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Observational Study
. 2025 Jul 16;96(8):736-743.
doi: 10.1136/jnnp-2024-334957.

Autoimmune encephalitis: recovery, residual symptoms and predictors of long-term sequelae

Smathorn Thakolwiboon  1   2 , Michael Gilligan  3 , Emma Orozco  1 , Jeffrey W Britton  1 , Divyanshu Dubey  1   3 , Eoin P Flanagan  1   3 , A Sebastian Lopez-Chiriboga  4 , Kelsey Smith  1 , Cristina Valencia-Sanchez  5 , Nicholas L Zalewski  5 , Anastasia Zekeridou  1   3 , Sean J Pittock  1   3 , Andrew McKeon  6   3
Affiliations
Observational Study

Autoimmune encephalitis: recovery, residual symptoms and predictors of long-term sequelae

Smathorn Thakolwiboon et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: Data regarding long-term recovery from autoimmune encephalitis (AE) remain limited.

Methods: This retrospective observational study investigated outcomes in 182 patients who met the 2016 criteria for definite AE. Recovery data were available in 172 patients. Follow-up data at ≥24 months post-attack were available for 119. Recovery trajectory, residual symptoms, outcome predictors and causes of post-AE death were assessed.

Results: Of 172 patients, 138 (80%) achieved good recovery (modified Rankin Scale (mRS) ≤2) with a median recovery time of 4 months (95% CI: 2 to 6 months). Recovery varied by associated neural antibody, with the best recovery observed in leucine-rich glioma-inactivated 1 (97% good recovery, median recovery time 0 (0 to 2) months). Paraneoplastic AE (p=0.007), severe attacks (eg, mRS ≥4 at attack, p=0.007) and cerebrospinal fluid pleocytosis (p=0.005) were associated with a lower likelihood of good recovery, while seizure presentation (p=0.026) was associated with better recovery. Despite good recovery, several residual symptoms persisted ≥24 months post-AE, including cognitive deficits (53%), seizures (26%), depression (23%), sleep disorders (25%), brainstem/cerebellar symptoms (13%), other movement disorders (14%) and autonomic symptoms (12%). Predictors of long-term sequelae included disabling cognitive deficit at onset and delayed immunotherapy for post AE-dementia, and medial temporal atrophy as well as escalation to cyclophosphamide therapy for both drug-resistant epilepsy and chronic depression. Of 182 patients, 20 (11%) died; the most common cause of death was progression of AE (6/20 (30%)).

Conclusion: While the majority of patients achieved functional independence after AE, several residual symptoms persisted. Several clinical and paraclinical features were associated with long-term sequelae.

Keywords: AUTOIMMUNE ENCEPHALITIS; NEUROIMMUNOLOGY; Patient Outcome Assessment.

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Conflict of interest statement

Competing interests: ST reports no disclosure relevant to this study. MG has a patent pending for CAMKV-IgG. EO reports no disclosure relevant to this study. JWB has an inventor agreement with Seer Medical. DD reports a patent for KLHL11 pending, a patent for LUZP4 pending, and a patent for CAVIN4 pending, has consulted for UCB, Astellas, Argenx, Immunovant and Arialys pharmaceuticals (all compensation paid directly to Mayo Clinic), and has participated in advisory boards for UCB who has upcoming treatment trial in LGI IgG autoimmune encephalitis; and Mayo Clinic Laboratories offer commercial testing for LGI1-IgG, but none of the authors receive financial compensation for this. EPF 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. EPF was a site primary investigator in a randomised clinical trial on Inebilizumab in neuromyelitis optica spectrum disorder run by Medimmune/Viela-Bio/Horizon Therapeutics. EPF has received funding from the NIH (R01NS113828). EPF is a member of the medical advisory board of the MOG project. EPF is an editorial board member of the Journal of the Neurological Sciences and Neuroimmunology Reports. A patent has been submitted on DACH1-IgG as a biomarker of paraneoplastic autoimmunity. ASL-C has received personal compensation for participating in scientific advisory boards for Genentech and Horizon. KS is a site primary investigator for a study funded by UCB Pharmaceuticals. CV-S reports no disclosure relevant to this study. NLZ reports no disclosure relevant to this study. AZ has received research funding from Roche and the Mayo Clinic Center for MS and Autoimmune Neurology relevant to this work. Roche funded this project. SJP reports grants, personal fees and non-financial support from Alexion Pharmaceuticals; grants, personal fees and non-financial support from Amgen (previously MedImmune /Viela Bio/Horizon); grants, personal fees and non-financial support from Genentech, Roche; grants from Adimune, and personal fees for consulting from UCB, Astellas and Arialys and Sage Therapeutics. He has two patents issued (8889102; application 12-678350; Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia; and 9891219B2; application 12-573942; Methods for Treating Neuromyelitis Optica [NMO] by Administration of Eculizumab to an individual that is Aquaporin-4 [AQP4]-IgG Autoantibody positive) for which he has received royalties. He also has patents pending for IgGs to the following proteins as biomarkers of autoimmune neurological disorders: septin-5, kelch-like protein 11, GFAP, PDE10A and MAP1B. He works at Mayo Clinic, which offers commercial MOG-IgG and AQP4-IgG testing. He receives no royalties from the sale of tests done at the neuroimmunology Laboratory at Mayo Clinic. AM reports research funding from National Institutes of Health (NIH: RO1NS126227, U01NS120901), patents issued for GFAP and MAP1B-IgGs and patents pending for CAMKV, PDE10A, Septin-5 and Septin -7 and KLHL11-IgGs, and has consulted for Janssen and Roche pharmaceuticals, without personal compensation.

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