Table. Autoimmune generalized PNH with or without CNS disturbance
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).
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.
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.
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