Central nervous system involvement, in the form of meningitis or vasculitis with or without meningeal nodules, is a rare complication of rheumatoid arthritis (RA).1 It can be independent of disease activity or duration.2 Exact pathology remains unclear but it is associated with infiltration of mononuclear cells around small vessels in the leptomeninges. Rheumatoid meningitis can present as altered mental status (most common), cranial neuropathies, hemiparesis/paraparesis, seizure, and headache. To our knowledge, strokelike symptoms as the initial presentation has rarely been reported.1,2 Here, we report a case of rheumatoid meningitis presenting with multiple strokelike episodes.
A woman in her late 50s with RA for many years, well controlled with methotrexate and sulfasalazine, initially developed mild aphasia and confusion lasting for several hours. A month later, she developed sudden-onset right leg weakness, which resolved within 2 days. Two months later, she presented to our hospital with mild headache and right facial droop. She had controlled hypertension and hyperlipidemia. She had never received any other immunomodulators. Her neurological examination was significant for some paraphasic errors, word-finding difficulty, mild right nasolabial flattening, and bilateral upgoing plantars without any motor or sensory deficits.
Magnetic resonance imaging of the brain showed extensive white matter changes with enhancement along the arachnoid surface in the interhemispheric fissure extending over the frontal lobes bilaterally without any evidence of acute infarct in diffusion-weighted imaging sequence or any vascular abnormality on magnetic resonance angiography (Figure). Her erythrocyte sedimentation rate and C-reactive protein level were elevated. A high titer of cyclic citrullinated peptide antibody confirmed RA. Cerebrospinal fluid (CSF) analysis showed a white blood cell count of 12/µL (to convert to ×109 per liter, multiply by 0.001), red blood cell count of 1/µL, protein level of 0.055 g/dL (to convert to grams per liter, multiply by 10), glucose level of 58 mg/dL, and 4 oligoclonal bands corresponding to serum sample. Results from infectious disease workups, including rapid plasma reagin, QuantiFERON (Qiagen), and human immunodeficiency virus, were negative. Chest computed tomography did not reveal any pathology or pulmonary nodules. Cerebrospinal fluid angiotensin-converting enzyme level was not elevated. Extensive workup was done to rule out coexisting immunological disorders, especially antiphospholipid syndrome. Lupus anticoagulant test results for partial thromboplastin time–lupus anticoagulant (PTT-LA) was 36 seconds and for dilute Russell viper venom test (DRVVT) was 27 seconds. Both were within normal range. Anticardiolipin IgG, IgA, and IgM levels were 8 IgG, 2 IgA, and 5 IgM phospholipid units, respectively, where values less than 23 IgG, less than 22 IgA, and less than 11 IgM phospholipid units, respectively, are considered negative. Anti–β-2-glycoprotein IgG, IgA, and IgM levels were 1, 7, and 8 U (<20 U is normal). These results eliminated antiphospholipid syndrome. Antineutrophil cytoplasmic antibody test results were negative (Table).
Magnetic resonance imaging of the brain showing enhancement along the arachnoid surface of the brain (white arrowhead) in the interhemispheric fissure extending over the frontal lobes bilaterally (B and C). D, Biopsy of the brain showing thick exudate in the subarachnoid space, the outer portion consisting of necrotic cells (black arrowhead) lying beneath the arachnoid membrane, the inner portion consisting of lymphocytes and plasma cells with multinucleated giant cells (black ellipse) in the interface between necrotic tissue and viable inflammatory cells (hematoxylin-eosin, original magnification ×40).
Brain biopsy showed thick exudate in the subarachnoid space. The outer portion had necrotic cells lying beneath the arachnoid membrane and the inner portion reflected lymphocytes and plasma cells with occasional Russell bodies and eosinophils. There were multinucleated giant cells between necrotic tissue and viable inflammatory cells (Figure). There was no evidence of vasculitis. The histopathological finding was consistent with rheumatoid meningitis. Special staining ruled out tuberculosis or any fungal infection. A diagnosis of rheumatoid meningitis was made based on imaging findings and histopathological findings after the exclusion of other potential causes of granulomatous meningitis and infections. The patient was empirically treated with mycophenolate mofetil and corticosteroid, while methotrexate was discontinued. She was doing well after 6 months from the date of discharge without recurrence of similar events.
Diagnosis of rheumatoid meningitis is challenging. No definitive diagnostic criteria have been established. It can involve Pachy or Lepto meninges. Pachymeningitis often presents with headaches and cranial neuropathies. Leptomeningeal involvement frequently leads to mental status changes, gait imbalance, memory loss, depression, seizures, or paresis.3 Histopathology is often required to establish the diagnosis. It generally shows rheumatoid nodules, nonspecific meningeal inflammation, or vasculitis pattern.1 It is important to rule out infections, especially when patients are taking immunosupressants. Cerebrospinal fluid analysis can be nonspecific with pleocytosis or elevated protein, but high rheumatoid factor or interleukin-6 level in CSF has diagnostic value.4 Data are limited regarding prognosis and treatment. It can be fatal in 60% to 70% of cases. Some reports have suggested potential benefit from treatment with corticosteroid along with methotrexate, cyclophosphamide, or azathioprine.4- 6 To our knowledge, it is still unproven whether early diagnosis and initiation of aggressive immunotherapy lead to improved morbidity and mortality rates.
Corresponding Author: Bhaskar Roy, MD, Department of Neurology, University of Connecticut, 85 Jefferson St, Hartford, CT 06106 (firstname.lastname@example.org).
Conflict of Interest Disclosures: None reported.
Roy B, Uphoff DF, Silverman IE. Rheumatoid Meningitis Presenting With Multiple Strokelike Episodes. JAMA Neurol. 2015;72(9):1073-1076. doi:10.1001/jamaneurol.2015.1105