Annals of Neurology最新文献

{"title":"Intracranial Mesenchymal Chondrosarcoma: A Rare Tumor Entity","authors":"Wan Zhu MD, Jin Zhou MD, Rui Hu MD, Baofa Luo MD","doi":"10.1002/ana.78279","DOIUrl":"10.1002/ana.78279","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"341-342"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248376","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 Financial Value of an Academic Neurologist","authors":"Ifrah Zawar MD, MS-CR, Adam De Havenon MD, MS, Joseph R. Berger MD","doi":"10.1002/ana.78269","DOIUrl":"10.1002/ana.78269","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"238-241"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337079","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":"Motor Aprosodia: When Stroke Speaks in Monotone","authors":"Ammar Jumah MD, RPNI, Miranda Allen MD, Digvijaya D. Navalkele MD","doi":"10.1002/ana.78267","DOIUrl":"10.1002/ana.78267","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"343-344"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142047","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: Adaptive Deep Brain Stimulation","authors":"Karlo J. Lizarraga MD, MS, Adeline L. Goss MD, Jennifer Hurley CHCP, CPHQ, Helen M. Bronte-Stewart MD, MSE","doi":"10.1002/ana.78260","DOIUrl":"https://doi.org/10.1002/ana.78260","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 2","pages":"233-234"},"PeriodicalIF":7.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534442","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":"Distribution of Big Tau Isoforms in the Human Central and Peripheral Nervous System.","authors":"Rama Krishna Koppisetti, Nicolas R Barthélemy, Kanta Horie, Cindy V Ly, Kaleigh F Roberts, Srinivas Koutarapu, Richard J Perrin, Erin E Franklin, Chiara Pedicone, Joshua Orrick, Justin Melendez, Timothy M Miller, Chihiro Sato, Nupur Ghoshal, Alison M Goate, Celeste M Karch, Randall J Bateman, Soumya Mukherjee","doi":"10.1002/ana.78300","DOIUrl":"10.1002/ana.78300","url":null,"abstract":"<p><strong>Objective: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Interpretation: </strong>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.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perivascular Spaces as Determinants of Amyloid, Tau, and Vascular Biomarker Progression.","authors":"Audrey Low, Jeffrey L Gunter, Mingzhao Hu, Sheelakumari Raghavan, Scott A Przybelski, Christopher G Schwarz, Kejal Kantarci, Val J Lowe, Ronald C Petersen, Jonathan Graff-Radford, Clifford R Jack, Prashanthi Vemuri","doi":"10.1002/ana.78299","DOIUrl":"https://doi.org/10.1002/ana.78299","url":null,"abstract":"<p><strong>Objective: </strong>Magnetic resonance imaging (MRI)-visible enlarged perivascular spaces (PVS) are markers of cerebral small vessel disease (SVD) and aging, processes implicated in both neurodegenerative and cerebrovascular pathologies. However, longitudinal positron emission tomography (PET) studies examining PVS as a mechanism underlying Alzheimer's disease (AD) pathophysiological progression are lacking. Our overall objective was to investigate the associations of baseline PVS burden with white matter hyperintensity (WMH) volume, amyloid-PET, and tau-PET, both cross-sectionally and longitudinally.</p><p><strong>Methods: </strong>We examined 2,229 participants across the aging-AD spectrum from the Mayo Clinic Study of Aging (MCSA) and the Mayo Alzheimer's Disease Research Center (ADRC) (mean age = 68.59 ± 12.70 and 48.94% women). PVS and WMH were quantified using a novel in-house algorithm. Amyloid on [¹¹C]Pittsburgh Compound B (PiB)-PET and tau on AV1451-PET were measured. Cross-sectional regional and global associations were examined using canonical correlation analysis (CCA). Longitudinal associations were examined using age- and sex-adjusted linear mixed effect (LME) models with natural splines and subject-wise 10-fold cross-validation.</p><p><strong>Result: </strong>Three distinct associations were observed: (1) PVS in the basal ganglia (PVS-BG) was associated with greater WMH volume both cross-sectionally and longitudinally; (2) PVS-BG covaried with higher PiB standardized uptake value ratio (SUVR) cross-sectionally, with longitudinal trajectory associations limited to amyloid-negative individuals; (3) PVS in the centrum semiovale (PVS-CSO) was not associated with amyloid or tau, but was associated with occipital WMH, a pattern characteristic of CAA.</p><p><strong>Interpretation: </strong>Findings lend support for PVS-BG as an early indicator of small vessel dysfunction and WMH pathogenesis. Individuals with higher PVS-BG burden exhibited higher WMH burden and faster WMH progression, suggesting that PVS-BG may identify individuals at increased risk of progressive SVD. Evidence linking PVS to downstream AD biomarker progression was weaker. Findings support the relevance of PVS-CSO to CAA, suggesting that they may reflect changes occurring early in the disease process. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467861","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":"Comparative Seizure Outcomes of Vagus Nerve Stimulation, Deep Brain Stimulation, and Their Combination in Lennox-Gastaut Syndrome.","authors":"Cheng-Yen Kuo, Raunak Singh, Shelja Sharma, Ryan D Nguyen, Lily Wong-Kisiel, Keith Starnes, Nicholas M Gregg, Jamie Van Gompel, Kai J Miller, Gregory A Worrell, Brian N Lundstrom","doi":"10.1002/ana.78308","DOIUrl":"https://doi.org/10.1002/ana.78308","url":null,"abstract":"<p><strong>Objective: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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%) (p = 0.54). However, a significant difference emerged when comparing the 3 treatment arms (p = 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%) (p_adj = 0.027) or VNS alone (50%, 95% CI, 44.4-75.0%) (p_adj = 0.048). Four patients attained sustained seizure freedom above 1 year at last follow-up.</p><p><strong>Interpretation: </strong>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.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-14","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":"Neurophysiological Recovery Following Nerve Transfer Surgery to Restore Upper Limb Function after Cervical Spinal Cord Injury.","authors":"Kyle J Missen, Justin M Brown, Ross M Mandeville, Harvey Wu, Sean Bristol, Peter K Broadhurst, Erin Brown, Christopher Doherty, Amy K Hanlan, Russell O'Connor, Lawrence R Robinson, Kayton Rotenberg, J Michael Hendry, Jana Dengler, Michael J Berger","doi":"10.1002/ana.78296","DOIUrl":"https://doi.org/10.1002/ana.78296","url":null,"abstract":"<p><strong>Objectives: </strong>Nerve transfer is a promising intervention for restoring hand and upper limb function after cervical spinal cord injury (SCI), but the timeline of neurophysiological recovery in humans remains unclear. This study aimed to define recovery profiles after nerve transfers to restore upper limb function.</p><p><strong>Methods: </strong>Individuals with traumatic cervical SCI who received nerve transfer surgery in at least 1 limb were evaluated during routine clinical visits for up to 2 years post-transfer. The primary outcome was the time to detect reinnervation, defined as the appearance of voluntary motor unit potentials on needle electromyography. Representative muscles were assessed for 5 nerve transfer procedures: (1) supinator to posterior interosseous nerve; (2) brachialis to anterior interosseous nerve (AIN); (3) extensor carpi radialis longus to AIN; (4) extensor carpi radialis brevis to AIN; and (5) axillary to triceps. In a subset of participants who continued needle electromyography after reinnervation was detected, an ordinal grading system characterized motor unit potential maturity and the presence of pathological spontaneous activity over time.</p><p><strong>Results: </strong>A total of 44 individuals with traumatic cervical SCI were enrolled. Mean times to detect reinnervation were 6.9 months (supinator-posterior interosseous nerve), 10.4 months (brachialis-AIN), 9.6 months (extensor carpi radialis longus-AIN), 9.6 months (extensor carpi radialis brevis-AIN), and 9.0 months (axillary-triceps). Over time, reinnervated muscles showed reduced pathological spontaneous activity and progression from nascent to mature motor unit potentials.</p><p><strong>Interpretation: </strong>These findings establish benchmark timelines for first detection of neurophysiological reinnervation after nerve transfer in cervical SCI, providing a foundation for setting clinical expectations, planning rehabilitation, and designing future interventional studies. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395450","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":"AQP4 and MOG Characterize the Autoantibody Landscape of Checkpoint Blockade-Induced Optic Neuritis.","authors":"Tong Wu, Yongluo Jiang, Jiacai Lin, Jingyao Zhang, Ao Zhang, Guanqing Zhong, Guangmin Jian, Yiwei Xu, Pengfei Zhu, Jun Lv, Xiaochang Wu, Yang Liu, Youlong Wang, Yiming Li, Zhenyun Guo, Ningnan Fang, Xinjia Wang, Weidong Wang, Jun Lu, Ruijie Yao, Xiaoping Hong, Chenyu Yang, Shangeng Weng, Rui Wang, Rui Li, Yifei Ma","doi":"10.1002/ana.78297","DOIUrl":"https://doi.org/10.1002/ana.78297","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the autoantibody profile in immune checkpoint inhibitor (ICI)-induced optic neuritis (CBON) and identify key autoantibodies for diagnostic and therapeutic purposes.</p><p><strong>Methods: </strong>In this multicenter retrospective study (January 2020-June 2025), we screened 327 neuro-ophthalmic patients from a bio-repository of 2,321 ICI-treated individuals, identifying 88 patients with CBON across 3 independent cohorts (n = 25, 29, and 34). Longitudinal serum samples (pre-ICI, prodromal, onset, and follow-up) were available for 12 patients. A matched control group of 49 ICI-treated patients without neuro-ophthalmic symptoms was included. Serum samples were analyzed using cell-based assays for 25 neural-specific IgG autoantibodies. Longitudinal samples were assessed for antibody dynamics. Correlations between serostatus and clinical features were evaluated.</p><p><strong>Results: </strong>Autoantibody profiling revealed a highly focused immune response concentrated against aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). Seropositivity rates for these antibodies ranged from 17.3% to 32.4% across cohorts, whereas other neural antibodies were detected at markedly lower frequencies (<12%). Longitudinal analysis demonstrated a clear seroconversion pattern, with antibodies undetectable at pre-ICI baseline but emerging at symptom onset, which remained detectable during follow-up in a subset of patients. These AQP4/MOG antibodies were virtually absent in control patients (0-2%).</p><p><strong>Interpretation: </strong>This study establishes AQP4 and MOG as the dominant autoantibodies in CBON, providing a serological framework for diagnosis and classification. The persistent antibody response following ICI-induced seroconversion offers direction for future mechanistic investigations. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381270","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":"Network Colocalization Correlates of Depression and Anxiety in Pediatric Focal Cortical Dysplasia-Related Epilepsy","authors":"Xiaotong Li BA,&nbsp;Ty Charde,&nbsp;Venkata Sita Priyanka Illapani MSc,&nbsp;Sonya M. Leikin BS,&nbsp;Hua Xie PhD,&nbsp;Chima O. Oluigbo MD,&nbsp;L. Gilbert Vezina MD,&nbsp;William D. Gaillard MD,&nbsp;Hayley J. Loblein PhD,&nbsp;Perrine Heymann PhD,&nbsp;Leigh N. Sepeta PhD,&nbsp;Madison M. Berl PhD,&nbsp;Adelaide S. Robb MD,&nbsp;Nathan T. Cohen MD","doi":"10.1002/ana.78219","DOIUrl":"10.1002/ana.78219","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Focal cortical dysplasia (FCD) is the most common cause of surgically treatable, drug-resistant epilepsy in children. Anxiety and depression are frequent comorbidities in epilepsy. This study examined whether FCD overlap with large-scale functional networks, the default mode network (DMN) and the limbic network, is associated with parent-reported anxiety or depressive symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty-nine patients with FCD-related epilepsy completed the Child Behavior Checklist (CBCL), among whom 56 finished the 6 to 18 years version of CBCL (CBCL_6–18). FCD overlap (%) with Yeo 7-networks was calculated. General linear models tested FCD_DMN or FCD_limbic overlap with CBCL Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition (DSM)-Anxiety Problems or DSM-Depressive Problems Scores controlling for age and gender.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-six patients had preoperative CBCL_6–18 (median age = 12.8 years, 55% male patients). FCD_DMN overlap (B = 0.08, 95% confidence interval [CI] = 0.002–0.16, partial <i>η</i>² = 0.086, <i>p</i> = 0.045) and female gender were associated with higher DSM-Depressive Problems T-scores. This lesion-network depressive-symptoms effect was stronger in an adolescent-only model (52% male patients): FCD_DMN overlap (B = 0.19, 95% CI = 0.068–0.32, partial <i>η</i>² = 0.37, <i>p</i> = 0.004). Network overlap was not associated with DSM-Anxiety Problems in any age group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>FCD_DMN overlap is associated with increased depressive symptoms, particularly for adolescents, whereas FCD_limbic overlap is not. These findings underscore the importance of lesion-network colocalization contributing to depression vulnerability in developmental epilepsy and highlight DMN colocalization involvement as a potential neurobiological marker of depressive risk. ANN NEUROL 2026;100:84–94</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"84-94"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588855","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}