Annals of Neurology最新文献

{"title":"Validating the Accuracy of Parkinson's Disease Clinical Diagnosis: A UK Brain Bank Case-Control Study.","authors":"Lazzaro di Biase, Pasquale Maria Pecoraro, Vincenzo Di Lazzaro","doi":"10.1002/ana.27190","DOIUrl":"https://doi.org/10.1002/ana.27190","url":null,"abstract":"<p><strong>Objective: </strong>Despite diagnostic criteria refinements, Parkinson's disease (PD) clinical diagnosis still suffers from a not satisfying accuracy, with the post-mortem examination as the gold standard for diagnosis. Seminal clinicopathological series highlighted that a relevant number of patients alive-diagnosed with idiopathic PD have an alternative post-mortem diagnosis. We evaluated the diagnostic accuracy of PD comparing the in-vivo clinical diagnosis with the post-mortem diagnosis performed through the pathological examination in 2 groups.</p><p><strong>Methods: </strong>In this retrospective case-control study, patients and healthy subjects who consented to the post-mortem pathological diagnosis at the UK Brain Bank were consecutively enrolled from the UK Brain Bank. Medical records were reviewed to classify participants and performance metrics were further calculated using neuropathological diagnosis as the gold standard.</p><p><strong>Results: </strong>Four thousand five hundred seventy one subjects were eligible for the study. The clinical diagnosis group was: 1,048 Parkinson's patients and 1,242 healthy subjects. Pathology diagnosis group were: 996 Parkinson's patients and 1,288 subjects with no post-mortem abnormality. For the group of clinical diagnosis, PD diagnosis showed: sensitivity of 99%, specificity of 86%, accuracy of 90.96%, F1-Score 0.89, and a receiver operating characteristics area under the curve (ROC AUC) 0.925 (SE ± 0.006) [95% confidence interval [CI]: 0.913, 0.937], 𝑝<0.001. In this group, the most frequent pathology diagnosis among clinically misdiagnosed PD (false positive) patients was dementia with Lewy bodies (19.4%). Conversely, the most frequent clinical diagnosis among PD missed clinical diagnosis (false negative) patients was Alzheimer's disease (18.5%).</p><p><strong>Interpretation: </strong>Our findings confirm a still significant diagnostic error and emphasize the need for more fine and homogeneous criteria to classify idiopathic Parkinson's patients correctly. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051112","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":"In Memoriam - Charles Warren Olanow, MD.","authors":"Karl Kieburtz, Barbara G Vickrey","doi":"10.1002/ana.27187","DOIUrl":"https://doi.org/10.1002/ana.27187","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031609","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":"Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.","authors":"Sandra Coppens, Nicolas Deconinck, Patricia Sullivan, Andrei Smolnikov, Joshua S Clayton, Kaitlyn R Griffin, Kristi J Jones, Catheline N Vilain, Hazim Kadhim, Samantha J Bryen, Fathimath Faiz, Leigh B Waddell, Frances J Evesson, Madhura Bakshi, Jason R Pinner, Amanda Charlton, Susan Brammah, Nicole S Graf, Michael Krivanek, Chee Geap Tay, Nicola C Foulds, Marjorie A Illingworth, Neil H Thomas, Sian Ellard, Ingrid Mazanti, Soo-Mi Park, Courtney E French, Jennifer Brewster, Gusztav Belteki, Shazia Hoodbhoy, Kieren Allinson, Deepa Krishnakumar, Gareth Baynam, Bradley M Wood, Michelle Ward, Kayal Vijayakumar, Amber Syed, Archana Murugan, Anirban Majumdar, Ingrid J Scurr, Miranda P Splitt, Corina Moldovan, Deepthi C de Silva, Kumudu Senanayake, Thatjana Gardeitchik, Yvonne Arens, Sandra T Cooper, Nigel G Laing, F Lucy Raymond, Heinz Jungbluth, Erik-Jan Kamsteeg, Adnan Manzur, Susan M Corley, Gianina Ravenscroft, Marc R Wilkins, Mark J Cowley, Mark Pinese, Rahul Phadke, Mark R Davis, Francesco Muntoni, Emily C Oates","doi":"10.1002/ana.27087","DOIUrl":"https://doi.org/10.1002/ana.27087","url":null,"abstract":"<p><p>Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.</p><p><strong>Objective: </strong>To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.</p><p><strong>Methods: </strong>We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.</p><p><strong>Results: </strong>Prenatal features included hypokinesia or akinesia and growth restriction. Six pregnancies were terminated. Nine infants were born at or near term with severe-to-profound weakness and required resuscitation. Seven died following withdrawal of life support. Two surviving children require ongoing respiratory support. Most cohort members had at least 1 disease-causing variant predicted to result in some near-normal-length titin expression. The exceptions, from 2 unrelated families, had homozygous truncating variants predicted to induce complete nonsense mediated decay. However, subsequent analyses suggested that the causative variant in each family had an additional previously unrecognized impact on splicing likely to result in some near-normal-length titin expression. This impact was confirmed by minigene assay for 1 variant.</p><p><strong>Interpretation: </strong>This study confirms the clinical variability of congenital titinopathy. Severely affected individuals succumb prenatally/during infancy, whereas others survive into adulthood. It is likely that this variability is because of differences in the amount and/or length of expressed titin. If confirmed, analysis of titin expression could facilitate clinical prediction and increasing expression might be an effective treatment strategy. Our findings also further-support the hypothesis that some near-normal-length titin expression is essential to early prenatal survival. Sometimes expression of normal/near-normal-length titin is due to disease-causing variants having an additional impact on splicing. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031606","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":"RETRACTION: Transcriptional Regulation of βsecretase-1 by 12/15-Lipoxygenase Results in Enhanced Amyloidogenesis and Cognitive Impairments.","authors":"","doi":"10.1002/ana.27184","DOIUrl":"https://doi.org/10.1002/ana.27184","url":null,"abstract":"<p><strong>Retraction: </strong>J. Chu , J.-M. Zhuo and D. Praticò , \"Transcriptional Regulation of βsecretase-1 by 12/15-Lipoxygenase Results in Enhanced Amyloidogenesis and Cognitive Impairments,\" Annals of Neurology 71, no. 1 (2012): 57-67, https://doi.org/10.1002/ana.22625. The above article, published online on 12 September 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, J.-M. Zhuo and D. Praticò; the journal Editor-in-Chief, Kenneth L. Tyler; the American Neurological Association and Wiley Periodicals LLC. The retraction has been agreed upon due to the duplication of the actin blots and one of the APP blots shown in figures 2A and 4A. The authors were unable to provide the original data. The editors and the authors, J.-M. Zhuo and D. Praticò, have lost confidence in the data presented and consider the conclusions to be substantially compromised. The author, J. Chu, could not be contacted to inform them of the retraction.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996766","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":"Adult Neurogenesis in the Subventricular Zone of Patients with Huntington's and Parkinson's Diseases and following Long-Term Treatment with Deep Brain Stimulation.","authors":"Marta Snapyan, Francis Desmeules, Jonathan Munro, Morgan Bérard, Stephan Saikali, Peter V Gould, Maxime Richer, Emmanuelle Pourcher, Mélanie Langlois, Anne-Marie Dufresne, Michel Prud'homme, Léo Cantin, André Parent, Armen Saghatelyan, Martin Parent","doi":"10.1002/ana.27181","DOIUrl":"https://doi.org/10.1002/ana.27181","url":null,"abstract":"<p><strong>Objective: </strong>Parkinson's and Huntington's diseases are characterized by progressive neuronal loss. Previous studies using human postmortem tissues have shown the impact of neurodegenerative disorders on adult neurogenesis. The extent to which adult neural stem cells are activated in the subventricular zone and whether therapeutic treatments such as deep brain stimulation promote adult neurogenesis remains unclear. The goal of the present study is to assess adult neural stem cells activation and neurogenesis in the subventricular zone of patients with Huntington's and Parkinson's diseases who were treated or not by deep brain stimulation.</p><p><strong>Methods: </strong>Postmortem brain samples from Huntington's and Parkinson's disease patients who had received or not long-term deep brain stimulation of the subthalamic nucleus were used.</p><p><strong>Results: </strong>Our results indicate a significant increase in the thickness of the subventricular zone and in the density of proliferating cells and activated stem cells in the brain of Huntington's disease subjects and Parkinson's disease patients treated with deep brain stimulation. We also observed an increase in the density of immature neurons in the brain of these patients.</p><p><strong>Interpretation: </strong>Overall, our data indicate that long-term deep brain stimulation of the subthalamic nucleus promotes cell proliferation and neurogenesis in the subventricular zone that are reduced in Parkinson's disease. Taken together, our results also provide a detailed characterization of the cellular composition of the adult human subventricular zone and caudate nucleus in normal condition and in Parkinson's and Huntington's diseases and demonstrate the plasticity of these regions in response to neurodegeneration. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996754","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":"Synaptic Density Reductions in MSA: A Potential Biomarker Identified Through [¹⁸F]SynVesT-1 PET Imaging.","authors":"Jian Li, Daji Chen, Yongxiang Tang, Zhao Chen, Ming Zhou, Linlin Wan, Ling Xiao, You Fu, Zhiyou He, Zhichao Tang, Zhengqun Hu, Xinrong Yuan, Jinhui Yang, Sudan Zhu, Xuan Guo, Riwei Ouyang, Rong Qiu, Beisha Tang, Jifeng Guo, Hong Jiang, Shuo Hu","doi":"10.1002/ana.27179","DOIUrl":"https://doi.org/10.1002/ana.27179","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to delineate synaptic density alterations in multiple system atrophy (MSA) and explore its potential role as a biomarker for MSA diagnosis and disease severity monitoring using [¹⁸F]SynVesT-1 positron emission tomography / computed tomography (PET CT).</p><p><strong>Methods: </strong>In this prospective study, 60 patients with MSA (30 patients with MSA-parkinsonian [MSA-P] subtype and 30 patients with MSA-cerebellar [MSA-C] subtype), 30 patients with Parkinson's disease (PD), and 30 age-matched healthy controls (HCs) underwent [¹⁸F]SynVesT-1 PET/CT for synaptic density assessment. Visual, voxel, and volumetric region of interest (VOI) analyses were used to elucidate synaptic density patterns in the MSA brain and establish diagnostic criteria. The diagnostic performances of both visual and VOI-based diagnostics were evaluated using receiver operating characteristic (ROC) analysis. Spearman correlation analyses were conducted to investigate the relationship between brain synaptic density and disease severity RESULTS: Patients with MSA displayed extensive reductions in synaptic density throughout the brain, notably affecting both primary VOIs (the cerebellum and putamen) and secondary VOIs including the medulla oblongata, ventral tegmental area, and pons. Notably, patients with MSA-C exhibited a remarkable decrease in cerebellar synaptic density, whereas patients with MSA-P demonstrated significant synaptic loss within the posterior putamen. Compared with patients with PD, the patients with MSA show a more pronounced reduction in synaptic density in infratentorial brain regions. VOI-based diagnosis significantly outperformed visual analysis in diagnosing and differentiating MSA and its subtypes. Synaptic density in primary and multiple secondary VOIs correlated significantly with motor scales in patients with MSA.</p><p><strong>Interpretation: </strong>Our study identified widespread synaptic density reductions in MSA, particularly in the basal ganglia and infratentorial region, suggesting [¹⁸F]SynVesT-1 PET as a potential biomarker for diagnosing and evaluating the disease, and guiding synaptic restoration trials. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996772","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":"Quantitative Pupillometry Predicts Neurologic Deterioration in Patients with Large Middle Cerebral Artery Stroke.","authors":"Yili Du, Jack E Pohlmann, Stefanos Chatzidakis, Benjamin Brush, Leigh Ann Malinger, Rebecca A Stafford, Anna M Cervantes-Arslanian, Emelia J Benjamin, Emily J Gilmore, Josée Dupuis, David M Greer, Stelios M Smirnakis, Shariq Mohammed, Charlene J Ong","doi":"10.1002/ana.27178","DOIUrl":"https://doi.org/10.1002/ana.27178","url":null,"abstract":"<p><strong>Objective: </strong>This study assesses whether longitudinal quantitative pupillometry predicts neurological deterioration after large middle cerebral artery (MCA) stroke and determines how early changes are detectable.</p><p><strong>Methods: </strong>This prospective, single-center observational cohort study included patients with large MCA stroke admitted to Boston Medical Center's intensive care unit (2019-2024). Associations between time-to-neurologic deterioration and quantitative pupillometry, including Neurological Pupil Index (NPi), were assessed using Cox proportional hazards models with time-dependent covariates adjusted for age, sex, and Alberta Stroke Program Early CT Score. Models using dilation velocity were compared with partial likelihood ratio tests. Pupillometric changes over 2-h intervals in the 12 h preceding deterioration were analyzed with linear mixed-effects modeling and Tukey's test. Matched referents (age, sex, stroke side, follow-up duration) were used for comparison. Optimal thresholds were identified using the Youden Index.</p><p><strong>Results: </strong>Among 71 patients (mean age 66.5 years; 59.2% women), 32 (45.1%) experienced deterioration. A 1-unit decrease in NPi was associated with a higher hazard of deterioration (hazard ratio 2.46; 95% confidence interval 1.68-3.61). Dilation velocity improved model performance compared to NPi alone. NPi was significantly lower at 0-2 h (3.81 vs. 4.38, p = 0.001) and 2-4 h (3.71 vs. 4.38, p < 0.001) before deterioration compared to 10-12 h prior. Optimal thresholds were 4.01 for NPi, 0.49 mm/s for dilation velocity, and -0.15 change in NPi over 12 h.</p><p><strong>Interpretation: </strong>Quantitative pupillometry predicts neurological deterioration in MCA stroke, with declines detectable up to 12 h prior. Dilation velocity shows promise as a novel biomarker. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996763","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":"Immunotherapy-Resistant Neuropathic Pain and Fatigue Predict Quality-of-Life in Contactin-Associated Protein-Like 2 Antibody Disease.","authors":"Bryan Ceronie, Christine Strippel, Christopher Uy, Sofija Paneva, Mateusz Makuch, Babak Soleimani, Sanchit Turaga, Sophie Binks, Sudarshini Ramanathan, Sophia Michael, James Varley, Ava Easton, Andreas Themistocleous, John Dawes, David L Bennett, Anushka Irani, Adam E Handel, Sarosh R Irani","doi":"10.1002/ana.27177","DOIUrl":"https://doi.org/10.1002/ana.27177","url":null,"abstract":"<p><p>The long-term clinical outcomes and associated prognostic factors in contactin-associated protein-like 2 (CASPR2)-antibody diseases are unknown. A total of 75 participants with CASPR2 antibodies were longitudinally assessed for disability, quality-of-life, and chronic pain. Although most symptoms improved within 6 months of treatment, neuropathic pain and fatigue were the most immunotherapy refractory, and persisted for up to 6 years. Furthermore, these two factors-but not CASPR2 antibody levels or subclasses-independently predicted worse disability and quality-of-life at 24 months. Quality-of-life varied widely for any given modified Rankin Scale score, indicating a divergence between patient and clinician assessed outcomes. Further work should study the relative importance of these measures, and the immunopathogenesis underlying intractable symptoms. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996761","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":"Subventricular Zone Microstructure in Pediatric-Onset Multiple Sclerosis.","authors":"Monica Margoni, Loredana Storelli, Elisabetta Pagani, Paolo Preziosa, Damiano Mistri, Mor Gueye, Martina Rubin, Lucia Moiola, Massimo Filippi, Maria Assunta Rocca","doi":"10.1002/ana.27180","DOIUrl":"https://doi.org/10.1002/ana.27180","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to explore the microstructural dynamics of the subventricular zone (SVZ) with aging and their associations with clinical disability and brain structural damage in pediatric-onset multiple sclerosis (MS) patients.</p><p><strong>Methods: </strong>One-hundred and forty-one pediatric-onset MS patients (67 pediatric and 74 adults with pediatric-onset) and 233 healthy controls (HC) underwent neurological and 3.0 T MRI assessment. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted from the SVZ and the thalamus (as control region).</p><p><strong>Results: </strong>In HC, SVZ FA was higher until age 40 then declined, whereas MD was lower until age 35 before rising (false discovery rate p value [pFDR] ≤ 0.008). Thalamic FA was higher until age 30 and then declined, whereas MD was higher until age 50 (pFDR ≤ 0.007). Pediatric MS patients showed significantly higher SVZ FA than pediatric HC (pFDR < 0.001), while adult patients showed no differences compared to adult HC (pFDR ≤ 0.724). Adult patients had lower thalamic FA and higher MD (pFDR < 0.001). Adults had lower SVZ FA and MD, but higher thalamic MD compared to pediatric patients (pFDR < 0.001). In pediatric MS, higher SVZ FA and MD were associated with higher white matter (WM) lesion volume (LV) and choroid plexus volume and lower brain and thalamic volumes (pFDR ≤ 0.047). In adult patients, higher SVZ MD associated with higher WM LV, lower brain volumes, and lower z-SDMT (pFDR≤0.019). Thalamic microstructural abnormalities were associated with more severe disability and brain damage in both groups (pFDR ≤ 0.018).</p><p><strong>Interpretation: </strong>Our findings suggest that microstructural changes in the SVZ occur early in pediatric MS and are associated with brain structural damage but not with clinical impairment. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996769","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":"Clinical Relevance of 'Cap' and 'Track' Development after Recent Small Subcortical Infarct.","authors":"Yajun Cheng, Carmen Arteaga-Reyes, Una Clancy, Daniela Jaime Garcia, Maria Del C Valdés Hernández, Michael J Thrippleton, Michael S Stringer, Gordon W Blair, Stewart Wiseman, Francesca M Chappell, Junfang Zhang, Xiaodi Liu, Angela C C Jochems, Susana Muñoz Maniega, Eleni Sakka, Mark E Bastin, Rosalind Brown, Caroline M J Loos, Stephen D J Makin, Ming Liu, Bo Wu, Fergus N Doubal, Joanna M Wardlaw","doi":"10.1002/ana.27182","DOIUrl":"https://doi.org/10.1002/ana.27182","url":null,"abstract":"<p><strong>Objective: </strong>After a recent small subcortical infarct (RSSI), some patients develop perilesional or remote hyperintensities ('caps/tracks') to the index infarct on T2/FLAIR MRI. However, their clinical relevance remains unclear. We investigated the clinicoradiological correlates of 'caps/tracks', and their impact on long-term outcomes following RSSI.</p><p><strong>Methods: </strong>We identified participants with lacunar stroke and MRI-confirmed RSSI from 3 prospective studies. At baseline, we collected risk factors, RSSI characteristics, small vessel disease (SVD) features, and microstructural integrity on diffusion imaging. Over 1-year, we repeated MRI and recorded 'caps/tracks' blinded to other data. We evaluated predictors of 'caps/tracks', and their association with 1-year functional (modified Rankin Scale score ≥2), mobility (Timed Up-and-Go), cognitive outcomes (Montreal Cognitive Assessment [MoCA] score <26), and recurrent cerebrovascular events (stroke/transient ischemic attack/incident infarct) using multivariable regression.</p><p><strong>Results: </strong>Among 185 participants, 93 (50.3%) developed 'caps/tracks' first detected at median 198 days after stroke. 'Caps/tracks' were independently predicted by baseline factors: larger RSSI, RSSI located in white matter, higher SVD score, and higher mean diffusivity in normal-appearing white matter (odds ratio [OR] [95% confidence interval {CI}], 1.15 [1.07-1.25], 6.01 [2.80-13.57], 1.77 [1.31-2.44], 1.42 [1.01-2.03]). At 1 year, 'cap/track' formation was associated with worse functional outcome (OR: 3.17, 95% CI: 1.28-8.22), slower gait speed (β: 0.13, 95% CI: 0.01-0.25), and recurrent cerebrovascular events (hazard ratio [HR]: 2.05, 95% CI: 1.05-4.02), but not with cognitive impairment.</p><p><strong>Interpretation: </strong>'Caps/tracks' after RSSI are associated with worse clinical outcomes, and may reflect vulnerability to progressive SVD-related injury. Reducing 'caps/tracks' may offer early efficacy markers in trials aiming to improve outcome after lacunar stroke. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996755","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}