Clinicopathological study of the peripheral nervous system in Machado-Joseph disease

Three cases of histologically-proven Machado-Joseph disease (MJD) (clinically, types II and III) are described with special reference to the peripheral nervous system. We systematically and quantitatively analyzed the myelinated fiber densities in various nerves of three MJD patients and compared the results with the patients' clinical features and the pathological findings for the central nervous system (CNS). The results obtained were (1) motor system: The number of intermediate gammamotoneuron fibers was decreased prominently in all three MJD patients. In the type III MJD cases, the number of large alpha-motoneuron fibers also were decreased. (2) Sensory system: it generally was less involved than the motor system at the root level; but the large fibers of the distal portion were vulnerable. (3) Oculomotor system: the number of large oculomotor fibers was decreased markedly in all three cases, but there was relative preservation of parasympathetic fibers. (4) Autonomic system: the preganglionic sympathetic fibers from the intermediate lateral nucleus generally were preserved. These results suggest that in MJD the vulnerability of the peripheral nerves reflects the degree of loss of their original neuronal cells and varies according to the clinical phenotype. The characteristic peripheral neuropathy of MJD may be the result of axonal degeneration due to perikaryal neuronal damage in the central nervous system.