Epidemiology of motor neuron disease in the Kii Peninsula of Japan, 1989-1993: active or disappearing focus?

During the period 1989-1993, the incidence and migration patterns of patients with motor neuron diseases (MND) in Wakayama Prefecture, including one of the high-incidence Kii Peninsula foci ('Kozagawa focus'), were surveyed to determine whether the focus had truly disappeared or not. Overall, the crude average annual incidence was 1.43 per 100000 population; when age-adjusted to the 1990 Japanese population, it was 1.25 (1.85 for males and 0.61 for females). The average annual age- and sex-specific incidence steadily increased to a peak between 60 and 69 years and dropped after 70. Geographically, the rates varied in the five regions of Wakayama Prefecture from 0.38 to 2.48. The areas with high incidence were distributed in the central and southernmost regions; the highest was in the Kozagawa focus with 9.54 (two ALS cases within five years; 4193 base population, 1990). During the study period, four emigrants from Kozagawa had developed MND one to four decades after leaving the focus. Although the remarkable clustering of MND was thought to have disappeared, the southern Kii Peninsula remains a high-risk area for MND, especially if one interprets the data so as to include the emigrants. In general, the age at onset has increased in the past 20 years from 56.5 to 61.7; male predominance is observed.

Involvement of Onuf's nucleus in ALS. Demonstration of intraneuronal conglomerate inclusions and Bunina bodies.

Onuf's nucleus of 3 ALS cases was examined histologically, morphometrically and for metal content. Case 1 showed conglomerate inclusions (CIs), cases 2 and 3 showed Bunina bodies in Onuf's nucleus. Electron microscopy showed that CIs were intracytoplasmic accumulations of 10 nm neurofilaments with discrete borders. Onuf's neurons in ALS showed a significant decrease (P less than 0.001) in the cytoplasmic, nuclear and nucleolar areas in comparison with neurons of age-matched controls and elderly controls. Metal analysis of the sacral spinal cords by alpha particle-excited X-ray fluorescence analysis (PIXE) showed relatively high Al levels in the ALS cases compared with controls. Morin staining revealed intense green fluorescence (indicating Al) in the nucleoli and cytoplasm of the CI-containing neurons, but not in the CIs themselves. The appearance of CIs or Bunina bodies and neuronal atrophy in Onuf's nucleus seems to indicate that this structure is also involved in the disease process of ALS, although it is less vulnerable than most other motor ganglia.

Progressive neurogenic muscle atrophy with fasciculation in mice treated with IDPN.

Spontaneous discharges recorded on the EMG appeared in experimental mice given repeated doses of IDPN according to a time schedule. Spontaneous discharges showing a polyphasic pattern and duration of over 10 ms were considered to be fasciculations. One group of mice, treated with IDPN for 4 weeks became active with an increase in muscle volume 2 months after initiation of experiment; spontaneous discharges were recorded in this group at 3-4 weeks after first IDPN injection and disappeared at 4 months. Histologically, neurogenic muscle atrophy, in terms of group atrophy of muscles, was seen in muscles of mice exhibiting spontaneous discharge patterns. Peripheral nerves showed marked atrophy with degeneration. Dissociation of neurofilaments and other organelles was observed. Axonal swellings, filled with numerous maloriented neurofilaments, were confirmed in the lumbar cord. IDPN given repeatedly to mice at a certain dose causes degeneration of the peripheral nerves and results in neurogenic muscle atrophy.

Wilson's disease; increased aluminum in liver.

Interaction of trace metal metabolism was studied in a patient with Wilson's dease. Atomic absorption analysis showed markedly increased urinary excretion of copper and aluminum and an increased aluminum content was found in the biopsied liver by neutron activation analysis. These findings suggest a complicated pathogenetic mechanism involving other metals besides copper in the Wilson's disease.