Pathophysiology of conduction block in multifocal motor neuropathy

2007 Swiss Archives of Neurology and Psychiatry  
Multifocal motor neuropathy (MMN) is a rare disorder of the peripheral nervous system characterised by the presence of focal motor conduction blocks. Although the pathological basis of conduction block is believed to be focal demyelination, in multifocal motor neuropathy this mechanism lacks definitive proof from morphological studies. In recent years special neurophysiological techniques for assessing axonal excitability non-invasively in humans have expanded knowledge on the pathophysiology
more » ... e pathophysiology of multifocal motor neuropathy. Nonetheless, several findings support the hypothesis that conduction blocks probably arise from more than one pathogenetic mechanism (hyperpolarisation or depolarisation) which can change during the course of the disease and probably represent the "tip of the iceberg" of axo-myelinic abnormalities. Multifocal motor neuropathy (MMN) is a rare disorder of the peripheral nervous system characterised by the presence of focal motor conduction blocks. Electrophysiological examination in patients with multifocal motor neuropathy discloses several features of demyelination including conduction block, increased temporal dispersion and usually focal conduction slowing [1] . Although the pathological basis of conduction block is believed to be focal demyelination, in multifocal motor neuropathy this mechanism lacks definitive proof from morphological studies [2] . The neurophysiological assessment of conduction block is also made difficult by the elevated threshold/rheobase ratio at the site of block that makes the nerve motor fibres almost unexcitable. In recent years special neurophysiological techniques for assessing axonal excitability non-invasively in humans have expanded knowledge on the pathophysiology of peripheral nervous system diseases. Several indirect observations, often made in only a few nerves, have been used to argue that the axonal membrane is depolarised at the site of conduction block [3] and that focal depolarisation leads to conduction block (i.e. a depolarising block).When hyperpolarisation involves the rest of the membrane above and below the conduction block [4, 5] , hyperpolarisation outside the block presumably compensates for depolarisation at the site of conduction block. Even if this is a key mechanism in the pathophysiology of multifocal motor neuropathy, definitive evidence of axonal depolarisation at the site of conduction block is still lacking because the markedly increased threshold [6] and rheobasic current at the site of conduction block make local membrane properties impossible to assess. An important issue arguing against focal depolarisation arises from the observation that instead of improving conduction block -as it should do if the membrane at the site of block is depolarised -activity-dependent hyperpolarisation worsens conduction block in multifocal motor neuropathy [7] . Indeed, when we delivered polarising pulses over conduction blocks in 6 patients with multifocal motor neuropathy [8], we obtained somewhat contrasting results. By reversing membrane depolarisation at the site of a depolarising block, anodal direct currents (DCs) should in theory improve motor conduction in multifocal motor neuropathy. In the patients with multifocal motor neuropathy we studied, polarising DC pulses delivered over conduction blocks
doi:10.4414/sanp.2007.01826 fatcat:cert2rredrhnth3gdis2kmiltq