Annals of Neurology最新文献

{"title":"Critical Care Decisions After Large Core Cerebral Infarctions: A Secondary Analysis From the SELECT2 Trial.","authors":"Scott E Kasner, Michael T Mullen, Michael DeGeorgia, Spiros Blackburn, Donna K George, Monisha Kumar, Steven Messe, Michael G Abraham, Michael Chen, Santiago Ortega-Gutierrez, Clark W Sitton, Jan-Karl Burkhardt, Muhammad Shazam Hussain, Leonid Churilov, Sophia Sundararajan, Yin C Hu, Nabeel A Herial, Pascal Jabbour, Daniel Gibson, Juan F Arenillas, Jenny P Tsai, Ronald F Budzik, William J Hicks, Osman Kozak, Bernard Yan, Dennis J Cordato, Nathan W Manning, Mark W Parsons, Ricardo A Hanel, Amin N Aghaebrahim, Teddy Y Wu, Pere Cardona Portela, Natalia Pérez de la Ossa, Joanna D Schaafsma, Jordi Blasco, Navdeep Sangha, Steven Warach, Chirag D Gandhi, Timothy J Kleinig, Daniel Sahlein, Edgar A Samaniego, Laith Maali, Mohammad A Abdulrazzak, Krishna Amuluru, Deep K Pujara, Faris Shaker, Hannah Johns, Rami Moussa, Faisal Al-Shaibi, Kelsey R Duncan, Stavropoula Tjoumakaris, Amanda Opaskar, Wei Xiong, Abhishek Ray, Sepideh Amin-Hanjani, Thanh N Nguyen, Johanna T Fifi, Stephen Davis, Lawrence Wechsler, Anthony Furlan, Cathy Sila, Nicholas Bambakidis, Michael D Hill, Vitor Mendes Pereira, Maarten G Lansberg, James C Grotta, Marc Ribo, Greg W Albers, Bruce C Campbell, Ameer E Hassan, Amrou Sarraj","doi":"10.1002/ana.27151","DOIUrl":"https://doi.org/10.1002/ana.27151","url":null,"abstract":"<p><strong>Objective: </strong>Among patients with large vessel occlusion (LVO) and large ischemic cores, critical decisions often need to be made about decompressive hemicraniectomy (DHC) or early withdrawal of life-sustaining therapy (WLST). In this study, we aimed to evaluate utilization of DHC and early WLST and factors associated with them in patients with large strokes from the SELECT2 trial.</p><p><strong>Methods: </strong>We analyzed the entire SELECT2 trial population, which randomized 352 patients with stroke due to LVO and large ischemic cores to endovascular thrombectomy (EVT) or medical management. We used the as-treated principle to compare the use of DHC and early WLST within 7 days after randomization. We further assessed functional outcomes (modified Rankin Score) after these decisions.</p><p><strong>Results: </strong>Of 352 patients enrolled in this study, 55 received DHC and 81 transitioned to early WLST. Patients treated with EVT were as likely to undergo DHC (16% vs 15%, adjusted relative risk [aRR] = 1.19, 95% CI:0.75-1.88, p = 0.46) or WLST (22% vs 24%, aRR = 0.94, 95% CI: 0.66-1.34, p = 0.72) as those given medical management. DHC was used more frequently in younger patients and WLST more in older patients. EVT efficacy was maintained after adjusting for DHC (adjusted generalized odds ratio [aGenOR] = 1.68, 95% CI: 1.24-2.11, p < 0.001), with no interaction between DHC and treatment (p-interaction = 0.93). At 1 year, 21% of DHC-treated patients were ambulatory; the outcomes were universally poor after early WLST.</p><p><strong>Interpretation: </strong>In the SELECT2 trial of patients with large ischemic core, DHC was performed in ~1 of 6 patients and early WLST in ~1 of 5 patients, without differences based on treatment with EVT or medical management, nor successful reperfusion. DHC or WLST did not detract from thrombectomy treatment benefit. Additionally, ~20% of patients achieved independent ambulation despite receiving DHC by the 1-year follow-up. The similar distribution of these critical care decisions provides reassurance that the overall trial outcomes were not biased by open-label treatment allocation. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794065","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":"Spontaneous Pneumocephalus Due to Skull Base Defect and Spinal Cerebrospinal Fluid-Venous Fistula.","authors":"Simon A Menaker, Gregory P Lekovic, Wouter I Schievink","doi":"10.1002/ana.27152","DOIUrl":"https://doi.org/10.1002/ana.27152","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794066","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":"Inhibition of Bone Morphogenetic Protein Signaling Prevents Tau Pathology in iPSC Derived Neurons and PS19 Mice.","authors":"Amira Affaneh, Anne K Linden, Elif Tunc-Ozcan, Yung-Hsu Tsai, Chian-Yu Peng, John A Kessler","doi":"10.1002/ana.27149","DOIUrl":"https://doi.org/10.1002/ana.27149","url":null,"abstract":"<p><strong>Objective: </strong>Many neurodegenerative disorders share a common pathologic feature involving the deposition of abnormal tau protein in the brain (tauopathies). This suggests that there may be some shared pathophysiologic mechanism(s). The largest risk factor for the majority of these disorders is aging, suggesting involvement of the aging process in the shared pathophysiology. We test the hypothesis that an increase in bone morphogenetic protein (BMP) signaling that occurs during aging contributes to the onset and progression of tauopathies.</p><p><strong>Methods: </strong>Human induced pluripotent stem cell (iPSC)-derived neurons from patients with Alzheimer's disease (AD) were used to investigate the effects of BMP signaling on tau phosphorylation and release and the mechanisms underlying these effects. Wildtype mice were used to examine effects of BMP signaling in vivo. P301S (PS19) mice were examined for the effects of BMP signaling in a model of tauopathy.</p><p><strong>Results: </strong>Here, we show that BMP signaling, mediated by non-canonical p38 signaling, increases tau phosphorylation and release of p-tau in human iPSC-derived AD neurons. Further, there is an interaction between BMP signaling and apolipoprotein E4 (ApoE4) that significantly increases tau phosphorylation and release compared with ApoE3 neurons. Inhibiting BMP signaling reduces the changes in tau in the cultured human neurons, and it limits tau pathology and prevents cognitive decline in PS19 mice.</p><p><strong>Interpretation: </strong>Our study suggests that the age-related increase in BMP signaling may participate in the onset and progression of tau pathology. Thus, therapeutic interventions that reduce BMP signaling in the aging brain could potentially slow or prevent development of diseases involving tau hyperphosphorylation. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790546","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":"NORSE, FIRES, and a Polygenic Trickle of Autoimmunity.","authors":"Ingo Helbig, Shiva Ganesan","doi":"10.1002/ana.27148","DOIUrl":"https://doi.org/10.1002/ana.27148","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790562","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":"Prophylactic Fetal Creatine Supplementation Improves Post-Asphyxial EEG Recovery and Reduces Seizures in Fetal Sheep: Implications for Hypoxic-Ischemic Encephalopathy.","authors":"Nhi T Tran, Stacey J Ellery, Sharmony B Kelly, Juliane Sévigny, Madeleine Chatton, Hui Lu, Graeme R Polglase, Rod J Snow, David W Walker, Robert Galinsky","doi":"10.1002/ana.27150","DOIUrl":"https://doi.org/10.1002/ana.27150","url":null,"abstract":"<p><strong>Objective: </strong>Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal brain injury. Creatine is a dietary supplement that can increase intracellular phosphocreatine to improve the provision of intracellular adenosine triphosphate (ATP) to meet the increase in metabolic demand of oxygen deprivation. Here, we assessed prophylactic fetal creatine supplementation in reducing acute asphyxia-induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology.</p><p><strong>Methods: </strong>Fetal sheep (118 ± 1 days' gestational age [dGA]; 0.8 gestation) were implanted with electrodes to continuously record EEG and nuchal electromyogram activity. At 121 dGA, fetuses were randomly assigned to sham control (i.v. saline infusion without umbilical cord occlusion [UCO]; SalCon), continuous i.v. creatine infusion (6 mg/kg/h; CrUCO) or isovolumetric saline (SalUCO) followed by UCO at 128 ± 2 dGA that lasted until the mean arterial blood pressure reached 19 mmHg. Brain tissue was collected for histopathology after 72 hours of recovery.</p><p><strong>Results: </strong>Creatine supplementation had no effects on basal systemic or neurological physiology. UCO duration did not differ between CrUCO and SalUCO. After reperfusion, CrUCO fetuses had improved EEG power and frequency recovery and reduced electrographic seizure incidence (SalUCO, 86% vs CrUCO, 29%) and burden. At 72 hours after UCO, cell death in the cerebral cortex and astrogliosis in the periventricular white matter were reduced in CrUCO fetuses compared with SalUCO.</p><p><strong>Interpretation: </strong>Creatine supplementation reduced post-asphyxial seizures and improved EEG recovery. Improvements in functional recovery with creatine were associated with regional reductions in cell death and astrogliosis. Prophylactic creatine treatment has the potential to mitigate functional indices of HIE in the late gestation fetal brain. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790565","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":"Longitudinal Imaging Biomarkers Correlate with Progressive Motor Deficit in the Mouse Model of Charlevoix-Saguenay Ataxia.","authors":"Valentina Gigliucci, Su-Chun Huang, Giorgio Boschetti, Alessandra Scaravilli, Valerio Castoldi, Paola Podini, Angelo Quattrini, Sirio Cocozza, Letizia Leocani, Francesca Maltecca","doi":"10.1002/ana.27146","DOIUrl":"https://doi.org/10.1002/ana.27146","url":null,"abstract":"<p><strong>Objective: </strong>In autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease, severity and age of onset vary greatly, hindering to objectively measure and predict clinical progression. Thickening of the retinal nerve fiber layer is distinctive of ARSACS patients, as assessed by optical coherence tomography, whereas conventional brain magnetic resonance imaging findings include both supratentorial and infratentorial changes. Because longitudinal imaging studies in ARSACS patients are not available to define these changes as biomarkers of disease progression, we aimed to address this issue in the ARSACS mouse model.</p><p><strong>Methods: </strong>We performed longitudinal retinal OCT and brain MRI in the Sacs^-/- ARSACS mouse model, alongside motor and coordination assessment in the beam walking test. We also investigated visual function and the molecular mechanisms underlying RNFL increased thickness by histology and immunofluorescence.</p><p><strong>Results: </strong>We demonstrated that RNFL thickening by OCT gradually increases in the early stages of pathology in the Sacs^-/- mouse model, reflecting the progression of motor impairment, and later reaches a plateau when thinning of the posterior corpus callosum becomes detectable by MRI. Mechanistically, we unveiled that RNFL thickening is associated with aberrant accumulation of non-phosphorylated neurofilament H and glial fibrillary acidic protein. We also uncovered mild signs of myelin pathology coherent with increased latency of visual evoked potentials, and altered retinal activation by photopic electroretinography.</p><p><strong>Interpretation: </strong>We show that both RNFL thickening and MRI changes may represent biomarkers of disease progression in the Sacs^-/- mouse model. Our data gathers knowledge instrumental to clinical studies, holding potential as readout for treatment efficacy. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783467","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":"A Prospective Multicenter Analysis of Mobile Stroke Unit Cost-Effectiveness.","authors":"Suja S Rajan, Jose-Miguel Yamal, Mengxi Wang, Jeffrey L Saver, Asha P Jacob, Nicole R Gonzales, Nneka Ifejika, Stephanie A Parker, Christopher Ganey, Michael O Gonzalez, David R Lairson, Patti L Bratina, William J Jones, Jason S Mackey, Mackenzie P Lerario, Babak B Navi, Ann W Alexandrov, Andrei Alexandrov, May Nour, Ilana Spokoyny, Ritvij Bowry, Alexandra L Czap, James C Grotta","doi":"10.1002/ana.27105","DOIUrl":"https://doi.org/10.1002/ana.27105","url":null,"abstract":"<p><strong>Objective: </strong>Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost-effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost-effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS).</p><p><strong>Methods: </strong>This study is a prospective, multicenter, alternating-week, cluster-controlled trial of MSU versus EMS. One-year and life-time cost-effectiveness analyses, using the incremental cost-effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality-adjusted life years (QALYs) estimated using patient-reported EQ-5D-5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre-existing disability, and limited to stroke-related costs were also calculated.</p><p><strong>Results: </strong>The first-year ICER for all tPA-eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre-existing disability was $61,199/QALY. The lifetime ICERs for all tPA-eligible patients and for those without pre-existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke-related costs and were highly dependent on the number of patients treated per year in an MSU.</p><p><strong>Interpretation: </strong>MSUs' cost-effectiveness is borderline if we consider total first-year costs and outcomes in all tPA-eligible patients. MSUs are cost-effective to highly cost-effective when calculations are based on patients without pre-existing disability, patients' lifetime horizon, stroke-related costs, and more patients treated per year in an MSU. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764605","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":"Unveiling the Clinical and Imaging Signatures of Intravascular Lymphoma of the Central Nervous System: A Multicentric Cohort Study.","authors":"Elodie Berthet, Antoine Guillonnet, Caroline Houillier, Renata Ursu, Carole Soussain, Mehdi Touat, Antoine Gueguen, Benoît de Renzis, Kevin Bigaut, Guido Ahle, Pierre Durozard, Deborah Grosset-Janin, Lucie Oberic, Antoine Bonnet, Anne-Pascale Grandjean, Cécile Moluçon-Chabrot, Khê Hoang-Xuan, Hugues Chabriat, Stéphanie Guey","doi":"10.1002/ana.27132","DOIUrl":"https://doi.org/10.1002/ana.27132","url":null,"abstract":"<p><strong>Objective: </strong>Intravascular lymphoma is a rare subtype of B-cell lymphoma characterized by a clonal proliferation restricted to the lumen of small vessels. Over 50% of patients exhibit central nervous system (CNS) involvement, but diagnosis is often delayed due to the lack of distinctive features. We aimed to identify key phenotypic features for early diagnosis of intravascular lymphoma with CNS involvement through an in-depth cohort study.</p><p><strong>Methods: </strong>We built up a multicenter retrospective cohort of 17 patients recruited in collaboration with the French Expert Network for Oculo-Cerebral Lymphomas (LOC network), and retrospectively analyzed data from medical records.</p><p><strong>Results: </strong>In this cohort, 15 of 17 (88%) patients developed focal neurological episodes, often fluctuating and/or recurrent, with a sudden onset in 68% of episodes, suggesting a vascular origin. Rapid cognitive deterioration occurred in 15 of 17 (88%) patients, psychiatric manifestations in 8 of 17 (47%), and \"B signs\" in 14 of 17 (82%). Brain MRI showed polymorphic FLAIR hyperintensities in 14 of 16 (87%) patients, and DWI-positive lesions in 13 of 16 (81%) of patients, which accumulated over time and had unusual characteristics for ischemic lesions (progressive growth, persistent DWI-hyperintensity over 1 month, surrounded by a wider FLAIR hyperintensity). Early-onset inflammatory syndrome, and elevated lactate dehydrogenase (LDH) levels were observed in over 90% of cases. Mild and inconsistent meningitis contrasted with a nearly-constant hyperproteinorachia. An increased interleukin 10/6 ratio over 0,7 was found in 4 of 7 (57%) patients, and skin biopsy led to a pathological diagnosis in 3 of 6 (50%) patients.</p><p><strong>Interpretation: </strong>The results of this study highlight \"red flags\" that could help accelerate the diagnosis of intravascular lymphoma involving the CNS. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737727","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":"Towards a Unified Set of Diagnostic Criteria for Multiple Sclerosis.","authors":"Wallace J Brownlee, Angela Vidal-Jordana, Madiha Shatila, Eva Strijbis, Lisa Schoof, Joep Killestein, Frederik Barkhof, Luca Bollo, Alex Rovira, Jaume Sastre-Garriga, Mar Tintore, Maria A Rocca, Federica Esposito, Matteo Azzimonti, Massimo Filippi, Benedetta Bodini, Andrea Lazzarotto, Bruno Stankoff, Xavier Montalban, Ahmed T Toosy, Alan J Thompson, Olga Ciccarelli","doi":"10.1002/ana.27145","DOIUrl":"https://doi.org/10.1002/ana.27145","url":null,"abstract":"<p><strong>Objective: </strong>The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS.</p><p><strong>Methods: </strong>We retrospectively identified patients evaluated for suspected PPMS at 5 European centers. The 2017 McDonald PPMS criteria was the gold standard against which the 2017 McDonald RRMS dissemination in space (DIS) and dissemination in time criteria were evaluated. We also investigated modified RRMS DIS criteria, including: (i) optic nerve lesions; (ii) ≥2 spinal cord lesions; and (iii) higher fulfilment of DIS criteria alone (lesions in ≥3 regions) without dissemination in time/positive cerebrospinal fluid, for a diagnosis of PPMS.</p><p><strong>Results: </strong>A total of 282 patients were diagnosed with PPMS using the 2017 McDonald criteria, and 40 with alternate disorders. The 2017 McDonald RRMS DIS criteria and the modified DIS criteria including the optic nerve or ≥2 spinal cord lesions performed well in PPMS diagnosis when combined with dissemination in time/positive cerebrospinal fluid (sensitivity 92.9-95.4%, specificity 95%, accuracy 93.2-95.3%). A diagnosis of PPMS based on high fulfillment of modified RRMS DIS criteria had high specificity, but low sensitivity. A diagnostic algorithm applicable to patients evaluated for suspected MS is proposed.</p><p><strong>Interpretation: </strong>The 2017 McDonald RRMS criteria and modifications to DIS criteria, currently under consideration, performed well in PPMS diagnosis. Forthcoming revisions to the McDonald criteria should consider a single, unified set of diagnostic criteria for MS. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737725","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":"Long-Term Follow Up in Anti-Contactin-1 Autoimmune Nodopathy.","authors":"Marta Caballero-Ávila, Lorena Martín-Aguilar, Elba Pascual-Goñi, Milou R Michael, Marleen J A Koel-Simmelink, Romana Höftberger, Julia Wanschitz, Alicia Alonso-Jiménez, Thais Armangué, Adája Elisabeth Baars, Álvaro Carbayo, Barbara Castek, Roger Collet-Vidiella, Jonathan De Winter, Maria Ángeles Del Real, Emilien Delmont, Luca Diamanti, Pietro Emiliano Doneddu, Fu Liong Hiew, Eduard Gallardo, Amaia Gonzalez, Susanne Grinzinger, Alejandro Horga, Stephan Iglseder, Bart C Jacobs, Amaia Jauregui, Joep Killestein, Elisabeth Lindeck Pozza, Laura Martínez-Martínez, Eduardo Nobile-Orazio, Nicolau Ortiz, Helena Pérez-Pérez, Kai-Nicolas Poppert, Paolo Ripellino, Jose Carlos Roche, Franscisco Javier Rodriguez de Rivera, Kevin Rostasy, Davide Sparasci, Clara Tejada-Illa, Charlotte C E Teunissen, Elisa Vegezzi, Tomàs Xuclà-Ferrarons, Fabian Zach, Luuk Wieske, Filip Eftimov, Cinta Lleixà, Luis Querol","doi":"10.1002/ana.27142","DOIUrl":"https://doi.org/10.1002/ana.27142","url":null,"abstract":"<p><strong>Objective: </strong>To analyze long-term clinical and biomarker features of anti-contactin-1 (CNTN1) autoimmune nodopathy (AN).</p><p><strong>Methods: </strong>Patients with anti-CNTN1⁺ autoimmune nodopathy detected in our laboratory from which clinical information was available were included. Clinical features and treatment response were retrospectively collected. Autoantibody, serum neurofilament light chain (sNfL), and serum CNTN1 levels (sCNTN1) were analyzed at baseline and follow up.</p><p><strong>Results: </strong>A total of 31 patients were included. Patients presented with progressive sensory motor neuropathy (76.7%) with proximal (74.2%) and distal involvement (87.1%), ataxia (71.4%), and severe disability (median INCAT at nadir of 8). A total of 11 patients (35%) showed kidney involvement. Most patients (97%) received intravenous immunoglobulin, but only 1 achieved remission with intravenous immunoglobulin. A total of 22 patients (71%) received corticosteroids, and 3 of them (14%) did not need further treatments. Rituximab was effective in 21 of 22 patients (95.5%), with most of them (72%) receiving a single course. Four patients (12.9%) relapsed after a median follow up of 25 months after effective treatment (12-48 months). Anti-CNTN1 titers correlated with clinical scales at sampling and were negative after treatment in all patients, but 1 (20/21). sNfL levels were significantly higher and sCNTN1 significantly lower in anti-CNTN1⁺ patients than in healthy controls (sNfL: 135.9 pg/ml vs 7.48 pg/ml, sCNTN1: 25.03 pg/ml vs 22,186 pg/ml, p < 0.0001). Both sNfL and sCNTN1 returned to normal levels after successful treatment.</p><p><strong>Interpretation: </strong>Patients with anti-CNTN1⁺ autoimmune nodopathy have a characteristic clinical profile. Clinical and immunological relapses are infrequent after successful treatment, suggesting that continuous treatment is unnecessary. Anti-CNTN1 antibodies, sNfL, and sCNTN1 levels are useful to monitor disease status in these patients. ANN NEUROL 2024.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724339","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}