Autoimmune Encephalitis Resembling Dementia Syndromes

Anna E M Bastiaansen; Robin W van Steenhoven; Marienke A A M de Bruijn; Yvette S Crijnen; Agnes van Sonderen; Marleen H van Coevorden-Hameete; Marieke M Nühn; Marcel M Verbeek; Marco W J Schreurs; Peter A E Sillevis Smitt; Juna M de Vries; Frank Jan de Jong; Maarten J Titulaer

doi:10.1212/NXI.0000000000001039

Autoimmune Encephalitis Resembling Dementia Syndromes

Neurol Neuroimmunol Neuroinflamm. 2021 Aug 2;8(5):e1039. doi: 10.1212/NXI.0000000000001039. Print 2021 Sep.

Affiliations

¹ From the Department of Neurology (A.E.M.B., R.W.v.S., Y.S.C., M.H.v.C.-H., P.A.E.S.S., J.M.d.V., M.J.T.), Erasmus MC University Medical Center, Rotterdam; Department of Neurology, VU University Medical Center, Amsterdam (R.W.v.S.); Department of Neurology (M.A.A.M.d.B.), Elisabeth Tweesteden Medical Center, Tilburg; Department of Neurology (A.v.S.), Haaglanden Medical Center, The Hague; Honours Student Bachelor Biomedical Sciences (M.M.N.), University Utrecht; Department of Neurology and Laboratory Medicine (M.M.V.), Donders Institute for Brain Cognition and Behavior, Radboud University Medical Center, Nijmegen; Department of Immunology (M.W.J.S.), Erasmus MC University Medical Center, Rotterdam; and Alzheimer Center Erasmus MC (F.J.d.J.), Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
² From the Department of Neurology (A.E.M.B., R.W.v.S., Y.S.C., M.H.v.C.-H., P.A.E.S.S., J.M.d.V., M.J.T.), Erasmus MC University Medical Center, Rotterdam; Department of Neurology, VU University Medical Center, Amsterdam (R.W.v.S.); Department of Neurology (M.A.A.M.d.B.), Elisabeth Tweesteden Medical Center, Tilburg; Department of Neurology (A.v.S.), Haaglanden Medical Center, The Hague; Honours Student Bachelor Biomedical Sciences (M.M.N.), University Utrecht; Department of Neurology and Laboratory Medicine (M.M.V.), Donders Institute for Brain Cognition and Behavior, Radboud University Medical Center, Nijmegen; Department of Immunology (M.W.J.S.), Erasmus MC University Medical Center, Rotterdam; and Alzheimer Center Erasmus MC (F.J.d.J.), Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. m.titulaer@erasmusmc.nl.

Abstract

Objective: As autoimmune encephalitis (AIE) can resemble neurodegenerative dementia syndromes, and patients do not always present as encephalitis, this study evaluates how frequently AIE mimics dementia and provides red flags for AIE in middle-aged and older patients.

Methods: In this nationwide observational cohort study, patients with anti-leucine-rich glioma-inactivated 1 (LGI1), anti-NMDA receptor (NMDAR), anti-gamma-aminobutyric acid B receptor (GABA_BR), or anti-contactin-associated protein-like 2 (CASPR2) encephalitis were included. They had to meet 3 additional criteria: age ≥45 years, fulfillment of dementia criteria, and no prominent seizures early in the disease course (≤4 weeks).

Results: Two-hundred ninety patients had AIE, of whom 175 were 45 years or older. Sixty-seven patients (38%) fulfilled criteria for dementia without prominent seizures early in the disease course. Of them, 42 had anti-LGI1 (48%), 13 anti-NMDAR (52%), 8 anti-GABA_BR (22%), and 4 anti-CASPR2 (15%) encephalitis. Rapidly progressive cognitive deterioration was seen in 48 patients (76%), whereas a neurodegenerative dementia syndrome was suspected in half (n = 33). In 17 patients (27%; 16/17 anti-LGI1), subtle seizures had been overlooked. Sixteen patients (25%) had neither inflammatory changes on brain MRI nor CSF pleocytosis. At least 1 CSF biomarker, often requested when dementia was suspected, was abnormal in 27 of 44 tested patients (61%), whereas 8 had positive 14-3-3 results (19%). Most patients (84%) improved after immunotherapy.

Conclusions: Red flags for AIE in patients with suspected dementia are: (1) rapidly progressive cognitive decline, (2) subtle seizures, and (3) abnormalities in ancillary testing atypical for neurodegeneration. Physicians should be aware that inflammatory changes are not always present in AIE, and that biomarkers often requested when dementia was suspected (including 14-3-3) can show abnormal results. Diagnosis is essential as most patients profit from immunotherapy.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Autoimmune Diseases of the Nervous System / epidemiology*
Autoimmune Diseases of the Nervous System / immunology
Cohort Studies
Dementia / epidemiology*
Dementia / immunology
Encephalitis / epidemiology*
Encephalitis / immunology
Female
Humans
Male
Middle Aged
Syndrome