Annals of Neurology最新文献

{"title":"Primary Lateral Sclerosis Natural History Study: Primary Lateral Sclerosis Functional Rating Scale and Other Outcomes Assessment.","authors":"Ikjae Lee, Grace Jang, Ying Kuen Ken Cheung, Alexander V Sherman, Wendy S Johnston, Frank Diaz, J Americo M Fernandes, Ali A Habib, Nicholas J Maragakis, Sabrina Paganoni, Katherine Burke, Bjorn Oskarsson, Jaimin Shah, Lorne Zinman, Mary Kay Floeter, Senda Ajroud-Driss, Kelly Gwathmey, Terry Heiman-Patterson, Omar Jawdat, Edward J Kasarskis, Yaz Y Kisanuki, James Wymer, Christina Fournier, Ghazala Hayat, Daragh Heitzman, Catherine Lomen-Hoerth, Michael T Pulley, Stephen N Scelsa, David Walk, Stephen A Goutman, Christen Shoesmith, Zachary Simmons, Eric Sorenson, Lauren Elman, Matthew B Harms, Benjamin N Hoover, Rebecca Y Yun, Regina M Santella, Hiroshi Mitsumoto","doi":"10.1002/ana.78056","DOIUrl":"https://doi.org/10.1002/ana.78056","url":null,"abstract":"<p><strong>Objective: </strong>The primary lateral sclerosis (PLS) consensus diagnostic criteria and functional rating scale (PLSFRS) were recently established to facilitate and optimize future PLS clinical trials. We examined the trajectory of the PLSFRS and other functional outcome measures and biomarkers in the PLS Natural History Study (PLS NHS) to understand their performance in this prospective cohort.</p><p><strong>Methods: </strong>The PLS NHS is a prospective, longitudinal, multicenter study of people living with PLS in different diagnostic categories: early (disease duration <2 years); probable (2-4 years); and definite PLS (4-15 years). PLSFRS scores and other functional outcome measures were collected at baseline, 3-, 6-, 9-, and 12-month follow-up visits. Baseline characteristics were compared between the groups. The slopes of the PLSFRS and other functional outcome measures over 12 months were examined in the overall cohort and subgroups using linear mixed-effect models. The associations between baseline characteristics and the rate of PLSFRS decline were analyzed with linear regression models.</p><p><strong>Results: </strong>A total of 76 participants were included: early (n = 6); probable (n = 26); and definite (n = 44) PLS. Baseline PLSFRS total scores were highest in the early PLS group, followed by the probable and definite PLS groups. In the overall cohort, the PLSFRS total score declined by 0.33 points/month (95% confidence interval [0.27-0.39], adjusted p < 0.05). The rate of decline was steepest in the early PLS group, followed by the probable and definite PLS groups. Baseline neurofilament light chain level was associated with the rate of PLSFRS decline over 1 year (p = 0.001).</p><p><strong>Interpretation: </strong>In PLS, the rate of functional decline, as measured by the PLSFRS total score, is faster during the early phase of the disease. Neurofilament light might serve as a prognostic biomarker in PLS. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184230","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":"Back Again to the Future: A New Era for Cerebroprotection.","authors":"Patrick Lyden","doi":"10.1002/ana.78041","DOIUrl":"https://doi.org/10.1002/ana.78041","url":null,"abstract":"<p><p>In multiple disease areas, neurology has failed to translate promising treatments from positive preclinical studies to successful clinical trial results. Despite this history, we persist in testing new, putative neuroprotectants using the same concepts, approaches, and methods without much modification. Recent novel data and new concepts offer an opportunity to break with past doctrine decisively, and open a new era of different approaches, methods, and strategies for studying future protections for brain injury. Cerebroprotection is a fresh framework for designing neurological therapy that targets glia and vascular cells, in addition to neurons. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147148","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":"Pro-Inflammatory c-Met⁺ CD4 T Cells in Multiple Sclerosis.","authors":"Gautier Breville, Mahdia Benkhoucha, Ayman Rezk, Ngoc Lan Tran, Isis Senoner, Amit Bar-Or, Patrice H Lalive","doi":"10.1002/ana.78035","DOIUrl":"https://doi.org/10.1002/ana.78035","url":null,"abstract":"<p><strong>Objective: </strong>Hepatocyte growth factor (HGF) binds exclusively the c-Met surface receptor, and the HGF/c-Met axis regulates T cell function in autoimmune diseases. We analyzed c-Met expression on human CD4 T cells in the blood and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) versus non-inflammatory neurological disease (NIND), to better understand the role of CD4 T cells in MS.</p><p><strong>Methods: </strong>We recruited 34 untreated MS patients (age 28-44 years) and 13 NIND (age 34-51 years) who underwent paired blood and CSF sampling at the time of diagnosis work-up. Phenotypic and functional CD4 T cells characterization was determined by flow cytometry and bulk RNA sequencing. Adhesion and transmigration capacities were studied to further characterize the function of c-Met⁺ CD4 T cells.</p><p><strong>Results: </strong>c-Met⁺ memory CD4 T cells were detected at higher levels in both blood (median of 1.98%) and CSF (5.88%) in MS compared to NIND (0.37% and 0.68%, respectively) (p < 0.0001). Ex vivo c-Met⁺ CD4 T cells exhibited higher levels of GM-CSF, interleukin (IL)-17, interferon (IFN)- <math> <semantics><mrow><mi>γ</mi></mrow> <annotation>$$ upgamma $$</annotation></semantics> </math> , and double positive IL-17⁺IFN- <math> <semantics><mrow><mi>γ</mi></mrow> <annotation>$$ gamma $$</annotation></semantics> </math> ⁺ expression, compared with c-Met^- CD4 T cells. c-Met⁺ CD4 T cells expressed increased levels of integrins-Itgα4β1 (VLA-4) and ItgαLβ2 (LFA-1)-compared with c-Met^- CD4 T cells. Anti-Itgα4 (natalizumab) and anti-ItgαLβ2 (odulimomab) inhibited CD4 T cell transmigration with predominant inhibition of CD4 T cells expressing c-Met.</p><p><strong>Interpretation: </strong>These results emphasize c-Met as an immune marker of highly pro-inflammatory and migratory CD4 T lymphocytes in both the periphery and central nervous system of MS patients. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147145","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":"Resilience to Endoplasmic Reticulum Stress Mitigates Membrane Hyperexcitability Underlying Late Disease Onset in a Murine Model of SCA6.","authors":"Haoran Huang, Taylor L Charron, Min Fu, Miranda Dunn, Deborah M Jones, Praveen Kumar, Satoshi Ishishita, Allan-Hermann Pool, Ashwinikumar Kulkarni, Genevieve Konopka, Vikram G Shakkottai","doi":"10.1002/ana.78042","DOIUrl":"10.1002/ana.78042","url":null,"abstract":"<p><strong>Objective: </strong>An enduring puzzle in many inherited neurological disorders is the late onset of symptoms despite expression of function-impairing mutant protein early in life. We examined the basis for onset of impairment in spinocerebellar ataxia type 6 (SCA6), a canonical late-onset neurodegenerative ataxia which results from a polyglutamine expansion in the voltage gated calcium channel, Cav2.1.</p><p><strong>Methods: </strong>We performed serial transcriptome analysis with weighted gene correlation network analysis to investigate mechanisms for resilience in SCA6 mice that prevent onset of symptoms. We examined changes in membrane excitability that result in cerebellar Purkinje neuron spiking abnormalities through patch-clamp recordings of Purkinje neurons in acute brain slices.</p><p><strong>Results: </strong>Using unbiased transcriptome analysis, we identified endoplasmic reticulum (ER) stress as a driver of disease. Using spatial transcriptome analysis, we identified Purkinje neuron specific changes in unfolded protein response (UPR) related pathways. Novel activation of a store-operated calcium current due to ER stress is the cause for Purkinje neuron spiking abnormalities in SCA6 mice. The impairments in Purkinje neuron spiking are unrelated to Cav2.1 ion-flux function. Redundant pathways of the UPR act through a HSP90-dependent mechanism to mitigate this ER stress.</p><p><strong>Interpretation: </strong>Our studies support a model whereby proteotoxicity from misfolded mutant Cav2.1 is mitigated by a HSP90-dependent UPR, and age-related breakdown of this response causes motor dysfunction and aberrant Purkinje neuron spiking. These studies elucidate a mechanism of resilience connecting aberrant proteostasis and calcium-dependent intrinsic membrane hyperexcitability to explain delayed disease onset more widely in age-dependent neurodegenerative disease. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129618","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":"Dual Antiplatelet Therapy After Ischemic Stroke Stratified by Intracranial or Extracranial Atherosclerotic Stenosis.","authors":"Yingying Yang, Jianbo Yang, Ying Gao, Weiqi Chen, Xuan Wang, Hongyi Yan, Tingting Wang, Yongjun Wang, Yuesong Pan, Yilong Wang","doi":"10.1002/ana.78049","DOIUrl":"https://doi.org/10.1002/ana.78049","url":null,"abstract":"<p><strong>Objective: </strong>This objective of this study was to assess the efficacy and safety of clopidogrel plus aspirin for acute mild stroke or high-risk transient ischemic attack (TIA) stratified by the status of symptomatic intracranial atherosclerotic stenosis (ICAS) or extracranial atherosclerotic stenosis (ECAS).</p><p><strong>Methods: </strong>The study was a subgroup analysis of a randomized clinical trial. Participants with mild ischemic stroke or TIA were assigned to receive either clopidogrel plus aspirin or aspirin monotherapy. Participants were categorized into 4 groups by the status of symptomatic ICAS or ECAS: ICAS + ECAS group, only ECAS group, only ICAS group, and no stenosis group. The primary efficacy end point was any new stroke and the primary safety end point was moderate-to-severe bleeding within 90 days.</p><p><strong>Results: </strong>The study enrolled 5,664 patients. Compared with other groups, the ICAS + ECAS group had a higher risk of recurrent stroke within 90 days (no stenosis = 5.7%; only ICAS = 7.2%; only ECAS = 10.3%; and ICAS + ECAS = 13.2%; p < 0.001). Although clopidogrel plus aspirin showed a numerically lower recurrence risk versus aspirin alone, no significant treatment effect difference emerged across the 4 groups. No significant interaction between antiplatelet therapy and the status of symptomatic ICAS or ECAS for recurrent stroke and moderate-to-severe bleeding was identified.</p><p><strong>Interpretation: </strong>For acute mild ischemic stroke or TIA, although patients with both symptomatic ICAS and ECAS exhibited an elevated risk of recurrent stroke than other patients, no interaction effect between antiplatelet therapy and the status of symptomatic ICAS or ECAS for the risk of new stroke and moderate-to-severe bleeding was observed. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129661","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":"MarkVCID2 Consortium for Clinical Validation of Biomarkers of Cerebral Small Vessel Disease: Validation Framework and Baseline Characteristics.","authors":"Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman, Gregory A Jicha, Amir H Kashani, Joel H Kramer, Christian Lachner, Jin-Moo Lee, Peiying Liu, Hanzhang Lu, Pauline Maillard, Ronald C Petersen, Bruce M Psaty, John M Ringman, Gary A Rosenberg, Claudia L Satizabal, Sean I Savitz, Julie A Schneider, Sudha Seshadri, Prashanthi Vemuri, Danny J J Wang, Donna M Wilcock, B Gwen Windham, Rong Zhang, Carissa Tuozzo, Herpreet Singh, Sue Moy, Vilma Okey-Ewurum, Courtney B Page, Hillary Mulder, Pia Kivisäkk, Deborah Blacker, Lidiya Mazina, Karl G Helmer, Kristin Schwab, Lisa M Wruck, Roderick A Corriveau","doi":"10.1002/ana.78040","DOIUrl":"https://doi.org/10.1002/ana.78040","url":null,"abstract":"<p><strong>Objective: </strong>To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.</p><p><strong>Methods: </strong>Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate-to-severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI.</p><p><strong>Results: </strong>MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non-Hispanic Black. Among enrollees, 44.8% were provisionally designated high-risk. After baseline MRI, 48.5% were categorized as adjudicated high-risk status, with substantial recategorization both from low- to high-risk (primarily because of MRI lesions without SVD risk factors) and high- to low-risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing).</p><p><strong>Interpretation: </strong>MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD-related cognitive decline. Changes over 3 years of longitudinal follow-up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111612","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":"Cross-Sectional FDG in Down Syndrome and Autosomal Dominant Alzheimer's Disease.","authors":"Omar Abdelmoity, Julie K Wisch, James T Kennedy, Manu Goyal, Andrei Vlassenko, Shaney Flores, Benjamin L Handen, Elizabeth Head, David Keator, Michael S Rafii, Patrick Lao, Florence Lai, H Diana Rosas, Sigan L Hartley, Shahid Zaman, Adam M Brickman, Dana Tudorascu, Joseph H Lee, Ricardo Francisco Allegri, Sarah Keefe, Christian la Fougere, Jorge Llibre-Guerra, Takeshi Ikeuchi, John C Morris, Jee Hoon Roh, Gregory S Day, Johannes Levin, Peter R Schofield, Brian A Gordon, Tammie L S Benzinger, Beau M Ances","doi":"10.1002/ana.78002","DOIUrl":"https://doi.org/10.1002/ana.78002","url":null,"abstract":"<p><strong>Objectives: </strong>Directly compare the brain glucose patterns seen with [F-18] fluorodeoxyglucose (FDG) positron emission tomography (PET) between 2 genetically determined forms of Alzheimer's disease: Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD).</p><p><strong>Methods: </strong>Cross-sectional analyses of FDG were performed in individuals with DS (n = 76) from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS), ADAD (n = 297), and neurotypical familial controls (n = 188) from the Dominantly Inherited Alzheimer Network (DIAN). Within-group linear regression models and generalized additive models were performed for select regional FDG uptake measures (isthmus cingulate and inferior parietal, precuneus, middle temporal gyrus, and precentral gyrus). Age, sex, apolipoprotein (APOE) ε4 carrier status, and cortical amyloid burden were included within these analyses.</p><p><strong>Results: </strong>Even 20 years before expected onset of clinical symptoms, FDG uptake was lower for DS compared to neurotypical familial controls (p < 0.01). ADAD baseline FDG was similar to neurotypical familial controls until 7 years before expected symptom onset. Both symptomatic individuals with DS and ADAD had lower FDG compared to neurotypical familial controls (p < 0.01). A higher amyloid burden was associated with lower FDG for both genetic forms, with similar rates of decline in FDG uptake for DS and ADAD who were amyloid positive.</p><p><strong>Interpretation: </strong>Brain glucose metabolism is substantially lower for people with DS, even in individuals who are cognitively stable. The patterns of FDG decline are distinct in these 2 genetically determined forms of AD. The diagnostic utility of FDG-PET is specific to the genetic form of AD. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111562","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":"Microneurography Reveals Unmyelinated Small Nerve Fiber Dysfunction in Long COVID.","authors":"Ana Ribeiro, Shahrzad Hadavi, Nick Gall, Robert D M Hadden, Jordi Serra","doi":"10.1002/ana.78045","DOIUrl":"https://doi.org/10.1002/ana.78045","url":null,"abstract":"<p><strong>Objective: </strong>To review the microneurography findings of long coronavirus disease 2019 (COVID) patients who presented to the clinic with multisystem involvement affecting neurological, cardiovascular, gastrointestinal, genitourinary, pulmonary, and immunological domains.</p><p><strong>Methods: </strong>We analyzed 36 consecutive long COVID patients using microneurography. We evaluated abnormalities in C nociceptors, including spontaneous activity, peripheral sensitization, multiple spikes, conduction failure, and alterations in activity-dependent slowing of conduction velocity. Sympathetic nerve fiber function was assessed using the recovery cycle of excitability. Results were compared with a large normative database.</p><p><strong>Results: </strong>The mean age was 40.9 ± 9.2 years (range 17-60 years), with a female predominance (30/36, 83.3%). Patients were seen from 15 to 61 months after onset of symptoms (35.7 ± 11.3 months). All patients presented with neuropathic symptoms, mainly pain and orthostatic intolerance. A total of 32 patients (88.9%) had objective electrophysiological abnormalities in peripheral C fibers, including spontaneous nociceptor activity (61.1%), peripheral sensitization (27.8%), and multiple spikes (11.1%). Long COVID patients also showed a significant shift in C nociceptor populations, with a higher prevalence of type 1B mechano-insensitive C nociceptors compared with healthy controls. Changes in activity-dependent slowing of conduction velocity differed in opposite directions between mechano-sensitive and mechano-insensitive C nociceptors. Postganglionic sympathetic fibers also showed abnormal recovery cycles with a lack of supernormality, suggesting impaired neuronal homeostasis.</p><p><strong>Interpretation: </strong>This study provides novel electrophysiological evidence linking small nerve fiber dysfunction to long COVID. These findings align with previous histological evidence of small nerve fiber loss, reinforcing the hypothesis that peripheral nerve dysfunction contributes to the multisystem symptoms of long COVID. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111615","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-Radiological Spectrum of Cerebral Amyloid Angiopathy-Related Inflammation.","authors":"Larysa Panteleienko, Gargi Banerjee, Dermot Mallon, Kitti Thiankhaw, Rupert Oliver, Victoria Harvey, Gareth Ambler, Michael Zandi, Hans Rolf Jäger, David J Werring","doi":"10.1002/ana.78029","DOIUrl":"https://doi.org/10.1002/ana.78029","url":null,"abstract":"<p><strong>Objective: </strong>To identify clinical and radiological features of cerebral amyloid angiopathy-related inflammation (CAA-ri), and compare these features with those of sporadic CAA, to improve the understanding, diagnosis, and clinical care of CAA-ri.</p><p><strong>Methods: </strong>We retrospectively reviewed routine clinical data from 37 patients with CAA-ri and 158 patients with sporadic CAA, including conventional vascular risk factors and comorbidities. We assessed brain magnetic resonance imaging for: radiological markers of CAA; features of amyloid-related imaging abnormalities with edema/effusion (ARIA-E) including parenchymal white matter hyperintensities, sulcal hyperintensities, and gyral swelling; and evidence of neurodegeneration (medial temporal atrophy and global cortical atrophy).</p><p><strong>Results: </strong>Compared with patients with sporadic CAA, patients with CAA-ri had more numerous lobar cerebral microbleeds (median 207[IQR 33-811] vs 19[IQR 7-58], p < 0.001), and higher rates of medial temporal and global cortical atrophy. In comparison with sporadic CAA, all ARIA-E features were much more common in patients with CAA-ri (parenchymal hyperintensities 89% vs 3%, sulcal hyperintensities 78% vs 9%, and gyral swelling 86% vs 0.6%), as were conventional vascular risk factors (hypertension, dyslipidemia) and long-term comorbidities (inflammatory and infectious disorders, autoimmune or connective tissue disorders, or malignancies).</p><p><strong>Interpretation: </strong>Features of ARIA-E (parenchymal white matter hyperintensities, sulcal hyperintensities, and gyral swelling) are more common in CAA-ri in comparison with \"non-inflammatory\" sporadic CAA, suggesting shared mechanisms with Alzheimer's disease immunotherapy and a potential role in improving diagnostic accuracy for CAA-ri. The high prevalence of atrophy and lobar cerebral microbleeds suggests a potential mechanistic role for capillary CAA, Alzheimer's disease, or both, in CAA-ri. Cardiovascular risk factors and other long-term comorbidities may also be relevant to the underlying mechanisms of CAA-ri. ANN NEUROL 2025 ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084801","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":"Letter to the Editor: \"Disease Characteristics and Treatments Associated with Outcome in Primary Angiitis of the Central Nervous System-A Multicenter Cohort Study in 163 Patients\".","authors":"Muhammad Owais, Muhammad Huzaifa Sabir, Muhammad Nouman Javed","doi":"10.1002/ana.70017","DOIUrl":"https://doi.org/10.1002/ana.70017","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084811","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}