.Neurologocal Rarities. Neuromyotonia.
Mr P. Maddison. Department of Neurology, Royal Victoria Infimary. Newcastle upon Tyne. UK
Neuromyotonia is a very rare condition of spontaneous, continuous muscle activity of peripheral nerve origin. It is characterized clinically by muscle twitching at rest (visible myokymia), cramps that can be triggered by voluntary or induced muscle contraction, and impaired muscle relaxation (pseudomyotonia). Often, patients also have symptoms of excessive sweating and more rarely mild muscular weakness, and paraesthesia Following the electrophysiological account in Denny-Brown & Foley 1948 of 'undulating myokymia' the first full description of the syndrome of 'continuous muscle fibre activity' was made by Isaacs (1961). He established the peripheral nerve origin of the spontaneously-occurring discharges by noting the persistence of abnormal EMG activity after proximal nerve block, no change in spontaneous muscle activity during general anaesthesia with thiopentone, and that the depolarizing muscle relaxant succinylcholine and neuromuscular blocking agent curare both produce electrical silence after a few minutes.
Neuromyotonia can sometimes be seen in isolation, or as a feature of genetically inherited diseases such as Episodic Ataxia Type I,or Hereditary Motor and Sensory Neuropathy. But most commonly, it is associated with other disorders and in many cases there seems to be an autoimmune association (Table 1).
The association of neuromyotonia with thymoma, myasthenia gravis, vitiligo, Hashimoto's thyroiditis and penicillamine treatment provided some clinical evidence of a possible autoimmune aetiology. Spontaneous remission has also been observed, a finding consistent with autoimmunity. In addition, neuromyotonia has been reported in patients with lung cancer, raising the possibility that tumour antigenic determinants are perhaps capable of triggering an autoimmune response producing antibodies that cross-react with neuronal voltage-gated ion channels.The first direct evidence of an autoimmune aetiology came from the demonstration of a significant reduction in the number of neuromyotonic discharges recorded by EMG after plasma exchange (Sinha et al. 1991). In addition, purified IgG from the same patient, when injected intraperitoneally into mice, enhanced in vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve hemidiaphragm preparations. Further studies showed significantly-increased acetylcholine quantal content at the neuromuscular junction in similarly treated mice, mimicking the K+ channel blocking effect of 3,4-diaminopyridine (Shillito et al. 1995). Therefore, it was proposed that the increase in nerve terminal excitability could be due to interference with the functionof neuronal K+ channels that ordinarily stabilize membrane potential. Several other patients were subsequently reported as showing an improvement in symptoms and signs following plasma exchange, confi rming the presence of a pathogenic circulating factor (Newsom-Davis & Mills 1993).
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Table1.Clinical associations of neuromyotonia Autoantibody-mediated or autoimmune-associated
Thymoma with or without myasthenia gravis
Small cell lung carcinoma
Plasmacytoma with IgM paraproteinaemia
Associated with other autoimmune disorders
Myasthenia gravis without thymoma
Diabetes mellitus (insulin or noninsulin dependent)
Chronic inflammatory demyelinating neuropathy
Guillain Barré syndrome
Penicillamine-induced in patients with rheumatoid disease
Systemic lupus erythematosus
Anterior horn cell degeneration (as part of motor neurone
Genetic: hereditary neuropathy
Idiopathic peripheral neuropathy
Infective: staphylococcal infection
Toxins: herbicide, insecticide, toluene, alcohol, timber rattle snake venom