Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in rapidly progressive motor neuron disease: immunohistochemical and electron microscopic studies

In an autopsy case of sporadic rapidly progressive lower motor neuron disea se (MND), Gallyas-positive argyrophilic and ubiquitinated filamentous intra cytoplasmic inclusions were found in the neurons. Clinically, 7 months prio r to death, a 68-year-old woman experienced a history of rapidly progressiv e muscle weakness of all four extremities and bulbar sign, without sensory and autonomic disturbance. Two months later, she became unable to stand or walk. Four months after onset, she needed respiratory support, and subseque ntly died due to cardiorespiratory arrest. Neuropathological examinations r evealed neuronal loss and associated gliosis in the lower motor neurons, ex cept for ocular motor nuclei, Clark's column, and accessory cuneate nucleus , and tract degeneration was observed in the middle root zone of the poster ior column and spinocerebellar tract. No Bunina bodies or Lewy body-like hy aline inclusions were found in the anterior hems. Gallyas-positive argyroph ilic filamentous inclusions were found in the lower motor neurons and in ne rve cells of the Clark's column, intermediate zone, posterior horn and acce ssory cuneate nucleus. These were positive with anti-ubiquitin antibody but negative with anti-tau (tau-2 and AT8) and neurofilament antibodies. Elect ron microscopic examinations disclosed randomly arranged tubular-like filam entous profiles, with a diameter of 12-14 nm, sometimes with amorphous gran ules in the perikaryon. This is the first report on the Gallyas-positive ar gyrophilic and ubiquitinated filamentous inclusions in neurons in MND.