The distribution of oligodendroglial inclusions in multiple system atrophy and its relevance to clinical symptomatology
Abstract
In this study a semiquantitative mapping of oligodendroglial cytoplasmic inclusions (GCIs), a feature of oligodendroglial degeneration in multiple system atrophy (MSA), was undertaken by means of a sensitive silver technique in 14 brains and 11 spinal cords of patients with various combinations of striatonigral degeneration, olivopontocerebellar atrophy and autonomic failure. The results show a system-bound extensive degeneration of interfascicular, perineuronal and perivascular oligodendrocytes. Oligodendroglial cytoplasmic inclusion-rich structures occur in the supra-segmental motor systems (primary motor and higher motor areas of cerebral cortex, 'pyramidal', 'extrapyramidal' and cortico-cerebellar systems), in the supraspinal autonomic systems and in their targets. In contrast, the visual and auditory pathways, olfactory structures, somatosensory systems, association and limbic cortical areas and subcortical limbic structures contain no or only a few GCIs. Comparison of the severity of oligodendroglial degeneration (GCI-density) with that of the neuronal alterations (neuronal cytoplasmic and nuclear inclusions, degenerated neuronal processes and loss of nerve cells) indicates a striking preponderance of oligodendroglial degeneration and that degeneration neither of axons, nor of neuronal cell bodies is a prerequisite of the development of GCIs. It also suggests that inclusion-bearing oligodendroglial degeneration may cause or contribute to the manifestation of clinical symptomatology in structures with GCI accumulation but without convincing neuronal alterations, i.e. cerebral motor cortical areas and reticular formation of the lower brainstem, both previously thought to be spared in MSA.
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The morphology of the GCIs in the model mimics the typical conical half-moon shape inclusions seen in human MSA.
“Moreover, the morphology of the GCIs (Fig. 3f, red channel) mimics the typical conical half-moon shape inclusions seen in the human disease [43].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [43]
GCIs are composed mainly of α-syn.
“These inclusions were later described to be composed mainly of α-syn [43].”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [43]
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BackgroundYazawa, I., Giasson, B. I., Sasaki, R., Zhang, B., Joyce, S., Uryu, K., Trojanowski, J. Q., & Lee, V. M.-Y. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.032 · Cited by 301 · see citing works
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Goedert, M., Spillantini, M. G., & Davies, S. W. (1998) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(98)80090-1 · Cited by 260 · see citing works
Wenning, G. K. (2000) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.68.4.434 · Cited by 261 · see citing works
Stanković, I., Krismer, F., Ješić, A., Antonini, A., Benke, T., Brown, R. G., Burn, D. J., Holton, J. L., Kaufmann, H., Kostić, V., et al. (2014) · Movement Disorders · doi:10.1002/mds.25880 · Cited by 248 · see citing works
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BackgroundAntonini, A. (1997) · Brain · doi:10.1093/brain/120.12.2187 · Cited by 241 · see citing works
“…studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson’s disease Angelo Antonini,1 Klaus L. Leenders,2 Peter Vontobel,1 R. Paul Maguire,1 John Missimer,1 Maria Psylla1 and Ilonka Gu¨nther1 1PET Department, Paul Scherrer Institute,…”
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Rockenstein, E., Nuber, S., Overk, C., Ubhi, K., Mante, M., Patrick, C., Adame, A., Trejo-Morales, M., Gerez, J., Picotti, P., et al. (2014) · Brain : a journal of neurology · doi:10.1093/brain/awu057 · Cited by 228 · see citing works
RetractedThe aetiology of sporadic adult‐onset ataxia
Abele, M., Bürk, K., Schöls, L. J., Schwartz, S., Besenthal, I., DICHGANS, J., Zühlke, C., Rieß, O., & Klockgether, T. (2002) · Brain · doi:10.1093/brain/awf107 · Cited by 233 · see citing works
“The ultrastructural hallmark of MSA is the presence of oligodendroglial cytoplasmic inclusions (Papp and Lantos, 1994).”
Braak, H., & Braak, E. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050096 · Cited by 225 · see citing works
“…atrophy) usually exhibit a marked development of abnormal tau protein in both oligodendroglial cells and astrocytes (Papp et al., 1989; Horoupian, 1990; Nakazato et al., 1990; Yamada and McGeer, 1990; Yamada et al., 1992; Probst et al., 1993; Papp and Lantos, 1994; Iwatsubo et al., 1994).”
BackgroundWhat Is the Accuracy of the Clinical Diagnosis of Multiple System Atrophy?
Litvan, I. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550200007003 · Cited by 213 · see citing works
Multiple System Atrophy: A Sporadic Synucleinopathy
Dickson, D. W., Lin, W.-L., Liu, W.-K., & Yen, S.-H. C. (1999) · Brain Pathology · doi:10.1111/j.1750-3639.1999.tb00553.x · Cited by 210 · see citing works
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Jellinger, K. A. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170397 · Cited by 209 · see citing works
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Tong, J., Wong, H., Guttman, M., Ang, L. C., Forno, L. S., Shimadzu, M., Rajput, A. H., Muenter, M. D., Kish, S. J., Hornykiewicz, O., et al. (2009) · Brain · doi:10.1093/brain/awp282 · Cited by 204 · see citing works
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BackgroundInfluentialBooij, J., Tissingh, G., Winogrodzka, A., & van Royen, E. A. (1999) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s002590050374 · Cited by 174 · see citing works
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BackgroundResultInfluentialBak, T. H., Crawford, L., Hearn, V., Mathuranath, P. S., & Hodges, J. R. (2005) · Neurocase · doi:10.1080/13554790590962997 · Cited by 168 · see citing works
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Duda, J. E., Giasson, B. I., Gur, T., Montine, T. J., Robertson, D., Biaggioni, I., Hurtig, H. I., Stern, M. B., Gollomp, S. M., Grossman, M., et al. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.9.830 · Cited by 150 · see citing works
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Armstrong, R. A., Lantos, P. L., & Cairns, N. J. (2005) · Neuropathology · doi:10.1111/j.1440-1789.2005.00605.x · Cited by 146 · see citing works
Self-citationInvolvement of vagal autonomic nuclei in multiple system atrophy and Lewy body disease
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Wakabayashi, K., & Takahashi, H. (2006) · Neuropathology · doi:10.1111/j.1440-1789.2006.00713.x · Cited by 144 · see citing works
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Blain, C. R. V., Barker, G. J., Jarosz, J., Coyle, N. A., Landau, S., Brown, R. G., Chaudhuri, К. R., Simmons, A., Jones, D. K., Williams, S., et al. (2006) · Neurology · doi:10.1212/01.wnl.0000249307.59950.f8 · Cited by 145 · see citing works
Papp–Lantos inclusions and the pathogenesis of multiple system atrophy: an update
Jellinger, K. A., & Lantos, P. L. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0672-3 · Cited by 144 · see citing works
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BackgroundSelf-citationCellular pathology of multiple system atrophy: a review.
Lantos, P. L., & Papp, M. I. (1994) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.57.2.129 · Cited by 143 · see citing works
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Gilman, S., Sima, A. A. F., Junck, L., Kluin, K., Koeppe, R., Lohman, M., & Little, R. J. A. (1996) · Annals of Neurology · doi:10.1002/ana.410390214 · Cited by 157 · see citing works
Araki, K., Yagi, N., Aoyama, K., Choong, C., Hayakawa, H., Fujimura, H., Nagai, Y., Goto, Y., & Mochizuki, H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906124116 · Cited by 132 · see citing works
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BackgroundRobitaille, Y., Schut, L., & Kish, S. (2004) · Acta Neuropathologica · doi:10.1007/bf00318569 · Cited by 102 · see citing works
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MethodHorimoto, Y., Aiba, I., Yasuda, T., et al. (2002) · Journal of Neurology · doi:10.1007/s00415-002-0734-0 · Cited by 133 · see citing works
Immunotherapy for neurodegenerative diseases: Focus on α-synucleinopathies
Valera, E., & Masliah, E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.013 · Cited by 132 · see citing works
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Koga, S., & Dickson, D. W. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-315813 · Cited by 130 · see citing works
Paviour, D. C., Thornton, J. S., Lees, A. J., & Jäger, H. R. (2006) · Movement Disorders · doi:10.1002/mds.21204 · Cited by 129 · see citing works
Multiple system atrophy: cellular and molecular pathology
Burn, D. J., & Jaros, E. (2001) · Molecular Pathology · doi:10.1136/mp.54.6.419 · Cited by 126 · see citing works
Soliveri, P. (2000) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.69.3.313 · Cited by 124 · see citing works
Myelin Degeneration in Multiple System Atrophy Detected by Unique Antibodies
Matsuo, A., Akiguchi, I., Lee, G. C., McGeer, E. G., McGeer, P. L., & Kimura, J. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65617-9 · Cited by 125 · see citing works
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BackgroundNishie, M., Mori, F., Yoshimoto, M., Takahashi, H., & Wakabayashi, K. (2004) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2004.00564.x · Cited by 123 · see citing works
Scherfler, C., Seppi, K., Donnemiller, E., Goebel, G., Brenneis, C., Virgolini, I. J., Wenning, G. K., & Poewe, W. H. (2005) · Brain · doi:10.1093/brain/awh485 · Cited by 120 · see citing works
“This would be in line with reported neuropathological findings in MSA-P patients, showing neuronal loss in brainstem areas containing DAT, SERT or NAT bearing neurons as the substantia nigra, the locus coeruleus and the raphe nuclei (Wenning et al., 1997, 2004; Papp and Lantos, 1994).”
ResultInoue, M., Yagishita, S., Ryo, M., Hasegawa, K., Amano, N., & Matsushita, M. (1997) · Acta Neuropathologica · doi:10.1007/s004010050655 · Cited by 117 · see citing works
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BackgroundResultInfluentialKikuchi, A., Takeda, A., Okamura, N., Tashiro, M., Hasegawa, T., Furumoto, S., Kobayashi, M., Sugeno, N., Baba, T., Miki, Y., et al. (2010) · Brain · doi:10.1093/brain/awq091 · Cited by 113 · see citing works
“…anterior cingulate cortex, globus pallidus, primary motor cortex and substantia nigra, in which glial cytoplasmic inclusions were densely distributed (Papp and Lantos, 1994; Inoue et al., 1997; Wakabayashi and Takahashi, 2006) and large increases of -synuclein content were found (Tong et al.,…”
BackgroundMinnerop, M., Specht, K., Ruhlmann, J., Schimke, N., Abele, M., Weyer, A., Wüllner, U., & Klockgether, T. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.04.028 · Cited by 114 · see citing works
Olivopontocerebellar pathology in multiple system atrophy
Wenning, G. K., Tison, F., Elliott, L., Quinn, N. P., & Daniel, S. E. (1996) · Movement Disorders · doi:10.1002/mds.870110207 · Cited by 106 · see citing works
Insulin resistance and exendin-4 treatment for multiple system atrophy
Bassil, F., Canron, M., Vital, A., Bézard, E., Li, Y., Greig, N. H., Gulyani, S., Kapogiannis, D., Fernagut, P., & Meissner, W. G. (2017) · Brain · doi:10.1093/brain/awx044 · Cited by 108 · see citing works
Visuospatial functions in atypical parkinsonian syndromes
Bak, T. H. (2006) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.068239 · Cited by 106 · see citing works
Electrophysiologic patterns of oral-pharyngeal swallowing in parkinsonian syndromes
Alfonsi, E., Versino, M., Merlo, I. M., Pacchetti, C., Martignoni, E., Bertino, G., Moglia, A., Tassorelli, C., & Nappi, G. (2007) · Neurology · doi:10.1212/01.wnl.0000254478.46278.67 · Cited by 106 · see citing works
Irving, E. A., Yatsushiro, K., McCulloch, J., & Dewar, D. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199706000-00003 · Cited by 103 · see citing works
Holmberg, B., Johnels, B., Blennow, K., & Rosengren, L. (2002) · Movement Disorders · doi:10.1002/mds.10321 · Cited by 104 · see citing works
Cantone, M., Pino, G. D., Capone, F., Piombo, M., Chiarello, D., Cheeran, B., Pennisi, G., & Lazzaro, V. D. (2014) · Clinical Neurophysiology · doi:10.1016/j.clinph.2014.04.010 · Cited by 102 · see citing works
Araki, K., Yagi, N., Ikemoto, Y., Yagi, H., Choong, C., Hayakawa, H., Beck, G., Sumi, H., Fujimura, H., Moriwaki, T., et al. (2015) · Scientific Reports · doi:10.1038/srep17625 · Cited by 100 · see citing works
Differential diagnosis of parkinsonism with [18F]fluorodeoxyglucose and PET
Antonini, A., Kazumata, K., Feigin, A., Mandel, F. S., DHAWAN, V. M., Margouleff, C., & Eidelberg, D. (1998) · Movement Disorders · doi:10.1002/mds.870130212 · Cited by 98 · see citing works
Wenning, G. K., & Braune, S. (2001) · CNS Drugs · doi:10.2165/00023210-200115110-00003 · Cited by 102 · see citing works
Diagnóstico diferencial das demências
Neto, J. G., Tamelini, M. G., & Forlenza, O. V. (2005) · Archives of Clinical Psychiatry (São Paulo) · doi:10.1590/s0101-60832005000300004 · Cited by 98 · see citing works
Dementia with Grains (Argyrophilic Grain Disease)
Jellinger, K. A. (1998) · Brain Pathology · doi:10.1111/j.1750-3639.1998.tb00161.x · Cited by 98 · see citing works
“ably tau and aB crystallin positive and neurofilamentantibody negative (11, 37).”
BackgroundInvolvement of precerebellar nuclei in multiple system atrophy
Braak, H., Rüb, U., & Tredici, K. D. (2003) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2003.00432.x · Cited by 93 · see citing works
Recent developments in multiple system atrophy
Wenning, G. K., & Stefanova, N. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5173-8 · Cited by 93 · see citing works
Chrysostome, V., Tison, F., Yekhlef, F., Sourgen, C., Baldi, I., & Dartigues, J. (2004) · Neuroepidemiology · doi:10.1159/000078506 · Cited by 92 · see citing works
Animal models of multiple system atrophy
Stefanova, N., & Wenning, G. K. (2015) · Clinical Autonomic Research · doi:10.1007/s10286-014-0266-6 · Cited by 93 · see citing works
Ahmed, Z., Asi, Y. T., Lees, A. J., Révész, T., & Holton, J. L. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00637.x · Cited by 92 · see citing works
Understanding the pathogenesis of multiple system atrophy: state of the art and future perspectives
Compagnoni, G. M., & Fonzo, A. D. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0730-6 · Cited by 89 · see citing works
Lyoo, C. H., Jeong, Y., Ryu, Y. H., Lee, S., Song, T., Lee, J. H., Rinne, J. O., & Lee, M. S. (2008) · Brain · doi:10.1093/brain/awm328 · Cited by 92 · see citing works
“Glial cytoplasmic inclusions (GCIs) were found in the frontal lobe, particularly in the supplementary motor, cingulate, primary motor and premotor cortices (Papp and Lantos, 1994).”
BackgroundResultInfluentialPatterns of abnormal motor cortex excitability in atypical parkinsonian syndromes
Kühn, A. A., Grosse, P., Holtz, K., et al. (2004) · Clinical Neurophysiology · doi:10.1016/j.clinph.2004.03.020 · Cited by 90 · see citing works
SLEEP AND DEGENERATIVE NEUROLOGIC DISORDERS
Chokroverty, S. (1996) · Neurologic Clinics · doi:10.1016/s0733-8619(05)70286-3 · Cited by 87 · see citing works
The morbid anatomy of dementia in Parkinson’s disease
Kalaitzakis, M. E., & Pearce, R. K. B. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0597-x · Cited by 89 · see citing works
“bodies in neurons and/or glial cells [46, 127] with the term encompassing diverse, but clinically overlapping entities, such as multiple system atrophy, PD, dementia with Lewy bodies (DLB), the LB variant of Alzheimer’s disease (LBVAD) and neurodegeneration with brain iron accumulation type 1 (NBIA I) [9, 13, 38, 45,…”
BackgroundStacpoole, S. R. L., Spitzer, S., Bilican, B., Compston, A., Káradóttir, R., Chandran, S., & Franklin, R. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.09.006 · Cited by 88 · see citing works
Meissner, W. G., Traon, A. P., Foubert‐Samier, A., et al. (2020) · Movement Disorders · doi:10.1002/mds.28218 · Cited by 88 · see citing works
Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress
Woulfe, J. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00819.x · Cited by 88 · see citing works
Multiple system atrophy with remarkable frontal lobe atrophy
Konagaya, M., Sakai, M., Matsuoka, Y., Konagaya, Y., & Hashizume, Y. (1999) · Acta Neuropathologica · doi:10.1007/s004010051008 · Cited by 88 · see citing works
“In MSA, involvement of the cerebral hemisphere, which is considered to be most resistant reticular formation [2, 10 ], has been reported in only a few cases [5, 16].”
Backgroundα-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy
May, V. E. L., Ettle, B., Poehler, A.-M., Nuber, S., Ubhi, K. K., Rockenstein, E. M., Winner, B., Wegner, M., Masliah, E., & Winkler, J. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.028 · Cited by 84 · see citing works
“Additionally, post mortem studies indicate a correlation of GCI load with neuronal degeneration (Ozawa, et al., 2004, Papp and Lantos, 1994) for striatonigral, Neurobiol Aging.”
BackgroundStemberger, S., Poewe, W., Wenning, G. K., & Stefanova, N. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.008 · Cited by 83 · see citing works
Urbano, F. J., Sierra, F., Colombo, J. A., Velasco, J. M., & Bu�o, W. (1997) · Glia · doi:10.1002/(sici)1098-1136(199702)19:2 · Cited by 9 · see citing works
Hanna, P. A., Jankovic, J. J., & Kirkpatrick, J. B. (1999) · Archives of Neurology · doi:10.1001/archneur.56.1.90 · Cited by 82 · see citing works
Wakabayashi, K., Ikeuchi, T., Ishikawa, A., & Takahashi, H. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00018-5 · Cited by 81 · see citing works
Benarroch, E. E. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a6b123 · Cited by 81 · see citing works
Davies, S. W., Turmaine, M., Cozens, B. A., Raza, A. S., Mahal, A., Mangiarini, L., & Bates, G. P. (1999) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1999.0448 · Cited by 81 · see citing works
“…not to our knowledge been described in postmortem human HD, DRPLA, SBMA or SCA brain, although it is of interest that inclusions composed of a-synuclein have been reported in nuclei of oligodendrocytes in post-mortem brain in multiple system atrophy (Papp & Lantos 1994; Spillantini et al. 1998).”
Olfactory dysfunction in cerebellar ataxia and multiple system atrophy
Abele, M., Riet, A., Hummel, T. R., Klockgether, T., & W�llner, U. (2003) · Journal of Neurology · doi:10.1007/s00415-003-0248-4 · Cited by 81 · see citing works
Characteristics of the Dysarthria of Multiple System Atrophy
Kluin, K. J., Gilman, S., Lohman, M., & Junck, L. (1996) · Archives of Neurology · doi:10.1001/archneur.1996.00550060089021 · Cited by 80 · see citing works
Shiga, K., Yamada, K., Yoshikawa, K., Mizuno, T., Nishimura, T., & Nakagawa, M. (2005) · Journal of Neurology · doi:10.1007/s00415-005-0708-0 · Cited by 79 · see citing works
“The pallor of myelin, gliosis, and GCIs are also observed in internal capsule [12], possibly disrupting tissue integrity in that area.”
BackgroundPiao, Y.-S., Hayashi, S., Hasegawa, M., Wakabayashi, K., Yamada, M., Yoshimoto, M., Ishikawa, A., Iwatsubo, T., & Takahashi, H. (2001) · Acta Neuropathologica · doi:10.1007/s004010000292 · Cited by 78 · see citing works
“GCIs are present in oligodendroglial cells and widely distributed in the brains of affected patients [ 32 ].”
Ishizawa, K., Komori, T., Arai, N., Mizutani, T., & Hirose, T. (2008) · Neuropathology · doi:10.1111/j.1440-1789.2007.00855.x · Cited by 74 · see citing works
“The exact effect of GCIs or microglia on white matter and gray matter still remains to be understood in MSA.”
BackgroundInfluentialA novel grading scale for striatonigral degeneration (multiple system atrophy)
Wenning, G. K., Seppi, K., Tison, F., & Jellinger, K. A. (2002) · Journal of Neural Transmission · doi:10.1007/s007020200025 · Cited by 76 · see citing works
Tsuchiya, K., Ozawa, E., Haga, C., WATABIKI, S., Ikeda, M., Sano, M., Ooe, K., Taki, K., & Ikeda, K. (2000) · Acta Neuropathologica · doi:10.1007/s004010051173 · Cited by 73 · see citing works
Monza, D., Soliveri, P., Radice, D., Fetoni, V., Testa, D., Caffarra, P., CARACENI, T., & Girotti, F. (1998) · Archives of Neurology · doi:10.1001/archneur.55.3.372 · Cited by 72 · see citing works
“Direct cortical involvement has also been found in MSA: the premotor areas show neural and oligodendroglial, basophilic, argyrophil, cytoplasmic inclusions that are relatively specific for this disease and point to a cortical origin of the motor disorganization in MSA.(49)”
BackgroundInfluential
- Authors
- Papp, M. I., & Lantos, P. L.
- Affiliations
- Semmelweis University (HU)
- Corresponding author
- Papp, M. I.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 1994
- Volume
- 117
- Issue
- 2
- Pages
- 235-243
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2148569529
- Cited by
- 389
- References
- 0
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 16 · 2020: 19 · 2019: 10 · 2018: 10 · 2017: 15 · 2016: 4 · 2015: 12 · 2014: 20 · 2013: 12 · 2012: 10
- FWCI
- 8.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- multiple system atrophy, oligodendrocyte degeneration, striatonigral degeneration, olivopontocerebellar atrophy, autonomic failure, motor cortex, reticular formation, brainstem, spinal cord, symptomatology, silver staining
- MeSH terms
- Aged, Atrophy, Autonomic Nervous System Diseases, Brain Diseases, Inclusion Bodies, Corpus Striatum, Female, Humans, Male, Middle Aged, Oligodendroglia, Olivopontocerebellar Atrophies, Substantia Nigra
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