Teaching Video NeuroImages: myokymia and nerve hyperexcitability as components of Morvan syndrome due to malignant thymoma.

A 50-year-old woman with a history of metastatic malignant thymoma presented with diffuse neuropathic pain involving the extremities and torso prior to chemotherapy and radiation. She also developed episodic diarrhea, diaphoresis, fevers, insomnia, and encephalopathy. Examination revealed rippling muscles (video on the Neurology® Web site at www.neurology.org). Prolonged afterdischarges were noted in motor nerve studies, suggestive for nerve hyperexcitability (figures 1 and 2). Electromyography (approximately 8 years after mediastinal radiation) revealed fasciculations, doublets, triplets, and myokymic discharges. Elevated serum antibodies for voltage-gated potassium channel (0.30 nmol/L, normal <0.02) and striational muscle (1:30,720, normal <1:60) were suggestive of paraneoplastic Morvan syndrome, which includes all of the features noted in our case.(1,2) The CNS features of Morvan syndrome differentiate it from Isaac syndrome, which is most often due to an autoimmune etiology. A substantial proportion of Morvan syndrome cases are paraneoplastic, the majority of which are due to thymomas.(1).

Paroxysmal neuromyotonia: a new sporadic channelopathy.

Neuromyotonia is a heterogeneous group of genetic and autoimmune channelopathies resulting in hyperexcitability of peripheral nerves. We report an unusual case of neuromyotonia, which to our knowledge has not been previously described. The patient developed intermittent attacks of severe painful muscle stiffness accompanied by sweating, myokymia and raised serum creatine kinase. Genetic analysis of KCNA1, KCNQ2 and SCN4A genes did not identify pathogenic mutation. Serum voltage-gated potassium channel antibody was also negative. He was successfully treated with acetazolamide and carbamazepine. This appears to be a new neuromuscular disease, "paroxysmal neuromyotonia", the etiology of which is still unknown.

Course and outcome of a voltage-gated potassium channel antibody negative Morvan's syndrome.

Morvan's syndrome is a rare disease characterized by peripheral nerve hyperexcitability, associated with CNS and autonomic systems involvement. High serum voltage-gated potassium channel (VGKC) antibody titers have been reported, and, till now, Morvan's syndrome has been considered as a VGKC antibody associated disease. We describe a patient with Morvan's syndrome associated with myasthenia gravis and a thymoma in his previous history, with surprisingly undetectable levels of VGKC antibodies. The clinical course is similar to those cases of Morvan's syndrome with VGKC-Ab, except for the lack of response to plasma exchange, previously considered as the first choice treatment. Nevertheless, the good response to corticosteroids therapy and the association with myasthenia confirm an autoimmune origin of the disease.

Morvan's syndrome: clinical, laboratory, and in vitro electrophysiological studies.

Morvan's syndrome is a rare disorder characterized by neuromyotonia, hyperhidrosis, and central nervous system dysfunction. We report a patient with features of this syndrome, but who initially presented with breathing difficulties. Concentric needle electromyography showed an abundance of myokymic and neuromyotonic discharges. Exercise tests and repetitive nerve stimulation showed a decrement-increment response of compound muscle action potentials. Antibodies against voltage-gated potassium channels were not detected on repeated testing, but the presence of oligoclonal bands in the cerebrospinal fluid (CSF) suggested an autoimmune etiology. At follow-up over 3 years, no cancer was found. Electrophysiological in vitro studies of effects of patient serum and CSF on rat nerves provided no evidence of altered voltage-gated sodium or potassium conductances. We conclude that putative humoral factors do not block ion channels acutely but may cause channel dysfunction with chronic exposure.