Peripheral Neuropathy of Machado-Joseph Disease in Taiwan: A Morphometric and Genetic Study

Abstract

Machado-Joseph disease (MJD) is a dominantly inherited cerebellar ataxia associated with spasticity, ophthalmoplegia, dystonia and peripheral neuropathy. Presented here are 5 MJD cases. A morphometric analysis of the histopathology of their sural nerves was carried out to know the relationship between axon size and myelin thickness. MJD cases were identified by polymerase chain reaction. On the basis of the clinical symptoms, there was 1 type I, 2 type II and 2 type III patients. The sural nerves were biopsied for single-fiber, ultrastructural and morphometric analysis. Morphometric parameters such as fiber and axon sizes, myelin thickness and g ratio (axon diameter:fiber diameter) were estimated. The pathological features of the sural nerves in the 2 type III and 1 of the type II patients revealed a loss of myelinated and unmyelinated fibers, and the morphometry studies showed a decreased fiber density, the loss of large myelinated fibers, a smaller size of the axons with thinner myelin sheaths and an increased percentage of myelinated fibers with a g ratio (axon diameter:fiber diameter) above 0.7. However, only subtle pathological changes were noted in the type I patient and the remaining type II patient. Our findings suggested that there is a loss of large myelinated fibers and distal axonopathy with relative hypomyelination in the neuropathy of patients with MJD.

The Relationship Between Sexually Dimorphic Peripheral Nerves and Diseases

“…Researchers have reported that a decrease in the number and size of myelinated axons influences the occurrence of peripheral nerve palsy or neuropathy [3][4][5][6], and a lower CR of myelinated axons has been partly implicated in the degeneration of nerve fibers [7]. A smaller NM, ATA, and lower ACR of myelinated axons would help explain the sex difference in the incidence of peripheral nerve palsy and neuropathy.…”

“…The data on the above pairs of groups were thus independent of the aging process. The methods for preparation of sections, also described in our previous report [1], were as follows: 6. Differentiate in 2% saturated lithium carbonate (= 0.03% Li2CO3) for 60 min 7.…”

Machado–Joseph disease/spinocerebellar ataxia type 3

“…Signs of neurodegeneration are widespread and variable, most often involving deeper structures of the basal ganglia, various brainstem nuclei and the cerebellum (Sequeiros and Coutinho, 1993; Koeppen et al, 1999; Lin and Soong, 2002; Rub et al, 2002a, b; Rub et al, 2003; Rub et al, 2004a, b). Brain atrophy and neuronal loss have been described in many areas, including the globus pallidus, various thalamic nuclei, subthalamic nucleus, substantia nigra, red nucleus, medial longitudinal fasciculus, various pontine nuclei and cranial motor nerve nuclei, superior and middle cerebellar peduncles, cerebellar dentate nucleus, Clarke's column and spinocerebellar tracts, vestibular nucleus, anterior horn cells, posterior columns and posterior root ganglia.…”

“…Ataxia, however, never occurs in isolation. Numerous other clinical problems reflect progressive dysfunction in the brainstem, oculomotor system, pyramidal and extrapyramidal pathways, lower motor neurons and peripheral nerves (Sequeiros and Coutinho, 1993; Takiyama et al, 1994; Cancel et al, 1995; Sasaki et al, 1995; Durr et al, 1996; Matsumura et al, 1996; Schols et al, 1996; Soong et al, 1997; Zhou et al, 1997; Watanabe et al, 1998; Friedman, 2002; Lin and Soong, 2002; Rub et al, 2002a,b; Rub et al, 2003; Rub et al, 2004a,b; Friedman et al, 2003). Most commonly, affected persons present in the young-adult to mid-adult years with progressive gait imbalance accompanied by vestibular and speech difficulties.…”

Sex differences in morphometric aspects of the peripheral nerves and related diseases

“…Researchers have reported that a decrease in the number and size of myelinated axons influences the occurrence of peripheral nerve palsy or neuropathy (Korinthenberg et al, 1997; Fukuda et al, 2000; Lin & Soong, 2002; Griffn & Höke, 2005), and a lower circularity ratio of myelinated axons has been partly implicated in the degeneration of nerve fibers (Moriyama et al, 1995). A smaller number, average transverse area, and lower average circularity ratio of myelinated axons would help explain the sex difference in the incidence of peripheral nerve palsy and neuropathy.…”