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August 20, 2018

Rheumatoid meningitis
A rare cause of aseptic meningitis with frequently stroke-like episodes

Simon Schuster, MD, Hanna Braass, MD, Christof Iking-Konert, MD, Ulrike Schnoor, MD, Jakob Matschke, MD, Christian Gerloff, MD, Götz Thomalla, MD, and Tim Magnus, MDAuthors Info & Affiliations
October 2018 issue
8 (5) 451-455
https://doi.org/10.1212/CPJ.0000000000000504
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Abstract

Background

Rheumatoid meningitis (RM) is a rare manifestation of rheumatoid arthritis (RA) and may present with stroke-like episodes. We describe diagnostic findings and the outcome in patients with RM.

Methods

We identified 6 patients with RM in different stages of RA mostly admitted with stroke-like episodes or common features of meningitis. We used MRI, CSF, and histology for in-depth characterization.

Results

We observed RM in 2 patients without history of RA, 1 patient with early seropositive RA, and 3 patients with late-stage RA. Recurrent stroke-like episodes occurred in 5 of 6 patients; headache and partial status epilepticus was in the foreground in 1 patient. Symptoms were accompanied by constitutional symptoms in all patients. MRI showed leptomeningeal or pachymeningeal fluid-attenuated inversion recovery hyperintensities with contrast enhancement. CSF mostly showed mild pleocytosis but can initially be normal. Anticitrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) were positive in all patients. Histopathology revealed granulomatous inflammation in 2 patients. Response to steroids was prompt and further immunosuppressive treatment prevented recurrence.

Conclusions

RM is a rare manifestation of RA and often presents with stroke-like episodes. It is currently not implemented in the workup of aseptic meningitis in national guidelines. Crucial clues for diagnosis included recurrent stroke-like episodes refractory to antiepileptic treatment, headache and constitutional symptoms, meningeal enhancement on MRI, CSF pleocytosis, and positive serology findings for ACPA and RF. Prognosis is favorable with early immunosuppressive treatment.

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Information & Authors

Information

Published In

Neurology® Clinical Practice
Volume 8 • Number 5 • October 2018
Pages: 451-455

Copyright

© 2018 American Academy of Neurology.

Publication History

Received: December 8, 2017
Accepted: May 8, 2018
Published online: August 20, 2018
Published in issue: October 2018

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Disclosure

S. Schuster has received funding for travel from Grifols. H. Braass has received funding for travel from Abbott and Boehringer Ingelheim. C. Iking-Konert serves on scientific advisory boards for Roche, Lilly, Jansen, Novartis, Sanofi, and GSK; has received funding for travel and/or speaker honoraria from Roche, Chugai, Lilly, Jansen, Medac, Novartis, Sanofi, MSD, and Pfizer; serves on the editorial board of Zeitschrift für Rheumatologie; serves on speakers' bureaus for GSK, Roche, Chugai, Lilly, Jansen, Medac, Novartis, MSD, Sanofi, and Pfizer; and receives research support from GSK, Roche, and Astra. U. Schnoor reports no disclosures. J. Matschke has participated in medico-legal cases. C. Gerloff serves on scientific advisory boards for Bayer Vital, Boehringer Ingelheim, Acticor Biotech, Amgen, and Prediction Biosciences; has received funding for travel and/or speaker/consulting honoraria from Bayer Vital, Boehringer Ingelheim, Sanofi Aventis, Amgen, EBS Technologies, GlaxoSmithKline, Lundbeck, Pfizer, Silk Road Medical, and UCB, and Abbott; serves on editorial boards for INFO Neurology Psychatrie and Aktuelle Neurologie and as editor of textbook Therapie und Verlauf neurologischer Erkrankungen; has received grants to supporting employees/scientists of his clinic from Merz Pharmaceuticals, Allergan, Novartis, and NeuroConn; and receives research support from Deutsche Forschungsgesellschaft, the European Union, Wegener Foundation, Schilling Foundation, and Werner-Otto-Foundation. G. Thomalla serves on a DSMB for the TEA Stroke Trial; has received travel for funding and/or speaker honoraria from Bayer, Boehringer Ingelheim, Daichii Sankyo, GlaxoSmithKline, and Bristol-Myers Squibb/Pfizer; serves as a consultant for Acandis and Stryker; and receives research support from Bayer, the European Union, Deutsche Forschungsgesellschaft, and Corona Foundation. T. Magnus has received funding for travel and/or speaker honoraria from Novartis, Merck-Serono, Grifols, Boehringer Ingelheim, and CSL Behring; and receives/has received research support from Novartis, Merck Serono, EU, BMBF, DFG, Schilling-Stiftung, and Werner Otto Society. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
Take-home Points
→ Recurrent stroke-like episodes with headache or constitutional symptoms should prompt further investigation for aseptic meningitis.
→ Rheumatoid meningitis should be considered in the differential diagnosis of aseptic meningitis even without history of rheumatoid disease.
→ Routine ACPA and RF testing in serum is useful in the diagnostic workup of patients with aseptic meningitis.
→ Steroids are an appropriate first-line therapy after exclusion of an infectious or malignant cause in aseptic meningitis.

Study Funding

No targeted funding reported.

Authors

Affiliations & Disclosures

Simon Schuster, MD*
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
funding for travel from Grifols
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Hanna Braass, MD*
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Abbott (St. Jude): travel-funding (DBS Akademie 2017 + Advanced Neurology Course 2017 in D?sseldorf, Germany) Boehringer Ingelheim Pharma GmbH & Co. KG: travel-funding and congress fee (DGN-Congress 2017, Leipzig, Germany)
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Christof Iking-Konert, MD
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
Roche, Lilly, Jansen, Novartis, Sanofi, GSK
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Roche, Chugai, Lilly, Jansen, Medac, Novartis, Sanofi, MSD, Pfizer
Editorial Boards:
1.
Zeitschrift f?r Rheumatologie
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
GSK, Roche, Chugai, Lilly, Jansen, Medac, Novartis, MSD, Sanofi, Pfizer
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
GSK, Roche, Astra
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Ulrike Schnoor, MD
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Jakob Matschke, MD
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
JM has given expert testimony for legal authorities in Germany as a Forensic Neuropathologist (all for cases totally unrelated to the present study)
View all articles by this author
Christian Gerloff, MD
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
(1) Bayer Vital (2) Boehringer Ingelheim (3) Acticor Biotech, (4) Amgene, (5) Prediction Bioscience, (6) EBS technologies, (7) Glaxo Smith Kline, (8) Lundbeck, (9) Pfizer, (10) Silk Road Medical, (11) UCB
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Bayer Vital, travel and speaker honoraria, (2) Boehringer Ingelheim, travel and speaker honoraria, (3) Sanofi Aventis, speaker honoraria
Editorial Boards:
1.
(1) INFO Neurology Psychatrie (2) Aktuelle Neurologie (3) Editor of Textbook "Therapie und Verlauf neurologischer Erkrankungen"
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Merz Pharmaceuticals*, (2) Allergan*, (3) Novartis*, (4) NeuroConn* *all grants were supporting employees/scientists of my clinic (no direct support of myself)
Research Support, Government Entities:
1.
(1) DFG: SFB 936, since 2011, ongoing, (2) BMBF/DFG NETS Trial, ongoing, (3) EU FP7: project grant WAKE-UP stroke trial, since 2011, ongoing, (4) DFG: TRR 169, since 2016, ongoing
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Wegener Foundation / Movement Disorders Science, (2) Schilling Foundation, translational stroke research, since 2016, ongoing program for two of my employees, (3) Werner-Otto-Foundation, (4) Wegener-Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Götz Thomalla, MD
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
(1) DSMB for the TEA Stroke Trial
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) Bayer, speaker honoraria; (2) Boheringer Ingelheim, speaker honoraria, travel; (3) Daichii Sankyo, speaker honoraria; (4) Bristol Myer Squibb/Pfizer, speaker honoraria, travel; (5) GlaxoSmithKline
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
(1) Acandis, consultant; (2) Stryker, consultant
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) Bayer
Research Support, Government Entities:
1.
1) European Union, Grant No. 278276 (WAKE-UP); (2) European Union, Grant No. 634809 (PRECIOUS); (3) European Union, Grant No. 754460 (TENSION)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Deutsche Forschungsgesellschaft, Grant SFB936, Project C2; (2) Corona Foundation, CONTEST study
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Tim Magnus, MD
Department of Neurology (SS, HB, CG, GT, TM), Center for Internal Medicine (US), and Institute of Neuropathology (JM), University Hospital Hamburg-Eppendorf; and Klinik für Rheumatologie und Immunologie (CI-K), Klinikum Bad Bramstedt, Germany.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
received honoraria as a speaker, research funding or advisor for Novartis, Merck-Serono, Grifols, Boehringer Ingelheim and CSL Behring
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
2013-2015: Novartis Research funds for the role of Fingolimod and BAF in stroke 100K? and Merk Serono Research funds for the role of P2X4 in neuroinflammation 120k?
Research Support, Government Entities:
1.
2012-2015: ERANET (EU/BMBF) funding of the ?NanoStroke? consortium ?Role of danger signals in stroke and therapeutic targeting by nanobodies? (Coordinator: Tim Magnus, Participants Friedrich Koch- Nolte, Hamburg; Christoph Kleinschnitz, W?rzburg; Anna Planas, Barcelona; Carlos Matute, Bilbao; Andrea La Sala, Rome) 1.2M? 2013-2016: Member of the ITN Marie Curie ?nEuroinflammation? coordinated by Prof. Dr. M. Schwanniger, L?beck 2014-2018: DFG Funding of 2 projects as part of the HAMPII - Hamburg Magnetic Particle Imaging Initiative 2016-2019: ERANET (EU/BMBF) funding of the ?NEUROSurv? consortium ?Neuronal Survival in Stroke? (Coordinator: Tim Magnus, Participants Christoph Kleinschnitz, W?rzburg; Simon DeMeyer, Leuven; Valerie Zinchenko, Moscow) 0.55M?
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
2011-2014: Werner Otto Society ?CD31 in stroke? 50K? Schilling-Stiftung
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author

Notes

Correspondence Dr. Schuster [email protected]
*
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/cp.

Author Contributions

S. Schuster: study concept and design, acquisition of data, analysis and interpretation of data, drafting the manuscript. H. Braass: study concept and design, acquisition of data, analysis and interpretation of data, drafting the manuscript. C. Iking-Konert: acquisition of data, analysis and interpretation of data, critical revision of manuscript. U. Schnoor: acquisition of data, analysis and interpretation of data. J. Matschke: acquisition of data, analysis and interpretation of data. C. Gerloff: analysis and interpretation of data, critical revision of manuscript. G. Thomalla: analysis and interpretation of data, critical revision of manuscript. T. Magnus: analysis and interpretation of data, critical revision of manuscript.

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