Case Report: Rheumatoid meningitis with positive NMDAR antibody: A case treated with intravenous immunoglobulin

Abstract

As a rare complication of rheumatoid arthritis (RA) in the central nervous system (CNS), rheumatoid meningitis (RM) mainly affects the meninges and has various clinical symptoms. The diagnostic and treatment approaches currently used are not practical. RM cases with positive NMDAR antibodies (Abs) have never been reported. In the present study, a 66-year-old man with a 1-year history of RA presented recurrent left lower limb weakness during activities for 1 month. The results showed that rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were positive in the serum, and NMDAR Abs were present in cerebrospinal fluid (CSF). Hyperintensity was observed in the leptomeninges of the right frontal and parietal lobes, and subtle hyperintensity was observed in the left frontal and parietal lobes, as indicated by brain MRI. A meningeal biopsy revealed non-specific inflammation with the absence of rheumatoid nodules. The patient was given IVIg on day 7 after admission. The clinical symptoms were relieved, the lesions were alleviated, and abnormal biochemical indicators were gradually recovered 1 week after initiation of the treatment, while NMDAR Abs were present in CSF even after treatment. After 5 months of follow-up, the patient’s serum and CSF ACPA and IL-6 levels were still high. The findings showed that brain MRI was adequate for the diagnosis of RM. ACPA and IL-6 might be the specific biomarkers for disease activity in RM. IVIg was effective as induction therapy for RM. Further studies should explore whether the presence of NMDAR Abs is associated with RM.

Overlapping rheumatoid meningitis with anti‐N‐methyl‐D‐aspartate receptor encephalitis: A case report

“… 23 As discussed in the above reports, 19 , 20 , 21 co‐exiting NMDAR antibodies should also be considered in infectious and autoimmune inflammatory pathologies of the CNS if the disease course is not monophasic, if the response to standard therapy is insufficient, or if atypical symptoms such as involuntary movements or psychiatric symptoms are also present. Although there are limited reports of the efficacy of IVIG in RM, 2 the present results suggest that IVIG may be effective in patients with RM with positive NMDAR antibodies. However, there have been limited case reports to date, and further cases and research on the frequency of NMDAR antibodies positivity in RM, pathological links, clinical course, and treatment methods are warranted.…”

“… 19 There is only one case of RM reported to date in which NMDAR antibodies in the CSF were positive. 2 However, in the previous report, the only symptom was paroxysmal weakness of the lower limbs, so the diagnostic criteria for anti‐NMDAR encephalitis were not met. In addition, NMDAR antibodies in the CSF were weakly positive (titer 1:1), suggesting that the involvement of NMDAR antibodies in the pathogenesis of the disease is uncertain.…”

“…The cause of anti‐NMDAR encephalitis is unknown, but possible mechanisms such as molecular homology or the release of NMDAR from neurons as a result of viral infection or autoimmune inflammation have been suggested 19 . There is only one case of RM reported to date in which NMDAR antibodies in the CSF were positive 2 . However, in the previous report, the only symptom was paroxysmal weakness of the lower limbs, so the diagnostic criteria for anti‐NMDAR encephalitis were not met.…”

“…Recently, there have been increasing reports of anti‐NMDAR encephalitis complicating demyelinating diseases of the CNS and autoimmune meningoencephalitis, but there are quite limited case reports of positive NMDAR antibodies in cerebrospinal fluid (CSF) in rheumatic meningitis (RM). 2 Furthermore, there have been no reports in which the presence of NMDAR antibodies in the CSF is thought to be directly related to clinical symptoms. Here, we report a case of overlapping RM with anti‐NMDAR encephalitis that was successfully treated with intravenous immunoglobulin (IVIG).…”

“…Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis caused by antibodies against NMDAR. Recently, there have been increasing reports of anti‐NMDAR encephalitis complicating demyelinating diseases of the CNS and autoimmune meningoencephalitis, but there are quite limited case reports of positive NMDAR antibodies in cerebrospinal fluid (CSF) in rheumatic meningitis (RM) 2 . Furthermore, there have been no reports in which the presence of NMDAR antibodies in the CSF is thought to be directly related to clinical symptoms.…”