Abstract
Background and Objectives Neurotropic viruses are suspected to play a role in the pathogenesis of autoimmune diseases of the CNS such as the association between the Epstein-Barr virus (EBV) and multiple sclerosis (MS). A group of autoimmune encephalitis (AE) is linked to antibodies against neuronal cell surface proteins. Because CNS infection with the herpes simplex virus can trigger anti–NMDA receptor (NMDAR) encephalitis, a similar mechanism for EBV and other neurotropic viruses could be postulated. To investigate for previous viral infections of the CNS, intrathecally produced virus-specific antibody synthesis was determined in patients with AE.
Methods Antibody-specific indices (AIs) against EBV and measles, rubella, varicella zoster, herpes simplex virus, and cytomegalovirus were determined in 27 patients having AE (anti-NMDAR encephalitis, n = 21, and LGI1 encephalitis, n = 6) and in 2 control groups comprising of 30 patients with MS and 21 patients with noninflammatory CNS diseases (NIND), which were sex and age matched.
Results An intrathecal synthesis of antibodies against EBV was found in 5/27 (19%) patients with AE and 2/30 (7%) of the patients with MS. All these patients had also at least 1 additional elevated virus-specific AI. In contrast, in none of the patients with NIND, an elevated virus-specific AI was detected.
Discussion Intrathecally produced antibodies against EBV can be found in patients with AE and MS but only together with antibodies against different neurotropic viruses. Evidence of these antibodies is the result of a polyspecific immune response similar yet distinct from MS response rather than an elapsed infection of the CNS.
Glossary
- AE=
- autoimmune encephalitis;
- AI=
- antibody-specific index;
- CMV=
- cytomegalovirus;
- EBNA-1=
- EBV-encoded nuclear antigen-I;
- EBV=
- Epstein-Barr virus;
- EBV-VCA=
- EBV-virus capsid antigen;
- HSV=
- herpes simplex virus;
- LGI1=
- leucine-rich, glioma-inactivated 1;
- mRS=
- modified Rankin Scale;
- MRZ=
- measles, rubella, varicella zoster;
- MS=
- multiple sclerosis;
- NIND=
- noninflammatory neurologic disease;
- NMDAR=
- NMDA receptor;
- NPH=
- normal pressure hydrocephalus;
- IIH=
- idiopathic intracranial hypertension;
- OCB=
- oligoclonal band;
- QAlb=
- CSF/serum albumin ratio;
- VZV=
- varicella zoster virus
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
German Network for Research on Autoimmune Encephalitis (GENERATE) coinvestigators are listed in Appendix 2 at links.lww.com/NXI/A541.
The Article Processing Charge was funded by Hannover Medical School.
- Received March 24, 2021.
- Accepted in final form June 21, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Letters: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.