Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Diversity, Equity, & Inclusion (DEI)
    • Innovations in Care Delivery
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

March 2019; 6 (2) Clinical/Scientific NotesOpen Access

Anti-NMDAR encephalitis with concomitant varicella zoster virus detection and nonteratomatous malignancy

Preeti A. Prakash, Jingxiao Jin, Kanwal Matharu, Tanu Garg, Wendy C. Tsai, Purvesh Patel, Jill E. Weatherhead, Joseph S. Kass
First published January 9, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000537
Preeti A. Prakash
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jingxiao Jin
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kanwal Matharu
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tanu Garg
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wendy C. Tsai
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Purvesh Patel
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jill E. Weatherhead
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph S. Kass
From the Department of Internal Medicine (P.A.P., K.M.), Department of Neurology (J.J., T.G., J.S.K.), Department of Anesthesia (W.C.T.), and Department of Pulmonary, Critical Care, and Sleep Medicine (P.P.), Baylor College of Medicine; and National School of Tropical Medicine (J.E.W.), Baylor College of Medicine, Houston, TX.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Full PDF
Citation
Anti-NMDAR encephalitis with concomitant varicella zoster virus detection and nonteratomatous malignancy
Preeti A. Prakash, Jingxiao Jin, Kanwal Matharu, Tanu Garg, Wendy C. Tsai, Purvesh Patel, Jill E. Weatherhead, Joseph S. Kass
Neurol Neuroimmunol Neuroinflamm Mar 2019, 6 (2) e537; DOI: 10.1212/NXI.0000000000000537

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
679

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Case presentation

A 50-year-old woman with a recent diagnosis of poorly differentiated nonteratomatous cervicouterine cancer presented to our hospital for breath-holding episodes resulting in perioral cyanosis. Her medical history was significant for chickenpox at age 8 and shingles at age 15. Before her admission and 10 days after her cancer diagnosis, she was admitted to an outside hospital for confusion and intermittent catatonia. Workup at the outside hospital was unremarkable, and she was diagnosed with adjustment disorder. At home, she continued to decompensate and ultimately became incomprehensible, anorexic, and bedbound, prompting admission to our hospital.

On presentation, the patient was encephalopathic and dysautonomic. She was unresponsive to pain and exhibited diffuse hyperreflexia, episodes of generalized body tremors, and trismus to the point of transecting her tongue. Because of breath-holding spells with oxygen desaturations and the need to acquire a brain MRI, she was intubated. Her continuous EEG and brain MRI were unremarkable. Acyclovir was empirically started for 2 days but discontinued after CSF studies revealed lymphocytic pleocytosis (17 white blood cells/μL with 86% lymphocytes) with negative herpes simplex virus (HSV) PCR (figure). A 5-day course of intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG) for presumed anti-N-methyl-D-aspartate receptor encephalitis (NMDAR) encephalitis was administered. CSF testing for varicella zoster virus (VZV) by PCR returned positive, prompting a 21-day course of IV acyclovir. The NMDAR antibody CSF titer later also returned positive (1:50; Dalmau Laboratory, University of Pennsylvania, Philadelphia, PA). A diagnosis of anti-NMDAR encephalitis with concomitant VZV detection was made. A week into antiviral treatment, the patient's vital signs normalized and agitation decreased. By discharge, the patient was alert, oriented, and following simple commands but not yet at neurologic baseline.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure Time course of the patient's diagnostics and treatment

The patient initially presented to an outside hospital for altered behavior and was discharged home with a psychiatric diagnosis. When she continued to deteriorate, she presented to our hospital with breath-holding spells, encephalopathy, and dysautonomia. The patient completed a 5-day course of IVMP and IVIG for presumed anti-NMDAR encephalitis. She was initially started on broad-spectrum antibiotics and acyclovir, which were discontinued after a negative HSV PCR. Once her CSF returned positive for VZV, she was started on a 21-day course of acyclovir. HSV = herpes simplex virus; IVIG = intravenous immunoglobulin; IVMP = intravenous methylprednisolone; LP = lumbar puncture; VZV = varicella zoster virus.

Discussion

This case report demonstrates a rare presentation of anti-NMDAR encephalitis with concomitant VZV detection in the setting of a nonteratomatous gynecologic tumor.1,2 In a seminal case series published in 2008, about 60% of patients with anti-NMDAR encephalitis had a tumor, most often an ovarian teratoma.3 Anti-NMDAR encephalitis has also been linked with tumors of endocervical and endometrial origin.4 These tumors express NMDA receptor 1 (NR1), as well as synaptophysin, neuron-specific enolase, CD56, and chromogranin. Resection of tumors that express NRs can shorten recovery time.5 Our patient's tumor expressed synaptophysin, but NR1 testing was not performed. Thus, it is unknown whether her cervicouterine tumor demonstrates a true association with NMDAR immunoreactivity.

Neurotropic viruses, most frequently HSV, have been linked to anti-NMDAR encephalitis.6 One proposed mechanism for this association is that these viruses may lyse neurons, releasing antigens that sensitize IgG antibodies to the NR and triggering autoimmune encephalitis.1,2 Another hypothesis is that CNS inflammation from anti-NMDAR encephalitis may cause shedding of latent viral DNA or a viral reactivation leading to secondary encephalitis.7

To date, VZV has been documented twice in the setting of anti-NMDAR encephalitis.1,2 One patient presented with cranial nerve palsies and improved significantly after treatment with IV acyclovir and immunoadsorption. The other patient had a teratoma and presented with confusion and behavioral changes after a viral-like illness. She was refractory to treatment with teratoma resection, acyclovir, IVIG, and plasma exchange.

Our patient completed the full first-line therapy for both anti-NMDAR and VZV encephalitis. Although her improvement in symptoms correlated temporally with antiviral therapy, the effects of the IVMP and IVIG treatment cannot be discounted because the response to immunotherapy often lags behind its completion. Because she was treated for both disease processes, it is unclear whether VZV triggered our patient's autoimmune condition or was present in the CSF as a result of latent viral shedding. Her presenting symptoms were more consistent with anti-NMDAR encephalitis than VZV encephalitis. Nevertheless, we recommend antiviral treatment in cases of anti-NMDAR encephalitis with concomitant VZV detection because the immunosuppressive regimen for anti-NMDAR encephalitis may worsen an underlying VZV infection.

Previous literature suggests that anti-NMDAR encephalitis should be considered in any person aged 50 years or younger who presents with acute psychotic changes of less than 4 weeks' duration, especially in the setting of a viral prodrome or abnormal movements.5 Current standard of care for patients with suspected anti-NMDAR encephalitis is to treat with acyclovir until HSV PCR testing is complete. Our case is part of a growing body of evidence that suggests providers should continue antiviral treatment until VZV PCR testing has resulted negative as well. Additional research could investigate the optimum treatment course and prognosis when anti-NMDAR encephalitis presents with concomitant viral detection.

Study funding

No targeted funding reported.

Disclosure

P.A. Prakash and J. Jin report no disclosures. K. Matharu owns stock in Johnson and Johnson. T. Garg, W.C. Tsai, P. Patel, and J.E. Weatherhead report no disclosures. J.S. Kass received travel funding and/or speaker honoraria from the National Board of Medical Examiners, American Academy of Neurology, BrainPac; is an associate editor for Continuum and Continuum Audio; received publishing royalties from Elsevier; and has been a paid speaker for Pri-Med. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

Acknowledgment

The authors thank Dr. Jennifer Chu for her invaluable help in interpreting the patient's EEG studies.

Appendix 1 Author contributions

Table

Footnotes

  • ↵* These authors contributed equally to this work.

  • Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.

  • The Article Processing Charge was funded by the authors.

  • Received September 26, 2018.
  • Accepted in final form November 30, 2018.
  • Copyright © 2019 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.

References

  1. 1.↵
    1. Schäbitz WR,
    2. Rogalewski A,
    3. Hagemeister C,
    4. Bien CG
    . VZV brainstem encephalitis triggers NMDA receptor immunoreaction. Neurology 2014;83:2309–2311.
    OpenUrl
  2. 2.↵
    1. Solís N,
    2. Salazar L,
    3. Hasbun R
    . Anti-NMDA Receptor antibody encephalitis with concomitant detection of Varicella zoster virus. J Clin Virol 2016;83:26–28.
    OpenUrl
  3. 3.↵
    1. Dalmau J,
    2. Gleichman AJ,
    3. Hughes EG, et al
    . Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol 2008;7:1091–1098.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Hara M,
    2. Morita A,
    3. Kamei S, et al
    . Anti-N-methyl-D-aspartate receptor encephalitis associated with carcinosarcoma with neuroendocrine differentiation of the uterus. J Neurol 2011;258:1351–1353.
    OpenUrlPubMed
  5. 5.↵
    1. Dalmau J,
    2. Lancaster E,
    3. Martinez-Hernandez E,
    4. Rosenfeld MR,
    5. Balice-Gordon R
    . Clinical experience and laboratory investigations in patients with NMDAR encephalitis. Lancet Neurol 2011;10:63–74.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Nosadini M,
    2. Mohammad SS,
    3. Corazza F, et al
    . Herpes simplex virus-induced anti-N-methyl-d-aspartate receptor encephalitis: a systematic literature review with analysis of 43 cases. Dev Med Child Neurol 2017;59:796–805.
    OpenUrl
  7. 7.↵
    1. Linnoila J,
    2. Binnicker M,
    3. Majed M,
    4. Klein C,
    5. McKeon A
    . CSF herpes virus and autoantibody profiles in the evaluation of encephalitis. Neurol Neuroimmunol Neuroinflamm 2016;3:245. doi: 10.1212/NXI.0000000000000245.
    OpenUrl

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

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.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Case presentation
    • Discussion
    • Study funding
    • Disclosure
    • Acknowledgment
    • Appendix 1 Author contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

SARS-CoV-2 Vaccination Safety in Guillain-Barré Syndrome, Chronic Inflammatory Demyelinating Polyneuropathy, and Multifocal Motor Neuropathy

Dr. Jeffrey Allen and Dr. Nicholas Purcell

► Watch

Related Articles

  • No related articles found.

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Article
    Intrathecal Antibody Production Against Epstein-Barr, Herpes Simplex, and Other Neurotropic Viruses in Autoimmune Encephalitis
    Philipp Schwenkenbecher, Thomas Skripuletz, Peter Lange et al.
    Neurology: Neuroimmunology & Neuroinflammation, August 24, 2021
  • Article
    Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis
    Don Gilden, Teresa White, Nelly Khmeleva et al.
    Neurology, February 18, 2015
  • Article
    Varicella zoster virus, a cause of waxing and waning vasculitis
    The New England Journal of Medicine case 5-1995 revisited
    D. H. Gilden, B. K. Kleinschmidt-DeMasters, M. Wellish et al.
    Neurology, December 01, 1996
  • Articles
    The varicella zoster virus vasculopathies
    Clinical, CSF, imaging, and virologic features
    M. A. Nagel, R. J. Cohrs, R. Mahalingam et al.
    Neurology, March 10, 2008
Neurology - Neuroimmunology Neuroinflammation: 10 (3)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise