Background: Autosomal dominant spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative disorders that typically show peripheral neuropathy. SCA7 is one of the rarest forms of SCA (<1/100,000 individuals). However, the disease shows a prevalence of ∼800/100,000 inhabitants in certain regions of Mexico. This low global prevalence may explain, at least in part, the isolated anecdotal and limited clinical data regarding peripheral neuropathy in SCA7 patients. Aim: To assess sensory and motor peripheral nerve action potentials in an SCA7 patients group and in healthy volunteers, and subsequently correlate the electrophysiological findings with clinical and genetic features. Materials and Methods: We enrolled in our study, 13 symptomatic SCA7 patients with a confirmed molecular and clinical diagnosis, and 19 healthy volunteers as the control group. Nerve conduction studies were carried out using standard electromyography recording methods. The sensory and motor latency, amplitude and conduction velocity were recorded in both experimental groups and analyzed using the Student's t-test. Results: SCA7 patients showed a significant prolongation of sensory nerve conduction latencies, as well as a decrease in sensory amplitudes. Decreases in motor amplitudes and peroneal conduction velocity were also observed. Finally, we found an association between CAG repeats and the severity of cerebellar and non-cerebellar symptoms with electrophysiological signs of demyelinization. Discussion: Our results reveal the existence of a critical sensorimotor peripheral neuropathy in SCA7 patients. Moreover, we show that using sensitive electrophysiological tools to evaluate nerve conduction can improve the diagnosis and design of therapeutic options based on pharmacological and rehabilitative strategies. Conclusion: These findings demonstrate that SCA7 is a disease that globally affects the peripheral nervous system.

1.
Harding AE: The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the ‘Drew family of Walworth'. Brain 1982;105:1-28.
2.
Matilla-Dueñas A, Corral-Juan M, Volpini V, Sanchez I: The spinocerebellar ataxias: clinical aspects and molecular genetics. Adv Exp Med Biol 2012;724:351-374.
3.
Trott A, Jardim LB, Ludwig HT, Saute JA, Artigalás O, Kieling C, Wanderley HY, Rieder CR, Monte TL, Socal M, Alonso I, Ferro A, Carvalho T, do Céu Moreira M, Mendonça P, Ferreirinha F, Silveira I, Sequeiros J, Giugliani R, Saraiva-Pereira ML: Spinocerebellar ataxias in 114 Brazilian families: clinical and molecular findings. Clin Genet 2006;70:173-176.
4.
Teive HA, Munhoz RP, Arrunda WO, Lopes-Cendes I, Raskin S, Werneck LC, Ashizawa T: Spinocerebellar ataxias: genotype-phenotype correlations in 104 Brazilian families. Clinics (Sao Paulo) 2012;67:443-449.
5.
Pedroso JL, Braga-Neto P, Radvany J, Barsottini OG: Machado-Joseph disease in Brazil: from the first descriptions to the emergence as the most common spinocerebellar ataxia. Arq Neuropsiquiatr 2012;70:630-632.
6.
Velázquez-Pérez L, Rodríguez-Labrada R, García-Rodríguez JC, Enrique Almaguer-Mederos LE, Cruz-Mariño T, Laffita-Mesa JM: A comprehensive review of spinocerebellar ataxia type 2 in Cuba. Cerebellum 2011;10:184-198.
7.
Velázquez Pérez L, Cruz GS, Santos Falcón N, Almaguer Mederos L, Escalona Batallan K, Rodríguez Labrada R, Paneque Herrera M, Laffita Mesa JM, Rodríguez Díaz JC, Rodríguez RA, González Zaldivar Y, Coello Almarales D, Almaguer Gotay D, Jorge Cedeño H: Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin. Neurosci Lett 2009;454:157-160.
8.
Alonso E, Martínez-Ruano L, De Biase I, Mader C, Ochoa A, Yescas P, Gutiérrez R, White M, Ruano L, Fragoso-Benítez M, Ashizawa T, Bidichandani SI, Rasmussen A: Distinct distribution of autosomal dominant spinocerebellar ataxia in the Mexican population. Mov Disord 2007;22:1050-1053.
9.
Moseley ML, Benzow KA, Schut LJ, Bird TD, Gomez CM, Barkhaus PE, Blindauer KA, Labuda M, Pandolfo M, Koob MD, Ranum LP: Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 1998;51:1666-1671.
10.
Benton CS, de Silva R, Rutledge SL, Bohlega S, Ashizawa T, Zoghbi HY: Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype. Neurology 1998;51:1081-1086.
11.
Magaña JJ, Tapia-Guerrero YS, Velázquez-Pérez L, Cerecedo-Zapata CM, Maldonado-Rodríguez M, Jano-Ito JS, Leyva-García N, González-Piña R, Martínez-Cruz E, Hernández-Hernández O, Cisneros B: Analysis of CAG repeats in five SCA loci in Mexican population: epidemiological evidence of a SCA7 founder effect. Clin Genet 2014;85:159-165.
12.
Magaña JJ, Gómez R, Maldonado-Rodríguez M, Velázquez-Pérez L, Tapia-Guerrero YS, Cortés H, Leyva-García N, Hernández-Hernández O, Cisneros B: Origin of the spinocerebellar ataxia type 7 gene mutation in Mexican population. Cerebellum 2013;12:902-905.
13.
David G, Abbas N, Stevanin G, Dürr A, Yvert G, Cancel G, Weber C, Imbert G, Saudou F, Antoniou E, Drabkin H, Gemmill R, Giunti P, Benomar A, Wood N, Ruberg M, Agid Y, Mandel JL, Brice A: Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 1997;17:65-70.
14.
Horton LC, Frosch MP, Vangel MG, Weigel-DiFranco C, Berson EL, Schmahmann JD: Spinocerebellar ataxia type 7: clinical course, phenotype-genotype correlations, and neuropathology. Cerebellum 2013;12:176-193.
15.
Denny-Brown D, David MD, Tyler HR: Handbook of neurological examination and case recording. Harvard University Press, MA, 1982.
16.
Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, Giunti P, Globas C, Infante J, Kang JS, Kremer B, Mariotti C, Melegh B, Pandolfo M, Rakowicz M, Ribai P, Rola R, Schöls L, Szymanski S, van de Warrenburg BP, Dürr A, Klockgether T, Fancellu R: Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology 2006;66:1717-1720.
17.
Schmitz-Hübsch T, Coudert M, Bauer P, Giunti P, Globas C, Baliko L, Filla A, Mariotti C, Rakowicz M, Charles P, Ribai P, Szymanski S, Infante J, van de Warrenburg BP, Dürr A, Timmann D, Boesch S, Fancellu R, Rola R, Depondt C, Schöls L, Zdienicka E, Kang JS, Döhlinger S, Kremer B, Stephenson DA, Melegh B, Pandolfo M, di Donato S, du Montcel ST, Klockgether T: Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms. Neurology 2008;71:982-989.
18.
Modi G, Modi M, Martinus I, Rodda J, Saffer D: The clinical and genetic characteristics of spinocerebellar ataxia type 7 (SCA 7) in three Black South African families. Acta Neurol Scand 2000;101:177-182.
19.
Michalik A, Martin JJ, Van Broeckhoven C: Spinocerebellar ataxia type 7 associated with pigmentary retinal dystrophy. Eur J Hum Genet 2004;12:2-15.
20.
Lebre AS, Brice A: Spinocerebellar ataxia 7 (SCA7) Cytogenet. Genome Res 2003;100:154-163.
21.
David G, Dürr A, Stevanin G, Cancel G, Abbas N, Benomar A, Belal S, Lebre AS, Abada-Bendib M, Grid D, Holmberg M, Yahyaoui M, Hentati F, Chkili T, Agid Y, Brice A: Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7). Hum Mol Genet 1998;7:165-170.
22.
Koeppen AH: The pathogenesis of spinocerebellar ataxia. Cerebellum 2005;4:62-73.
23.
Rolón-Lacarriere O, Rasmussen-Almaraz A, Hernández-Cruz H, Carranza del Río J, González Cruz M, Gutiérrez Moctezuma J: Ataxia espinocerebelosa de tipo 7: descripción de una familia mexicana. Rev Neurol 2004;38:736-740.
24.
Han Y, Deng B, Liu M, Jiang J, Wu S, Guan Y: Clinical and genetic study of a Chinese family with spinocerebellar ataxia type 7. Neurol India 2010;58:622-626.
25.
Kubis N, Dürr A, Gugenheim M, Chneiweiss H, Mazzetti P, Brice A, Bouche P: Polyneuropathy in autosomal dominant cerebellar ataxias: phenotype-genotype correlation. Muscle Nerve 1999;22:712-717.
26.
van de Warrenburg BP, Notermans NC, Schelhaas HJ, van Alfen N, Sinke RJ, Knoers NV, Zwarts MJ, Kremer BP: Peripheral nerve involvement in spinocerebellar ataxias. Arch Neurol 2004;61:257-261.
27.
Schols L, Linnemann C, Globas C: Electrophysiology in spinocerebellar ataxias: spread of disease and characteristic findings. Cerebellum 2008;7:198-203.
28.
Velázquez-Pérez L, Rodríguez-Labrada R, Canales-Ochoa N, Montero JM, Sánchez-Cruz G, Aguilera-Rodríguez R, et al: Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study. Lancet Neurol 2014;13:482-489.
29.
Klockgether T, Schöls L, Abele M, Bürk K, Topka H, Andres F, Amoiridis G, Lüdtke R, Riess O, Laccone F, Dichgans J: Age related axonal neuropathy in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). J Neurol Neurosurg Psychiatry 1999;66:222-224.
30.
Velázquez-Pérez L, Rodríguez-Labrada R, García-Rodríguez JC, Almaguer-Mederos LE, Cruz-Mariño T, Laffita-Mesa JM: A comprehensive review of spinocerebellar ataxia type 2 in Cuba. Cerebellum 2011;10:184-198.
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