Comorbidities and Their Influence on Outcomes and Infectious Complications in Autoimmune Encephalitis A Multicenter Cohort Study

Bohn A, Angstwurm K, Bien CG, Doppler K, Ehmke L, Havla J, Hoffmann F, Hudasch D, Klausewitz J, Konen FF, Korporal-Kuhnke M, Kraft A, Kümpfel T, Leypoldt F, Madlener M, Pfeffer LK, Pfeuffer S, Pul D, Rada A, Rauer S, Sänger C, Seifert-Held T, Sühs KW, Thaler FS, Tsaktanis T, Vlad B, Wandinger KP, Wickel J, Tauber SC (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 12

Article Number: e200434

Journal Issue: 5

DOI: 10.1212/NXI.0000000000200434

Abstract

Background and Objectives Comorbidities greatly influence the course of many diseases. However, systematic data on comorbidities in patients with autoimmune encephalitis (AE) are scarce. We aimed to characterize comorbidities in patients with common AE variants and assess their influence on outcome and occurrence of infectious complications. Methods This multicenter, retrospective cohort study analyzed adult patients with definite anti-N-methyl-D-aspartate receptor (NMDAR), anti-leucine–rich glioma-inactivated-1 (LGI1), anti-contactin–associated protein-like-2 (CASPR2), and anti-immunoglobulin–like cell adhesion molecule-5 (IgLON5) AE registered by the GErman NEtwork for REsearch on AuToimmune Encephalitis between June 2004 and July 2023. Preexisting conditions (PECs), secondary diagnoses, and infectious complications documented during hospitalization were analyzed. Outcome was evaluated using a modified Rankin Scale (mRS), with unfavorable outcome defined as mRS >2 after a minimum of 12 months of follow-up. Results Among 308 patients with AE (144 NMDAR-AE, 98 LGI1-AE, 47 CASPR2-AE, and 19 IgLON5-AE), nearly half had cardiovascular and metabolic/endocrine, one-third neurologic, and one-fifth psychiatric comorbidities. Accompanying autoimmunity was observed in 12.7%. Univariable analysis showed that the presence of ≥3 PECs (OR 2.80, 95% CI 1.57–4.92), especially cardiovascular (OR 1.93, 95% CI 1.09–3.30) and psychiatric PECs (OR 3.84, 95% CI 1.96–7.31), was associated with unfavorable outcome. Multivariable regression analysis confirmed psychiatric PECs as independent risk factors (OR 4.55, 95% CI 1.99–10.60). During hospitalization, 13.6% of patients developed severe infections, although these were not associated with unfavorable outcome (OR 1.94, 95% CI 0.97–3.89). AE disease severity (OR 5.41, 95% CI 1.38–27.67) and intensive care unit admission emerged as the only independent predictors of severe infections (OR 20.76, 95% CI 7.02–75.10). Glossary Ab+ = antibody-positive; AE = autoimmune encephalitis; CASE = Clinical Assessment Scale in Autoimmune Encephalitis; CASEfu = Clinical Assessment Scale in Autoimmune Encephalitis after a minimum follow-up period of 12 months; CASEmax = Clinical Assessment Scale in Autoimmune Encephalitis at disease peak; CASPR2 = contactin-associated protein-like-2; GENERATE = GErman NEtwork for REsearch on AuToimmune Encephalitis; HLA = human leukocyte antigen; HSE = herpes simplex encephalitis; ICU = intensive care unit; IgLON5 = immunoglobulin-like cell adhesion molecule-5; LGI1 = leucine-rich glioma-inactivated-1; mRS = modified Rankin Scale; mRSdis = modified Rankin Scale at the time of hospital discharge; mRSfu = modified Rankin Scale after a minimum follow-up period of 12 months; mRSmax = modified Rankin Scale at disease peak; MS = multiple sclerosis; NMDAR = N-methyl-D-aspartate receptor; NMOSD = neuromyelitis optica spectrum disorder; PEG = percutaneous endoscopic gastrostomy; PEC = preexisting condition; SD = secondary diagnosis; SIADH = syndrome of inappropriate antidiuretica hormone secretion. Discussion As premorbid psychiatric conditions are main factors associated with unfavorable outcomes, these patients would highly benefit from integrated interdisciplinary treatment centers, or at least heightened awareness of these factors. Concomitant autoimmunity affecting other organs is frequent and should be sought. The risk of severe infections during the acute phase of AE is moderate and, given their lack of effect on outcome, should not justify withholding appropriate immunotherapy, even in elderly patients with comorbidities. Future prognostic models should incorporate comorbidities, particularly psychiatric ones, to enhance risk assessment and guide personalized care strategies.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Aachen (UKA) Germany (DE) Universitätsklinikum Regensburg Germany (DE) Universität Bielefeld Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Klinikum der Universität München Germany (DE) Krankenhaus Martha-Maria Halle-Dölau Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Köln Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Universitätsklinikum Freiburg Germany (DE) Alfried Krupp Krankenhaus Germany (DE) LKH Mural Austria (AT) Universitätsklinikum Jena Germany (DE)

How to cite

APA:

Bohn, A., Angstwurm, K., Bien, C.G., Doppler, K., Ehmke, L., Havla, J.,... Tauber, S.C. (2025). Comorbidities and Their Influence on Outcomes and Infectious Complications in Autoimmune Encephalitis A Multicenter Cohort Study. Neurology, Neuroimmunology and Neuroinflammation, 12(5). https://doi.org/10.1212/NXI.0000000000200434

MLA:

Bohn, Amelie, et al. "Comorbidities and Their Influence on Outcomes and Infectious Complications in Autoimmune Encephalitis A Multicenter Cohort Study." Neurology, Neuroimmunology and Neuroinflammation 12.5 (2025).

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