1. Long-term outcomes in antibody-negative autoimmune encephalitis: a retrospective study.
- Author
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Mangioris G, Orozco E, Dubey D, Flanagan EP, Pittock SJ, Zekeridou A, and McKeon A
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Retrospective Studies, Aged, 80 and over, Young Adult, Hashimoto Disease immunology, Hashimoto Disease diagnosis, Follow-Up Studies, Autoantibodies cerebrospinal fluid, Autoantibodies blood, Autoimmune Diseases of the Nervous System immunology, Autoimmune Diseases of the Nervous System physiopathology, Autoimmune Diseases of the Nervous System diagnosis, Encephalitis immunology, Encephalitis diagnosis, Encephalitis cerebrospinal fluid
- Abstract
Background and Objective: Despite constituting one-third of suspected autoimmune encephalitis (AE) patients, antibody-negative cases without typical AE features are understudied. We aim to characterize the clinical phenotypes and long-term outcomes of "possible only" and "probable" AE cases., Methods: We conducted a retrospective analysis of adult patients evaluated at Mayo Clinic's Autoimmune Neurology Clinic (01/01/2006-12/31/2020), meeting diagnostic criteria for "possible only" or "probable but antibody-negative" AE, with ≥ 1 year of follow-up. All patients underwent neural antibody testing., Results: Among fifty-one patients, six had a change in diagnosis (non-autoimmune, 2) and were excluded from further analysis. Forty-five patients were analyzed [median age, 61 years (range 20-88); female, 21 (47%); median follow-up, 36 months (range 12-174)]. A nadir modified Rankin Scale (mRS) ≥ 3 was recorded in 41/45 (91%). CSF was inflammatory in 20/44 (45%) and MRI had encephalitic changes in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two patients (4%) had paraneoplastic causation. Relapses (> 3 months from onset) were noted in 14 (31%). Memory dysfunction (69%), attention deficits (38%), and gait instability (29%) were the most frequent at the last follow-up. Most patients (76%) were independent at the last follow-up and only two required an assistive device to ambulate; 11 patients (24%) had poor neurological outcome (mRS ≥ 3). Higher mRS score and gait assistance requirement at 3 months were predictive of poor outcome (P ≤ 0.01)., Discussion: Despite significant disability at initial disease stages, most antibody-negative AE patients regain independent functioning. Early functional status and gait assistance requirements may predict long-term prognosis., Competing Interests: Declarations. Conflict of interest: Georgios Mangioris and Emma Orozco report no disclosures. Divyanshu Dubey has consulted for UCB, Immunovant, Argenx, Arialys and Astellas pharmaceuticals. All compensations for consulting activities are paid directly to Mayo Clinic. He is a named inventor on filed patent that relates to KLHL11 as marker of autoimmunity and germ cell tumor. He has patents pending for LUZP4-IgG, cavin-4-IgG and SKOR2 IgG as markers of neurological autoimmunity. He has received funding from the DOD (CA210208 & PR220430), David J. Tomassoni ALS Research Grant Program and UCB. Eoin P. Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics and UCB. He has received research support from UCB. He has received speaker honoraria from Pharmacy Times. He received royalties from UpToDate. He is a site principal investigator in a randomized clinical trial of Rozanolixizumab for relapsing myelin oligodendrocyte glycoprotein antibody-associated disease run by UCB. He is a site principal investigator and a member of the steering committee for a clinical trial of satralizumab for relapsing myelin oligodendrocyte glycoprotein antibody-associated disease run by Roche/Genentech. He has received funding from the NIH (R01NS113828). He is a member of the medical advisory board of the MOG project. He is an editorial board member of Neurology, Neuroimmunology and Neuroinflammation, The Journal of the Neurological Sciences and Neuroimmunology Reports. A patent has been submitted on DACH1-IgG as a biomarker of paraneoplastic autoimmunity. Sean J. Pittock has received personal compensation for serving as a consultant for F. Hoffman-LaRoche AG, Genentech, Sage Therapeutics, Astellas and Arialis. He’s received personal compensation for serving on scientific advisory boards or data safety monitoring boards for F. Hoffman-LaRoche AG, Genentech, and UCB. His institution has received compensation for serving as a consultant for Astellas, Alexion/Astra Zeneca Rare Diseases, and Horizon/Amgen. All compensation is paid to Mayo Clinic. He has received research support from Alexion/Astra Zeneca Rare Diseases, Horizon/Amgen, F. Hoffman-LaRoche AG, Genentech and Adimmune. He has a patent, Patent# 8,889,102 (Application#12-678350, Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia)—issued; a patent, Patent# 9,891,219B2 (Application#12-573942, Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive)-issued and from which he has received royalties. He is working as a consultant in the Mayo Clinic Neuroimmunology laboratory clinical service. He has patents issued for a variety of target antigens including MAP1B-IgGs, KLCHL11, SKOR2, and LUZP4 IgGs. Anastasia Zekeridou has patents submitted for Tenascin-R-IgG, PDE10A-IgG, CAMKV-IgG, and DACH1-IgG as biomarkers of paraneoplastic neurological autoimmunity. She has received research funding from Roche not relevant to this work and the Mayo Clinic Center for MS and Autoimmune Neurology. She’s consulted, without personal compensation, for Alexion Pharmaceuticals. Andrew McKeon reports research funding from National Institutes of Health (NIH: RO1NS126227, U01NS120901), patents issued for GFAP and MAP1B-IgGs and patents pending for CAMKV, PDE10A, Septins-5 and -7, and KLCHL11-IgGs, and has consulted for Janssen and Roche pharmaceuticals, without personal compensation. Ethical approval: This retrospective study was approved by the Mayo Clinic Institutional Review Board (IRB, 21-001297). Medical records of patients who consented to research review were included., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.) more...
- Published
- 2024
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