Atrofia multisistémica del tipo cerebelosa: implicaciones patológicas de la conectividad neuronal
DOI:
https://doi.org/10.28957/rcmfr.354Palabras clave:
Atrofia de múltiples sistemas, alfa-sinucleína, ataxia cerebelos, red en modo predeterminado, imagen de difusión por resonancia magnéticaResumen
Introducción. La atrofia multisistémica (MSA) es una enfermedad neurodegenerativa progresiva que afecta principalmente la materia blanca (WM, por su sigla en inglés). Este tipo de atrofia se caracteriza por ocasionar inclusiones citoplasmáticas gliales de la proteína alfa-sinucleína, además de disminuir la integridad, la desmielinización y los cambios en los diámetros axonales de la WM (trastornos del movimiento).
Objetivo. Evaluar los hallazgos patológicos de la conectividad encontrados en casos de atrofia multisistémica de tipo cerebelosa (MSA-C) y las posibles conexiones que estos muestran con las señales clínicas, la fisiopatología de la enfermedad, la imagenología y los blancos terapéuticos mediante una revisión sistemática de la literatura científica disponible.
Métodos. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, ResearchGate, Embase y Scopus con los siguientes términos claves: “Multiple system atrophy” AND “therapy” OR “diagnostic imagining” OR “physiopathology” OR epidemiology”. Se seleccionaron artículos, en español e inglés, publicados entre 1989 y 2022. Tras aplicar los criterios de inclusión y exclusión y eliminar duplicados, se seleccionaron 61 estudios que comparaban los temas objetivo del estudio.
Resultados. La conectividad funcional disminuida en la red de control ejecutivo izquierdo (ECN), relacionada con los circuitos de los ganglios basales y el tálamo, ocasiona desconexión cerebelo-prefrontal y cerebelo-amigdaloide/parahipocampal, lo cual tiene manifestaciones neuro histopatológicas que están correlacionadas con ciertos hallazgos imagenológicos.
Conclusión. Se evidenció que resultados de diversos estudios han permitido dar viabilidad a la comprensión de la conectividad nodal identificada y sus manifestaciones anatomo-patológicas y funcionales en el curso natural de la MSA-C.
Referencias bibliográficas
Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989;94(1-3):79-100. Disponible en: https://doi.org/10.1016/0022-510x(89)90219-0.
Raccagni C, Nonnekes J, Bloem BR, Peball M, Boehme C, Seppi K, et al. Gait and postural disorders in parkinsonism: a clinical approach. J Neurol. 2020;267(11):3169-76. Disponible en: https://doi.org/10.1007/s00415-019-09382-1.
Wenning GK, Geser F, Krismer F, Seppi K, Duerr S, Boesch S, et al. The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol. 2013;12(3):264-74. Disponible en: https://doi.org/10.1016/S1474-4422(12)70327-7.
Bower JH, Maraganore DM, McDonnell SK, Rocca WA. Incidence of progressive supranuclear palsy and multiple system atrophy in Olmsted County, Minnesota, 1976 to 1990. Neurology. 1997;49(5):1284-8. Disponible en: https://doi.org/ https://doi.org/10.1212/WNL.49.5.1284.
Schrag A, Ben-Shlomo Y, Quinn NP. Prevalence of progressive supranuclear palsy and multiple system atrophy: a cross-sectional study. Lancet. 1999;354(9192):1771-5. Disponible en: https://doi.org/10.1016/s0140-6736(99)04137-9.
Yabe I, Soma H, Takei A, Fujiki N, Yanagihara T, Sasaki H. MSA-C is the predominant clinical phenotype of MSA in Japan: analysis of 142 patients with probable MSA. J Neurol Sci. 2006;249(2):115-21. Disponible en: https://doi.org/10.1016/j.jns.2006.05.064.
Ozawa T, Onodera O. Multiple system atrophy: clinicopathological characteristics in Japanese patients. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(5):251-8. Disponible en: https://doi.org/10.2183/pjab.93.016.
Seo JH, Yong SW, Song SK, Lee JE, Sohn YH, Lee PH. A case-control study of multiple system atrophy in Korean patients. Mov Disord. 2010;25(12):1953-9. Disponible en: https://doi.org/10.1002/mds.23185.
Tseng FS, Deng X, Ong YL, Li HH, Tan EK. Multiple System Atrophy (MSA) and smoking: a meta-analysis and mechanistic insights. Aging (Albany NY). 2020;12(21):21959-70. Disponible en: https://doi.org/10.18632/aging.104021.
Vanacore N, Bonifati V, Fabbrini G, Colosimo C, de Michele G, Marconi R, et al. Case-control study of multiple system atrophy. Mov Disord. 2005;20(2):158-63. Disponible en: https://doi.org/10.1002/mds.20303.
Vanacore N. Epidemiological evidence on multiple system atrophy. J Neural Transm (Vienna). 2005;112(12):1605-12. Disponible en: https://doi.org/10.1007/s00702-005-0380-7.
Folke J, Rydbirk R, Løkkegaard A, Salvesen L, Hejl AM, Starhof C, et al. Distinct Autoimmune Anti-α-Synuclein Antibody Patterns in Multiple System Atrophy and Parkinson’s Disease. Front Immunol. 2019;10:2253. Disponible en: https://doi.org/10.3389
/fimmu.2019.02253.
Carmona-Abellan M, del Pino R, Murueta-Goyena A, Acera M, Tijero B, Berganzo K, et al. Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases. Neurologia (Engl Ed). 2021;S0213-4853(21)00073-6 Disponible en: https://doi.org/10.1016/j.nrl.2021.04.007.
Trinkaus VA, Riera-Tur I, Martínez-Sánchez A, Bäuerlein FJB, Guo Q, Arzberger T, et al. In situ architecture of neuronal α-Synuclein inclusions. Nat Commun. 2021;12(1):2110. Disponible en: https://doi.org/10.1038/s41467-021-22108-0.
Van der Perren A, Gelders G, Fenyi A, Bousset L, Brito F, Peelaerts W, et al. The structural differences between patient-derived α-synuclein strains dictate characteristics of Parkinson’s disease, multiple system atrophy and dementia with Lewy bodies. Acta neuropathol. 2020;139(6):977-1000. Disponible en: https://doi.org/10.1007/s00401-020-02157-3.
Honjo Y, Ayaki T, Horibe T, Ito H, Takahashi R, Kawakami K. FKBP12-immunopositive inclusions in patients with α-synucleinopathies. Brain Res. 2018;1680:39-45. Disponible en: https://doi.org/10.1016/j.brainres.2017.12.012.
Heras-Garvin A, Weckbecker D, Ryazanov S, Leonov A, Griesinger C, Giese A, et al. Anle138b modulates α-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019;34(2):255-63. Disponible en: https://doi.org/10.1002/mds.27562.
Jao CW, Soong BW, Huang CW, Duan CA, Wu CC, Wu YT, et al. Diffusion Tensor Magnetic Resonance Imaging for Differentiating Multiple System Atrophy Cerebellar Type and Spinocerebellar Ataxia Type 3. Brain Sci. 2019;9(12):254. Disponible en: https://doi.org/10.3390/brainsci9120354.
Lu CF, Soong BW, Wu HM, Teng S, Wang PS, Wu YT. Disrupted cerebellar connectivity reduces whole-brain network efficiency in multiple system atrophy. Mov Disord. 2013;28(3):362-9. Disponible en: https://doi.org/10.1002/mds.25314.
Kawabata K, Hara K, Watanabe H, Bagarinao E, Ogura A, Masuda M, et al. Alterations in Cognition - Related Cerebello-Cerebral Networks in Multiple System Atrophy. Cerebellum. 2019;18(4):770-80. Disponible en: https://doi.org/10.1007/s12311-019-01031-7.
Lee MJ, Shin JH, Seoung JK, Lee JH, Yoon U, Oh JH, et al. Cognitive impairments associated with morphological changes in cortical and subcortical structures in multiple system atrophy of the cerebellar type. Eur J Neurol. 2016;23(1):92-100. Disponible en: https://doi.org/10.1111/ene.12796.
Cao C, Wang Q, Yu H, Yang H, Li Y, Guo M, et al. Morphological Changes in Cortical and Subcortical Structures in Multiple System Atrophy Patients With Mild Cognitive Impairment. Front Hum Neurosci. 2021;15:15:649051. Disponible en: https://doi.org/10.3389/fnhum.2021.649051.
Santangelo G, Cuoco S, Picillo M, Erro R, Squillante M, Volpe G, et al. Evolution of neuropsychological profile in motor subtypes of multiple system atrophy. Parkinsonism Relat Disord. 2020;70:67-73. Disponible en: https://doi.org/10.1016/j.parkreldis.2019.12.010.
Kim M, Ahn JH, Cho Y, Kim JS, Youn J, Cho JW. Differential value of brain magnetic resonance imaging in multiple system atrophy cerebellar phenotype and spinocerebellar ataxias. Sci Rep. 2019;9(1):17329. Disponible en: https://doi.org/10.1038/s41598-019-53980-y.
Shah A, Prasad S, Rastogi B, Dash S, Saini J, Pal PK, et al. Altered structural connectivity of the motor subnetwork in multiple system atrophy with cerebellar features. Eur Radiol. 2019;29(6):2783-91. Disponible en: https://dx.doi.org/10.1007/s00330-018-5874-4.
Wang N, Zhang L, Yang HG, Liu H, Luo XG, Fan GG. Similarities and differences in cerebellar grey matter volume and disrupted functional connectivity in idiopathic Parkinson’s disease and multiple system atrophy. Neuropsychologia. 2019;124:125-32. Disponible en: https://doi.org/10.1016/j.neuropsychologia.2018.12.019.
Ren S, Zhang H, Zheng W, Liu M, Gao F, Wang Z, et al. Altered Functional Connectivity of Cerebello-Cortical Circuit in Multiple System Atrophy (Cerebellar-Type). Front Neurosci. 2019;12:996. Disponible en: https://doi.org/10.3389/fnins.2018.00996.
Rosskopf J, Gorges M, Müller HP, Pinkhardt EH, Ludolph AC, Kassubek J. Hyperconnective and hypoconnective cortical and subcortical functional networks in multiple system atrophy. Parkinsonism Relat Disord. 2018;49:75-80. Disponible en: https://doi.org/10.1016/j.parkreldis.2018.01.012.
Fukui Y, Hishikawa N, Sato K, Kono S, Matsuzono K, Nakano Y, et al. Dynamic Cerebrospinal Fluid Flow on MRI in Cortical Cerebellar Atrophy and Multiple System Atrophy-cerebellar Type. Intern Med. 2015;54(14):1717-23. Disponible en: https://doi.org/10.2169/internalmedicine.54.4747.
Miao Y, Wang K, Han J, Wang Z, Bian Y, Guo Q, et al. Differential value of external anal- and urethral-sphincter electromyography in multiple system atrophy cerebellar type and spinocerebellar ataxias. J Clin Neurosci. 2020;80:16-22. Disponible en: https://doi.org/10.1016/j.jocn.2020.07.067.
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, et al. Parkinsonism and spastic paraplegia type 7: Expanding the spectrum of mitochondrial Parkinsonism. Mov Disord. 2019;34(10):1547-61. Disponible en: https://doi.org/10.1002/mds.27812.
Bellini G, Del Prete E, Unti E, Frosini D, Siciliano G, Ceravolo R. Positive DAT-SCAN in SPG7: a case report mimicking possible MSA-C. BMC Neurol. 2021;21(1):328. Disponible en: https://doi.org/10.1186/s12883-021-02345-y.
Zhang H, Ji S, Ren S, Liu M, Ran W, Zhang X, et al. Cerebellar Atrophy in Multiple System Atrophy (Cerebellar Type) and Its Implication for Network Connectivity. Cerebellum. 2020;19(5):636-44. Disponible en: https://doi.org/10.1007/s12311-020-01144-4.
Gama RL, Távora DG, Bomfim RC, Silva CE, de Bruin VM, de Bruin PFC. Sleep disturbances and brain MRI morphometry in Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy - a comparative study. Parkinsonism Relat Disord. 2010;16(4):275-9. Disponible en: https://doi.org/10.1016/j.parkreldis.2010.01.002.
Testa C, Calandra-Buonaura G, Evangelisti S, Giannini G, Provini F, Ratti S, et al. Stridor-related gray matter alterations in multiple system atrophy: A pilot study. Parkinsonism Relat Disord. 2019;62:226-30. Disponible en: https://doi.org/10.1016/j.parkreldis.2018.11.018.
Pellecchia MT, Picillo M. Female sexual dysfunction in multiple system atrophy: does it matter? Clin Auton Res. 2021;31(6):649-50. Disponible en: https://doi.org/10.1007/s10286-021-00831-4.
Terao Y, Fukuda H, Tokushige SI, Inomata-Terada S, Yugeta A, Hamada M, et al. Distinguishing spinocerebellar ataxia with pure cerebellar manifestation from multiple system atrophy (MSA-C) through saccade profiles. Clin Neurophysiol. 2017;128(1):31-43. Disponible en: https://doi.org/10.1016/j.clinph.2016.10.012.
Sugiyama A, Sato N, Kimura Y, Fujii H, Maikusa N, Shigemoto Y, et al. Quantifying iron deposition in the cerebellar subtype of multiple system atrophy and spinocerebellar ataxia type 6 by quantitative susceptibility mapping. J Neurol Sci. 2019;407:116525. Disponible en: https://doi.org/10.1016/j.jns.2019.116525.
Chelban V, Catereniuc D, Aftene D, Gasnas A, Vichayanrat E, Iodice V, et al. An update on MSA: premotor and non-motor features open a window of opportunities for early diagnosis and intervention. J Neurol. 2020;267(9):2754-70. Disponible en: https://doi.org/10.1007/s00415-020-09881-6.
Sakakibara R, Panicker JN, Aiba Y, Tateno F, Ogata T, Yano M, et al. Possible “Premotor” Multiple System Atrophy-Cerebellar Form. Eur Neurol. 2020;83(1):80-6. Disponible en: https://doi.org/10.1159/000506983.
Matsuse D, Yamasaki R, Maimaitijiang G, Yamaguchi H, Masaki K, Isobe N, et al. Early decrease in intermediate monocytes in peripheral blood is characteristic of multiple system atrophy-cerebellar type. J Neuroimmunol. 2020;349:577395. Disponible en: https://doi.org/10.1016/j.jneuroim.2020.577395.
Urbizu A, Canet-Pons J, Munoz-Marmol AM, Aldecoa I, Lopez MT, Compta Y, et al. Cystatin C is differentially involved in multiple system atrophy phenotypes. Neuropathol Appl Neurobiol. 2015;41(4):507-19. Disponible en: https://doi.org/10.1111/nan.12134.
Del Campo N, Phillips O, Ory-Magne F, Brefel-Courbon C, Galitzky M, Thalamas C, et al. Broad white matter impairment in multiple system atrophy. Hum Brain Mapp. 2021;42(2):357-66. Disponible en: https://doi.org/10.1002/hbm.25227.
Krejciova Z, Carlson GA, Giles K, Prusiner SB. Replication of multiple system atrophy prions in primary astrocyte cultures from transgenic mice expressing human α-synuclein. Acta Neuropathol Commun. 2019;7(1):81. Disponible en: https://doi.org/10.1186/s40478-019-0703-9.
Yang HG, Wang N, Luo XG, Lv H, Liu H, Fan GG. Altered functional connectivity of dentate nucleus in parkinsonian and cerebellar variants of multiple system atrophy. Brain Imaging Behav. 2019;13(6):1733-45. Disponible en: https://doi.org/10.1007/s11682-019-00097-5.
Nimmo JT, Verma A, Dodart JC, Wang CY, Savistchenko J, Melki R, et al. Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy. Alzheimers Res Ther. 2020;12(1):159. Disponible en: https://doi.org/10.1186/s13195-020-00727-x.
Schwarz J, Weis S, Kraft E, Tatsch K, Bandmann O, Mehraein P, et al. Signal changes on MRI and increases in reactive microgliosis, astrogliosis, and iron in the putamen of two patients with multiple system atrophy. J Neurol Neurosurg Psychiatry. 1996;60(1):98-101. Disponible en: https://doi.org/10.1136/jnnp.60.1.98.
Zhang M, He T, Wang Q. Effects of Non-invasive Brain Stimulation on Multiple System Atrophy: A Systematic Review. Front Neurosci. 2021;15:771090. Disponible en: https://doi.org/10.3389/fnins.2021.771090.
Konagaya M, Sakai M, Matsuoka Y, Konagaya Y, Hashizume Y. Multiple system atrophy with remarkable frontal lobe atrophy. Acta Neuropathol. 1999;97(4):423-8. Disponible en: https://doi.org/10.1007/s004010051008.
Zheng W, Ren S, Zhang H, Liu M, Zhang Q, Chen Z, et al. Spatial Patterns of Decreased Cerebral Blood Flow and Functional Connectivity in Multiple System Atrophy (Cerebellar-Type): A Combined Arterial Spin Labeling Perfusion and Resting State Functional Magnetic Resonance Imaging Study. Front Neurosci. 2019;13:777. Disponible en: https://doi.org/10.3389/fnins.2019.00777.
Ito K, Ohtsuka C, Yoshioka K, Maeda T, Yokosawa S, Mori F, et al. Differentiation Between Multiple System Atrophy and Other Spinocerebellar Degenerations Using Diffusion Kurtosis Imaging. Acad Radiol. 2019;26(11):e333-9. Disponible en: https://doi.org/10.1016/j.acra.2018.12.015.
Valera E, Masliah E. Combination therapies: The next logical Step for the treatment of synucleinopathies? Mov Disord. 2016;31(2):225-34. Disponible en: https://doi.org/10.1002/mds.26428.
Meissner WG, Traon AP, Foubert-Samier A, Galabova G, Galitzky M, Kutzelnigg A, et al. A Phase 1 Randomized Trial of Specific Active α-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy. Mov Disord. 2020;35(11):1957-65. Disponible en: https://doi.org/10.1002/mds.28218.
Levin J, Maaß S, Schuberth M, Giese A, Oertel WH, Poewe W, et al. Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2019;18(8):724-35. Disponible en: https://doi.org/10.1016/S1474-4422(19)30141-3.
Liu Z, Ma H, Poole V, Wang X, Wang Z, Yang Y, et al. Effects of Multi-Session Repetitive Transcranial Magnetic Stimulation on Motor Control and Spontaneous Brain Activity in Multiple System Atrophy: A Pilot Study. Front Behav Neurosci. 2018;12:90. Disponible en: https://doi.org/10.3389/fnbeh.2018.00090.
Balzan P, Tattersall C, Palmer R. Non-invasive brain stimulation for treating neurogenic dysarthria: A systematic review. Ann Phys Rehabil Med. 2021;65(5):101580. Disponible en: https://doi.org/10.1016/j.rehab.2021.101580.
Halko MA, Farzan F, Eldaief MC, Schmahmann JD, Pascual-Leone A. Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network. J Neurosci. 2014;34(36):12049-56. Disponible en: https://doi.org/10.1523 JNEUROSCI.1776-14.2014.
Song P, Li S, Wang S, Wei H, Lin H, Wang Y. Repetitive transcranial magnetic stimulation of the cerebellum improves ataxia and cerebello-fronto plasticity in multiple system atrophy: a randomized, double-blind, sham-controlled and TMS-EEG study. Aging (Albany NY). 2020;12(20):20611-21. Disponible en: https://doi.org/10.18632/aging.103946.
Burns MR, McFarland NR. Current Management and Emerging Therapies in Multiple System Atrophy. Neurotherapeutics. 2020;17(4):1582-602. Disponible en: https://doi.org/10.1007/s13311-020-00890-x.
Ruesink H, Reimer L, Gregersen E, Moeller A, Betzer C, Jensen PH. Stabilization of α-synuclein oligomers using formaldehyde. PloS One. 2019;14(10):e0216764. Disponible en: https://doi.org/10.1371/journal.pone.0216764.
Uwatoko H, Hama Y, Iwata IT, Shirai S, Matsushima M, Yabe I, et al. Identification of plasma microRNA expression changes in multiple system atrophy and Parkinson’s disease. Mol Brain. 2019;12(1):49. Disponible en: https://doi.org/10.1186/s13041-019-0471-2.
Cómo citar
Descargas
Publicado
Número
Sección
Licencia
Derechos de autor 2023 Revista Colombiana de Medicina Física y Rehabilitación
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
