Summary
We describe a patient with progressive spastic ataxia and ophthalmoparesis. His clinical and neuropathological findings were consistent with Joseph's disease. The most characteristic neuropathological features in the present case were ubiquitin-immunoreactive filamentous or dense inclusions in spinal anterior horn cells and hypoglossal neurons, which have been considered to be a specific finding in amyotrophic lateral sclerosis (ALS). The occurrence of ubiquitin-immunoreactive inclusions suggests that such inclusions are not totally specific to ALS and could occur in occasional degenerating motor neurons without apparent ALS neuropathology.
Similar content being viewed by others
References
Coutinho P, Andrade C (1978) Autosomal dominant system degeneration in Portuguese families of the Azores islands. A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 28:703–709
Hirano A (1991) Cytopathology of amyotrophic lateral sclerosis. Adv Neurol 56:91–101
Leigh PN, Anderton BH, Dodson A, Gallo J-M, Swash M, Power DM (1988) Ubiquitin deposits in anterior horn cells in motor neuron disease. Neurosci Lett 93:197–203
Leigh PN, Probst A, Dale GE, Power DP, Brion J-P, Dodson A, Anderton BH (1989) New aspects of the pathology of neurodegenerative disorders as revealed by ubiquitin antibodies. Acta Neuropathol 79:61–72
Leigh PN, Whitwell H, Garofalo O, Buller J, Swash M, Martin JE, Gallo J-M, Weller RO, Anderton BH (1991) Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. Brain 114:775–788
Lima L, Coutinho P (1980) Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorean Portuguese family. Neurology 30:319–322
Lowe J, Blanchard A, Morrel K, Lennox G, Raynold L, Billett M, Landon M, Mayer RJ (1988) Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease, and Alzheimer's disease, as well as Rosenthal fibers in cerebellar astrocytomas, cytoplastic bodies in muscle, and Mallory bodies in alcoholic liver disease. J Pathol 155:9–15
Lowe J, Lennox G, Jefferson D, Morrell K, McQuire D, Gray T, Landon M, Doherty FJ, Mayer RJ (1988) A filamentous inclusion body within anterior horn neurones in motor neuron disease defined by immunocytochemical localization of ubiquitin. Neurosci Lett 94:203–210
Manetto V, Perry G, Tabaton M, Mulvihill P, Fried VA, Smith HT, Gambetti P, Autilio-Gambetti L (1988) Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases. Proc Natl Acad Sci USA 85:4501–4505
Matsumoto S, Hirano A, Goto S (1990) Ubiquitin-immunoreactive filamentous inclusions in anterior horn cells of Guamanian and non-Guamanian amyotrophic lateral sclerosis. Acta Neuropathol 80:233–238
Migheli A, Autilio-Gambetti L, Gambetti P, Mocellini C, Vigliani MC, Schiffer D (1990) Ubiquitinated filamentous inclusions in spinal cord of patients with motor neuron disease. Neurosci Lett 114:5–10
Mizusawa H, Nakamura H, Wakayama I, Yen S-H, Hirano A (1991) Skein-like inclusions in the anterior horn cells in motor neuron disease. J Neurol Sci 105:14–21
Nakano KK, Dawson DM, Spence A (1972) Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology 22:49–55
Rosenberg RN, Nyhan WL, Bay C, Shore P (1976) Autosomal dominant striatonigral degeneration. A clinical, pathological, and biochemical study of a new genetic disorder. Neurology 26:703–714
Sakai T, Ohta M, Ishino H (1983) Joseph disease in a non-Portuguese family. Neurology 33:74–80
Schiffer D, Autilio-Gambetti L, Chiò A, Gambetti P, Giordana MT, Gulllotta F, Migheli A, Vigliani MC (1991) Ubiquitin in motor neuron disease: study at the light and electron microscope. J Neuropathol Exp Neurol 50:463–473
Suenaga T, Hirano A, Llena JF, Ksiezak-Reding H, Yen S-H, Dickson DW (1990) Modified Bielschowsky and immunocytochemical studies on cerebellar plaques in Alzheimer's disease. J Neuropathol Exp Neurol 49:31–40
Woods BT, Schaumburg HH (1972) Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia. A unique and partially treatable clinico-pathological entity. J Neurol Sci 17:149–166
Yuasa T, Ohama E, Harayama H, Yamada M, Kawase Y, Wakabayashi M, Atsumi T, Miyatake T (1986) Joseph's disease: clinical and pathological studies in a Japanese family. Ann Neurol 19:152–157
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Suenaga, T., Matsushima, H., Nakamura, S. et al. Ubiquitin-immunoreactive inclusions in anterior horn cells and hypoglossal neurons in a case with Joseph's disease. Acta Neuropathol 85, 341–344 (1993). https://doi.org/10.1007/BF00227732
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00227732