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.

Rheumatoid Meningitis a Rare Extra-Articular Manifestation of Rheumatoid Arthritis: Report of 6 Cases and Literature Review

“…Nissen et al described an elevated number of B-lymphocytes (7.8%), plasma cells (1.8%) associated with a remarkable high ACPA level (19,000 UI/mL), high IgG index (1.45), and overexpression of CXCL13 in CSF of RA patient with RM. After IV high dose methylprednisolone and Rituximab treatment, ACPA and CXCL13 levels were seriously decreased in CSF in accordance with clinical symptoms resolution [32]. These data can suggest a local CNS synthesis of ACPA.…”

CXCL13/CXCR5 signalling is pivotal to preserve motor neurons in amyotrophic lateral sclerosis

“…Measuring CXCL13 concentration in the CSF could be a clinical adjunct to discriminate ALS from other neurological diseases. This because, unlike ALS, CXCL13 dramatically increased in the CSF of patients with other inflammatory diseases such as encephalitis [66], chronic inflammatory demyelinating polyneuropathy [67], MS [26,68], LMN [51] or rheumatoid meningitis [69].…”

Rheumatoid arthritis with pachymeningitis – a case presentation and review of the literature

“…Elevated serum ACE and β-2 microglobulin were reported by Pellerin et al [15] and McKenna et al [8] although, these findings haven't been clearly associated with RM [8,15]. Some patients had pulmonary manifestations in the form of nodules or pleural effusions which were attributed as extra-articular manifestations of RA after examinations [22,32,35].…”

“…In some cases there was presence of RF or ACPA [3,34,35] antibodies in undiluted CSF therefore presence of RF or ACPA antibodies in the CSF could be a good diagnostic marker of RM, but these are not present in all the cases. Current biomarkers include serum RF, ACPA and these findings are quite persistent in RM patients with either one or both being present in all the 29 cases.…”

“…Preferred treatment method was intravenous methylprednisolone followed by oral prednisolone. Treatment for RA was continued or was changed to rituximab which successfully managed the RA progression [1,3,7,25,35]. Elevated serum ACE and β-2 microglobulin were reported by Pellerin et al [15] and McKenna et al [8] although, these findings haven't been clearly associated with RM [8,15].…”