Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press37610.17650/2222-8721-2020-10-1-81-87CLINICAL CASEКЛИНИЧЕСКИЙ РАЗБОРSpinal and bulbar muscular atrophy as a multisystem disease with motor neuron and muscle involvement: literature review and a case reportСпинально-бульбарная мышечная атрофия как мультисистемная патология с поражением мотонейронов и мышц: обзор литературы и описание клинического случаяhttps://orcid.org/0000-0003-3337-1759IvanovaE. O.ИвановаЕ. О.
Russian Federation

80 Volokolamskoe shosse, Moscow 125367, Russia

Екатерина Олеговна Иванова 

Россия, 125367 Москва, Волоколамское шоссе, 80

kate-fileo@mail.ruhttps://orcid.org/0000-0001-8070-7644FedotovE. Yu.ФедотоваЕ. Ю.
Russian Federation

80 Volokolamskoe shosse, Moscow 125367, Russia

Россия, 125367 Москва, Волоколамское шоссе, 80

https://orcid.org/0000-0002-2704-6282IllarioshkinS. N.ИллариошкинС. Н.
Russian Federation

80 Volokolamskoe shosse, Moscow 125367, Russia

Россия, 125367 Москва, Волоколамское шоссе, 80

Research Center of NeurologyФГБНУ «Научный центр неврологии»0306202010181870306202003062020Copyright ©; 2020, Ivanova E.O., Fedotov E.Y., Illarioshkin S.N.Copyright ©; 2020, Иванова Е.О., Федотова Е.Ю., Иллариошкин С.Н.2020Ivanova E.O., Fedotov E.Y., Illarioshkin S.N.Иванова Е.О., Федотова Е.Ю., Иллариошкин С.Н.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/376

The spinal and bulbar muscular atrophy is a slowly progressive X-linked polysystemic disease associated with polyglutamine expansion in the androgen receptor gene. The mutant protein exhibits toxic properties towards neurons and myocytes. The main motor manifestations of the spinal and bulbar muscular atrophy are weakness, atrophy and fasciculation of the muscles of the limbs and bulbar group. Traditionally spinal and bulbar muscular atrophy belongs to the group of motor neuron diseases, but in recent years there is increasing evidence of a significant role of primary muscle pathology in the pathogenesis and clinical picture of this disease. This article provides a review of the literature on the pathogenesis, clinical manifestations and diagnosis of the spinal and bulbar muscular atrophy. We present a case report of the spinal and bulbar muscular atrophy with a clinical findings resembling metabolic myopathy.

Спинально-бульбарная мышечная дистрофия – медленно прогрессирующее X-сцепленное полисистемное заболевание, ассоциированное с полиглутаминовой экспансией в гене андрогенного рецептора. Мутантный белок проявляет токсические свойства по от- ношению к нейронам и миоцитам. К основным его двигательным проявлениям заболевания относятся слабость, атрофии и фасцикуляции мышц конечностей и бульбарной группы. Традиционно спинально-бульбарная мышечная дистрофия относится к группе болезней мотонейрона, однако в последние годы появляется все больше доказательств значительной роли первично-мышечной патологии в патогенезе и клинической картине этого заболевания. В статье приводится обзор литературы по патогенезу, клиническим проявлениям и диагностике спинально-бульбарной мышечной дистрофии. Также представлен клинический случай спинально-бульбарной мышечной дистрофии с клинической картиной, напоминающей метаболическую миопатию.

spinal and bulbar muscular atrophySBMAKennedy’s diseasemotor neuron diseasemyopathymultiple system involvementpathogenesisспинально-бульбарная мышечная атрофияСБМАболезнь Кеннедиболезнь мотонейронамиопатиямультисистемное поражениепатогенезLa Spada A., Wilson E.M., Lubahn D.B. et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991;352:77–9. DOI: 10.1038/352077a0. PMID: 2062380.Pennuto M., Rinaldi C. From gene to therapy in spinal and bulbar muscular atrophy: are we there yet? Mol Cell Endocrinol 2018;465:113–21. DOI: 10.1016/j.mce.2017.07.005. PMID: 28688959.Atsuta N., Watanabe H., Ito M. et al. Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain 2006;129:1446–55. DOI: 10.1093/brain/awl096. PMID: 16621916.Querin G., Bertolin C., Da Re E. et al. Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients. J Neurol Neurosurg Psychiatry 2016;87(8):810–6. DOI: 10.1136/jnnp-2015-311305. PMID: 26503015.Chua J.P., Lieberman A.P. Pathogenic mechanisms and therapeutic strategies in spinobulbar muscular atrophy. CNS Neurol Disord Drug Targets 2013;12(8):1146–56. DOI: 10.2174/187152731131200124. PMID: 24040817.Adachi H., Katsuno M., Minamiyama M. et al. Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. Brain 2005;128(Pt 3):659–70. DOI: 10.1093/brain/awh381. PMID:15659427.Fischbeck K.H. Spinal and bulbar muscular atrophy overview. J Mol Neurosci 2016;58(3):317–20. DOI: 10.1007/s12031-015-0674-7. PMID: 26547319.Johansen J.A., Yu Z., Mo K. et al. Recovery of function in a myogenic mouse model of spinal bulbar muscular atrophy. Neurobiol Dis 2009;34(1):113–20. DOI: 10.1016/j.nbd.2008.12.009. PMID: 19211034.Ishihara H., Kanda F., Nishio H. et al. Clinical features and skewed X-chromosome inactivation in female carriers of X-linked recessive spinal and bulbar muscular atrophy. J Neurol 2001;248(10):856–60. DOI: 10.1007/s004150170069. PMID: 11697521. 10. Finsterer J., Soraru G. Onset manifestations of spinal and bulbar muscular atrophy (Kennedy’s Disease). J Mol Neurosci 2016;58(3):321–9. DOI: 10.1007/s12031-015-0663-x. PMID: 26482145.Rhodes L.E., Freeman B.K., Auh S. et al. Clinical features of spinal and bulbar muscular atrophy. Brain 2009; 132(Pt 12):3242–51. DOI: 10.1093/brain/awp258. PMID: 19846582.Orsucci D., Rocchi A., Caldarazzo Ienco E. et al. Myopathic involvement and mitochondrial pathology in Kennedy disease and in other motor neuron diseases. Curr Mol Med 2014;14(5): 598–602. DOI: 10.2174/1566524014666140603100131. PMID: 24894177.Sorarù G., D’Ascenzo C., Polo A. et al. Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females. J Neurol Sci 2008;264(1–2):100–5. DOI: 10.1016/j.jns.2007.08.012. PMID: 17854832.Borgia D., Malena A., Spinazzi M. et al. Increased mitophagy in the skeletal muscle of spinal and bulbar muscular atrophy patients. Hum Mol Genet 2017;26(6):1087–103. DOI: 10.1093/hmg/ddx019. PMID: 28087734.Yu Z., Dadgar N., Albertelli M. et al. Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model. J Clin Invest 2006;116(10):2663–72. DOI: 10.1172/JCI28773. PMID: 16981011.Rocchi A., Milioto C., Parodi S. et al. Glycolytic-to-oxidative fiber-type switch and mTOR signaling activation are early-onset features of SBMA muscle modified by high-fat diet. Acta Neuropathol 2016;132:127–44. DOI: 10.1007/s00401-016-1550-4. PMID: 26971100.Cortes C.J., Ling S-C., Guo L.T. et al. Muscle expression of mutant androgen receptor protein accounts for systemic and motor neuron disease phenotypes in spinal & bulbar muscular atrophy. Neuron 2014;82(2):295–307. DOI: 10.1016/j.neuron.2014.03.001. PMID: 24742458.Monks D.A., Johansen J.A., Mo K. et al. Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease. Proc Natl Acad Sci U S A 2007;104(46):18259–64. DOI: 10.1073/pnas.0705501104. PMID: 17984063.Lombardi V., Querin G., Ziff O.J. et al. Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy. Neurology 2019;92(11):e1205–11. DOI: 10.1212/WNL.0000000000007097. PMID: 30787165.Hijikata Y., Katsuno M., Suzuki K. et al. Impaired muscle uptake of creatine in spinal and bulbar muscular atrophy. Ann Clin Transl Neurol 2016;3(7):537–46. DOI: 10.1002/acn3.324. PMID: 27386502.Manzano R., Sorarú G., Grunseich C. et al. Beyond motor neurons: expanding the clinical spectrum in Kennedy’s disease. J Neurol Neurosurg Psychiatry 2018;89(8):808–12. DOI: 10.1136/jnnp-2017-316961. PMID: 29353237.Finsterer J., Scorza F.A. Central nervous system abnormalities in spinal and bulbar muscular atrophy (Kennedy’s disease). Clin Neurol Neurosurg 2019;184:105426. DOI: 10.1016/j.clineuro.2019.105426. PMID: 31351215.Guber R.D., Takyar V., Kokkinis A. et al. Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy. Neurology 2017;89(24):2481–90. DOI: 10.1212/wnl.0000000000004748. PMID: 29142082.Francini-Pesenti F., Querin G., Martini C. et al. Prevalence of metabolic syndrome and non-alcoholic fatty liver disease in a cohort of italian patients with spinalbulbar muscular atrophy. Acta Myol 2018;37(3):204–9. PMID: 30838350.Araki A., Katsuno M., Suzuki K. et al. Brugada syndrome in spinal and bulbar muscular atrophy. Neurology 2014;82:1813–21. DOI: 10.1212/WNL.0000000000000434. PMID: 24759840.Querin G., Bede P., Marchand-Pauvert V. et al. Biomarkers of spinal and bulbar muscle atrophy(SBMA): a comprehensive review. Front Neurol 2018;9:844. DOI: 10.3389/fneur.2018.00844. PMID: 30364135.Grunseich C., Fischbeck K.H. Spinal and bulbar muscular atrophy. Neurol Clin 2015;33(4):847–54. DOI: 10.1016/j.ncl.2015.07.002. PMID: 26515625.Hashizume A., Katsuno M., Banno H. et al. Longitudinal changes of outcome measures in spinal and bulbar muscular atrophy. Brain 2012;135(Pt 9):2838–48. DOI: 10.1093/brain/aws170. PMID: 22773541.Sorenson E.J., Klein C.J. Elevated creatine kinase and transaminases in asymptomatic SBMA. Amyotroph Lateral Scler 2007;8(1):62–4. DOI: 10.1080/17482960600765040. PMID: 17364438.Dahlqvist J.R., Oestergaard S.T., Poulsen N.S. et al. Refining the spinobulbar muscular atrophy phenotype by quantitative MRI and clinical assessments. Neurology 2019;92(6):e548–59. DOI: 10.1212/WNL.0000000000006887. PMID: 30610091.Klickovic U., Zampedri L., Sinclair C.D.J. et al. Skeletal muscle MRI differentiates SBMA and ALS and correlates with disease severity. Neurology 2019;93(9):e895–907. DOI: 10.1212/WNL.0000000000008009. PMID: 31391248.