A Comprehensive Review and Evaluation of the Diagnostic Methods of a Multiple System Atrophy Diagnosis
DOI:
https://doi.org/10.58445/rars.1509Keywords:
multiple system atrophy, diagnosis, neuroscienceAbstract
Multiple System Atrophy (MSA) is a rare neurodegenerative disorder belonging to a group called synucleinopathies. It is characterized by the abnormal accumulation of α-synuclein in oligodendrocytes, causing glial cytoplasmic inclusions. MSA is commonly misdiagnosed due to its overlapping symptoms with other diseases, namely Parkinson's Disease (PD). This study reviews the diagnostic methods used for MSA and discusses their benefits and how they can be improved for future research. These methods include the current diagnostic criteria, MRIs, biomarkers, and genetic screening. Through a comprehensive search of the current literature, utilizing PubMed and Google Scholar, I analyzed and compiled numerous research articles for their relevance and content. Emphasizing the accurate and distinctive diagnosis of MSA allows individuals to better manage the consequences of this devastating disease.
References
Overk, C., Rockenstein, E., Valera, E., Stefanova, N., Wenning, G., & Masliah, E. (2018). Multiple system atrophy: experimental models and reality. Acta neuropathologica, 135(1), 33–47. https://doi.org/10.1007/s00401-017-1772-0
Jellinger K. A. (2022). Heterogeneity of Multiple System Atrophy: An Update. Biomedicines, 10(3), 599. https://doi.org/10.3390/biomedicines10030599
Tseng, F. S., Foo, J. Q. X., Mai, A. S., & Tan, E. K. (2023). The genetic basis of multiple system atrophy. Journal of translational medicine, 21(1), 104. https://doi.org/10.1186/s12967-023-03905-1
Wenning, G. K., Stankovic, I., Vignatelli, L., Fanciulli, A., Calandra-Buonaura, G., Seppi, K., Palma, J. A., Meissner, W. G., Krismer, F., Berg, D., Cortelli, P., Freeman, R., Halliday, G., Höglinger, G., Lang, A., Ling, H., Litvan, I., Low, P., Miki, Y., Panicker, J., … Kaufmann, H. (2022). The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy. Movement disorders : official journal of the Movement Disorder Society, 37(6), 1131–1148. https://doi.org/10.1002/mds.29005
Shahnawaz, M., Mukherjee, A., Pritzkow, S., Mendez, N., Rabadia, P., Liu, X., Hu, B., Schmeichel, A., Singer, W., Wu, G., Tsai, A. L., Shirani, H., Nilsson, K. P. R., Low, P. A., & Soto, C. (2020). Discriminating α-synuclein strains in Parkinson's disease and multiple system atrophy. Nature, 578(7794), 273–277. https://doi.org/10.1038/s41586-020-1984-7
Krismer, F., Beliveau, V., Seppi, K., Mueller, C., Goebel, G., Gizewski, E. R., Wenning, G. K., Poewe, W., & Scherfler, C. (2021). Automated Analysis of Diffusion-Weighted Magnetic Resonance Imaging for the Differential Diagnosis of Multiple System Atrophy from Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society, 36(1), 241–245. https://doi.org/10.1002/mds.28281
Specht K, Minnerop M, Abele M, Reul J, Wüllner U, Klockgether T. In Vivo Voxel-Based Morphometry in Multiple System Atrophy of the Cerebellar Type. Arch Neurol. 2003;60(10):1431–1435. doi:10.1001/archneur.60.10.1431
Krismer, F., Seppi, K., Göbel, G., Steiger, R., Zucal, I., Boesch, S., Gizewski, E. R., Wenning, G. K., Poewe, W., & Scherfler, C. (2019). Morphometric MRI profiles of multiple system atrophy variants and implications for differential diagnosis. Movement disorders : official journal of the Movement Disorder Society, 34(7), 1041–1048. https://doi.org/10.1002/mds.27669
Osaki, Y., Wenning, G. K., Daniel, S. E., Hughes, A., Lees, A. J., Mathias, C. J., & Quinn, N. (2002). Do published criteria improve clinical diagnostic accuracy in multiple system atrophy?. Neurology, 59(10), 1486–1491. https://doi.org/10.1212/01.wnl.0000028690.15001.00
Takado, Y., Igarashi, H., Terajima, K., Shimohata, T., Ozawa, T., Okamoto, K., Nishizawa, M., & Nakada, T. (2011). Brainstem metabolites in multiple system atrophy of cerebellar type: 3.0-T magnetic resonance spectroscopy study. Movement disorders : official journal of the Movement Disorder Society, 26(7), 1297–1302. https://doi.org/10.1002/mds.23550
Wan, L., Zhu, S., Chen, Z., Qiu, R., Tang, B., & Jiang, H. (2023). Multidimensional biomarkers for multiple system atrophy: an update and future directions. Translational neurodegeneration, 12(1), 38. https://doi.org/10.1186/s40035-023-00370-0
Monzio Compagnoni, G., Kleiner, G., Bordoni, A., Fortunato, F., Ronchi, D., Salani, S., Guida, M., Corti, C., Pichler, I., Bergamini, C., Fato, R., Pellecchia, M. T., Vallelunga, A., Del Sorbo, F., Elia, A., Reale, C., Garavaglia, B., Mora, G., Albanese, A., . . . Di Fonzo, A. (2018). Mitochondrial dysfunction in fibroblasts of Multiple System Atrophy. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1864(12), 3588-3597. https://doi.org/10.1016/j.bbadis.2018.09.018
Al-Chalabi, A., Dürr, A., Wood, N. W., Parkinson, M. H., Camuzat, A., Hulot, J. S., Morrison, K. E., Renton, A., Sussmuth, S. D., Landwehrmeyer, B. G., Ludolph, A., Agid, Y., Brice, A., Leigh, P. N., Bensimon, G., & NNIPPS Genetic Study Group (2009). Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PloS one, 4(9), e7114. https://doi.org/10.1371/journal.pone.0007114
Butler, B., Sambo, D., & Khoshbouei, H. (2017). Alpha-synuclein modulates dopamine neurotransmission. Journal of chemical neuroanatomy, 83-84, 41–49. https://doi.org/10.1016/j.jchemneu.2016.06.001
Tsika, E., & Moore, D. J. (2012). Mechanisms of LRRK2-mediated neurodegeneration. Current neurology and neuroscience reports, 12(3), 251–260. https://doi.org/10.1007/s11910-012-0265-8
Riboldi, G. M., Palma, J. A., Cortes, E., Iida, M. A., Sikder, T., Henderson, B., Raj, T., Walker, R. H., Crary, J. F., Kaufmann, H., & Frucht, S. (2019). Early-onset pathologically proven multiple system atrophy with LRRK2 G2019S mutation. Movement disorders : official journal of the Movement Disorder Society, 34(7), 1080–1082. https://doi.org/10.1002/mds.27710
Carrer, T., Bonato, G., Sandre, M., Emmi, A., Campagnolo, M., Musso, G., Carecchio, M., Parchi, P., & Antonini, A. (2024). Rapidly progressive multiple system atrophy in a patient carrying LRRK2 G2019S mutation. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 45(1), 309–313. https://doi.org/10.1007/s10072-023-07056-5
Labbé, C., Heckman, M. G., Lorenzo-Betancor, O., Murray, M. E., Ogaki, K., Soto-Ortolaza, A. I., Walton, R. L., Fujioka, S., Koga, S., Uitti, R. J., van Gerpen, J. A., Petersen, R. C., Graff-Radford, N. R., Younkin, S. G., Boeve, B. F., Cheshire, W. P., Jr, Low, P. A., Sandroni, P., Coon, E. A., Singer, W., … Ross, O. A. (2016). MAPT haplotype diversity in multiple system atrophy. Parkinsonism & related disorders, 30, 40–45. https://doi.org/10.1016/j.parkreldis.2016.06.010
Brenneis, C., Seppi, K., Schocke, M. F., Müller, J., Luginger, E., Bösch, S., Löscher, W. N., Büchel, C., Poewe, W., & Wenning, G. K. (2003). Voxel-based morphometry detects cortical atrophy in the Parkinson variant of multiple system atrophy. Movement disorders : official journal of the Movement Disorder Society, 18(10), 1132–1138. https://doi.org/10.1002/mds.10502
Rulseh, A. M., Keller, J., Rusz, J., Syka, M., Brozova, H., Rusina, R., Havrankova, P., Zarubova, K., Malikova, H., Jech, R., & Vymazal, J. (2016). Diffusion tensor imaging in the characterization of multiple system atrophy. Neuropsychiatric disease and treatment, 12, 2181–2187. https://doi.org/10.2147/NDT.S109094
Burns, M. R., & McFarland, N. R. (2020). Current Management and Emerging Therapies in Multiple System Atrophy. Neurotherapeutics, 17(4), 1582–1602. https://doi.org/10.1007/s13311-020-00890-x
Katzeff, J. S., Phan, K., Purushothuman, S., Halliday, G. M., & Kim, W. S. (2019). Cross-examining candidate genes implicated in multiple system atrophy. Acta Neuropathologica Communications, 7(1). https://doi.org/10.1186/s40478-019-0769-4
Sailer, A., Scholz, S. W., Nalls, M. A., Schulte, C., Federoff, M., Price, T. R., Lees, A., Ross, O. A., Dickson, D. W., Mok, K., Mencacci, N. E., Schottlaender, L., Chelban, V., Ling, H., O’Sullivan, S. S., Wood, N. W., Traynor, B. J., Ferrucci, L., Federoff, H. J., . . . Cortelli, P. (2016). A genome-wide association study in multiple system atrophy. Neurology, 87(15), 1591–1598. https://doi.org/10.1212/wnl.0000000000003221
Sun, Z., Xiang, X., Tang, B., Chen, Z., Peng, H., Xia, K., & Jiang, H. (2015). SNP rs11931074 of the SNCA gene may not be associated with multiple system atrophy in Chinese population. The International journal of neuroscience, 125(8), 612–615. https://doi.org/10.3109/00207454.2014.990013
Multiple-System Atrophy Research Collaboration (2013). Mutations in COQ2 in familial and sporadic multiple-system atrophy. The New England journal of medicine, 369(3), 233–244. https://doi.org/10.1056/NEJMoa1212115
Sun, Z., Ohta, Y., Yamashita, T., Sato, K., Takemoto, M., Hishikawa, N., & Abe, K. (2016). New susceptible variant of COQ2 gene in Japanese patients with sporadic multiple system atrophy. Neurology. Genetics, 2(2). https://doi.org/10.1212/nxg.0000000000000054
Yuan, X., Chen, Y., Cao, B., Zhao, B., Wei, Q., Guo, X., Yang, Y., Yuan, L., & Shang, H. (2015). An association analysis of the R1628P and G2385R polymorphisms of the LRRK2 gene in multiple system atrophy in a Chinese population. Parkinsonism & related disorders, 21(2), 147–149. https://doi.org/10.1016/j.parkreldis.2014.11.022
Chen, Y. P., Zhao, B., Cao, B., Song, W., Guo, X., Wei, Q. Q., Yang, Y., Yuan, L. X., & Shang, H. F. (2015). Mutation scanning of the COQ2 gene in ethnic Chinese patients with multiple-system atrophy. Neurobiology of Aging, 36(2), 1222.e7-1222.e11. https://doi.org/10.1016/j.neurobiolaging.2014.09.010
Soma, H., Yabe, I., Takei, A., Fujiki, N., Yanagihara, T., & Sasaki, H. (2006). Heredity in multiple system atrophy. Journal of the neurological sciences, 240(1-2), 107–110. https://doi.org/10.1016/j.jns.2005.09.003
Hara, K., Momose, Y., Tokiguchi, S., Shimohata, M., Terajima, K., Onodera, O., Kakita, A., Yamada, M., Takahashi, H., Hirasawa, M., Mizuno, Y., Ogata, K., Goto, J., Kanazawa, I., Nishizawa, M., & Tsuji, S. (2007). Multiplex families with multiple system atrophy. Archives of neurology, 64(4), 545–551. https://doi.org/10.1001/archneur.64.4.545
Li, X. Y., Yang, W., Li, X., Li, X. R., Li, W., Song, Q., Sun, L., Lin, F., Chen, Z., Wang, C., & Yu, S. (2020). Phosphorylated Alpha-Synuclein in Red Blood Cells as a Potential Diagnostic Biomarker for Multiple System Atrophy: A Pilot Study. Parkinson's disease, 2020, 8740419. https://doi.org/10.1155/2020/8740419
Abdul‐Rahman, T., Herrera‐Calderón, R. E., Ahluwalia, A., Wireko, A. A., Ferreira, T., Tan, J. K., Wolfson, M., Ghosh, S., Horbas, V., Garg, V., Perveen, A., Papadakis, M., Ashraf, G. M., & Alexiou, A. (2024). The potential of phosphorylated α‐synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy. CNS Neuroscience & Therapeutics, 30(4). https://doi.org/10.1111/cns.14678
Foulds, P. G., Yokota, O., Thurston, A., Davidson, Y., Ahmed, Z., Holton, J., Thompson, J. C., Akiyama, H., Arai, T., Hasegawa, M., Gerhard, A., Allsop, D., & Mann, D. M. (2012). Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies. Neurobiology of disease, 45(1), 188–195. https://doi.org/10.1016/j.nbd.2011.08.003
Sekiya, H., Kowa, H., Koga, H., Takata, M., Satake, W., Futamura, N., Funakawa, I., Jinnai, K., Takahashi, M., Kondo, T., Ueno, Y., Kanagawa, M., Kobayashi, K., & Toda, T. (2019). Wide distribution of alpha-synuclein oligomers in multiple system atrophy brain detected by proximity ligation. Acta Neuropathologica, 137(3), 455–466. https://doi.org/10.1007/s00401-019-01961-w
Doppler, K., Weis, J., Karl, K., Ebert, S., Ebentheuer, J., Trenkwalder, C., Klebe, S., Volkmann, J., & Sommer, C. (2015). Distinctive distribution of phospho-alpha-synuclein in dermal nerves in multiple system atrophy. Movement Disorders, 30(12), 1688–1692. https://doi.org/10.1002/mds.26293
Donadio, V., Incensi, A., Rizzo, G., Westermark, G. T., Devigili, G., De Micco, R., Tessitore, A., Nyholm, D., Parisini, S., Nyman, D., Tedeschi, G., Eleopra, R., Ingelsson, M., & Liguori, R. (2023). Phosphorylated α-synuclein in skin Schwann cells: a new biomarker for multiple system atrophy. Brain, 146(3), 1065–1074. https://doi.org/10.1093/brain/awac124
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