Introduction

Nervous system involvement of rheumatoid arthritis (RA) is uncommon. It is usually the result of spinal cord compression due to subluxation of the cervical vertebrae; a cerebral infarct and/or hemorrhage due to vasculitis; or by direct involvement of central nervous system (CNS) structures by inflammatory cells. Characteristic pathologic findings are rheumatoid nodules in the CNS, pachymeningitis or leptomeningitis and vasculitis [1, 2]. Since the clinical symptoms and radiologic signs are rather nonspecific, short of doing a brain biopsy, the diagnosis is one of exclusion. In addition it is reported that the strongly positive rheumatoid factor in the cerebrospinal fluid (CSF) is quite specific [2–5]. We here report a patient who had not been diagnosed as RA before he was admitted with neurological findings, who was diagnosed as RA later and treated successfully.

Case report

A 70-year-old man was hospitalized with the complaints of fever, headache, nausea, vomiting and confusion of 5 days duration. He was living in a rural region of Turkey and had joint pains for 10 years. On admission he had a fever 38°C, nuchal rigidity, positive Kerning and Brudzinski signs. There was swelling in his metacarpophalangeal joints, radial deviation at the wrist with ulnar deviation of the digits and had swan-nack deformities of his fingers. Laboratory studies showed a leukocyte count of 11 × 103/μl (neutrophils 73%, lymphocytes 22% and monocytes 5%), an erythrocyte sedimentation rate of 124 mm/h, a C-reactive protein of 6.5 mg/dl (normal <0.8 mg/dl). Rheumatoid factor was positive (108 IU/ml) in serum. Antinuclear antibody, antimyeloperoxidase antineutrophil antibody (MPO-ANCA), antiproteinase-3 antineutrophil antibody (PR3-ANCA) and angiotensin converting enzyme were within normal ranges. Computed tomography and magnetic resonance imaging of brain were normal. CSF analysis showed 140 cells/mm3 (neutrophils 62%, lymphocytes 28%); protein 113 mg/dl; glucose 34 mg/dl (blood glucose 96 mg/dl) on his first hospital day. Ceftriaxone 2 × 2 g/day, ampicillin 4 × 3 g/day were administered. On the fourth hospital day, CSF analysis showed 148 cells/mm3 (lymphocytes: 82%, neutrophils: 18%); protein: 267 mg/dl; glucose: 46 mg/dl (blood glucose: 96 mg/dl); rheumatoid factor was positive at 98 IU/ml. There was no improvement in his general condition and the clinical findings, and acyclovir 3 × 10 mg/kg/day and quadruple anti-tuberculous therapy (isoniazid, rifampicin, ethambutol and pyrazinamide) were initiated. Cytological examinations of the CSF did not show any malignant cells. Serology and cultures for bacteria, mycobacterium and fungi were negative, so were the polymerase chain reactions for Herpes simplex virus and Mycobacterium tuberculosis. The purified protein derived skin test was 0 mm and chest radiograph was normal.

Radiographs of the hands demonstrated juxta articular osteoporosis, marginal erosions and narrowing of the joint spaces of all metacarpophalangeal, proximal interphalangeal and carpal joints, bilaterally (Fig. 1). He was diagnosed as having RA. On the seventh hospital day, somnolence, nuchal rigidity, Kerning and Brudzinski signs were still present. A dural biopsy was considered but was not done both due to his poor general condition and the reluctance of the family members to give permission. He was diagnosed as having CNS involvement due to RA. Intravenous methylprednisolone (1,000 mg/day for three consecutive days) was initiated. His clinical findings improved dramatically on the third day of the treatment. Oral prednisolone (1 mg/kg/day) was administered for 1 month, azathioprine 3 × 50 mg was added, and then prednisolone was gradually tapered. Control cranial MRI with contrast was evaluated as normal after 1 month of his hospital discharge. On follow-up (3, 6 and 12 months later), the patient was still doing well. CSF cell count protein and glucose levels and RF were within normal ranges at 12 months (Table 1). Now, 5 years later, he is still free of any symptoms of CNS disease. His RA is also in good remission.

Fig. 1
figure 1

X-ray of the hands: juxta-articular osteopenia, marginal erosions and narrowing of the joint spaces

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Table 1 Summary of CNS investigation results
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Discussion

CNS involvement is a rare but a serious presentation of RA. We are aware of only a limited number of case reports of RA meningitis in the English literature [1, 6]. A definite diagnosis of CNS rheumatoid disease is in general difficult without autopsy, since there are very few clinical markers specific for this manifestation. In short of doing biopsy, the diagnosis of rheumatoid meningitis is one of exclusion. However, rheumatoid factor in the CSF is often used as a diagnostic marker and a strongly positive result is highly indicative [2–5].

Our patient apparently had rheumatoid meningitis mainly based on the clinical findings and his response to treatment. Rheumatoid meningitis frequently develops in patients who had a long term history of RA, irrespective of the disease activity of their systemic arthritis [1, 2]. It has a high, 70%, mortality rate despite treatment [2]. There is some evidence that steroids alone may not be sufficient and other agents should be added to treatment [6–9]. Because methotrexate can cause rheumatoid nodulosis on the extremities and leptomeninges, it is best avoided [7, 10].