Peripheral nerve hyperexcitability (neuromyotonia)

Clinical features
Generalized peripheral nerve hyperexcitability (PNH; neuromyotonia) is often a non-paraneoplastic condition, but many cases are associated with autoimmunity or with other autoimmune disorders (see Table).

In about 25% of cases, PNH is paraneoplastic and can predate the detection of a tumour by up to 4 years. The most commonly associated tumours are thymoma with or without MG and small cell lung cancer. Skeletal muscle overactivity usually dominates the presentation and tends to be triggered by exercise. Muscle twitching (fasciculations) and/or rippling (clinical myokymia) and painful cramps are the commonest, and often the only, presenting features. In the fully developed syndrome, however, there can also be stiffness, pseudomyotonia, pseudotetany, and weakness. Muscle hypertrophy can develop. The limbs, or limbs and trunk, muscles are most commonly affected, although facial, bulbar and respiratory muscles can also be involved.

The classic electrical features are shown in Fig 1.

	Typical needle electromyography recording in peripheral nerve hyperexcitability. There is a multiplet discharge with an intraburst frequency of 150 Hertz followed at irregular intervals by several doublet and single discharges (fasciculations), all from a single motor unit.

About 33% of patients also have sensory symptoms such as paraesthesia and numbness, and about 50% have hyperhidrosis, which may reflect autonomic involvement. Central nervous system features may be present, ranging from personality change and insomnia to a psychosis with delusions, hallucinations, and autonomic disturbance (when CNS symptoms are florid it may be referred to as Morvan’s syndrome).

Associated autoantibodies
There is no autoantibody that indicates whether PNH is paraneoplastic.
VGKC antibodies are found in about 35% of all PNH patients, although this rises to 80% in those with thymoma. VGKC antibodies can also be associated with limbic encephalitis and thymoma without PNH, or with non-paraneoplastic limbic encephalitis. Thymoma-associated cases are likely also to have striated muscle antibodies.

Management
Paraneoplastic PNH often improves with treatment of the underlying malignancy. Symptomatic treatment with anti-epilepsy drugs such as carbamazepine, lamotrigine, or phenytoin is usually helpful. Plasma exchange, 3 or intravenous immunoglobulin, can help temporarily in refractory patients. Long-term immunosupression with prednisolone, with or without azathioprine or methotrexate, has been useful in selected autoimmune PNH patients with severe disability, including a few post-thymectomy patients with thymoma-associated PNH.

Selected references

1. Hart IK, Waters C, Vincent A, et al. Autoantibodies detected to expressed potassium channels are implicated in neuromyotonia. Ann Neurology 1997; 41: 238-246.

2. Hart IK, Maddison P, Newsom-Davis J, Vincent A, Mills KR. 2002. Phenotypic variants of peripheral nerve hyperexcitability. Brain, 125, 1887-1895.

3. Newsom-Davis J, Mills KR. Immunological associations of acquired neuromyotonia (Isaacs' Syndrome). Report of five cases and literature review. Brain 1993; 116: 453-469.

4. Liguori R, Vincent A, Clover L, et al. Morvan’s syndrome: peripheral and central nervous system and cardiac involvement with antibodies to voltage-gated potassium channels. Brain 2001; 124: 2417-2426.

5. Toepfer M, Schroeder M, Unger JM et al. Neuromyotonia, myoclonus, sensory neuropathy and cerebellar symptoms in a patient with antibodies to neuronal nucleoproteins (anti-Hu-antibodies).Clin Neurol Neurosurg 1999; 101:207-209.

6. Buckley C, Oger J, Clover L, et al. Potassium channel antibodies in two patients with reversible limbic encephalitis. Ann Neurol 2001 50: 74-79.

7. Vincent A, Buckley C, Schott JM et al. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Brain. 2004 in press

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