Annals of Neurology最新文献

{"title":"Speech Biomarkers for Quantifying Effects of Subthalamic Deep Brain Stimulation in Parkinson's Disease","authors":"Petr Krýže MSc,&nbsp;Mário Sousa MD,&nbsp;Vojtěch Illner PhD,&nbsp;Adriana Jorge MSc,&nbsp;Matilde Castelli MSc,&nbsp;Ines Debove MD,&nbsp;Andreia D. Magalhães MD,&nbsp;Julia Waskönig MD,&nbsp;Lenard Lachenmayer MD, PhD,&nbsp;Joan Philipp Michelis MD,&nbsp;Gerd Tinkhauser MD, PhD,&nbsp;Deborah Amstutz MD,&nbsp;Marie Elise Maradan-Gachet MD,&nbsp;Katrin Petermann MSc,&nbsp;Claudio Pollo MD, PhD,&nbsp;Tobias Nef PhD,&nbsp;Paul Krack MD, PhD,&nbsp;Jan Rusz PhD","doi":"10.1002/ana.78276","DOIUrl":"10.1002/ana.78276","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Dysarthria is one of the most common and disabling side effects of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). Stimulation often exacerbates speech dysfunction beyond the effects of PD progression, likely because of current spread to structures surrounding the STN. This study aimed to develop speech biomarkers sensitive to DBS-induced dysarthria by isolating stimulation side effects and mapping their emergence across incrementally increased amplitudes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four PD patients with bilateral STN-DBS completed a standardized speech assessment in each hemisphere separately, including sustained phonations, rapid syllable repetitions, and reading passages across 7 increasing stimulation amplitudes defined relative to a clinically determined stimulation-induced dysarthria threshold. A composite dysarthria index based on 7 key acoustic features, patient perceptual self-ratings, and intelligibility scores were extracted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>More than 2,500 speech task recordings were analyzed. Both the composite dysarthria index and subjective self-ratings worsened rapidly with increasing stimulation amplitude above a threshold (<i>p</i> &lt; 0.001), whereas intelligibility scores varied markedly and did not reach significance. Among individual acoustic features, phonation duration, voice quality, and monopitch exhibited significant sensitivity to increasing stimulation amplitudes. Left-sided stimulation induced greater speech deterioration than right-sided stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We systematically identified speech biomarkers that capture DBS-induced dysarthria, characterized the progressive deterioration of speech with increasing amplitude, and highlighted the pivotal role of left basal ganglia circuitry in speech production. Our objective metric holds promise as safety outcome measure for surgical therapies, guidepost for initial and troubleshooting DBS programming, and input for adaptive, closed-loop stimulation control. ANN NEUROL 2026;100:628–640</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"628-640"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248418","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 3, September 2026","authors":"","doi":"10.1002/ana.78330","DOIUrl":"https://doi.org/10.1002/ana.78330","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784947","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":"ANA Investigates: The Evolution of the ANA Podcast","authors":"Ifrah Zawar,&nbsp;Romergryko G. Geocadin,&nbsp;Megan Richie,&nbsp;Jennifer Hurley,&nbsp;Adeline L. Goss","doi":"10.1002/ana.78263","DOIUrl":"https://doi.org/10.1002/ana.78263","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"451-452"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785103","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":"Imaging of Neurovascular Compression in Thoracic Outlet Syndrome","authors":"Qing Sun MD,&nbsp;Tongxi Liu MD,&nbsp;Yibo Feng BM,&nbsp;Renbin Wang MD","doi":"10.1002/ana.78288","DOIUrl":"10.1002/ana.78288","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"641-643"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343475","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":"Cerebral Small Vessel Disease in a Neonate","authors":"Ye Han MD,&nbsp;Ping Zheng MD,&nbsp;Xinna Ji MD,&nbsp;Qian Chen MD","doi":"10.1002/ana.78307","DOIUrl":"10.1002/ana.78307","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"653-654"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417030","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":"The Case for Master Protocols for Rare Neurological Diseases","authors":"Jennifer Vermilion MD,&nbsp;Sabrina Paganoni MD, PhD,&nbsp;Scott R. Plotkin MD, PhD,&nbsp;Melanie Quintana PhD,&nbsp;Sara B. Calvert PharmD,&nbsp;Ineka T. Whiteman PhD,&nbsp;Raymond Y. Wang MD,&nbsp;Nadia Moore BS,&nbsp;Erika F. Augustine MD, MS","doi":"10.1002/ana.78311","DOIUrl":"10.1002/ana.78311","url":null,"abstract":"<p>Master protocol trials allow for simultaneous multiple hypothesis testing within a common framework and might be applicable for rare diseases. In May 2025, the Network for Excellence in Neuroscience Clinical Trials convened a multistakeholder conference to discuss master protocol trials in rare neurological disorders. In this paper, we explore how master protocol trial designs may apply to rare neurological disorders, using the neuronal ceroid lipofuscinoses as an example. Through shared protocol elements and trial infrastructure, master protocols may decrease cost and improve efficiency in testing potential therapeutics in rare disease, accelerating the delivery of urgently needed therapies to patients. ANN NEUROL 2026;100:477–486</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"477-486"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534516","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":"Change in Amyloid-β Deposition and Diffusion Tensor Image Analysis along the Perivascular Space Index in Incident Neurodegenerative Disease","authors":"Sewon Lim MS,&nbsp;Youngjin Lee PhD,&nbsp;Chang-Soo Yun PhD,&nbsp;Kyuseok Kim PhD,&nbsp;Chang-Ho Yun MD, PhD,&nbsp;Alzheimer's Disease Neuroimaging Initiative","doi":"10.1002/ana.78301","DOIUrl":"10.1002/ana.78301","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated the longitudinal association between cognitive decline, amyloid-β deposition, and perivascular diffusivity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This 2-year longitudinal study included 211 participants from the Alzheimer's Disease Neuroimaging Initiative, categorized into sustained cognitively normal, incident mild cognitive impairment, persistent mild cognitive impairment, and incident Alzheimer's disease (AD). The DTI-ALPS index and amyloid-β standardized uptake value ratio (SUVR) from amyloid positron emission tomography were obtained at baseline and follow-up. Linear mixed-effects models were used to examine longitudinal changes in the DTI-ALPS index and their associations with cognitive decline and amyloid-β accumulation. Multiple mediation analyses were performed to evaluate whether amyloid burden and gray matter atrophy mediated the relationship between changes in the DTI-ALPS index and cognitive performance. Additional analyses assessed the effect of baseline amyloid-β positivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The incident mild cognitive impairment and incident AD groups showed greater longitudinal declines in the DTI-ALPS index than the sustained cognitively normal group. Longitudinal reductions in the DTI-ALPS index were associated with greater cognitive decline and increased amyloid-β accumulation. Mediation analyses showed no significant indirect effects through SUVR or gray matter volume. Although baseline amyloid-β positivity alone was not associated with longitudinal DTI-ALPS changes, significant interactions with clinical progression were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Longitudinal alterations in the DTI-ALPS index are associated with cognitive decline and amyloid-β accumulation. These findings support the DTI-ALPS index as a non-invasive imaging marker reflecting disease progression in AD. ANN NEUROL 2026;100:559–571</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"559-571"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467856","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":"Monitoring Antiseizure Medication Change Using Ultra Long-Term Electroencephalogram: A Multicenter Study","authors":"Pedro F. Viana,&nbsp;Matthew McWilliam,&nbsp;Johannes Koren,&nbsp;Christina Duarte,&nbsp;Tamara Lisy,&nbsp;Christoph Baumgartner,&nbsp;Karl Rössler,&nbsp;Matthias Tomschik,&nbsp;Adriana Celdrán de Castro,&nbsp;Rodrigo Rocamora,&nbsp;Laura Vilella,&nbsp;Guido Rubboli,&nbsp;Sigge Weisdorf,&nbsp;Cecilia Friedrichs-Maeder,&nbsp;Troels W. Kjaer,&nbsp;Sanchita Bhatia,&nbsp;Dympna McAleer,&nbsp;Khalid Hamandi,&nbsp;Deborah Spencer,&nbsp;Rajiv Mohanraj,&nbsp;Mark P. Richardson","doi":"10.1002/ana.78305","DOIUrl":"10.1002/ana.78305","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Medication dose adjustments are common in treatment-resistant epilepsy, but lack robust evidence, and patient-reported seizure diaries have known limitations. We assessed whether ultra long-term subcutaneous electroencephalogram (sqEEG) improves detection of seizure frequency changes after antiseizure medication adjustments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective, multicenter cohort study was carried out across 9 centers in adults with treatment-resistant epilepsy. SqEEG seizure frequency was compared with seizure diaries before and after medication dose increases and reductions, over 7-, 14-, and 30-day windows, using categorical analyses, mixed-effects models and survival analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 65 participants (mean age 40.6 years; 59% female) contributed &gt;280,000 hours of sqEEG, 9,190 electrographic seizures and 4,850 diary events, including across 160 medication changes. Categorical disagreement between modalities ranged from 36% to 50%, with significant differences at 7 and 14 days for dose reductions, and at 14 days for dose increases. sqEEG recorded 2.2- to 3.4-fold more seizures than diary across all seizure count models (all p &lt; 0.01). Seizure count models showed no statistically significant difference between modalities in detecting treatment-related changes (interaction estimates: 5–38% larger increases with sqEEG for dose reductions, and 13–38% larger reductions with sqEEG for dose increases). SqEEG identified return to baseline seizure counts significantly earlier than diary after dose reductions at 7- and 14-day windows (median 7 vs 13 days and 10 vs 17 days, respectively; adjusted p = 0.046 and 0.042).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>SqEEG detects more seizures than patient-reported diaries and identifies treatment-related changes earlier, even after modest medication adjustments, particularly after dose reductions, highlighting the potential of objective ultra long-term EEG monitoring in treatment-resistant epilepsy. ANN NEUROL 2026;100:600–612</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"600-612"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519651","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":"Pancake-Like Enhancement in Spondylotic Compressive Myelopathy.","authors":"Wei Z Yeh, Shisheng Lu","doi":"10.1002/ana.78341","DOIUrl":"https://doi.org/10.1002/ana.78341","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoallelic POLR3A Variants Cause Early-Onset Peripheral Neuropathy","authors":"Luiza L. P. Ramos MD,&nbsp;Jevin M. Parmar BSc Hons,&nbsp;Robin Wijngaard MSc,&nbsp;Bianca R. Grosz PhD,&nbsp;Tamas Lazar PhD,&nbsp;Ligia Mateiu MD, PhD,&nbsp;Steve Vucic DSc,&nbsp;Kishore R. Kumar PhD,&nbsp;Dennis Yeow MBBS,&nbsp;Laura I. Rudaks MMed,&nbsp;Lonneke de Boer MD, PhD,&nbsp;Annemarie de Vreugd MSc,&nbsp;David A. Koolen MD, PhD,&nbsp;Thatjana Gardeitchik MD, PhD,&nbsp;Anita Cairns MD,&nbsp;Krishnan Iyengar MD,&nbsp;Fernando Kok MD, PhD,&nbsp;Fernanda Barbosa Figueiredo PhD,&nbsp;Alzira Alves de Siqueira Carvalho MD, PhD,&nbsp;Luiz S. Mageste Barbosa MD,&nbsp;Rodrigo Rezende Arantes MD,&nbsp;Tyler Rehbein MD,&nbsp;Jordan E. Bontrager MSc, CGC,&nbsp;Elizabeth P. Wood MA,&nbsp;Janet E. Sowden BSc,&nbsp;Gavin Monahan BSc,&nbsp;Meutia Kumaheri MD,&nbsp;Ivy Cuijt MSc,&nbsp;Melina Ellis BSc Hons,&nbsp;Gonzalo Perez-Siles PhD,&nbsp;Elyshia McNamara BSc Hons,&nbsp;Ronald van Beek BASc,&nbsp;Celine B. Meijers BASc,&nbsp;Ivaylo Tournev MD, PhD, DSc,&nbsp;Stephan Zuchner MD, PhD,&nbsp;Shoshana J. Wodak PhD,&nbsp;Clara D. M. van Karnebeek MD, PhD,&nbsp;Nigel Laing PhD,&nbsp;Liana N. Semcesen BSc Hons,&nbsp;David A. Stroud PhD,&nbsp;David N. Herrmann MBBCh,&nbsp;Velina Guergueltcheva MD, PhD,&nbsp;Marina L. Kennerson PhD,&nbsp;Machteld M. Oud PhD,&nbsp;Gianina Ravenscroft PhD,&nbsp;Ayse Candayan PhD,&nbsp;Albena Jordanova PhD","doi":"10.1002/ana.78268","DOIUrl":"10.1002/ana.78268","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Biallelic variants in genes encoding the RNA polymerase III complex (Pol III) cause a spectrum of neurological disorders primarily affecting the central nervous system. Monoallelic variants have been reported in the <i>POLR3B</i> subunit only, associated with neurodevelopmental disorder, epilepsy, and peripheral neuropathy. We describe a novel Pol III-related disorder caused by monoallelic variants in <i>POLR3A</i> and presenting primarily with peripheral neuropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed clinical and genetic investigation of the affected families. Biophysical characterization of mutant proteins was performed in silico. Immunoblotting, interactomics, and transcriptomics characterization were done in cellular models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 11 patients across 8 unrelated families harboring heterozygous missense variants in <i>POLR3A,</i> occurring de novo or segregating in an autosomal-dominant fashion. The patients presented with an early-onset, progressive sensorimotor peripheral polyneuropathy with intermediate to demyelinating ranges of nerve conduction slowing, occasionally accompanied with neurological or non-neurological features. White matter abnormalities, characteristic for the biallelic Pol III-related disorders, where not observed in the brain magnetic resonance imaging (MRI) evaluations. The neuropathy-associated variants cluster in regions critical for Pol III activity. We observed mis-regulation of individual Pol III targets and global downregulation of tRNA pools in patient-derived cells. This Pol III dysfunction was not due to impaired POLR3A expression, subcellular localization, or subunit interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our findings expand the Pol III-related disease spectrum beyond the known biallelic phenotypes and establish <i>POLR3A</i> as a novel peripheral neuropathy-associated gene. This work highlights a central role of Pol III dysfunction in disease and reinforces the link between tRNA metabolism and peripheral neurodegeneration. ANN NEUROL 2026;100:655–671</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 3","pages":"655-671"},"PeriodicalIF":7.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203445","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}