Decreased axon caliber and neurofilaments in hereditary motor and sensory neuropathy, type I.
The axons of large- and intermediate-diameter myelinated fibers of sural nerves of patients with hereditary motor and sensory neuropathy, type I (HMSN-I), were previously found to be attenuated relative to their myelin spiral length. We inferred that axonal atrophy might account for secondary segmental demyelination and remyelination. To assess whether the observed axonal atrophy could be explained by a decrease in neurofilaments, we have evaluated the number of neurofilaments, microtubules, and other axon organelles in sural nerves of patients with HMSN-I. Whereas the density per square micrometer of neurofilaments or microtubules in diseased nerves was not significantly different from that in control specimens, the number of neurofilaments per axon as related to myelin spiral length was significantly less for intermediate and large myelinated fibers in HMSN-I nerves. The regression lines for the number of microtubules per axon on myelin spiral lengths were also less steep in HMSN-I, but the difference did not reach statistical significance. These results indicate that the number of neurofilaments is proportional to axon diameter but significantly below that expected considering myelin spiral length. Decreased neurofilament synthesis, assembly, or transport may underlie the axonal atrophy in HMSN-I.
D000293:Adolescent; D000328:Adult; D001369:Axons / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000648:ultrastructure*; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000648:ultrastructure; D009046:Motor Neurons / Q000648:ultrastructure*; D009186:Myelin Sheath / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000648:ultrastructure; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology; D013497:Sural Nerve / Q000473:pathology