding MD,&nbsp;Haoxuan Zhu MD,&nbsp;Sheng Zhou MD,&nbsp;Linyu Li MD,&nbsp;Zhenqian Liu MD,&nbsp;Fei Gao MD,&nbsp;Xu Xu MD,&nbsp;Jinfu Ma MD,&nbsp;Zhixi Wang MD,&nbsp;Jiayu Li MD,&nbsp;Qiuyi Yang MD,&nbsp;Yian Chen MD,&nbsp;Binghan Wang MD,&nbsp;Mingyang Chen MD,&nbsp;Yihui Yang MD,&nbsp;Yuhan Fan MD,&nbsp;Junjie Yuan MD,&nbsp;Jiaxing Song MD,&nbsp;Gaoming Li MD","doi":"10.1002/ana.78304","DOIUrl":"10.1002/ana.78304","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate the safety and effectiveness of adjunctive intra-arterial tenecteplase (TNK) in patients with acute ischemic stroke (AIS) due to cardioembolism (CE) and non-CE who achieved near-complete to complete reperfusion (defined as an expanded thrombolysis in cerebral infarction score of 2c-3) following endovascular treatment (EVT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prespecified secondary analysis of the POST-TNK randomized, open-label, blinded outcome assessment trial categorized 540 patients by stroke etiology into CE (n = 272) and non-CE (n = 268) subgroups. The primary outcome was freedom from disability at 90 days, defined as a modified Rankin Scale score of 0 to 1. Safety outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH) within 48 hours, and any intracranial hemorrhage (ICH) within 48 hours.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 272 patients with CE (median age, 73 years [interquartile range, 66–78]; 47.1% male), 137 were assigned to the control group and 135 to the intra-arterial TNK group. Compared with the control group, intra-arterial TNK was associated with significantly higher odds of freedom from disability at 90 days (adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.02–3.16; <i>p</i> = 0.04; inverse probability of treatment weighting adjusted odds ratio, 1.58; 95% CI, 1.12–2.22; <i>p</i> = 0.01). No significant differences were observed in 90-day mortality, sICH, or any ICH within 48 hours between groups. Conversely, intra-arterial TNK was not associated with improved functional outcomes in patients with AIS due to non-CE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In patients with AIS due to CE who achieved near-complete to complete reperfusion after EVT, adjunctive intra-arterial TNK was associated with a higher likelihood of freedom from disability at 90 days, without increasing the risk of mortality or ICH. However, this benefit was not observed in AIS patients due to non-CE. ANN NEUROL 2026;100:841–849</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"841-849"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148682910","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":"Cardiovascular Exercise Drives Neuroprotection in a Mouse Model of Spinocerebellar Ataxia 1 Via Rescue of Aberrant Splicing","authors":"Isabel Soto PhD,&nbsp;Michael Bonomo BS, MS,&nbsp;Brianna S. Nelthrope BS, MS,&nbsp;Benjamin D. Carr BS, MS,&nbsp;Emma Palmer BS,&nbsp;Mariana Sierra BS,&nbsp;Ilkim Erturk DVM,&nbsp;David Peppercorn BS,&nbsp;Eleonor Cox,&nbsp;Tiare K. Vasconcellos,&nbsp;Henry L. Paulson MD, PhD,&nbsp;Hannah K. Shorrock MSci, PhD,&nbsp;Sharan R. Srinivasan MD, PhD","doi":"10.1002/ana.78282","DOIUrl":"10.1002/ana.78282","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Spinocerebellar ataxia 1 (SCA1) is a fatal hereditary neurodegenerative disorder with no approved therapies, and gene-targeting strategies have thus far failed in clinical trials. Exercise remains the only intervention shown to provide clinical benefit in patients with spinocerebellar ataxias (SCAs), yet the underlying mechanisms remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the Atxn1^154Q/2Q knock-in mouse model, we implemented a prolonged voluntary wheel-running paradigm from 4 to 16 weeks of age. Mice were then phenotyped using motor and cognitive behavioral assays. Following euthanasia, cerebellar tissue was harvested for histological analysis and unbiased transcriptomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Unrestricted exercise rescued motor ataxia but not degeneration in this SCA1 mouse model at the ages in this study. Transcriptional profiling of cerebellar tissue separated wild-type (WT) sedentary and exercise mice by differential gene expression, but in SCA1 mice the most pronounced changes occurred at the level of RNA splicing, particularly in ion channel modules. Exercise led to a significant rescue of splicing events in SCA1 mice, with minimal impact on gene expression changes. Further, both exercised SCA1 and WT mice exhibited splicing patterns more similar to each other than their sedentary counterparts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Together with emerging evidence in other SCAs, our findings confirm aberrant splicing as a central driver of SCA pathophysiology and identify splicing-regulated networks as actionable therapeutic targets. The observed benefits in SCA1 mice suggest that correcting mis-spliced ion channels may be a viable strategy for disease modification across SCAs and related neurodegenerative disorders. ANN NEUROL 2026;100:850–866</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"850-866"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269402","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":"Distribution of Big Tau Isoforms in the Human Central and Peripheral Nervous System","authors":"Rama Krishna Koppisetti MSc,&nbsp;Nicolas R. Barthélemy PhD,&nbsp;Kanta Horie PhD,&nbsp;Cindy V. Ly PhD,&nbsp;Kaleigh F. Roberts PhD,&nbsp;Srinivas Koutarapu PhD,&nbsp;Richard J. Perrin PhD,&nbsp;Erin E. Franklin MS,&nbsp;Chiara Pedicone PhD,&nbsp;Joshua Orrick BS,&nbsp;Justin Melendez PhD,&nbsp;Timothy M. Miller MD, PhD,&nbsp;Chihiro Sato PhD,&nbsp;Nupur Ghoshal MD, PhD,&nbsp;Alison M. Goate PhD,&nbsp;Celeste M. Karch PhD,&nbsp;Randall J. Bateman MD,&nbsp;Soumya Mukherjee PhD","doi":"10.1002/ana.78300","DOIUrl":"10.1002/ana.78300","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Tau is widely studied in neurodegeneration, yet most work has focused on canonical brain tau isoforms. A longer isoform, “big tau,” produced by inclusion of exon 4a, is expressed in the peripheral nervous system (PNS) and central nervous system (CNS) regions. We sought to characterize big tau composition, anatomic distribution, and disease relevance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mass spectrometry (MS) was used to sequence big tau and map its distribution across the human nervous system. Postmortem samples included brain tissue from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and controls; spinal cord and peripheral nerves. Big and canonical (“small”) tau isoforms were also quantified in cerebrospinal fluid (CSF) from controls and participants stratified by amyloid status and cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Human big tau results from insertion of either 355 or 251 amino acids encoded by exon 4a-long and exon 4a-short, respectively. Alternative splicing of exons 2, 3, and 10 generates multiple big tau isoforms. Total tau levels were approximately 1,000-fold higher in the brain than in the PNS; however, the relative abundance of big tau increased from the CNS to the PNS, comprising 50% of the total tau in the periphery and approximately 1% in the brain, primarily localized to the cerebellum. In CSF, big tau levels were unchanged by amyloid abnormalities or cognitive impairment, whereas canonical tau increased with AD pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Big tau represents a distinct tau population enriched in the PNS and uncoupled from disease-associated changes in brain-derived tau, suggesting that distinguishing big tau from canonical tau may improve interpretation of tau biomarkers and help differentiate CNS neurodegeneration from peripheral nerve pathology. ANN NEUROL 2026;100:709–736</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"709-736"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519716","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":"Comparative Seizure Outcomes of Vagus Nerve Stimulation, Deep Brain Stimulation, and Their Combination in Lennox–Gastaut Syndrome","authors":"Cheng-Yen Kuo MD,&nbsp;Raunak Singh MD,&nbsp;Shelja Sharma MD,&nbsp;Ryan D. Nguyen MD,&nbsp;Lily Wong-Kisiel MD,&nbsp;Keith Starnes MD,&nbsp;Nicholas M. Gregg MD,&nbsp;Jamie Van Gompel MD,&nbsp;Kai J. Miller MD, PhD,&nbsp;Gregory A. Worrell MD, PhD,&nbsp;Brian N. Lundstrom MD, PhD","doi":"10.1002/ana.78308","DOIUrl":"10.1002/ana.78308","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Lennox–Gastaut syndrome (LGS) is a severe treatment-resistant epilepsy. Although vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are established therapies, comparative data and the impact of dual neuromodulation remain limited. We compared seizure outcomes across VNS, DBS, and combined DBS + VNS therapy in LGS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study at Mayo Clinic (2005–2024) included LGS patients treated with VNS and/or DBS. Seizure frequency was assessed at 6, 12, and 24 months post-stimulation. Responder was defined as 50% or more seizure reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty patients were included (42% female, median, 150 seizures/month). Eleven patients underwent sequential VNS followed by DBS and contributed data to 2 treatment epochs, yielding 3 treatment groups: VNS alone (n = 29), DBS alone (n = 12), and DBS + VNS (n = 10). At 24 months, median seizure reduction rate was comparable between VNS (50%; 95% confidence interval [CI], 44–75%) and the overall DBS cohort (59%, 95% CI, 33–86%) (<i>p</i> = 0.54). However, a significant difference emerged when comparing the 3 treatment arms (<i>p</i> = 0.027). Specifically, DBS + VNS therapy yielded significantly greater median reduction rate (81%, 95% CI, 60–99%) than DBS alone (43%, 95% CI, 0–58%) (<i>p</i>_adj = 0.027) or VNS alone (50%, 95% CI, 44.4–75.0%) (<i>p</i>_adj = 0.048). Four patients attained sustained seizure freedom above 1 year at last follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>VNS and DBS provide comparable seizure reduction in LGS over a 2-year follow-up period. DBS + VNS was associated with further improvements in seizure reduction in this small, retrospective dataset. This possibility warrants further investigation. ANN NEUROL 2026;100:879–892</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"879-892"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434673","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":"Pancake-Like Enhancement in Spondylotic Compressive Myelopathy","authors":"Wei Z. Yeh PhD,&nbsp;Shisheng Lu MBBS","doi":"10.1002/ana.78341","DOIUrl":"10.1002/ana.78341","url":null,"abstract":"&lt;p&gt;A 41-year-old man was initially admitted to hospital with a 12-month history of progressive bilateral lower limb weakness, lower limb and upper limb paresthesia, and bladder urgency. Prior spinal magnetic resonance imaging (MRI) showed severe canal stenosis at C5/6 with T2 hyperintensity and swelling of the lower cervical cord, and a transverse band of gadolinium enhancement affecting white and sparing gray matter at the level of maximal compression (Fig 1A; top, T2 sagittal view; middle, T1 fat-saturated contrast-enhanced sagittal view; bottom, T1 fat-saturated contrast-enhanced axial view). He underwent decompressive surgery with partial improvement to symptoms.&lt;/p&gt;&lt;p&gt;MRI carried out at 9 months post-surgery showed persistent cord signal change and enhancement (Fig 1B), prompting referral to the neuroimmunology clinic for opinion. Brain MRI was normal. Examination showed upper motor neuron signs of spasticity of the lower and upper limbs, brisk reflexes, and upgoing plantar responses. A diagnosis of spondylotic myelopathy with pancake-like enhancement was made. The patient received symptomatic and supportive treatment, and serial monitoring and MRI surveillance.&lt;/p&gt;&lt;p&gt;At 4 years post-decompression, the patient remained clinically stable, with MRI showing near-complete resolution of enhancement with focal atrophy and mild T2 hyperintensity in keeping with myelomalacia (Fig 1C).&lt;/p&gt;&lt;p&gt;Cervical spondylosis is a common cause for myelopathy.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; In patients with features suspicious for a progressive myelopathy, spinal MRI without contrast administration is often the first investigation. When contrast is administered, a pattern of “pancake-like” enhancement may be seen in patients with spondylotic compressive myelopathy.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This pattern of enhancement is characterized by a transverse band of enhancement at or just below the level of maximal stenosis, and with involvement of white matter and sparing of the gray matter.&lt;/p&gt;&lt;p&gt;In patients with progressive myelopathy and spondylotic canal stenosis with T2 cord signal change, pancake-like enhancement is an imaging finding strongly indicative for spondylotic compressive myelopathy.&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt; However, its association with spondylotic compressive myelopathy is likely underrecognized. Its misrecognition for an inflammatory or neoplastic etiology may lead to unnecessary and sometimes invasive investigations (such as spinal cord biopsy), delays in management with decompressive surgery, or inappropriate immunosuppression.&lt;/p&gt;&lt;p&gt;Enhancement can persist for years after decompression, as was the case in the present patient, and does not necessarily indicate an alternative etiology. The present case is unique in illustrating the progress and imaging of our patient over longitudinal follow up to 4 years post-surgery, which is longer than other reports with pancake-like enhancement. Recognition of this imaging sign assists in prompt diagnosis of spondy","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"893-895"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786085","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":"Facial Weakness Revealing Rare Familial Polyneuropathy","authors":"Sanem Pinar Uysal MD,&nbsp;Ciersten A. Burks MD,&nbsp;Rex N. Smith MD, PhD,&nbsp;Paloma Gonzalez-Perez MD, PhD","doi":"10.1002/ana.78318","DOIUrl":"10.1002/ana.78318","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"876-878"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617668","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":"ANA Investigates Pediatric Epilepsy Surgeries","authors":"Ifrah Zawar MD, MS-CR,&nbsp;Howard P. Goodkin MD, PhD,&nbsp;Jennifer Hurley CHCP, CPHQ,&nbsp;Ahsan Moosa Naduvil Valappil MD","doi":"10.1002/ana.78323","DOIUrl":"10.1002/ana.78323","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"896-898"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786103","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":"Two Years of Ocrelizumab Treatment in Black and Hispanic People with Multiple Sclerosis in CHIMES: A Single-Arm Clinical Trial","authors":"Lilyana Amezcua MD, MS,&nbsp;Anthony T. Reder MD,&nbsp;Evanthia Bernitsas MD,&nbsp;Nancy L. Monson PhD,&nbsp;Timothy Vartanian MD, PhD,&nbsp;Gregory F. Wu MD, PhD,&nbsp;Mansoor Saleh MD,&nbsp;Annette Okai MD,&nbsp;Ahmed Z. Obeidat MD, PhD,&nbsp;Dilraj Sokhi MRCP,&nbsp;Rikisha Parekh BS,&nbsp;Jinglan Pei PhD,&nbsp;Christopher Harp PhD,&nbsp;David Clayton PhD,&nbsp;Ibraheem Abioye MD, PhD,&nbsp;Mitzi J. Williams MD,&nbsp;for the CHIMES Study Group","doi":"10.1002/ana.78290","DOIUrl":"10.1002/ana.78290","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To evaluate the effectiveness and safety of ocrelizumab in self-identified black and Hispanic people with relapsing multiple sclerosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Characterization of Ocrelizumab in Minorities with Multiple Sclerosis (CHIMES) trial, a prospective, open-label, single-arm, phase 4 study, intentionally recruited underrepresented populations in the US, Puerto Rico, and Kenya. Black and Hispanic people with relapsing multiple sclerosis aged 18–65 years with Expanded Disability Status Scale score 0–5.5 received ocrelizumab for 2 years. The primary endpoint was the proportion of participants with no evidence of disease activity in 3 components at week 48: protocol-defined relapse, 24-week confirmed disability progression, and disease activity on magnetic resonance imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 113 black and 69 Hispanic people with relapsing multiple sclerosis, most were women (72%), with a mean age of 35.5 (SD 10.5) years, body mass index of 31.0 (SD 7.4) kg/m², and Expanded Disability Status Scale score of 2.4 (SD 1.4). Genetic ancestry aligned with self-identified race or ethnicity. At week 48, 50.5% of CHIMES participants had no evidence of disease activity, including 94.5% free from 24-week confirmed disability progression, 95.1% free from relapse, 95.6% free from T1-contrast-enhancing lesions, and 52.7% free from new/enlarging T2 lesions. Serious adverse events were experienced by 8.2%, and 2.2% discontinued treatment. Infusion-related reactions were more frequent in Hispanic versus black participants (42.0% vs 29.2%), whereas gastrointestinal adverse events were more frequent in black versus Hispanic participants (23.0% vs 1.4%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Ocrelizumab treatment controlled disease activity in black and Hispanic people with relapsing multiple sclerosis. Results were consistent with pivotal ocrelizumab trials, supporting ocrelizumab's effectiveness and tolerability in these populations. ANN NEUROL 2026;100:793–807</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":"793-807"},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617718","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":"Annals of Neurology: Volume 100, Number 4, October 2026","authors":"","doi":"10.1002/ana.78370","DOIUrl":"https://doi.org/10.1002/ana.78370","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 4","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78370","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981429","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":"Patient-Derived Fibroblasts as a Clinically Relevant Model of Kearns-Sayre Syndrome.","authors":"Laura Valls-Roca, Adrià Vilaseca-Capel, Judith Cantó-Santos, Ester Tobías, Félix Andújar-Sánchez, Laia Farré-Tarrats, Frederic Tort, Carles Rentero, Carlos Enrich, Virginia López, Juan R Tejedor, Anna Esteve-Codina, Cristina Núñez de Arenas, Pedro J Moreno-Lozano, José C Milisenda, Mar O'Callaghan, Teresa García-Silva, Montserrat Morales-Conejo, Mario F Fraga, Rafael Artuch, Miguel Á Martín, José M Cuezva, Ana Matas, Glòria Garrabou, Mariona Guitart-Mampel","doi":"10.1002/ana.78351","DOIUrl":"10.1002/ana.78351","url":null,"abstract":"<p><strong>Objective: </strong>Kearns-Sayre syndrome (KSS) is characterized by single large-scale mitochondrial DNA deletions and by severe early-onset clinical manifestations with neurological involvement. Reliable disease models, as well as validated biomarkers or effective treatments, are lacking. We aimed to determine whether patient-derived fibroblasts represent a suitable cellular model for translational research.</p><p><strong>Methods: </strong>In a cross-sectional multicenter study, fibroblasts from 12 patients with KSS, and 10 age- and sex-matched controls were analyzed to comprehensively characterize their genetic and transcriptomic profiles, mitochondrial functional signature, and secretion of soluble signaling molecules (lactate and growth differentiation factor-15).</p><p><strong>Results: </strong>Fibroblasts derived from patients with KSS harbored single large-scale mitochondrial DNA deletions in 75% of cases and showed significant mitochondrial DNA depletion. Transcriptomic profiling identified 71 differentially expressed genes and multiple significantly enriched pathways. Despite mitochondrial respiratory chain enzymatic activities being preserved, ubiquinol-cytochrome c reductase core protein 2 complex III and MTCO1 complex IV protein expression was significantly decreased, and mitochondrial respiration was markedly impaired. Total adenosine triphosphate production rate was conserved, likely due to a metabolic shift toward glycolysis. Patient fibroblasts showed abnormal mitochondrial network organization and morphology, significant altered expression of fusion and fission proteins, a tendency to increase mitochondrial reactive oxygen species, and notably dysregulated antioxidant defenses. Mitochondrial content did not affect the functional signature. Lactate and growth differentiation factor-15 secretion were significantly increased, and demonstrated high sensitivity and specificity scores in distinguishing KSS.</p><p><strong>Interpretation: </strong>Patient-derived fibroblasts show a reproducible mitochondrial phenotype in KSS, supporting their use as a translational model for mechanistic studies, biomarker discovery, and therapeutic screening. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987345","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}