Use of Cerebrospinal Fluid Biomarkers in Diagnosis and Monitoring of Rheumatoid Meningitis

Abstract

Rheumatoid meningitis is a rare extra-articular manifestation of rheumatoid arthritis, often with non-specific symptoms. In most cases brain MRI shows a patchy lepto- and pachymeningeal enhancement, but the diagnosis currently relies on examination of a meningeal biopsy with presence of plasma cells and rheumatoid noduli. Presence of IgM rheumatic factor (RF) has been found in several cases and recently four cases have shown high titer anti-cyclic citrullinated peptide (anti-CCP) in CSF, suggesting this as a potential marker for rheumatoid meningitis. We present a 62 year-old woman with sero-positive (IgM RF and anti-CCP) rheumatoid arthritis, presenting with headache and gait impairment. Brain MRI revealed the classical patchy meningeal enhancement and the diagnosis of rheumatoid meningitis was confirmed by neuropathological examination of a meningeal biopsy. Analysis of the CSF revealed positive IgM RF (92.7 IU/mL) and strongly positive anti-CCP (19,600 IU/mL) and CXCL-13 (>500 ng/L). After treatment with high-dose steroid and Rituximab the clinical symptoms resolved. A 6 month follow-up analysis of CSF showed a dramatic decrease in all these markers with negative IgM RF and a decrease in both anti-CCP (64 IU/mL) and CXCL-13 (<10 ng/L). Our case further underlines the potential use of CSF anti-CCP and IgM RF in the diagnosis of RM and the use of these markers and CXCL-13 in evaluation of treatment response. A case review of 48 cases of rheumatoid meningitis published since 2010, including, symptoms, serum, and CSF findings, treatment, and outcome is provided.

Keywords: CXCL13; anti-CCP; biomarker; inflammation; rheumatoid meningitis.

Figure 1

T1-weighted brain MRI showing interhemispheric leptomeningeal Gd+ enhancement before (A) and after (B) treatment with high dose steroids, Methotrexate and Rituximab. On gross inspection meninges appear severely inflamed (C) and pathological examination reveals massive meningeal granulomatous inflammation (D) with pre-dominant CD138 positive plasma cells (E), but also CD3 positive T cells (F). Massive infiltration with CD68 positive histiocytes with rheumatic granuloma formation was also seen (G).