Multiple sclerosis or Sjogren's syndrome: A clinical dilemma

Background: Multiple sclerosis (MS) like disease may be a feature of central nervous system (CNS) involvement in Sjogren''s syndrome prompting some difficulties in differential diagnosis with typical MS. Objectives: To describe the clinical course, response to therapy and long term outcome of CNS Sjogren''s syndrome presenting as multiple sclerosis-like (MS) disease in a large series of primary Sjogren''s syndrome (pSS). Methods: A cohort of 380 patients with pSS, consecutively observed at our unit from January 1990 to December 2002, was evaluated for CNS involvement with particular attention to MS-like disease. All the patients fulfilled the revised 2002 ECSG criteria for primary pSS. Clinical course, seroimmunological parameters and response to therapy of patients with MS-like clinical picture are described. Results: Among 25 pts with CNS involvement, 4 pts (16%) had MS-like disease. All the pts were women, with a middle age of 41.5 years. In all cases, neurological symptoms preceded the diagnosis of pSS and occurred at a mean age of 33.5 years. Two patients had a monolateral visual loss due to retrobulbar optic neuritis. In two other cases there was also a spinal cord involvement, with a MRI imaging showing incomplete transverse myelitis. One patient developed brain stem involvement, with recurrent episodes of dizziness and sensorineural hearing loss. CSF analysis was performed in all patients showing mild lymphocytosis, raised IgG index and the presence of oligoclonal bands suggesting intyratechal immunological activation. In three pts brain MRI exhibited multiple areas of increased signal intensity on T2 weighted images, predominantly located in subcortical and periventricular white matter, with involvement of corpus callosum and cerebellum in one case. ANA were positive in 3 out 4 of pts, anti-Ro/SSA antibodies in 2 out of 4. Rheumatoid factor was positive in only one patient. No patient had anti-dsDNA or lupus anticoagulant. Only one patient presented a transient positivity for IgG anticardiolipin antibodies (low titer). All the patient had low levels of C4 (<15 mg/dl). Minor salivary glands biopsy was obtained in all patients showing a focal lymphocytic sialoadenytis with a focus score ≥ 1. All the patient were treated with IV high doses of methylprednisolone during the acute phase of neurological manifestations; two patients received cyclosporine A 3 mg/kg/die, and one patient was treated with azathioprine 2 mg/kg/die. One patient with transverse myelitis had a good response to IV methylprednisolone and remained in remission with cyclosporine A, showing at instrumental follow-up evaluation a gradual disappearance of MRI lesions. Another patient suffered from a slowly primary progressive course with brainstem involvement following the first episode of optic neuritis. The remaining two pts had a relapsing-remitting course poorly influenced by immunosuppressive therapy (cyclosporine and azathioprine). Conclusion: MS-like disease may be a rare but serious complication of pSS. Differential diagnosis from true MS is a troublesome challenge for the physician, expecially when the neurological syndrome represents the heralding picture as in the reported cases. Seroimmunological picture and salivary gland histopathology could be useful in the diagnostic interpretation permitting to avoid potentially dangerous immunomodulating therapies such as beta-IFN. In our opinion demyelinating disease should be considered in the CNS spectrum of pSS and should be carefully evaluated when dealing with MS disease with atypical presentation and/or in presence of warning signs of autoimmunity.