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We present two cases with multiple sclerosis who developed myasthenia gravis during treatment with interferon 1β.
A 41 year old right-handed woman was diagnosed 3 years ago with relapsing-remitting multiple sclerosis (MS) with positive MRI findings and positive CSF for oligoclonal bands. Her neurological symptoms were long-standing, starting at the age of 20. Her family history was positive for MS, her father being a sufferer. Her past medical history was unremarkable. Since March 2001 she has been receiving interferon 1β and symptomatic treatment for neurogenic pain and occasional tonic muscle spasms.
On her pre-treatment assessment she demonstrated long-standing pyramidal weakness, mild ataxia, and urinary bladder symptoms such as urgency and frequency. Her disability EDSS score was 3.5. Nine months following initiation of interferon β treatment she developed progressive weakness of the neck muscles (drooping head), bilateral ptosis, intermittent double vision, and mild dysphagia. Her routine blood and biochemical tests, including thyroid function, were normal. Her electrophysiological study with repetitive stimulation was positive for myasthenia gravis. A test for acetylcholine receptor antibodies was positive at 2.2 nM/l (borderline values 0.4–1 nM/l, positive above 1 nM/l). CT of the thorax showed no thymus enlargement.
The patient was started on pyridostigmine and had a favourable clinical response.
A 39 year old right-handed woman had a clinical history suggestive of MS from the age of 18 with recurrent episodes of sensory-motor disturbances involving her lower limbs, ataxia, and fatigue. She was diagnosed with MS at the age of 22 with positive MRI scan finding and positive CSF for oligoclonal bands. She was started on interferon β at the beginning of 2001.
On her pre-treatment assessment she demonstrated bilateral lower limb pyramidal weakness and signs, urinary bladder urgency and frequency, and chronic fatigue. Her disability EDSS score was 4.5. Approximately 12 months following the initiation of interferon β treatment she presented with progressive dysarthria, dysphagia, generalised weakness, and episodic double vision. Her routine blood and biochemical tests, including thyroid function, were normal. Her electrophysiological study with repetitive stimulation was positive for myasthenia gravis. Screening for acetylcholine receptor antibodies was positive at 1.4 nM/l (borderline values 0.4–1 nM/l, positive above 1 nM/l). CT scan of the thorax showed no thymus enlargement.
The patient was started on pyridostigmine with a favourable clinical response.
MS is a putative autoimmune condition. The prevailing hypothesis is that autoreactive T cells of the CD4+ T helper Th1 population orchestrate the pathogenetic process in MS.1 Interferon β is one of the first effective immunotherapies in MS. Interferon β acts at multiple levels, on activation of T cells,2 on immune deviation in favour of Th2,3,4 and on the blood–brain barrier function, and possibly exerts antiviral effects.
The development of sero-positive myasthenia gravis in our two cases during interferon β treatment may have two explanations:
it may be a coincidental autoimmune disorder, as sporadically described in the literature5 or
it may be triggered by interferon β treatment via deviation of immune response towards a predominantly Th2 reaction.
Development of myasthenia gravis in one patient with MS during interferon-1β treatment has been reported6 while exacerbation of myasthenia gravis has been reported in a patient receiving interferon β for chronic active hepatitis C.7 Of interest is the observation of induction of increased production of auto-antibodies in MS patients treated with interferon 1a and 1β.8 The longstanding history of MS in our cases with no manifestation of other autoimmune disorders would favour the suggestion of β interferon induced auto-antibodies.
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