Summary
Dentate nucleus pathology was studied histologically and immunohistochemically in four cases and ultrastructurally in three cases of progressive supranuclear palsy (PSP). In addition to neurofibrillary changes, there were ill-defined clumps of eosinophilic granular structures, named grumose degeneration (GD). GD was observed in three of the four cases; it was not seen in a case exhibiting severe Purkinje cell loss. In areas with prominent GD, neuronal loss was also marked and the remaining neurons were atrophic. GD, which was once believed to represent degenerated cell bodies of dentate neurons, could be histologically distinguished from perikarya of dentate neurons. Argentophilic rings and knobs were only a part of GD and the rest of GD was only faintly or not argentophilic. Immunostain for phosphorylated neurofilament proteins positively stained round structures of various sizes in GD, but a large part of GD did not react with the antibody. As described in other disorders, electron microscopy revealed that the GD consisted of clusters of numerous axon terminals and preterminal axons. Many appeared swollen to a varying extent and contained mitochondria, synaptic vesicles, neurofilaments, lamellar bodies, multivesicular structures, vacuoles or combinations of these organelles. A few were markedly swollen with accumulation of neurofilaments and other organelles, corresponding to the round structures which stained positively for phosphorylated neurofilament proteins. A considerable number of axon terminals with no apparent abnormal accumulations of organelles were found in areas of GD.
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Anzil AP (1969) Progressive supranuclear palsy: case report with pathological findings. Acta Neuropathol (Berl) 14:72–76
Arai N, Amano N, Iwabuchi K, Yagishita S, Yokoi S, Saito A, Misugi K (1988) Three categories of the degenerative appearance of the human cerebellar dentate nucleus. A morphometric and morphological study. J Neurol Sci 83:129–143
Behrman S, Carroll JD, Janota I, Matthews WB (1969) Progressive supranuclear palsy: clinico-pathological study of four cases. Brain 92:663–678
Bestetti G, Rossi GL (1980) The occurrence of cytoplasmic lamellar bodies in normal and pathologic conditions. Acta Neuropathol (Berl) 49:75–78
Binder LI, Frankfurter A, Kebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101:1371–1378
Blumenthal H, Miller C (1969) Motor nuclear involvement in progressive supranuclear palsy. Arch Neurol 20:362–367
Chan-Palay V (1977) Cerebellar dentate nucleus organization, cytology and transmitters. Springer, Berlin Heidelberg New York, pp 86–146
Chan-Palay V (1977) Cerebellar dentate nucleus organization, cytology and transmitters. Springer, Berlin Heidelberg New York, pp 158–167
Cummings JF, deLahunta A (1988) A study of cerebellar and cerebral cortical degeneration in Miniature Poodle pups with emphasis on the ultrastructure of Purkinje cell changes. Acta Neuropathol (Berl) 75:261–271
David NJ, Mackey EA, Smith JL (1968) Further observation in progressive supranuclear palsy. Neurology 18:349–356
Dickson DW, Yen S-H, Suzuki KI, Davies P, Garcia JH, Hirano A (1986) Ballooned neurons in select neurodegenerative diseases contain phosphorylated neurofilament epitopes. Acta Neuropathol (Berl) 71:216–223
Dix MR, Harrison MJG, Lewis PD (1971) Progressive supranuclear palsy: the Steele-Richardson-Olszewski syndrome: a report of nine cases with particular reference to the mechanism of the oculomotor disorder. J Neurol Sci 13:237–256
Ghadially FN (1975) Ultrastructural pathology of the cell and matrix. A textbook and atlas of physiological and pathological alternations in the fine structure of cellular and extracellular components. 2nd edn Butterworths, London, pp 448–451
Greenfield JG, Bosanquet FD (1953) The brain stem lesion in parkinsonism. J Neurol Neurosurg Psychiatry 16:212–226
Herndon RM (1964) Lamellar bodies, an unusual arrangement of the granular endoplasmic reticulum. J Cell Biol 20:338–342
Hirano A, Donnenfeld H, Sasaki S, Nakano I (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43:461–470
Ishino H, Higashi H, Kuroda S, Yabuki S, Hayahara T, Otsui S (1974) Motor nuclear involvement in progressive supranuclear palsy. J Neurol Sci 22:235–244
Janota I (1973) Pathological changes in the terminal parts of Purkinje cell axons in the dentate nucleus of the cerebellum. J Neurol Neurosurg Psychiatry 36:596–603
Janota I (1974) Neurofibrillary change in the terminal part of Purkinje cell axons in the dentate nucleus of the cerebellum following destructive cortical lesions in the cerebellum following destructive cortical lesions in the cerebellar hemisphere of the cat. An electron microscopic study. J Neurol Sci 22:367–373
Jellinger K (1971) Progressive supranuclear palsy: subcortical argyrophilic dystrophy. Acta Neuropathol (Berl) 19:347–352
Jellinger K (1973) Neuroaxonal dystrophy: its natural history of related disorders. Prog Neuropathol 2:129–180
Kato T, Hirano A, Weinberg MN, Jacobs AK (1986) Spinal cord lesions in progressive supranuclear palsy: some new observations. Acta Neuropathol (Berl) 71:11–14
Kristensen MO (1985) Progressive supranclear palsy −20 years later. Acta Neurol Scand 71:177–189
Ksiezak-Reding H, Dickson DW, Davis P, Yen S-H (1987) Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer's neurofibrillary tangles. Proc Natl Acad Sci USA 84:3410–3414
Kurihara T, Landau WM, Torack RM (1974) Progressive supranuclear palsy with action myoclonus seizures. Neurology 24:219–223
Martin JJ, Dehaene I, Shiraki H (1981) Alteration grumeleuse du noyau dentele du cervelet dans deux cas de paralysie supranucleaire progressive de Steele-Richardson-Olszewski. Acta Neurol Belg 81:137–143
Morales R, Duncan D (1966) Multilaminated bodies and other unusual configurations of endoplasmic reticulum in the cerebellum of the cat. An electron microscopic study. J Ultrastruct Res 15:480–489
Neuman MA (1959) Combined degeneration of globus pallidus and dentate nucleus and their projections. Neurology 9:430–438
Okumura A, Oda M, Iwase S, Shiraki H (1975) Pathomorphological and clinicopathological study of so-called grumose degeneration in the cerebellar dentate nucleus. Shinkei Kenkyu No Shinpo 19:483–492
Oyanagi S (1981) “Grumose degeneration” in the human degenerative dentate nucleus. Shinkei Kenkyu No Shinpo 25:181–191
Oyanagi S, Kosaka K, Nakamura Y, Naito H, Iizuka R, Hirayama K (1980) An electron microscopic observation on the human degenerative dentate nuclei from two autopsied cases with a combined degeneration in the dentatorubral pathway and pallido-luysian system. Shinkei Kenkyu No Shinpo 24:315–329
Raisman G, Matthews MR (1972) Degeneration and regeneration of synapses. In: Guyton AC (ed) Structure and function of the nervous system, vol 4. Saunders, Philadelphia, pp 81–84
Rosenbluth J, Wissig SL (1964) The distribution of exogenous ferritin in Toad spinal ganglia and the mechanism of its uptake by neurons. J Cell Biol 23:307–325
Sasaki S, Okamoto K, Hirano A (1982) An electron microscopic study of small argyrophilic bodies in the human spinal cord. Neurol Med Chir (Tokyo) 17:570–576
Schlaepfer WW (1987) Neurofilaments: structure, metabolism and implications in disease. J Neuropathol Exp Neurol 46:117–129
Schmidt ML, Charden MJ, Lee VM-Y, Trojanowski JO (1987) Phosphates-dependent and-independent neurofilament epitopes in the axonal swellings of patients with motor neuron disease and controls. Lab Invest 56:282–294
Seitelberger F (1969) Heterogenous system degeneration. Acta Neurol (Napoli) 24:276–284
Shiraki H, Okumura A, Oyanagi S (1977) Neuropathology of “grumose degeneration” of the cerebellar dentate nucleus with special reference to certain neurotoxic disorders and other pathological processes. In: Roizin L, Shiraki H, Grvevic N (eds) Neurotoxicology. Raven Press, New York, pp 43–55
Steele JC, Richardson JC, Olszewski J (1964) Progressive supranuclear palsy. Arch Neurol 10:333–359
Tretiakoff C (1919) Contribution à l'etude de l'anatomie pathologique du locus niger de Soemmering. Thèse de Paris (cited in [5])
Weinmann RL (1967) Heterogenous system degeneration of the central nervous system associated with peripheral neuropathy. Neurology 17:597–603
Yen SH, Crowe A, Dickson DW (1985) Monoclonal antibodies to Alzheimer neurofibrillary tangles. 1. Identification of polypeptides. Am J Pathol 120:282–291
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Mizusawa, H., Yen, S.H., Hirano, A. et al. Pathology of the dentate nucleus in progressive supranuclear palsy: a histological, immunohistochemical and ultrastructural study. Acta Neuropathol 78, 419–428 (1989). https://doi.org/10.1007/BF00688179
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DOI: https://doi.org/10.1007/BF00688179