Abstract Details

Title Demyelination Associated with Tumour Necrosis Factor alpha Antagonists

Topic MS and Related Diseases

Presentation(s) P02 - (-)

Poster/Presentation
Number 107

Objective

Background BACKGROUND: Anti-TNF? agents are routinely used to treat common autoimmune conditions. In vitro and post-mortem studies initially suggested a role for the treatment of MS but early trials with infliximab and lenercept were discontinued due to increased disease activity. There is growing evidence supporting an association between these drugs and both central and peripheral nervous system demyelination.

Design/Methods DESIGN/METHODS: Case histories and imaging findings of 6 patients with evidence of demyelination and concomitant anti-TNF? drug use were reviewed.

Results RESULTS: 5 cases of CNS and 1 case of PNS demyelination were identified from clinical and imaging findings. 4 female and 2 male patients, age ranging from 26-46 years. Medications included etanercept (3), adalimumab (4) and infliximab (3). Presentations included optic neuritis (1), transverse myelitis (1), bilateral intranuclear opthalmoplegia (1), brainstem syndrome (1), incidental finding on MRI (1) and peripheral neuropathy (1). Duration of treatment ranged from 5-72 months, mean 27 months and 4 patients were treated with more than 1 agent. MRI findings were compatible with demyelination and 3 patients had CSF examination with negative oligoclonal bands. Symptoms persisted in the case of optic neuritis and 1 patient progressed to clinically definite MS. All others made a complete recovery.

Conclusions CONCLUSIONS: Biologically active TNF? binds to 2 functionally distinct TNF receptors (TNFR). In animal models it has been shown that TNF? causes primary demyelination but those deficient in TNF? show a delayed onset with rapid progression and marked severity. TNFR1 and TNFR1 + 2 knockout mice had milder or absent symptoms. TNFR2 knockout mice had higher disease severity and demyelination. This suggests TNF? accelerates demyelination but is necessary for re-myelination. These findings coupled with clinical and radiological improvement on withdrawal of these agents in the majority of our cohort, supports a causal association between anti-TNF? medication and demyelination.

Authors/Disclosures
Karen A. O'Connell, PhD (Tallaght University Hospital) PRESENTER	Dr. O'Connell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.
	No disclosure on file
Claudio Gasperini, MD	Dr. Gasperini has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche, Merck, Genzyme, Novartis,Bayer, Teva, Almirall.

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