Evidence for axonal membrane hyperpolarization in multifocal motor neuropathy with conduction block

Multiple nerve excitability measurements were used to investigate axonal membrane properties of patients diagnosed with multifocal motor neuropathy (MMN). Six patients were selected, all with evidence of distal focal motor conduction block involving the median nerve in the forearm. In all patients, the median nerve was stimulated at the wrist, just distal to the site of block, and the resulting compound muscle action potentials were recorded from abductor pollicis brevis. Stimulus-response behaviour, the strength--duration time constant, threshold electrotonus to 100 ms polarizing currents, a current-threshold relationship and the recovery of excitability following supramaximal activation were recorded using a protocol described recently. When compared with control values, patients demonstrated significantly greater superexcitability, a 'fanning out' of threshold electrotonus recordings, and a significant change in the slope of the current--threshold relationship. These abnormalities in axonal membrane excitability parameters closely resembled those in normal axons hyperpolarized following release from ischaemia. To test for axonal hyperpolarization, DC depolarizing currents were applied to the nerves of three patients, and all the excitability parameters were normalized by depolarization. Attempts to trace excitability measures proximally towards the site of block were unsuccessful, as the nerve became inexcitable in all cases. It is suggested that the distal hyperpolarization is probably linked to focal depolarization and that the clinical features of MMN are consistent with a depolarizing/hyperpolarizing lesion.