Top

Published in:

19-04-2021 | Spinal Muscular Atrophy | Review Article

Spinal muscular atrophy: state of the art and new therapeutic strategies

Authors: Sonia Messina, Maria Sframeli, Lorenzo Maggi, Adele D’Amico, Claudio Bruno, Giacomo Comi, Eugenio Mercuri

Published in: Neurological Sciences | Special Issue 2/2022

Abstract

Spinal muscular atrophy (SMA) is a severe disorder of motor neurons and the most frequent cause of genetic mortality, due to respiratory complications. We are facing an exciting era with three available therapeutic options in a disease considered incurable for more than a century. However, the availability of effective approaches has raised up ethical, medical, and financial issues that are routinely faced by the SMA community. Each therapeutic strategy has its weaknesses and strengths and clinicians need to know them to optimize clinical care. In this review, the state of the art and the results and challenges of the new SMA therapeutic strategies are highlighted.

D’Amico A, Mercuri E, Tiziano FD, Bertini E (2011) Spinal muscular atrophy. rphanet. J Rare Dis 6:71. https://doi.org/10.1186/1750-1172-6-71CrossRef

Kolb SJ, Kissel JT (2011) Spinal muscular atrophy: a timely review. Arch Neurol 68(8):979–984. https://doi.org/10.1001/archneurol.2011.74CrossRef

Wirth B, Karakaya M, Kye MJ, Mendoza-Ferreira N (2020) Twenty-five years of spinal muscular atrophy research: from phenotype to genotype to therapy, and what comes next. Annu Rev Genomics Hum Genet 21:231–261. https://doi.org/10.1146/annurev-genom-102319-103602CrossRef

Ogino S, Leonard DG, Rennert H, Ewens WJ, Wilson RB (2002) Genetic risk assessment in carrier testing for spinal muscular atrophy. Am J Med Genet 110:301–307. https://doi.org/10.1002/ajmg.10425CrossRef

Prior TW, Snyder PJ, Rink BD, Pearl DK, Pyatt RE, Mihal DC, Conlan T, Schmalz B, Montgomery L, Ziegler K, Noonan C, Hashimoto S, Garner S (2010) Newborn and carrier screening for spinal muscular atrophy. Am J Med Genet A 152A:1605–1607CrossRef

MacLeod MJ, Taylor JE, Lunt PW, Mathew CG, Robb SA (1999) Prenatal onset spinal muscular atrophy. Eur J Paediatr Neurol 3:65–72. https://doi.org/10.1053/ejpn.1999.0184CrossRef

Dubowitz V (1999) Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. Eur J Paediatr Neurol 3:49–51. https://doi.org/10.1053/ejpn.1999.0181CrossRef

Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I (1997) A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. J Neurol Sci 146:67–72. https://doi.org/10.1016/s0022-510x(96)00284-5CrossRef

Lefebvre S, Burlet P, Liu Q, Bertrandy S, Clermont O, Munnich A, Dreyfuss G, Melki J (1997) Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet 16:265–269. https://doi.org/10.1038/ng0797-265CrossRef

10.

Calucho M, Bernal S, Alías L, March F, Venceslá A, Rodríguez-Álvarez FJ, Aller E, Fernández RM, Borrego S, Millán JM, Hernández-Chico C, Cuscó I, Fuentes-Prior P, Tizzano EF (2018) Correlation between SMA type and SMN2 copy number revisited: san analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases. Neuromuscul Disord 28(208–215):s9–s11. https://doi.org/10.1016/j.nmd.2018.01.003CrossRef

11.

Bernal S, Alías L, Barceló MJ, Also-Rallo E, Martínez-Hernández R, Gámez J, Guillén-Navarro E, Rosell J, Hernando I, Rodríguez-Alvarez FJ, Borrego S, Millán JM, Hernández-Chico C, Baiget M, Fuentes-Prior P, Tizzano EF (2010) The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor. J Med Genet 47(9):640–642. https://doi.org/10.1136/jmg.2010.079004CrossRef

12.

Mercuri E, Lucibello S, Perulli M, Coratti G, De Sanctis R, Pera MC, Pane M, Montes J, De Vivo DC, Darras BT, Kolb SJ, Finkel RS (2020) Longitudinal natural history of type I spinal muscular atrophy: a critical review. Orphanet J Rare Dis 15(1):84. https://doi.org/10.1186/s13023-020-01356-1CrossRef

13.

Glanzman AM, McDermott MP, Montes J, Martens WB, Flickinger J, Riley S et al (2011) Validation of the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Pediatr Phys Ther 23:322–326. https://doi.org/10.1097/PEP.0b013e3182351f04CrossRef

14.

Valori CF, Ning K, Wyles M, Mead RJ, Grierson AJ, Shaw PJ, Azzouz M (2010) Systemic delivery ofscAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy. Sci Transl Med 2(35):35ra42. https://doi.org/10.1126/scitranslmed.3000830CrossRef

15.

Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, Lowes L, Alfano L, Berry K, Church K et al (2017) Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med 377:1713–1722. https://doi.org/10.1056/NEJMoa1706198CrossRef

16.

Kuntz NL, Peña LDN, Shieh PB et al (2020) Onasemnogene Abeparvovec-xioi gene-replacement therapy for spinal muscular atrophy type 1 (SMA1): phase 3 US study (STR1VE) update (1828) Presented at the American Academy of Neurology Conference 2020. Neurology 94:1828

17.

Hua Y, Sahashi K, Hung G, Rigo F, Passini MA, Bennett CF, Krainer AR (2010) Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev 24:1634–1644CrossRef

18.

Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, de Vivo DC (2017) Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med 377:1723–1732CrossRef

19.

Mercuri E, Darras BT, Chiriboga CA, Day JW, Campbell C, Connolly AM, Iannaccone ST, Kirschner J, Kuntz NL, Saito K, Shieh PB, Tulinius M, Mazzone ES, Montes J, Bishop KM, Yang Q, Foster R, Gheuens S, Bennett CF, Farwell W, Schneider E, de Vivo DC, Finkel RS (2018) Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med 378:625–635CrossRef

20.

De Vivo DC, Bertini E, Swoboda KJ, Hwu W, Crawford TO, Finkel RS, Kirschner J, Kuntz NL, Parsons JA, Ryan MM et al (2019) Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study. Neuromuscul Disord 29:842–856CrossRef

21.

Pane M, Coratti G, Sansone VA, Messina S, Bruno C, Catteruccia M, Sframeli M, Albamonte E, Pedemonte M, D’Amico A et al (2019) Nusinersen in type 1 spinal muscular atrophy: twelve-month real-world data. Ann Neurol 86:443–451CrossRef

22.

Servais L, Baranello G, Masson R, Mazurkiewicz-Bełdzińska M, Rose K, Vlodavets D, Xiong H, Zanoteli E, El-Khairi M, Fuerst-Recktenwald S, et al. (2020) FIREFISH Part 2: efficacy and safety of risdiplam (RG7916) in infants with type 1 spinal muscular atrophy (SMA). Presented at the American Academy of Neurology Conference 2020. Neurology 2020, 94, 1302

23.

Mercuri E, Barisic N, Boespflug-Tanguy O, Deconinck N, Kostera-Pruszczyk A, Masson R, Mazzone E, Nascimento R, Osorio A, Saito K et al (2020) SUNFISH Part 2: efficacy and safety of risdiplam (RG7916) in patients with type 2 or non-ambulant type 3 spinal muscular atrophy (SMA) Presented at the American Academy of Neurology Conference 2020. Neurology 2020(94):1260

24.

Yeo CJJ, Darras BT (2020 Aug) (2020) Overturning the paradigm of spinal muscular atrophy as just a motor neuron disease. Pediatr. Neurol. 109:12–19. https://doi.org/10.1016/j.pediatrneurol.2020.01.003CrossRef

25.

Poirier A, Weetall M, Heinig K, Bucheli F, Schoenlein K, Alsenz J, Bassett S, Ullah M, Senn C, Ratni H et al (2018) Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs. Pharmacol Res Perspect 6(6):e00447. https://doi.org/10.1002/prp2.447CrossRef

26.

Hwee DT, Kennedy A, Ryans J, Russell AJ, Jia Z, Hinken AC, Morgans DJ, Malik FI, Jasper JR (2014) Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model. PLoS One 9(5):e96921. https://doi.org/10.1371/journal.pone.0096921CrossRef

27.

Cheng AJ, Hwee DT, Kim LH, Durham N, Yang HT, Hinken AC, Kennedy AR, Terjung RL, Jasper JR, Malik FI et al Fast skeletal muscle troponin activator CK-2066260 increases fatigue resistance by reducing the energetic cost of muscle contraction. J Physiol 597(17):4615–4625. https://doi.org/10.1113/JP278235

28.

Rudnicki, S.A.; Andrews, J.A.; Malik, F.I. CY 5021 (2018) A phase 2, double-blind, randomized, placebo-controlled, multiple-dose study of reldesemtiv 2 ascending-dose cohorts of patients with Spinal Muscular Atrophy (SMA). In Proceedings of the Cure SMA 2018, Dallas, TX, USA, 16 June 2018

29.

Feng Z, Ling KK, Zhao X, Zhou C, Karp G, Welch EM, Naryshkin N, Ratni H, Chen KS, Metzger F et al (2016) Pharmacologically induced mouse model of adult spinal muscular atrophy to evaluate effectiveness of therapeutics after disease onset. Hum Mol Genet 25(5):964–975. https://doi.org/10.1093/hmg/ddv629CrossRef

30.

Long KK, O’Shea KM, Khairallah RJ, Howell K, Paushkin S, Chen KS, Cote SM, Webster MT, Stains JP, Treece E et al (2019) Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy. Hum Mol Genet 28(7):1076–1089. https://doi.org/10.1093/hmg/ddy382CrossRef

31.

Kaufmann P, McDermott MP, Darras BT et al (2012) Prospective cohort study of spinal muscular atrophy types 2 and 3. Neurology 79(18):1889–1897. https://doi.org/10.1212/WNL.0b013e318271f7e4CrossRef

32.

Mercuri E, Finkel R, Montes J et al (2016) Patterns of disease progression in type 2 and 3 SMA: implications for clinical trials. Neuromuscul Disord 26(2):126–131. https://doi.org/10.1016/j.nmd.2015.10.006CrossRef

33.

Finkel RS, Mercuri E, Meyer OH et al (2018) Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord 28(3):197–207. https://doi.org/10.1016/j.nmd.2017.11.004CrossRef

34.

Montes J, McDermott MP, Mirek E, Mazzone ES, Main M, Glanzman AM, Duong T, Young SD, Salazar R, Pasternak A, Gee R, De Sanctis R et al (2018) Ambulatory function in spinal muscular atrophy: age-related patterns of progression. PLoS One 13(6):e0199657. https://doi.org/10.1371/journal.pone.0199657CrossRef

35.

Mercuri E, Lucibello S, Pera MC, Carnicella S, Coratti G, De Sanctis R, Messina S, Mazzone E, Forcina N, Fanelli L, Norcia G, Antonaci L, Frongia A:L; Pane M. (2019) Long-term progression in type II spinal muscular atrophy: a retrospective observational study. Neurology 93(13):e1241–e1247. https://doi.org/10.1212/WNL.0000000000008166CrossRef

36.

Coratti G, Messina S, Lucibello S, Pera MC, Montes J, Pasternak A, Bovis F, Exposito Escudero J, Mazzone ES, Mayhew A, Glanzman AM, Young SD et al (2020) Clinical variability in spinal muscular atrophy type III. Ann Neurol 88(6):1109–1117. https://doi.org/10.1002/ana.25900CrossRef

37.

Pera MC, Coratti G, Mazzone ES, Montes J, Scoto M, De Sanctis R, Main M, Mayhew A, Muni Lofra R, Dunaway Young S, Glanzman AM, Duong T, Pasternak A et al (2019) Revised upper limb module for spinal muscular atrophy: 12 month changes. Muscle Nerve 59(4):426–430. https://doi.org/10.1002/mus.26419CrossRef

38.

Wijngaarde CA, Stam M, Otto LAM, Bartels B, Asselman FL, van Eijk RPA, van den Berg LH, Goedee HS, Wadman RI, van der Pol WL (2020) Muscle strength and motor function in adolescents and adults with spinal muscular atrophy. Neurology 95(14):e1988–e1998. https://doi.org/10.1212/WNL.0000000000010540CrossRef

39.

Sansone VA, Walter MC, Attarian S, Delstanche S, Mercuri E, Lochmüller H, Neuwirth C, Vazquez-Costa JF, Kleinschnitz C, Hagenacker T (2020) Measuring outcomes in adults with spinal muscular atrophy - challenges and future directions - meeting report. J Neuromuscul Dis 7(4):523–534. https://doi.org/10.3233/JND-200534CrossRef

40.

Bonati U, Holiga Š, Hellbach N, Risterucci C, Bergauer T, Tang W, Hafner P, Thoeni A, Bieri O, Gerlach I, Marquet A, Khwaja O, Sambataro F, Bertolino A, Dukart J, Fischmann A, Fischer D, Czech C (2017) Longitudinal characterization of biomarkers for spinal muscular atrophy. Ann Clin Transl Neurol 4(5):292–304. https://doi.org/10.1002/acn3.406CrossRef

41.

Totzeck A, Stolte B, Kizina K, Bolz S, Schlag M, Thimm A, Kleinschnitz C, Hagenacker T (2019) Neurofilament heavy chain and tau protein are not elevated in cerebrospinal fluid of adult patients with spinal muscular atrophy during loading with nusinersen. Int J Mol Sci. https://doi.org/10.3390/ijms20215397

42.

Wurster CD, Günther R, Steinacker P, Dreyhaupt J, Wollinsky K, Uzelac Z, Witzel S, Kocak T, Winter B, Koch JC, Lingor P, Petri S, Ludolph AC, Hermann A, Otto M (2019) Neurochemical markers in CSF of adolescent and adult SMA patients undergoing nusinersen treatment. Ther Adv Neurol Disord 12:1756286419846058. https://doi.org/10.1177/1756286419846058CrossRef

43.

Brogna C, Cristiano L, Verdolotti T, Pichiecchio A, Cinnante C, Sansone V, Sconfienza LM, Berardinelli A, Garibaldi M, Antonini G, Pane M, Pera MC, Antonaci L, Ficociello L, Albamonte E, Tasca G, Begliuomini C, Tartaglione T, Maggi L, Govoni A, Comi G, Colosimo C, Mercuri E (2020) MRI patterns of muscle involvement in type 2 and 3 spinal muscular atrophy patients. J Neurol 267(4):898–912. https://doi.org/10.1007/s00415-019-09646-wCrossRef

44.

Faravelli I, Meneri M, Saccomanno D, Velardo D, Abati E, Gagliardi D, Parente V, Petrozzi L, Ronchi D, Stocchetti N, Calderini E, D’Angelo G, Chidini G, Prandi E, Ricci G, Siciliano G, Bresolin N, Comi GP, Corti S, Magri F, Govoni A Nusinersen treatment and cerebrospinal fluid neurofilaments: an explorative study on Spinal Muscular Atrophy type 3 patients. J Cell Mol Med 24(5):3034–3039. https://doi.org/10.1111/jcmm.14939

45.

Barp A, Carraro E, Albamonte E, Salmin F, Lunetta C, Comi GP, Messina C, Albano D, Chianca V, Sconfienza LM, Mercuri EM, Sansone VA (2020) Muscle MRI in two SMA patients on nusinersen treatment: a two years follow-up. J Neurol Sci 417:117067. https://doi.org/10.1016/j.jns.2020.117067CrossRef

46.

Mongiovi P, Dilek N, Garland C, Hunter M, Kissel JT, Luebbe E, McDermott MP, Johnson N, Heatwole C (2018) Patient reported impact of symptoms in spinal muscular atrophy (PRISM-SMA). Neurology. 91(13):e1206–e1214. https://doi.org/10.1212/WNL.0000000000006241CrossRef

47.

Walter MC, Wenninger S, Thiele S, Stauber J, Hiebeler M, Greckl E, Stahl K, Pechmann A, Lochmüller H, Kirschner J, Schoser B (2019) Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3 - a prospective observational study. J Neuromuscul Dis 6(4):453–465. https://doi.org/10.3233/JND-190416CrossRef

48.

Veerapandiyan A, Eichinger K, Guntrum D, Kwon J, Baker L, Collins E, Ciafaloni E (2020) Nusinersen for older patients with spinal muscular atrophy: a real-world clinical setting experience. Muscle Nerve 61(2):222–226. https://doi.org/10.1002/mus.26769CrossRef

49.

Jochmann E, Steinbach R, Jochmann T et al (2020) Experiences from treating seven adult 5q spinal muscular atrophy patients with nusinersen. Ther Adv Neurol Disord 13:1756286420907803. https://doi.org/10.1177/1756286420907803CrossRef

50.

Yeo CJJ, Simeone SD, Townsend EL, Zhang RZ, Swoboda KJ (2020) Prospective cohort study of nusinersen treatment in adults with spinal muscular atrophy. J Neuromuscul Dis 7(3):257–268. https://doi.org/10.3233/JND-190453CrossRef

51.

Moshe-Lilie O, Visser A, Chahin N, Ragole T, Dimitrova D, Karam C (2020) Nusinersen in adult patients with spinal muscular atrophy: observations from a single center. Neurology. 95(4):e413–e416. https://doi.org/10.1212/WNL.0000000000009914CrossRef

52.

Hagenacker T, Wurster CD, Günther R et al (2020) Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional,multicentre, observational cohort study. Lancet Neurol 19(4):317–325. https://doi.org/10.1016/S1474-4422(20)30037-5CrossRef

53.

Maggi L, Bello L, Bonanno S, Govoni A, Caponnetto C, Passamano L, Grandis M, Trojsi F, Cerri F, Ferraro M, Bozzoni V, Caumo L et al (2020) Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3. J Neurol Neurosurg Psychiatry 91(11):1166–1174. https://doi.org/10.1136/jnnp-2020-323822CrossRef

54.

Chiriboga CA, Marra J, LaMarca NM, Young SD, Weimer LH, Levin B, McCabe B (2020) Lack of effect on ambulation of dalfampridine-ER (4-AP) treatment in adult SMA patients. Neuromuscul Disord 30(8):693–700. https://doi.org/10.1016/j.nmd.2020.07.007CrossRef

55.

Kariyawasam DST, D’Silva A, Lin C, Ryan MM, Farrar MA (2019) Biomarkers and the development of a personalized medicine approach in spinal muscular atrophy. Front Neurol 10:898. https://doi.org/10.3389/fneur.2019.00898CrossRef

56.

Olsson B, Alberg L, Cullen NC, Michael E, Wahlgren L, Kroksmark AK, Rostasy K, Blennow K, Zetterberg H, Tulinius M (2019) NFL is a marker of treatment response in children with SMA treated with nusinersen. J Neurol 266(9):2129–2136. https://doi.org/10.1007/s00415-019-09389-8CrossRef

57.

Darras BT, Crawford TO, Finkel RS, Mercuri E, De Vivo DC, Oskoui M, Tizzano EF, Ryan MM, Muntoni F, Zhao G et al (2019) Neurofilament as a potential biomarker for spinal muscular atrophy. Ann Clin Transl Neurol 6:932–944. https://doi.org/10.1002/acn3.779CrossRef

58.

Jeong-Ki Kim J, Jha N, Feng Z, Faleiro MR, Chiriboga CA, Wei-Lapierre A, Dirksen RT, Ko C, Monani UR (2020) Muscle-specific SMN reduction reveals motor neuron-independent disease in spinal muscular atrophy models. J Clin Invest 130:1271–1287. https://doi.org/10.1172/JCI131989CrossRef

59.

Ripolone M, Ronchi D, Violano R, Vallejo D, Fagiolari G, Barca E, Lucchini V, Colombo I, Villa L, Berardinelli A, Balottin U, Morandi L, Mora M, Bordoni A, Fortunato F, Corti S, Parisi D, Toscano A, Sciacco M, DiMauro S, Comi GP, Moggio M (2015) Impaired muscle mitochondrial biogenesis and myogenesis in spinal muscular atrophy. JAMA Neurol 72:666–675. https://doi.org/10.1001/jamaneurol.2015.0178CrossRef

60.

Montes J, Goodwin AM, McDermott MP, Uher D, Hernandez FM, Coutts K, Cocchi J, Hauschildt M, Cornett KM, Rao AK, Monani UR, Ewing GC, de Vivo DC (2021) Diminished muscle oxygen uptake and fatigue in spinal muscular atrophy. Ann Clin Transl Neurol. Online ahead of print. https://doi.org/10.1002/acn3.51353

61.

Dabbous O, Maru B, Jansen JP, Lorenzi M, Cloutier M, Guérin A, Pivneva I, Wu EQ, Arjunji R, Feltner D, Sproule DM (2019) Survival, motor function, and motor milestones: comparison of AVXS-101 relative to nusinersen for the treatment of infants with spinal muscular atrophy type 1. Adv Ther 36(5):1164–1176. https://doi.org/10.1007/s12325-019-00923-8CrossRef

62.

Schorling DC, Pechmann A, Kirschner J (2020) Advances in treatment of spinal muscular atrophy—new phenotypes, new challenges, new implications for care. J Neuromuscul Dis 7:1–13. https://doi.org/10.3233/JND-190424CrossRef

63.

Polido GJ, de Miranda MMV, Carvas N, Mendonça RH, Caromano FA, Reed UC, Zanoteli E, Voos MC (2019) Cognitive performance of children with spinal muscular atrophy: a systematic review. Dement Neuropsychol 13:436–443. https://doi.org/10.1590/1980-57642018dn13-040011CrossRef

Title: Spinal muscular atrophy: state of the art and new therapeutic strategies
Authors: Sonia Messina
Maria Sframeli
Lorenzo Maggi
Adele D’Amico
Claudio Bruno
Giacomo Comi
Eugenio Mercuri
Publication date: 19-04-2021
Publisher: Springer International Publishing
Keywords: Spinal Muscular Atrophy
Gene Therapy in Oncology
Published in: Neurological Sciences / Issue Special Issue 2/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05258-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Spinal muscular atrophy: state of the art and new therapeutic strategies

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Special Issue 2/2022

Update on therapy of chronic immune-mediated neuropathies

Therapeutic opportunities and clinical outcome measures in Duchenne muscular dystrophy

Hereditary transthyretin amyloidosis overview

2020 Joint conference of the Italian Association of Miology (AIM) and the Italian Association for the study of the Peripheral Nervous System (ASNP), Abstracts

Preface