Multifocal motor neuropathy: pathologic alterations at the site of conduction block.
The pathologic changes of nerves in multifocal motor neuropathy (MMN), a rare neuropathy with selective focal conduction block of motor fibers in mixed nerves, remain essentially unstudied. Fascicular nerve biopsy of 8 forearm or arm nerves in 7 patients with typical MMN was undertaken for diagnostic reasons at the site of the conduction block. Abnormalities were seen in 7 of 8 nerves, including a varying degree of multifocal fiber degeneration and loss, an altered fiber size distribution with fewer large fibers, an increased frequency of remyelinated fiber profiles, and frequent and prominent regenerating fiber clusters. Small epineurial perivascular inflammatory infiltrates were observed in 2 nerves. We did not observe overt segmental demyelination or onion bulb formation. We hypothesize that an antibody-mediated attack directed against components of axolemma at nodes of Ranvier could cause conduction block, transitory paranodal demyelination and remyelination, and axonal degeneration and regeneration. Alternatively, the antibody attack could be directed at components of paranodal myelin. We favor the first hypothesis because in nerves studied by us, axonal pathological alteration predominated over myelin pathology. Irrespective of which mechanism is involved, we conclude that the unequivocal multifocal fiber degeneration and loss and regenerative clusters at sites of conduction block explains the observed clinical muscle weakness and atrophy and alterations of motor unit potentials. The occurrence of conduction block and multifocal fiber degeneration and regeneration at the same sites suggests that the processes of conduction block and fiber degeneration and regeneration are linked. Finding discrete multifocal fiber degeneration may also provide an explanation for why the functional abnormalities remain unchanged over long periods of time at discrete proximal to distal levels of nerve and may emphasize a need for early intervention (assuming that efficacious treatment is available).
Department of Neurology, Royal Hobart Hospital, Hobart Tasmania, Australia.
Bruce V
BV
Taylor
P James B
PJ
Dyck
JaNean
J
Engelstad
Gregory
G
Gruener
Ian
I
Grant
Peter J
PJ
Dyck
D000328:Adult; D003710:Demography; D004594:Electrophysiology; D005260:Female; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D009186:Myelin Sheath / Q000473:pathology / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000648:ultrastructure; D009431:Neural Conduction / Q000502:physiology*; D013194:Staining and Labeling