Annals of Neurology最新文献

{"title":"Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose Studies to Assess the Safety and Efficacy of Elezanumab when Added to Standard of Care in Relapsing and Progressive Forms of Multiple Sclerosis.","authors":"Bruce A C Cree, Mark S Freedman, Michael Gold, Kimberly Pfleeger, Brittany Schwefel, Annette Wundes, Adam Ziemann","doi":"10.1002/ana.27262","DOIUrl":"https://doi.org/10.1002/ana.27262","url":null,"abstract":"<p><strong>Objective: </strong>Elezanumab is a monoclonal antibody that binds repulsive guidance molecule a (RGMa), an inhibitor of central nervous system regeneration after inflammation or injury. The aim was to assess the safety and efficacy of elezanumab in relapsing and progressive forms of multiple sclerosis (MS).</p><p><strong>Methods: </strong>RADIUS-R and RADIUS-P were phase 2 trials in relapsing (RADIUS-R) or progressive (RADIUS-P) MS. Participants were randomized to intravenous elezanumab 400mg, 1800mg, or placebo every 4 weeks through week 48. The primary endpoint was the mean Overall Response Score (ORS).</p><p><strong>Results: </strong>In RADIUS-R, 208 participants received elezanumab 400mg (n = 69), elezanumab 1800mg (n = 69), or placebo (n = 70). In RADIUS-P, 123 participants received elezanumab 400mg (n = 40), elezanumab 1800mg (n = 40), or placebo (n = 43). The primary endpoint of ORS was not met in either study. For RADIUS-R, mean ORS was -0.2 with effect size of -0.2 for elezanumab 400mg and -0.2 with effect size of -0.2 for elezanumab 1800mg. For RADIUS-P, mean ORS was 0.0 with effect size of 0.0 for elezanumab 400mg and 0.1 with effect size of 0.1 for elezanumab 1800mg. Elezanumab was well tolerated; the rate of serious adverse events was similar across treatment groups in both studies. Adverse events with ≥10% of elezanumab population were falls, urinary tract infections, headaches in RADIUS-R and RADIUS-P, and also fatigue, infusion-related reactions, and muscular weakness in RADIUS-P.</p><p><strong>Interpretation: </strong>Elezanumab was safe and well tolerated, but did not meet the primary endpoint in either study. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688457","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":"Annals of Neurology: Volume 98, Number 2, August 2025","authors":"","doi":"10.1002/ana.26987","DOIUrl":"https://doi.org/10.1002/ana.26987","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 2","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666572","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":"Sternocleidomastoid Muscle Overactivity: A Potentially Critical Contributor to Postural Abnormalities in Parkinson's Disease.","authors":"Sha Zhu, Ronghua Hong, Zhuang Wu, Yunjun Bao, Yunping Song, Guojiong Hu, Zhongfei Bai, Feifei Zhu, Zhenhua Liao, Lizhen Pan, Qiang Guan, Zhuoyu Zhang, Lingjing Jin","doi":"10.1002/ana.27310","DOIUrl":"https://doi.org/10.1002/ana.27310","url":null,"abstract":"<p><strong>Objective: </strong>Overactivity of muscles is thought to be involved in postural abnormalities (PA) in Parkinson's disease (PD). Here, we investigated the relationship between muscle activity and postural parameters to explore the peripheral mechanisms of PA.</p><p><strong>Methods: </strong>A total of 90 PD patients and 19 healthy controls were enrolled. Posture features (F1-F8) and the index for PA were collected. Surface electromyography was acquired from cervical and thoracolumbar muscles during lying, sitting, standing, and walking, respectively. Follow-up was completed for a subset of PD patients.</p><p><strong>Results: </strong>Root mean square (RMS) amplitudes of the sternocleidomastoid muscle (SCM) and external oblique muscle, were higher in PD patients with PA (PD_PA) than PD patients without PA (PD_NPA) and healthy controls during lying and standing. Extensor activity in PD_PA patients increased only in the antigravity position compared with PD_NPA patients. Spearman's correlation showed that RMS amplitude of SCM in the lying position was associated with index for PA and forward flexion angles including F3-F8, whereas RMS amplitude of the external oblique muscle in the lying position was correlated with F5 alone. Longitudinal analysis showed that changes in F3, F4, and index for PA were significantly correlated with changes in RMS amplitude of the SCM in the lying position. Additionally, PD_NPA patients with SCM overactivity had a significantly higher risk of progressing to PA than those with normal SCM activity.</p><p><strong>Interpretation: </strong>The SCM and external oblique muscle are involved in forward trunk flexion in PD patients, while extensors may play a compensatory role. SCM may be the key muscle in PA for PD patients, participating in the pathogenesis of PA. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641318","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":"Sex Differences in Associations of Lewy Body Disease with Alzheimer's Disease and Cognitive Decline.","authors":"Madeline Wood Alexander, D Luke Fischer, Lawren VandeVrede, Emma Nichols, Lei Yu, James R Pike, Walter Swardfager, Che-Yuan Wu, Mario Masellis, Liisa A M Galea, Katherine Zukotynski, Gillian Einstein, Sandra E Black, Lisa L Barnes, Julie A Schneider, Zoe Arvanitakis, Kaitlin B Casaletto, Jennifer S Rabin","doi":"10.1002/ana.27308","DOIUrl":"https://doi.org/10.1002/ana.27308","url":null,"abstract":"<p><strong>Objective: </strong>To investigate how sex and age at menopause influence the interplay between Alzheimer's disease (AD) and Lewy body disease (LBD) neuropathologies, and their associations with cognitive decline.</p><p><strong>Methods: </strong>We analyzed data from: (1) three Rush Alzheimer's Disease Center cohorts (i.e., the Religious Orders Study, Rush Memory and Aging Project, and Minority Aging Research Study), and (2) the National Alzheimer's Coordinating Center Neuropathology Data Set. Neuropathological evaluation assessed LBD (neocortical/limbic-type vs none) and AD, including neuritic plaques (β-amyloid plaques surrounded by dystrophic neurites) and neurofibrillary tangles. In each dataset, we tested interactive associations between LBD and sex on neuritic plaques, neurofibrillary tangles, and cognitive decline. Additionally, in the Rush dataset, we tested whether age at spontaneous menopause modified the associations of LBD with neuritic plaques, neurofibrillary tangles, and cognitive decline in women.</p><p><strong>Results: </strong>In the Rush dataset, we included 1,277 women and 579 men. In the National Alzheimer's Coordinating Center dataset, we included 3,283 women and 3,563 men. Across both datasets, men were more likely to have LBD, whereas women showed greater neuritic plaque and neurofibrillary tangle burdens. Sex modified the associations of LBD with neurofibrillary tangles (but not neuritic plaques), whereby LBD was more strongly associated with greater neurofibrillary tangle burden in women than men. Men showed faster LBD-related cognitive decline, whereas women showed faster neurofibrillary tangle-related decline, after adjusting for copathologies (neuritic plaques, neurofibrillary tangles, and LBD, as appropriate). In women, earlier age at menopause exacerbated the associations of LBD with neurofibrillary tangle burden and episodic memory decline.</p><p><strong>Interpretation: </strong>Sex may influence AD and LBD neuropathologies, highlighting the need for precision approaches to dementia prevention and intervention. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615592","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":"Mapping Postictal Aphasia through Signal Complexity: A Stereo-Electroencephalography Study.","authors":"Ionuț-Flavius Bratu, Christian G Bénar, Samuel Medina Villalon, Lison Ciavatti, Fantine Mazel, Fabrice Bartolomei, Agnès Trébuchon","doi":"10.1002/ana.27307","DOIUrl":"https://doi.org/10.1002/ana.27307","url":null,"abstract":"<p><strong>Objective: </strong>The postictal period provides an opportunity to investigate the pathophysiology underlying aphasia and recovery following epileptic seizures. This study examines postictal aphasia in stereo-electroencephalography (SEEG)-explored patients to identify brain regions associated with task-specific language deficits using signal complexity analysis.</p><p><strong>Methods: </strong>We evaluated video-SEEG-recorded focal seizures with and without postictal aphasia in patients with SEEG-confirmed hemispheric language dominance. SEEG traces were analyzed using permutation entropy (PE), with the postictal period quantified by a PE-based metric, the Postictal Alteration Time (PAT). Brain region PAT was correlated with language function recovery (eg, repetition). Electro-clinical recuperation was also assessed within the dorsal-ventral language stream framework. Additionally, a bedside testing battery was developed to evaluate postictal aphasia severity and task-specific deficits.</p><p><strong>Results: </strong>A total of 322 seizures from 98 patients were analyzed. Seizures with postictal aphasia had longer PAT than those without. Task-specific language recovery correlated with regional PAT (eg, naming - middle temporal gyrus). Moreover, the dorsal stream recovered faster than the ventral stream. Additionally, the Postictal Aphasia Scale (PAS) was developed, evaluating naming, reading, repetition, and comprehension (verbal and written) and automatic speech. Higher PAS scores (indicating milder deficits) correlated with faster regional complexity recovery. At 5 and 10 minutes postictally, PAS revealed a global aphasia pattern, with comprehension deficits gradually resolving. By 15 minutes, aphasia was primarily production-related, particularly affecting naming.</p><p><strong>Interpretation: </strong>This study provides new insights into the pathophysiology of postictal aphasia and introduces PAS as a tool for assessing postictal aphasia severity and domain-specific deficits, aiding surgical planning and rehabilitation. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615591","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":"Cognitive Performance in Early Neuronal Synuclein Disease with Hyposmia but without Motor Disability: Association with Dopamine Deficiency and Isolated Rapid Eye Movement Sleep Behavior Disorder.","authors":"Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic","doi":"10.1002/ana.27263","DOIUrl":"10.1002/ana.27263","url":null,"abstract":"<p><strong>Objective: </strong>To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.</p><p><strong>Methods: </strong>Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).</p><p><strong>Results: </strong>Participants were stage 2A (n = 101), stage 2B (N = 227), and HCs (n = 158). Although stage 2 had intact Montreal Cognitive Assessment scores (mean [SD] = 27.0 [2.3]), stage 2A had a numerically worse CSS (z-score mean difference = 0.05, p = NS; effect size = 0.09) and stage 2B a statistically worse CSS (z-score mean difference = 0.23, p < 0.05; effect size = 0.40) compared with HCs. In stage 2A, hyposmia alone was associated with normal cognition, but those with comorbid iRBD had significantly worse cognition (z-score mean difference = 0.33, p < 0.05, effect size =0.50). In stage 2B, hyposmia alone had abnormal cognition (z-score mean difference = 0.18, p = 0.0078, effect size = 0.29), and superimposed iRBD had a statistically significant additive effect.</p><p><strong>Interpretation: </strong>Using a novel CSS, we demonstrated that hyposmia is associated with cognitive deficits in prodromal NSD without motor disability, particularly when comorbid dopamine system impairment or comorbid iRBD is present. Therefore, it is critical to include and assess cognition at all stages when studying synuclein disease, even in the absence of motor disability. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606932","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":"Chronic Striatal Cholinergic Interneuron Excitation Causes Cerebral Palsy-Related Dystonic Behavior in Mice.","authors":"Kat Gemperli, Xinguo Lu, Keerthana Chintalapati, Alyssa Rust, Rishabh Bajpai, Nathan Suh, Joanna Blackburn, Rose Gelineau-Morel, Michael C Kruer, Dararat Mingbunjerdsuk, Jennifer O'Malley, Laura Tochen, Jeff L Waugh, Steve Wu, Timothy Feyma, Joel Perlmutter, Steven Mennerick, Jordan G McCall, Bhooma R Aravamuthan","doi":"10.1002/ana.27299","DOIUrl":"10.1002/ana.27299","url":null,"abstract":"<p><strong>Objective: </strong>Mouse models of genetic dystonias have demonstrated abnormal striatal cholinergic interneuron excitability, but do not consistently demonstrate subjective dystonic features. To determine whether striatal cholinergic interneuron excitation can cause potentially dystonic motor behaviors, we first determined features correlated specifically with dystonia severity in people and then determined whether these features emerged in mice following striatal cholinergic interneuron excitation.</p><p><strong>Methods: </strong>Eight movement disorders experts rated dystonia severity in 193 videos of people with cerebral palsy doing a seated task. Leg adduction variability metrics, which are known to correlate with leg dystonia severity during gait, were quantified in these videos of seated tasks. Metrics significantly associated with leg dystonia severity during seated tasks in people were then quantified in mice and compared between mice who underwent chemogenetic striatal cholinergic interneuron excitation (n = 17) and mice who did not (n = 17).</p><p><strong>Results: </strong>Leg adduction variability correlated well with experts' leg dystonia severity scores in people. Leg adduction variability was also significantly increased in mice that underwent striatal cholinergic interneuron excitation compared to mice that did not (p < 0.05). This difference was not present with acute excitation and emerged only after 14 days of ongoing excitation.</p><p><strong>Interpretation: </strong>We demonstrate that leg adduction variability correlates with leg dystonia severity in people with cerebral palsy and that chronic, but not acute, striatal cholinergic interneuron excitation can cause leg adduction variability in mice. These results support targeting striatal cholinergic interneurons for dystonia drug development and demonstrate the potential value of using quantifiable leg adduction metrics to study dystonia pathophysiology. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551498","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 Spectrum of Neurologic Phenotypes Associated With NUS1 Pathogenic Variants: A Comprehensive Case Series.","authors":"Sarah M Brooker, Maria Novelli, Robert Coukos, Neha Prakash, Walaa A Kamel, Marta Amengual-Gual, Mathieu Anheim, Giulia Barcia, Tanya Bardakjian, Franciska Baur, Steffen Berweck, Bigna K Bölsterli, Melanie Brugger, Thomas Cassini, Nicolas Chatron, Brian Corner, Hormos Salimi Dafsari, Jean-Madeleine de Sainte Agathe, Colin A Ellis, Kimberly M Ezell, Cendrine Foucard, Steven J Frucht, Maria C Garcia, Deepak Gill, Anne Guimier, Rizwan Hamid, Damià Heine-Suñer, Peter Herkenrath, Marie Hully, Ioannis U Isaias, Louis Januel, Chloe Laurencin, Taylor Laut, Alinoe Lavillaureix, Gaetan Lesca, Marion Lesieur-Sebellin, Luca Magistrelli, Cecilia Marelli, Heather C Mefford, Bryce A Mendelsohn, Saadet Mercimek-Andrews, Claire Miller, Shekeeb S Mohammad, Francesca Morgante, Sirisha Nandipati, Thomas Opladen, Mahesh Padmanaban, Micaela Pauni, Gianni Pezzoli, Amelie Piton, Francis Ramond, Giulietta M Riboldi, Christelle Rougeot-Jung, Fernando Santos-Simarro, Ingrid E Scheffer, Naoual Serari, Christine M Stahl, Ann Stembridge Kung, Susana Tarongí Sanchez, Christel Thauvin-Robinet, Marianne Till, Christine Tranchant, Christopher Troedson, Thomas F Tropea, Olivier Vanakker, Patricia Vega, Maxi Leona Wiese, Udo Wieshmann, Laura J Williams, Thomas Wirth, Michael Zech, Hans Zempel, Emmanuel Roze, Vincenzo Leuzzi, Serena Galosi, Victor S C Fung, Gemma Carvill, Dimitri Krainc, Elizabeth Gerard, Niccolò E Mencacci","doi":"10.1002/ana.27272","DOIUrl":"10.1002/ana.27272","url":null,"abstract":"<p><strong>Objective: </strong>A growing body of evidence indicates a strong genetic overlap between developmental and epileptic encephalopathies (DEEs) and movement disorders. De novo loss-of-function variants in NUS1 have been recently identified in DEE cases. Herein, we report a large cohort of cases with pathogenic NUS1 variants and describe their clinical presentation and the details of the associated epilepsy and movement disorders.</p><p><strong>Methods: </strong>Cases with NUS1-related disorders were identified through a multicentric international collaboration made possible by the GeneMatcher platform. Clinical data were acquired through retrospective case-note review.</p><p><strong>Results: </strong>We identified 41 subjects carrying 38 different pathogenic or likely pathogenic heterozygous NUS1 variants. The majority of cases displayed developmental delays and intellectual disability of variable severity. Epilepsy was present in 68.3% of cases (28/41) with onset typically in early childhood. Strikingly, 87.8% of cases (36/41) presented with movement disorders and for 13 of these cases the movement disorder was not accompanied by epilepsy. The phenomenology of the movement disorders was complex with myoclonus observed in 68.3% of cases (28/41), either in isolation or in combination with dystonia, ataxia, and/or parkinsonism. Seven cases that otherwise did not have prominent movement disorders had mild incoordination and intention tremor, suggestive of cerebellar dysfunction. There was no observed genotype-phenotype correlation, suggesting that other genetic or acquired factors impact the clinical presentation.</p><p><strong>Interpretation: </strong>Heterozygous NUS1 pathogenic variants cause a complex neurological disorder, variably featuring developmental and epileptic encephalopathies and a broad spectrum of movement disorders, which represent the major source of neurological disability for most cases. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537544","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":"Toward Natural Limb Function: A New Era in Prosthetic Innovation.","authors":"Yucheng Tian, Dylan M Wallace, Paul S Cederna, Cynthia A Chestek, Stephen W P Kemp","doi":"10.1002/ana.27287","DOIUrl":"https://doi.org/10.1002/ana.27287","url":null,"abstract":"<p><p>The past decade has witnessed groundbreaking clinical implementation of neuroprosthetic limbs driven by signals from peripheral targets (eg, nerves and muscle) and the brain to restore limb function for individuals with limb loss or impairment. In this review, we highlight recent key clinical trials in peripheral neuroprosthetic interfaces directly with nerve, residual muscle, and reinnervated muscle. We then highlight the key advances in brain interfaces, including clinical trials using electroencephalography, electrocorticography, and intracortical electrodes to control neuroprosthetics. Finally, we explore the future of neuroprosthetic control where both peripheral and brain interfaces can be combined to improve neuroprosthetic performance. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525672","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":"Clonal Hematopoiesis of Indeterminate Potential Associated with Covert Cerebral Changes.","authors":"Yijuan Li, Dingding Zhang, Fei Han, Lixin Zhou, Jun Ni, Ming Yao, Zhengyu Jin, Shuyang Zhang, Liying Cui, Xinzhuang Yang, Yi-Cheng Zhu","doi":"10.1002/ana.27304","DOIUrl":"https://doi.org/10.1002/ana.27304","url":null,"abstract":"<p><strong>Objective: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardio-cerebrovascular diseases. This study aimed to investigate CHIP's association with cerebrovascular or glymphatic changes in a community-based population.</p><p><strong>Methods: </strong>This study examined Chinese community cohort participants. CHIP mutations were identified through whole-exome sequencing. Intracranial arterial stenosis, silent brain infarcts, cerebral small vessel disease markers, and diffusion along the perivascular space index were identified by magnetic resonance imaging. The correlation between CHIP and neuroimaging outcomes was investigated through univariate and multivariate logistic/linear regression. The multivariate regression model was adjusted for cerebrovascular disease risk factors, including age, sex, body mass index, smoking status, hypertension, diabetes, and hyperlipidemia.</p><p><strong>Results: </strong>In total, 18.2% (224 out of 1,229) participants were identified as carriers of CHIP mutations. The prevalence of CHIP generally increases with age (p = 0.009). After adjusting for vascular risk factors using multivariate regression, CHIP mutations were found to be significantly associated with increased odds of large magnetic resonance imaging-defined infarcts (>15 mm; OR 3.20; 95% CI 1.18 to 8.43; p = 0.018), inversely associated with diffusion along the perivascular space (β = -0.02; 95% CI -0.04 to 0; p = 0.034), and showed a borderline association with intracranial arterial stenosis (OR 1.52; 95% CI 0.99 to 2.30; p = 0.053). Notably, no statistically significant correlations were observed between CHIP and cerebral small vessel disease markers or brain atrophy measures.</p><p><strong>Interpretation: </strong>CHIP was significantly associated with glymphatic dysfunction and large infarcts, and marginally associated with intracranial arterial stenosis. Further research is needed to elucidate the pathophysiology linking CHIP to cerebral covert changes. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504315","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}