Machado‐Joseph Disease in Japan: Clinicopathological Study of 6 Autopsy Cases with Special Reference to the Clinicopathological Correlation to Cerebellar Ataxia and Lower Motor Neuron Signs

This report concerns a clinicopathological study of six Japanese patients with Machado-Joseph disease. All were unrelated females; their ages at disease onset ranged from 17 to 36, and the length of the clinical course from 12 to 50 years. The results of neurological examinations indicated that lower motor neuron signs such as ophthalmoparesis, dysphagia, atrophy of the tongue, and muscular weakness of the extremities appeared in the intermediate stages of the disease, and that from these to the end stages, involvement of the lower motor neurons became cardinal signs of the disease. Urinary and/or fecal incontinence was evident in four patients. Post-mortem investigations revealed that, in comparison with European and American cases, the involvement of the globus pallidus (particularly the medial segment) and grumose degeneration of the dentate nucleus were salient pathological features of Japanese Machado-Joseph disease patients. We also noticed involvement of the Onufs nucleus of the two cases in which this structure was examined. The application of a semiquantitative method revealed that neuronal loss in the pontine nucleus, hypoglossal nucleus, and anterior horn of the cervical cord increased in relation to the duration of the disease. By contrast, the severe loss of neurons in the dentate nucleus and Clarke's colum was not related to the length of the clinical course. We suggest that in the initial stages of Machado- Joseph disease the cerebellar ataxia is probably due to the involvement of the dentate nucleus and Clarke's column, and that in the advanced stages it is caused by alterations of the pontine nucleus as well. We believe that bulbar signs and muscular weakness of the extremities that appear in the middle stages of the disease are due to progressive neuronal loss in the hypoglossal nucleus and anterior horn. The issue regarding the neuropathological similarities of Machado-Joseph disease in Japanese patients, “Marie's ataxia” and spinopontine degeneration is addressed in the discussion.