Central Nervous System Demyelination complicating tumour necrosis factor-α inhibitor therapy
Introduction: CNS demyelination is a rare but serious and debilitating complication of TNF-α inhibitor therapy. These agents are increasingly used in the treatment of inflammatory disorders including inflammatory arthritis, Crohn’s disease and psoriasis with excellent disease modifying effects. While worsening of pre-existing Multiple Sclerosis (MS) is a well described consequence of these agents, the clinical course of initial demyelinating events in this setting is less well defined.
Purpose: We present three cases of CNS demyelination occurring in the setting of TNF-α inhibitor therapy in patients without a pre existing diagnosis of MS or clinically isolated syndrome (CIS).
Methods: Clinical presentation together with laboratory and radiological findings are described over 1-3 years in three patients. Data on prevalence, disease associations, postulated pathogenesis and treatment of this condition was established by review of the adverse event reporting system (FDA) and a literature review.
Results: Three female patients aged 36, 48 and 49 years presented with acute neurological syndromes. Neurological symptoms and signs varied for each patient. Patients were receiving Etanercept (TNF-α receptor fusion protein) for the treatment of Bechet’s disease, ankylosing spondylitis and rheumatoid arthritis, respectively. None of the patients had a history of neurological disease. Duration of therapy prior to presentation ranged from 12 to 24 months. CNS demyelination was confirmed as the cause of all three presentations by magnetic resonance imaging and neurophysiological testing. Alternative diagnoses were excluded. With mean follow up of twelve months one patient developed CDMS, one remains a CIS with CSF oligoclonal bands, and the third an atypical monophasic demyelinating event.
Conclusion: CNS demyelination complicating TNF-α inhibitor therapy may represent a monophasic illness or the initial demyelinating event in clinically definite MS. Whether these agents initiate disease directly, or by some means unmask an underlying predilection to develop multiple sclerosis remains to be determined.