Rheumatoid meningitis: A systematic review and meta-analysis

Eur J Neurol. 2021 Sep;28(9):3201-3210. doi: 10.1111/ene.14904. Epub 2021 Jun 29.


Background and purpose: Rheumatoid meningitis (RM) is a neurological complication of rheumatoid arthritis (RA). Current evidence is based on case reports and partial reviews.

Methods: This is a systematic review and meta-analysis following the PRISMA statement. The aim is to describe the characteristics of the disease, including clinical, imaging and laboratory findings, treatment, outcomes and prognosis reported in the literature.

Results: In all, 103 studies with 130 cases were included. RM affected adults with an average age of 62 years, with or without a previous RA diagnosis. RA activity and time with the disease were associated with a worse prognosis. Most common clinical manifestations were transient focal neurological signs (64.6%), systemic symptoms (51.3%), episodic headache (50.4%) and neuropsychiatric alterations (47.7%). Joint manifestations were present in only 27.4% of cases. Brain magnetic resonance imaging showed unilateral or bilateral involvement, predominantly frontoparietal. Both pachymeninges and leptomeninges were affected, the latter more frequently (82.88%). The laboratory findings included increased levels of rheumatoid factor (89.71%), anti-cyclic citrullinated peptide (89.47%), C-reactive protein (82.54%) and erythrocyte sedimentation rate (81.81%). Cerebrospinal fluid analysis showed an increase in the protein level (76.14%), with pleocytosis (85.19%) of mononuclear predominance (89.19%). Biopsy was performed in 72.52% of the patients. Corticosteroid pulse therapy was the main induction therapy. Disease relapse occurred in 31.17% of patients, whilst 54.54% had a full recovery.

Conclusions: Rheumatoid meningitis must be considered in adult patients with or without RA diagnosis, high-dose corticosteroid induction therapy should be installed and maintenance therapy plays a key role. It is not recommended to use anti-TNF as an induction therapy. Nowadays, RM has a significantly better outcome. These findings may aid clinicians in timely RM diagnosis and treatment, thus improving its outcomes.

Keywords: meningitis; meta-analysis; rheumatoid arthritis; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / diagnosis
  • Arthritis, Rheumatoid* / drug therapy
  • Brain
  • Humans
  • Magnetic Resonance Imaging
  • Meningitis* / diagnosis
  • Meningitis* / epidemiology
  • Middle Aged
  • Tumor Necrosis Factor Inhibitors


  • Tumor Necrosis Factor Inhibitors