Annals of Neurology最新文献

{"title":"Multimodal Image Guidance in Subthalamic Deep Brain Stimulation for Parkinson's Disease","authors":"Patricia Zvarova MSc,&nbsp;Christina van der Linden MD,&nbsp;Ningfei Li PhD,&nbsp;Konstantin Butenko PhD,&nbsp;Thea Berger,&nbsp;Garance M. Meyer PhD,&nbsp;Ilkem Aysu Sahin MD,&nbsp;Lukas L. Goede MD,&nbsp;Bahne H. Bahners MD,&nbsp;Barbara Hollunder PhD,&nbsp;Till A. Dembek MD,&nbsp;Andrew R. Pines MD,&nbsp;Martin Reich MD, PhD,&nbsp;Jens Volkmann MD, PhD,&nbsp;Vincent J. J. Odekerken MD,&nbsp;Rob M. A. de Bie MD, PhD,&nbsp;Xin Xu MD,&nbsp;Zhipei Ling MD,&nbsp;Chen Yao MD,&nbsp;Andrea A. Kühn MD,&nbsp;Surjo R. Soekadar MD, PhD,&nbsp;Kerstin Ritter PhD,&nbsp;Michael T. Barbe MD,&nbsp;Veerle Visser-Vandewalle MD,&nbsp;Michael D. Fox MD, PhD,&nbsp;Jan Niklas Petry-Schmelzer MD,&nbsp;Nanditha Rajamani PhD,&nbsp;Andreas Horn MD, PhD","doi":"10.1002/ana.78206","DOIUrl":"10.1002/ana.78206","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Accurate electrode placement and individual stimulation parameters influence the outcomes of subthalamic deep brain stimulation in Parkinson's disease. Neuroimaging-based models can help evaluate how electrode placement impacts improvement, aiming to reduce the burden of programming. However, most existing models have been developed to explain differences between patients rather than differences between contacts within the same patient, leaving the clinical relevance of image-guided programming unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from patients with Parkinson's disease treated with subthalamic deep brain stimulation to develop and validate a neuroimaging-informed model of motor improvement measured by the Unified Parkinson's Disease Scale. Five approaches were tested: active contact coordinates, electric fields, tract activations, as well as structural and functional networks. All approaches were integrated into a combined ridge regression model and validated using 2 hold-out datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The sample included 236 patients (604 stimulation sites), divided into a training cohort (N = 129), a retrospective validation cohort (N = 89), and a prospectively acquired validation cohort (N = 21 electrodes). Consistent with expectations, our model explained approximately 12% of the variance in unseen group-level data (<i>R</i>² = 0.12, <i>p</i> = 0.001). At the individual level, the model identified the optimal clinical contact or its neighboring contact in all but one case (mixed-effects <i>R</i>² = 0.31, <i>p</i> = 3.67 × 10⁻¹⁰).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>An imaging-informed model explained the expected variance at the group level and demonstrated potential for guiding stimulation programming, suggesting that image-guided approaches may improve clinical decision making while reducing the need for lengthy postoperative testing. ANN NEUROL 2026;100:22–35</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"22-35"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696927","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":"AI-Driven Mapping of Seizure Spread Patterns","authors":"Andrew Y. Revell MD, PhD,&nbsp;Marc Jaskir BS,&nbsp;Akash R. Pattnaik BS,&nbsp;William K. S. Ojemann BS,&nbsp;Erin Conrad MD,&nbsp;Nishant Sinha PhD,&nbsp;Brittany H. Scheid PhD,&nbsp;Alfredo Lucas MD, PhD,&nbsp;John M. Bernabei MD, PhD,&nbsp;John Beckerle BS,&nbsp;Joel M. Stein MD, PhD,&nbsp;Sandhitsu R. Das PhD,&nbsp;Brian Litt MD,&nbsp;Kathryn A. Davis MD","doi":"10.1002/ana.78203","DOIUrl":"10.1002/ana.78203","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The focus of epilepsy research has largely been on seizure onset; however, physicians typically examine the patterns of seizure spread past seizure onset as well. This study aims to align automated seizure analysis with clinical practice, leverage deep learning to standardize seizure annotations that varies among physicians, and understand common seizure spread patterns across patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed deep learning algorithms on a small subset of patients to detect seizure activity and deployed these algorithms across 275 seizures in 71 patients to analyze the patterns of seizure spread (extent, timing, surgical outcomes, and common patterns) along with incorporating diffusion-weighted imaging to understand how these patterns relate to the structural connections of the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Deep learning algorithms outperform single features (line length, absolute slope, and power) in ranking seizure onset contacts using physician annotations as a benchmark. We also find that poor outcome patients have more extensive brain regions involved in their seizures while also having more rapid spread between temporal lobes. Incorporating diffusion-weighted imaging, we find that an increase in structural connectivity between temporal lobes is associated with quicker seizure spread. Finally, we identify clusters of spread patterns common across patients based on spread timing, location, and extent.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Analyzing seizure spread can reveal new insights into seizure evolution and its relationship with surgical outcomes in patients with epilepsy. The findings also suggest that focusing beyond seizure onset is crucial for understanding and treating epilepsy. ANN NEUROL 2026;100:59–73</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"59-73"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831273","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":"The Dynamics of Neurofilament Light Chain in Spinal Muscular Atrophy","authors":"Arlene D'Silva PhD,&nbsp;Karen Herbert GradDip Phys,&nbsp;Lakshmi Balaji PhD,&nbsp;Jia Mei He BSc,&nbsp;Tejaswi Kandula PhD,&nbsp;Hugo A. Sampaio MPhil,&nbsp;Hooi-Ling Teoh MPhil,&nbsp;Esther Tantsis PhD,&nbsp;Jihee Sohn PhD,&nbsp;Nancy Briggs PhD,&nbsp;Nickson Ning PhD,&nbsp;Matthew C. Kiernan DSc,&nbsp;Didu S. Kariyawasam PhD,&nbsp;Michelle A. Farrar PhD","doi":"10.1002/ana.78207","DOIUrl":"10.1002/ana.78207","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Newborn screening (NBS) for spinal muscular atrophy (SMA) facilitates early diagnosis and treatment for affected individuals. However, fluid biomarkers that provide early insights into disease activity and outcomes in a neonatal cohort and those unable to access (due to reimbursement criteria) or deferring immediate treatment are lacking. This study evaluated neurofilament light chain (NfL) levels to provide insights into disease activity and outcomes in newborns and children with SMA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study correlated pretreatment NfL levels in the serum and cerebrospinal fluid (CSF) in a cross-sectional cohort of individuals with SMA against clinical, neurophysiological, molecular genetic variables, and treatment characteristics. Longitudinal NfL levels were evaluated in individuals that did not immediately commence treatment (governed by Australian reimbursement policies) and in those treated with nusinersen monotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants included 45 individuals with SMA (age range = 4 days to 42 years). Pretreatment serum NfL (sNfL) in 2 <i>SMN2</i> copy neonates were significantly higher (2 <i>SMN2</i>, mean[SE] 680.9 [163.7]; ≥ 3 <i>SMN2</i> 146.9 [59.8] pg/ml, <i>p</i> = 0.01), correlating with increasing post-natal age (2 <i>SMN2 r</i>[12] = 0.75, <i>p</i> = 0.005). Combining sNfL and compound muscle action potential (CMAP) with pretreatment CHOP-INTEND in a regression model provided a stronger prediction of motor outcomes for neonates at 2 years (<i>p</i> = 0.02). Pretreatment sNfL in infants with ≥3 <i>SMN2</i> copies who did not initiate immediate treatment increased despite motor function remaining stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>There is a malignant disease course with active denervation in children with 2 <i>SMN2</i> copies within the neonatal period. sNfL gives early insights into underlying pathophysiology prior to a clinical phenotype and may expedite access to the initiation of treatment. ANN NEUROL 2026;100:109–122</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"109-122"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472058","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":"Effects of Blood Pressure Lowering Across Hematoma Volume in Acute Intracerebral Hemorrhage: Pooled Analysis of the Four INTERACT and ATACH-2 Trials","authors":"Xinwen Ren MPH,&nbsp;Qiang Li MBiostat,&nbsp;Menglu Ouyang PhD,&nbsp;Xiaoying Chen PhD,&nbsp;Chen Chen PhD,&nbsp;Candice Delcourt PhD,&nbsp;Jiguang Wang PhD,&nbsp;Thompson Robinson MD,&nbsp;Hisatomi Arima PhD,&nbsp;Lu Ma MD,&nbsp;Chao You MD,&nbsp;Gang Li PhD,&nbsp;Jie Yang PhD,&nbsp;Yapeng Lin MD,&nbsp;Leibo Liu PhD,&nbsp;Paula Muñoz-Venturelli PhD,&nbsp;Sheila Martins PhD,&nbsp;Octavio Marques Pontes-Neto PhD,&nbsp;Adnan I. Qureshi MD,&nbsp;Xin Hu MD,&nbsp;Lili Song PhD,&nbsp;Craig S. Anderson PhD,&nbsp;Xia Wang PhD,&nbsp;for the INTERACT and ATACH-2 Investigators","doi":"10.1002/ana.78216","DOIUrl":"10.1002/ana.78216","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to assess the heterogeneity in treatment effect of intensive blood pressure (BP)-lowering across hematoma volume after acute intracerebral hemorrhage (ICH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We undertook a pooled analysis of individual patient data from the pivotal trials of early intensive BP-lowering in ICH (the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial 4 [INTERACT4] and Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 [ATACH-2] studies). The primary outcome was functional recovery, defined by the distribution of scores on modified Rankin scale (mRS). Secondary outcomes were hematoma expansion (HE) over 24 hours, defined by absolute (&lt;0, 0–6, 6–12.5, and &gt;12.5 ml) and relative HE (&lt;0, 0–33, 33–66, and &gt;66%). Generalized linear mixed models with trial as a random effect were conducted. We further assessed effect modification by hematoma volume and plotted the treatment effect curve.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 6,125 individuals with available hematoma volume, intensive BP-lowering improved functional recovery (odds ratio [OR] for unfavorable shift in mRS score = 0.90, 95% confidence interval [CI] = 0.82 to 0.99, <i>p</i> = 0.027). In 3,897 participants with available HE, intensive BP-lowering reduced the risk of absolute (OR = 0.88, 95% CI = 0.78 to 0.99, <i>p</i> = 0.043) and relative (OR = 0.88, 95% CI = 0.78 to 0.99, <i>p</i> = 0.034) HE. We found effect modification of treatment on functional outcome and absolute HE by hematoma volume (p for interaction = 0.043 and 0.025, respectively). U-shaped curves were observed, with benefits seen in cases with hematoma volume of 7.5 to 27.5 and 7.0 to 32.5 ml, respectively, both peaking at 20 ml.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Early intensive BP-lowering improves functional outcome and reduces HE in ICH. Heterogeneity by hematoma volume indicates the importance of patient selection in future trials and clinical practice. ANN NEUROL 2026;100:171–179</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"171-179"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588852","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":"Biochemical and Immunohistochemical Associations of TDP-43 and Cryptic RNA With Hippocampal and Amygdala Volumetrics in Alzheimer's Disease","authors":"Hossam Youssef MBBCh,&nbsp;Rodolfo G. Gatto MD, PhD,&nbsp;Nikhil B. Ghayal BS,&nbsp;Virginia Estades Ayuso,&nbsp;Karen R. Jansen-West,&nbsp;Judith A. Dunmore MS,&nbsp;Yuping Song MS,&nbsp;Mei Yue,&nbsp;Casey N. Cook PhD,&nbsp;Michael DeTure PhD,&nbsp;Bailey D. Rawlinson,&nbsp;Monica Castanedes-Casey HT,&nbsp;Clifford R. Jack Jr MD,&nbsp;Ronald C. Petersen MD, PhD,&nbsp;Dennis W. Dickson MD,&nbsp;Leonard Petrucelli PhD,&nbsp;Jennifer L. Whitwell PhD,&nbsp;Mercedes Prudencio PhD,&nbsp;Keith A. Josephs MD, MST, MSc","doi":"10.1002/ana.78223","DOIUrl":"10.1002/ana.78223","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Immunohistochemically (IHC) measured transactive response DNA-binding protein 43 (TDP-43) inclusions are observed in Alzheimer's disease (AD) and are associated with medial temporal lobe atrophy. Accumulation of cryptic exons occurs in AD in response to TDP-43 pathology. We aimed to assess relationships between IHC and biochemically measured insoluble TDP-43 and cryptic exons and assess associations with hippocampal and amygdala volume loss and atrophy rates on magnetic resonance imaging (MRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty-one neuropathologically diagnosed AD cases were analyzed. For biochemistry, insoluble TDP-43 was quantified using a Meso-scale discovery (MSD) immunoassay. IHC-TDP burden was quantified with digital histopathology. Cryptic RNAs were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). Thirty-eight cases had serial brain MRI. Hippocampal and amygdala volumes were calculated using FreeSurfer. Regression models were used to investigate associations among IHC-TDP-43 status/burden, MSD-TDP status/levels, cryptic RNAs, and hippocampal and amygdala volumes and atrophy rates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IHC-TDP(+) cases exhibited elevated levels of MSD-TDP and cryptic RNAs (<i>KCNQ2</i>, <i>STMN2</i>, and <i>UNC13A</i>) and increased MSD-TDP levels were associated with increased cryptic RNA levels, in the hippocampus and amygdala. IHC-TDP(+) cases had smaller hippocampal and amygdala volumes compared to IHC-TDP(−) cases. MSD-TDP(+) cases had smaller hippocampal volumes and faster amygdala rates of atrophy compared with MSD-TDP(−) cases. Higher <i>KCNQ2</i> and <i>UNC13A</i> levels were associated with smaller amygdala volumes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>MSD-TDP level is a reliable surrogate for IHC-based TDP-43 status. Both TDP-43 and cryptic RNA levels are associated with reduced medial temporal volumes, suggesting cryptic exons may be playing a role in brain volume loss in AD. ANN NEUROL 2026;100:193–205</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"193-205"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637345","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":"Cerebrospinal Fluid from Restless Legs Syndrome Patients Reduces Iron Uptake in Blood–Brain Barrier Endothelial Cells by Disrupting the Regulation of Transferrin Receptors","authors":"Kondaiah Palsa PhD,&nbsp;Aurosman Pappus Sahu MSc,&nbsp;David B. Rye MD PhD,&nbsp;Lynn Marie Trotti MD,&nbsp;Irina A. Elcheva PhD,&nbsp;Vladimir S. Spiegelman MD PhD,&nbsp;James R. Connor PhD","doi":"10.1002/ana.78221","DOIUrl":"10.1002/ana.78221","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Restless legs syndrome (RLS) is a sensorimotor disorder marked by an uncontrollable urge to move the legs. A pathophysiological hallmark of RLS is brain iron deficiency. The endothelial cells (ECs) of the blood–brain barrier (BBB) are responsible for regulating brain iron uptake. Our objective is to determine if brain iron uptake is altered in ECs in RLS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human ECs were generated from induced pluripotent stem cells (iPSCs). ECs were exposed to RLS (n = 14) or control cerebrospinal fluid (CSF) (n = 15), and ⁵⁷Fe-Transferrin transport was determined. Immunoblotting and quantitative polymerase chain reaction were used to analyze protein, microRNA (miRNA), and messenger RNA (mRNA) expressions. We performed miRNA and transferrin receptor 1 (TfR1) 3′ iron-responsive elements (IRE) interaction in HEK-293 cells by using a pMIR-REPORTER luciferase vector.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Free and protein-bound iron in CSF from RLS subjects were decreased compared to controls. Exposure of ECs to RLS CSF significantly decreased the uptake and transport of ⁵⁷Fe compared to the control. TfR1 expression decreased while iron regulatory proteins (IRP) increased in RLS-CSF exposed ECs. TfR1 expression was also regulated by miRNAs. The miR-124-3p levels were higher in RLS CSF-derived extracellular vesicles than in the control. It binds the TfR1 3′ IRE sequence in the pMIR-REPORTER vector, reducing luciferase expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>When ECs are treated with CSF from RLS patients, they show a profile of iron deficiency, except that the TfR1 expression does not increase as would be predicted. The decrease in TfR1 protein expression is because of a reduction in TfR1 mRNA stability by the binding of increased miR-124-3p. ANN NEUROL 2026;100:48–58</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"48-58"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147631956","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":"Relapses, Comorbidities, and Predictors of Outcome in Anti-GABAA Receptor Encephalitis","authors":"Claudia Papi,&nbsp;Chiara Milano,&nbsp;Laura Marmolejo,&nbsp;Ana Beatriz Serafim,&nbsp;Esther Aguilar,&nbsp;Mar Guasp,&nbsp;Elianet Fonseca,&nbsp;Mateus Mistieri Simabukuro,&nbsp;Raffaele Iorio,&nbsp;Yuki Fukami,&nbsp;Maria Lucia Schmitz Ferreira Santos,&nbsp;Takashi Miwa,&nbsp;Takashi Araga,&nbsp;Yuto Uchida,&nbsp;Masanori Kurihara,&nbsp;Satoshi Okada,&nbsp;Luz Victoria Garcia,&nbsp;Kenichi Kaida,&nbsp;Natalia Spinola Costa da Cunha,&nbsp;Alberto Vogrig,&nbsp;Florian Lamblin,&nbsp;Juna M. de Vries,&nbsp;Livia Almeida Dutra,&nbsp;Romana Höftberger,&nbsp;Maarten J. Titulaer,&nbsp;Jesús Planagumà,&nbsp;Lidia Sabater,&nbsp;Eugenia Martinez-Hernandez,&nbsp;Thais Armangué,&nbsp;Francesc Graus,&nbsp;Takahiro Iizuka,&nbsp;Josep Dalmau,&nbsp;Marianna Spatola,&nbsp;Anti-GABAAR encephalitis study group","doi":"10.1002/ana.78208","DOIUrl":"10.1002/ana.78208","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To characterize the magnetic resonance imaging (MRI) lesion dynamics, comorbidities, predictors of relapse, and outcomes in anti-<i>γ</i>-aminobutyric acid type A receptor (GABA_AR) encephalitis, and assess the utility of LIM-domain-only-protein 5 (LMO5) antibodies as tumor markers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GABA_AR antibodies were confirmed by 2 techniques in serum or cerebrospinal fluid. Long-term outcomes were defined as good (modified Rankin scale, mRS = 0–1) or poor (mRS 2–5) at ≥12 months. LMO5 antibodies were assessed by cell-based assays and Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-three patients were identified (4 children, 29 adults; median age, 5.5 and 60 years; 61% male). Ten patients (10/32, 31%) had concurrent systemic autoimmunity. Adults presented with seizures and cognitive/behavioral symptoms, often with thymoma, gastrointestinal, or other tumors (18/33, 55%), whereas children frequently had seizures and ataxia with cerebellar MRI lesions. Multifocal T2/fluid-attenuated inversion recovery hyperintensities were present at onset in 23 of 31 (74%) or developed later in those with absent or single lesions. Lesions showed dynamic changes, suggesting ongoing inflammation even without clinical correlate. Relapses occurred in 17 of 31 (55%, all adults) and were associated with older age (<i>p</i> = 0.02) and lack of second-line immunotherapy (<i>p</i> = 0.02). Four patients (4/33, 12%) died. After a 32.5-month median follow-up, 9 of 20 (45%) had persistent cognitive deficits, and 6 of 20 (30%) had a poor outcome, which was associated with relapses (<i>p</i> = 0.04). LMO5 antibodies were absent in patients and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Anti-GABA_AR encephalitis shows age-dependent presentations, most commonly seizures. MRI reveals dynamic changes consistent with an ongoing “clinically silent” inflammation. Relapses and cognitive sequelae are common and associate with not receiving second-line immunotherapy. LMO5 antibodies lack tumor-predictive value. ANN NEUROL 2026;100:139–150</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"139-150"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669369","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":"Population-Based Epidemiology of Autoimmune Seizures and Epilepsies","authors":"Smathorn Thakolwiboon MD,&nbsp;Kathryne N. Wood MD,&nbsp;Andrea Stabile MD,&nbsp;Naveen Paramasivan MBBS, MD,&nbsp;Jeffrey W. Britton MD,&nbsp;Kelsey M. Smith MD,&nbsp;Surendra Dasari PhD,&nbsp;Michelle F. Devine MD,&nbsp;Andrew McKeon MD,&nbsp;Anastasia Zekeridou MD, PhD,&nbsp;Eoin P. Flanagan MB, BCh,&nbsp;Sean J. Pittock MD,&nbsp;Divyanshu Dubey MD","doi":"10.1002/ana.78204","DOIUrl":"10.1002/ana.78204","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To estimate the prevalence, incidence, and disease burden of autoimmune seizures and epilepsies in Olmsted County.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective, population-based study using the Rochester Epidemiology Project (1996–2019). Age- and sex-standardized rates (2019 United States standard population) per 100,000 were calculated with 95% confidence intervals (95% CIs). Temporal trends in incidence were assessed over 3 consecutive 8-year intervals (1996–2003, 2004–2011, and 2012–2019) using Poisson regression to estimate rate ratios per period and trend. Disability-adjusted life years (DALYs), years of life lost (YLL), and years lived with disability (YLD) and 95% uncertainty intervals (95% UIs) were estimated for 2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-three patients were identified between 1996 and 2019. In 2019, the standardized prevalence of all autoimmune seizures and epilepsies was 9.81 (95% CI, 5.59–15.21) per 100,000, including autoimmune-associated epilepsy (AAE) 7.27 (3.74–11.95) and acute symptomatic seizures secondary to autoimmune encephalitis (ASSAE) 2.55 (0.69–5.60). From 1996 to 2019, the standardized incidence was 0.50 (0.29–0.77) per 100,000 person-years overall, with AAE 0.36 (0.19–0.59) and ASSAE 0.15 (0.05–0.30). By period, the standardized incidence of all autoimmune seizures and epilepsies suggested a rising trend from 0.28 (95% CI, 0.06–0.68) in 1996 to 2003 to 0.60 (95% CI, 0.24–1.12) in 2004–2011, then plateaued at 0.53 (95% CI, 0.21–1.00) in 2012 to 2019 (rate ratio per 8-year interval 1.30, 95% CI, 0.71–2.38), largely driven by the seropositive subgroup. The standardized DALY rate was 26.27 (95% Uncertainly intervals [UI], 5.30–67.09) per 100,000 (YLL 20.07 [0.00–60.21] and YLD 6.20 [5.06–7.39]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Although autoimmune seizures and epilepsies remain rare, they result in a disproportionately high disease burden. ANN NEUROL 2026;100:74–83</p>\u0000 </section>\u0000 </div>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"74-83"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508247","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":"Pies in the Sky","authors":"Shivangi D. Pandya MD,&nbsp;Bernard P.L. Chan MD,&nbsp;Vijay K. Sharma MD","doi":"10.1002/ana.78253","DOIUrl":"10.1002/ana.78253","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":"191-192"},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831342","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 100, Number 1, July 2026","authors":"","doi":"10.1002/ana.78293","DOIUrl":"https://doi.org/10.1002/ana.78293","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148373007","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}