Differential diagnosis.

Autoimmune neuromyotonia probably represents the severe end of the clinical and electrophysiological spectrum of autoimmune peripheral nerve hyperexcitability, and is only one of a number of disorders that can present with clinically-visible myokymic muscle twitching. Of those without an underlying cause, such as the Guillain Barré syndrome or radiation plexopathy, it is possible that similar anti-VGKC antibodies underlie disease pathogenesis, even if the peripheral nerve hyperexcitability, or visible myokymia is clinically and electrophysiologically well localized (Maddison et al. 2000). The motor unit discharge rate in facial or limb myokymia is generally slower than neuromyotonia, usually not exceeding 60 Hz.The stiff-man syndrome is a similar condition of continuous motor unit activity, where abnormal excitability of spinal interneuronal networks and descending control over the anterior horn cell is thought to be the underlying pathophysiology. Unlike neuromyotonia, axial rigidity is a prominent feature and patients have a characteristic gait, with marked hyperlordosis. Autoantibodies to glutamic acid decarboxylase are present in about 40% of these patients. The central rather than peripheral origin of the excess motor unit activity in stiff-man syndrome, in contrast to neuromyotonia, is confirmed by the disappearance of discharges during sleep, general anaesthesia and peripheral nerve block.

Treatment.

The symptoms of peripheral nerve hyperexcitability often respond well to anticonvulsants such as phenytoin, carbamazepine, sodium valproate and lamotrigine, all of which primarily reduce neuronal repetitive firing through interaction with voltage-gated sodium channels. Patients with acquired neuromyotonia may require immunosuppression in the form of prednisolone and azathioprine, although not all respond fully. Severe symptoms may be ameliorated for up to 4 weeks following plasma exchange. In my experience, quantitative clinical and electrophysiological responses to intravenous immunoglobulin therapy are disappointing, although there have been no randomised controlled trials of this, or of any other treatments. The association of neuromyotonia with thymoma, small cell lung cancer and lymphoma necessitates the search for, and subsequent treatment of these malignancies. However, the treatment of the tumour often has little effect on the clinical severity of the peripheral nerve hyperexcitability.

Figure 4

Following supramaximal electrical stimulation of the posterior tibial nerve, five consecutive compound muscle action potentials are followed directly by trains of asynchronous after-discharges.

REFERENCES Denny-Brown D & Foley JM (1948) Myokymia and the benign fasciculation of muscular cramps. Transactions of the Association of American Physicians, 61, 8896. Hart IK, Maddison P, Newsom-Davis J et al. (2002) Phenotypic variants of autoimmune peripheral nerve hyperexcitability. Brain, in press. Hart IK, Waters C, Vincent A et al. (1997) Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia. Annals of Neurology, 41, 23846. Isaacs H (1961) A syndrome of continuous muscle-fi bre activity. Journal of Neurology, Neurosurgery and Psychiatry, 24, 31925. Liguori R, Vincent A, Clover L et al. (2001) Morvan?s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain, 124, 241726. Maddison P, Mills KR, Vincent A et al. (2000) Persistent facial myokymia an autoimmune aetiology? Journal of Neurology, 247, 5545. Newsom-Davis J & Mills KR (1993) Immunological associations of acquired neuromyotonia (Isaac?s syndrome). Brain, 116, 45369. Shillito P, Molenaar PC, Vincent A et al. (1995) Acquired neuromyotonia: evidence for autoantobodies directed against K+ channels of peripheral nerves. Annals of Neurology, 38, 71422.Sinha S, Newsom-Davis J, Mills KR et al. (1991) Autoimmune aetiology for acquired neuromyotonia (Isaac?s syndrome). Lancet, 338, 757.
THE MAIN CLINICAL FEATURES OF NEUROMYOTONIA

* Muscle twitching
* Muscle cramps
* Muscle stiffness
* Muscle hypertrophy
* Pseudomyotonia
* Muscle weakness rarely
* Increased sweating