Antibodies Associated With Autoimmune Encephalitis in Patients With Presumed Neurodegenerative Dementia

Anna E.M. Bastiaansen, Robin W. van Steenhoven, Esmee S. Te Vaarwerk, Wiesje M. van der Flier, Charlotte Teunissen, Esther de Graaff, Mariska M.P. Nagtzaam, Manuela Paunovic, Suzanne C. Franken, Marco W.J. Schreurs, Frank Leypoldt, Peter A.E. Smitt, Juna M. de Vries, Harro Seelaar, John van Swieten, Frank Jan de Jong, Yolande A.L. Pijnenburg, Maarten J. Titulaer*

*Corresponding author for this work

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Abstract

BACKGROUND & OBJECTIVES: Autoimmune encephalitis (AIE) may present with prominent cognitive disturbances without overt inflammatory changes in MRI and CSF. Identification of these neurodegenerative dementia diagnosis mimics is important because patients generally respond to immunotherapy. The objective of this study was to determine the frequency of neuronal antibodies in patients with presumed neurodegenerative dementia and describe the clinical characteristics of the patients with neuronal antibodies. METHODS: In this retrospective cohort study, 920 patients were included with neurodegenerative dementia diagnosis from established cohorts at 2 large Dutch academic memory clinics. In total, 1,398 samples were tested (both CSF and serum in 478 patients) using immunohistochemistry (IHC), cell-based assays (CBA), and live hippocampal cell cultures (LN). To ascertain specificity and prevent false positive results, samples had to test positive by at least 2 different research techniques. Clinical data were retrieved from patient files. RESULTS: Neuronal antibodies were detected in 7 patients (0.8%), including anti-IgLON5 (n = 3), anti-LGI1 (n = 2), anti-DPPX, and anti-NMDAR. Clinical symptoms atypical for neurodegenerative diseases were identified in all 7 and included subacute deterioration (n = 3), myoclonus (n = 2), a history of autoimmune disease (n = 2), a fluctuating disease course (n = 1), and epileptic seizures (n = 1). In this cohort, no patients with antibodies fulfilled the criteria for rapidly progressive dementia (RPD), yet a subacute deterioration was reported in 3 patients later in the disease course. Brain MRI of none of the patients demonstrated abnormalities suggestive for AIE. CSF pleocytosis was found in 1 patient, considered as an atypical sign for neurodegenerative diseases. Compared with patients without neuronal antibodies (4 per antibody-positive patient), atypical clinical signs for neurodegenerative diseases were seen more frequently among the patients with antibodies (100% vs 21%, p = 0.0003), especially a subacute deterioration or fluctuating course (57% vs 7%, p = 0.009). DISCUSSION: A small, but clinically relevant proportion of patients suspected to have neurodegenerative dementias have neuronal antibodies indicative of AIE and might benefit from immunotherapy. In patients with atypical signs for neurodegenerative diseases, clinicians should consider neuronal antibody testing. Physicians should keep in mind the clinical phenotype and confirmation of positive test results to avoid false positive results and administration of potential harmful therapy for the wrong indication.

Original languageEnglish
JournalNeurology(R) neuroimmunology & neuroinflammation
Volume10
Issue number5
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Study Funding:
M.J. Titulaer was supported by an Erasmus MC fellowship
and has received funding from the Netherlands Organization
for Scientific Research (NWO, Veni incentive), ZonMw
(Memorabel program), the Dutch Epilepsy Foundation
(NEF 14-19 & 19-08), Dioraphte (2001 0403), and E-RARE
JTC 2018 (UltraAIE, 90030376505). F. Leypoldt has received
funding from the German Ministry of Education and Research (01GM1908A) and the Era-Net funding program
(LE3064/2-1).

Publisher Copyright:
Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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