Background Central nervous system (CNS) demyelination is the hallmark of multiple sclerosis (MS), but may rarely occur in connective tissue diseases (CTD), mainly systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Objectives To examine whether patients with demyelinating syndrome and atypical features for MS may exhibit an underlying connective tissue disease.

Methods Patients referred to the Rheumatology and Clinical Immunology Unit of “Attikon” University Hospital for a demyelinating disorder characterized as “atypical for MS” following neurologic evaluation, were included in the study. All cases were discussed with a neurologist with expertise in MS and CNS magnetic resonance imaging were assessed by an experienced neuroimagist. Cases included either i) a clinical syndrome suggestive of a demyelinating process (demyelinating optic neuropathy, myelopathy, internuclear opthalmoplegia etc.) and/or ii) abnormal imaging of the central nervous system (CNS) with features suggestive of demyelination (ie. presence of supra- and infratentorial lesions, periventricular location, gadolinium enhancement, Dawson's fingers, hypointense T1-lesions (“black holes”), “dirty” white matter). Patients with brain lesions in MRI more compatible with non-specific white matter hyperintensities (WMHI, ie. of possible ischemic/microvascular etiology) were excluded from the study.

Results 21 patients were included in the study [all women, mean (SD) age at first neurologic manifestation 37.7 (10.6) years]. 17 patients had MRI findings of a demyelinating process in the CNS (brain lesions only in 7, spinal cord lesions only in 4 and both brain and spinal cord lesions in 5 patients); WMHI or normal findings were found in 4 patients with optic neuritis. In this selected group of patients, detailed rheumatologic evaluation revealed clinical and laboratory findings suggestive of a CTD in all patients. The most common findings were: arthritis (80.5%), Raynaud's phenomenon (42.8%), photosensitivity (38.1%), malar rash/erythema (33.3%), livedo reticularis (23.8%) and leukopenia (23.8%). Antinuclear antibodies were positive in two-thirds of patients (66.7%), anti-Ro/La in 19.0% and aPL only in one patient (4.8%). Final diagnoses were undifferentiated CTD, in 10 patients, frank SLE in 9 patients, primary obstetric APS and RA, in one patient each. After a median (range) follow-up of 3 (1–14) years, three patients fulfilled the criteria for MS and received MS-specific therapy, thus were subsequently classified as having an overlap of two diseases.

Conclusions CNS lesions suggestive of demyelination on MRI must be distinguished from non-specific lesions of microvascular etiology. In cases of demyelinating syndromes not fulfilling criteria for MS, features of an underlying CTD, suggestive of SLE, are frequently found. A small percentage of patients may go on to develop frank MS during follow-up, thus longitudinal monitoring is necessary.

References

1. Differential diagnosis of suspected multiple sclerosis: a consensus approach. Miller DH, Weinshenker BG, Filippi M, et al. Multiple Sclerosis 2008; 14: 1157–1174.

References

Disclosure of Interest None declared