Rheumatoid meningitis: a rare cause of unilateral pachymeningitis

Abstract

An 87-year-old woman with quiescent rheumatoid arthritis, not on immunosuppressive therapy, presented with unilateral arm weakness, confusion and visual hallucinations. There were no infective symptoms or history of malignancy. Cerebrospinal fluid (CSF) analysis demonstrated lymphocytosis and raised protein, without flow cytometric or cytological abnormalities. Viral, bacterial, mycobacterial and fungal testing of CSF and serum were negative. MRI brain indicated unilateral leptomeningeal enhancement. There was no evidence of occult malignancy on CT imaging of the chest, abdomen and pelvis. Rheumatoid factor and anticyclic citrullinated peptide were strongly positive. The patient declined meningeal biopsy but responded to treatment with corticosteroid therapy.

Background

This is an uncommon case of rheumatoid pachymeningitis in a patient with quiescent rheumatoid arthritis (RA), who was not on treatment. Rheumatoid meningitis is an uncommon sequalae of RA and is usually seen in patients with active disease.

In most case reports, the authors have relied on a histopathological diagnosis, which leaves no doubt as to the diagnosis. In the event that a biopsy is contraindicated or declined, other clinical or investigative features may be sufficient to establish a diagnosis. A presumptive diagnosis of rheumatoid meningitis was made in our patient on the basis of significant antibody titres and brain imaging. Infective and malignant causes of meningitis were excluded as the treatment of these conditions is diametrically opposed to that of rheumatoid meningitis.

Case presentation

An 87-year-old Caucasian woman, who emigrated from Italy to Australia 40 years ago, presented with left unilateral arm weakness, confusion and visual hallucinations. There were no infective symptoms. Her family provided a collateral history of subacute deterioration in cognitive and physical function. Despite this, the patient lived independently and mobilised without aid.

Her medical history was significant for quiescent RA. The diagnosis had been made many years prior to her current presentation and she had not been on any immunomodulatory agents for more than 10 years. There was no history suggestive of cancer or chronic infection.

On examination, the patient was drowsy and confused, consistent with delirium. Vital signs were normal and she was afebrile. The tone and reflexes were normal but she had isolated left upper limb weakness. Her cranial nerves were intact and there was no nuchal rigidity. There was no gross articular or extra-articular evidence of RA. There was no clinical evidence of malignancy.

Investigations

CT brain demonstrated subtle gyral thickening and sulcal effacement overlying the right frontal parietal region. MRI brain T1 postgadolinium contrast (figure 1A) and Fluid-attenuated inversion recovery (figure 1B) sequences demonstrated right leptomeningeal enhancement with gyral oedema and sulcal effacement.

Figure 1.

MRI brain T1 postgadolinium contrast (A) and Fluid-attenuated inversion recovery (B) sequences demonstrating right frontoparietal, focal leptomeningeal thickening and enhancement. The left cerebral hemisphere appears unaffected.

Cerebrospinal fluid (CSF) analysis demonstrated raised protein (1.55 g/L) and lymphocytosis (104×10⁶/high power field), without flow cytometric or cytological abnormalities. Viral, bacterial, mycobacterial and fungal testing of CSF and serum were negative. There was no evidence of malignancy on CT imaging of chest, abdomen and pelvis.

Rheumatoid factor (143 kIU/L) and anticyclic citrullinated peptide (>200 U/mL) were strongly positive. The antinuclear antibody titre (1:640) was raised and extractable nuclear antigen screen was negative. The patient and family declined a leptomeningeal biopsy.

A vasculitis screen, lymphoma screen and ACE level were unremarkable.

Differential diagnosis

Based on the CT findings, initial investigations were targeted at ruling out an infective or malignant cause. We excluded common bacterial and viral causes of meningoencephalitis and investigated for tuberculosis, cryptococcosis, syphilis and retroviral disease. Imaging of the chest, abdomen and pelvis did not show evidence of malignancy, tumour markers and antineuronal antibodies were negative. We also investigated for the presence of an underlying lymphoma, sarcoidosis, vasculitis and other relevant autoimmune conditions. A delirium screen was negative.

Treatment

The patient was initially treated with empirical intravenous antibiotics and acyclovir until an infective aetiology was excluded. Once the diagnosis of rheumatoid meningitis was made, she was commenced on a weaning dose of prednisolone, starting at 30 mg daily.

Outcome and follow-up

She responded clinically to steroid therapy within 3 months of diagnosis, with improved confusion and reduced hallucinations. She declined further imaging. She was discharged to a residential aged-care facility after a period of rehabilitation and is scheduled to be reviewed in the outpatient clinic.

Discussion

RA is an autoimmune disease, primarily affecting the joints, and has well-established extra-articular manifestations. Rheumatoid meningitis is a rare and poorly recognised sequela of RA and can mimic a wide range of neurological conditions. Presenting symptoms include headache, stroke-like neurological deficit, seizures and neuropsychiatric symptoms.^1–5 The condition commonly presents in patients with long-standing RA. There have been reports of RA and rheumatoid meningitis being diagnosed at the same time.²

Neurological sequelae, such as rheumatoid meningitis, must be considered as a differential for patients presenting with neurological deficits on a background of RA. Other neurological complications of RA include encephalopathy, myelopathy, peripheral neuropathy and myopathy.⁶

A definitive diagnosis of rheumatoid meningitis is based on histopathology. The three features generally described are meningeal inflammation, rheumatoid nodules and vasculitis.⁷ There is an evidence that rheumatoid factor in CSF may specifically indicate disease,⁷ but we did not include this test in our assessment of the patient. Previously published case reports have highlighted the role of MRI in the diagnosis of rheumatoid meningitis. The typical features are meningeal thickening which demonstrates contrast enhancement.¹

There are no consensus guidelines for the treatment of rheumatoid meningitis. Previous case reports have documented good responses to one of or both corticosteroids^{2–4 7} and steroid-sparing immunosuppressive agents including cyclophosphamide,^{8 9} methotrexate¹⁰ and rituximab.¹⁰ Typically, there is an induction period achieved using high dose steroids which is followed by disease modifying antirheumatic drugs are used as maintenance therapy. Left untreated, the condition carries a high risk of mortality.⁷

Learning points.

• Rheumatoid meningitis is an uncommon but recognised manifestation of rheumatoid arthritis (RA).

• In patients with RA presenting with neurological deficit, rheumatoid meningitis should be considered among the differential diagnoses.

• Although definitive diagnosis is made on the basis of a meningeal biopsy, a reliable diagnosis can be made on the basis of appropriate imaging and serological findings.

• Rheumatoid meningitis generally responds well to corticosteroid therapy but may require other forms of immunosuppressive therapy.

• Untreated rheumatoid meningitis carries a high risk of mortality.