Abstract
In this article, we highlight some of the most important developments from the last few years in the field of muscle diseases, including new additions to the congenital myasthenic syndromes (CMS) and limb-girdle muscular dystrophies (LGMD), advances in our understanding of the pathophysiology of certain muscle disorders and progress in diagnostics and therapeutics. Unsurprisingly, the most prominent developments have come from the field of genetics, with significant advances in diagnosis and gene therapy giving hope to those with hitherto untreatable conditions.
Similar content being viewed by others
References
Allenbach Y, Drouot L, Rigolet A, Charuel JL, Jouen F, Romero NB, Maisonobe T, Dubourg O, Behin A, Laforet P, Stojkovic T, Eymard B, Costedoat-Chalumeau N, Campana-Salort E, Tournadre A, Musset L, Bader-Meunier B, Kone-Paut I, Sibilia J, Servais L, Fain O, Larroche C, Diot E, Terrier B, De Paz R, Dossier A, Menard D, Morati C, Roux M, Ferrer X, Martinet J, Besnard S, Bellance R, Cacoub P, Arnaud L, Grosbois B, Herson S, Boyer O, Benveniste O, Network FM (2014) Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Medicine (Baltimore) 93:150–157
Barbacki A, Fallavollita SA, Karamchandani J, Hudson M (2018) Immune-mediated necrotizing myopathy and dietary sources of statins. Ann Intern Med. https://doi.org/10.7326/L17-0620
Belaya K, Finlayson S, Slater CR, Cossins J, Liu WW, Maxwell S, McGowan SJ, Maslau S, Twigg SR, Walls TJ, Pascual Pascual SI, Palace J, Beeson D (2012) Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. Am J Hum Genet 91:193–201
Benveniste O, Stenzel W, Hilton-Jones D, Sandri M, Boyer O, van Engelen BG (2015) Amyloid deposits and inflammatory infiltrates in sporadic inclusion body myositis: the inflammatory egg comes before the degenerative chicken. Acta Neuropathol 129:611–624
Bisceglia L, Zoccolella S, Torraco A, Piemontese MR, Dell’Aglio R, Amati A, De Bonis P, Artuso L, Copetti M, Santorelli FM, Serlenga L, Zelante L, Bertini E, Petruzzella V (2010) A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H. Eur J Hum Genet 18:636–641
Blalock A, Mason MF, Morgan HJ, Riven SS (1939) Myasthenia gravis and tumors of the thymic region: report of a case in which the tumor was removed. Ann Surg 110:544–561
Boncompagni S, Protasi F, Franzini-Armstrong C (2012) Sequential stages in the age-dependent gradual formation and accumulation of tubular aggregates in fast twitch muscle fibers: SERCA and calsequestrin involvement. Age (Dordr) 34:27–41
Brady S, Squier W, Sewry C, Hanna M, Hilton-Jones D, Holton JL (2014) A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis. BMJ Open 4:e004552
Brockington M, Blake DJ, Prandini P, Brown SC, Torelli S, Benson MA, Ponting CP, Estournet B, Romero NB, Mercuri E, Voit T, Sewry CA, Guicheney P, Muntoni F (2001) Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Am J Hum Genet 69:1198–1209
Burakiewicz J, Sinclair CDJ, Fischer D, Walter GA, Kan HE, Hollingsworth KG (2017) Quantifying fat replacement of muscle by quantitative MRI in muscular dystrophy. J Neurol 264(10):2053–2067
Böhm J, Chevessier F, Maues De Paula A, Koch C, Attarian S, Feger C, Hantaï D, Laforêt P, Ghorab K, Vallat JM, Fardeau M, Figarella-Branger D, Pouget J, Romero NB, Koch M, Ebel C, Levy N, Krahn M, Eymard B, Bartoli M, Laporte J (2013) Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum Genet 92:271–278
Chevessier F, Bauché-Godard S, Leroy JP, Koenig J, Paturneau-Jouas M, Eymard B, Hantaï D, Verdière-Sahuqué M (2005) The origin of tubular aggregates in human myopathies. J Pathol 207:313–323
Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL (2010) A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum 62:2757–2766
Chung CS, Morton NE (1959) Discrimination of genetic entities in muscular dystrophy. Am J Hum Genet 11:339–359
Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, Abbs S, Garralda ME, Bourke J, Wells DJ, Dickson G, Wood MJ, Wilton SD, Straub V, Kole R, Shrewsbury SB, Sewry C, Morgan JE, Bushby K, Muntoni F (2011) Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378:595–605
del Ser T, Steinwachs KC, Gertz HJ, Andrés MV, Gómez-Carrillo B, Medina M, Vericat JA, Redondo P, Fleet D, León T (2013) Treatment of Alzheimer’s disease with the GSK-3 inhibitor tideglusib: a pilot study. J Alzheimers Dis 33:205–215
Engel WK, Bishop DW, Cunningham GG (1970) Tubular aggregates in type II muscle fibers: ultrastructural and histochemical correlation. J Ultrastruct Res 31:507–525
Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–185
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, Group ES (2017) Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med 377:1723–1732
Fischmann A, Hafner P, Fasler S, Gloor M, Bieri O, Studler U, Fischer D (2012) Quantitative MRI can detect subclinical disease progression in muscular dystrophy. J Neurol 259:1648–1654
Gang Q, Bettencourt C, Machado PM, Brady S, Holton JL, Pittman AM, Hughes D, Healy E, Parton M, Hilton-Jones D, Shieh PB, Needham M, Liang C, Zanoteli E, de Camargo LV, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R, Zanotti S, Singleton AB, Hanna MG, Houlden H, Consortium MSGaTIIG (2016) Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Neurobiol Aging 47:218.e211–218.e219
Greenberg SA (2014) Cytoplasmic 5′-nucleotidase autoantibodies in inclusion body myositis: isotypes and diagnostic utility. Muscle Nerve 50:488–492
Greenberg SA, Bradshaw EM, Pinkus JL, Pinkus GS, Burleson T, Due B, Bregoli L, Bregoli LS, O’Connor KC, Amato AA (2005) Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology 65:1782–1787
Greenberg SA, Sanoudou D, Haslett JN, Kohane IS, Kunkel LM, Beggs AH, Amato AA (2002) Molecular profiles of inflammatory myopathies. Neurology 59:1170–1182
Guergueltcheva V, Müller JS, Dusl M, Senderek J, Oldfors A, Lindbergh C, Maxwell S, Colomer J, Mallebrera CJ, Nascimento A, Vilchez JJ, Muelas N, Kirschner J, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Schlotter B, Schoser B, Herrmann R, Voit T, Steinlein OK, Najafi A, Urtizberea A, Soler DM, Muntoni F, Hanna MG, Chaouch A, Straub V, Bushby K, Palace J, Beeson D, Abicht A, Lochmüller H (2012) Congenital myasthenic syndrome with tubular aggregates caused by GFPT1 mutations. J Neurol 259:838–850
Henricson EK, Abresch RT, Cnaan A, Hu F, Duong T, Arrieta A, Han J, Escolar DM, Florence JM, Clemens PR, Hoffman EP, McDonald CM, Investigators C (2013) The cooperative international neuromuscular research group Duchenne natural history study: glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures. Muscle Nerve 48:55–67
Herbert MK, Stammen-Vogelzangs J, Verbeek MM, Rietveld A, Lundberg IE, Chinoy H, Lamb JA, Cooper RG, Roberts M, Badrising UA, De Bleecker JL, Machado PM, Hanna MG, Plestilova L, Vencovsky J, van Engelen BG, Pruijn GJ (2016) Disease specificity of autoantibodies to cytosolic 5′-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Ann Rheum Dis 75:696–701
Hilton-Jones D, Brady S (2016) Diagnostic criteria for inclusion body myositis. J Intern Med 280:52–62
Jones K, Wei C, Iakova P, Bugiardini E, Schneider-Gold C, Meola G, Woodgett J, Killian J, Timchenko NA, Timchenko LT (2012) GSK3β mediates muscle pathology in myotonic dystrophy. J Clin Invest 122:4461–4472
Khirani S, Ramirez A, Aubertin G, Boulé M, Chemouny C, Forin V, Fauroux B (2014) Respiratory muscle decline in Duchenne muscular dystrophy. Pediatr Pulmonol 49:473–481
Larman HB, Salajegheh M, Nazareno R, Lam T, Sauld J, Steen H, Kong SW, Pinkus JL, Amato AA, Elledge SJ, Greenberg SA (2013) Cytosolic 5′-nucleotidase 1A autoimmunity in sporadic inclusion body myositis. Ann Neurol 73:408–418
Mammen AL, Chung T, Christopher-Stine L, Rosen P, Rosen A, Doering KR, Casciola-Rosen LA (2011) Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum 63:713–721
Markello T, Chen D, Kwan JY, Horkayne-Szakaly I, Morrison A, Simakova O, Maric I, Lozier J, Cullinane AR, Kilo T, Meister L, Pakzad K, Bone W, Chainani S, Lee E, Links A, Boerkoel C, Fischer R, Toro C, White JG, Gahl WA, Gunay-Aygun M (2015) York platelet syndrome is a CRAC channelopathy due to gain-of-function mutations in STIM1. Mol Genet Metab 114:474–482
Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, Kaye EM, Mercuri E, Network ESGaTFDI (2016) Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 79:257–271
Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM, Group ES (2013) Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 74:637–647
Mercuri E, Clements E, Offiah A, Pichiecchio A, Vasco G, Bianco F, Berardinelli A, Manzur A, Pane M, Messina S, Gualandi F, Ricci E, Rutherford M, Muntoni F (2010) Muscle magnetic resonance imaging involvement in muscular dystrophies with rigidity of the spine. Ann Neurol 67:201–208
Morin G, Bruechle NO, Singh AR, Knopp C, Jedraszak G, Elbracht M, Brémond-Gignac D, Hartmann K, Sevestre H, Deutz P, Hérent D, Nürnberg P, Roméo B, Konrad K, Mathieu-Dramard M, Oldenburg J, Bourges-Petit E, Shen Y, Zerres K, Ouadid-Ahidouch H, Rochette J (2014) Gain-of-function mutation in STIM1 (P.R304W) is associated with Stormorken syndrome. Hum Mutat 35:1221–1232
Nesin V, Wiley G, Kousi M, Ong EC, Lehmann T, Nicholl DJ, Suri M, Shahrizaila N, Katsanis N, Gaffney PM, Wierenga KJ, Tsiokas L (2014) Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis. Proc Natl Acad Sci USA 111:4197–4202
Neves VC, Babb R, Chandrasekaran D, Sharpe PT (2017) Promotion of natural tooth repair by small molecule GSK3 antagonists. Sci Rep 7:39654
Penttilä S, Palmio J, Suominen T, Raheem O, Evilä A, Muelas Gomez N, Tasca G, Waddell LB, Clarke NF, Barboi A, Hackman P, Udd B (2012) Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. Neurology 78:897–903
Picard C, McCarl CA, Papolos A, Khalil S, Lüthy K, Hivroz C, LeDeist F, Rieux-Laucat F, Rechavi G, Rao A, Fischer A, Feske S (2009) STIM1 mutation associated with a syndrome of immunodeficiency and autoimmunity. N Engl J Med 360:1971–1980
Pluk H, van Hoeve BJ, van Dooren SH, Stammen-Vogelzangs J, van der Heijden A, Schelhaas HJ, Verbeek MM, Badrising UA, Arnardottir S, Gheorghe K, Lundberg IE, Boelens WC, van Engelen BG, Pruijn GJ (2013) Autoantibodies to cytosolic 5′-nucleotidase 1A in inclusion body myositis. Ann Neurol 73:397–407
Ramanathan S, Langguth D, Hardy TA, Garg N, Bundell C, Rojana-Udomsart A, Dale RC, Robertson T, Mammen AL, Reddel SW (2015) Clinical course and treatment of anti-HMGCR antibody-associated necrotizing autoimmune myopathy. Neurol Neuroimmunol Neuroinflamm 2:e96
Richard I, Roudaut C, Saenz A, Pogue R, Grimbergen JE, Anderson LV, Beley C, Cobo AM, de Diego C, Eymard B, Gallano P, Ginjaar HB, Lasa A, Pollitt C, Topaloglu H, Urtizberea JA, de Visser M, van der Kooi A, Bushby K, Bakker E, Lopez de Munain A, Fardeau M, Beckmann JS (1999) Calpainopathy—a survey of mutations and polymorphisms. Am J Hum Genet 64:1524–1540
Rose MR, Group EIW (2013) 188th ENMC international workshop: inclusion body myositis, 2–4 December 2011, Naarden, The Netherlands. Neuromuscul Disord 23:1044–1055
Salajegheh M, Lam T, Greenberg SA (2011) Autoantibodies against a 43 KDa muscle protein in inclusion body myositis. PLoS One 6:e20266
Salviati G, Pierobon-Bormioli S, Betto R, Damiani E, Angelini C, Ringel SP, Salvatori S, Margreth A (1985) Tubular aggregates: sarcoplasmic reticulum origin, calcium storage ability, and functional implications. Muscle Nerve 8:299–306
Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Pénisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, Schreiber H, Gläser D, Eagle M, Bailey G, Walters R, Longman C, Norwood F, Winer J, Muntoni F, Hanna M, Roberts M, Bindoff LA, Brierley C, Cooper RG, Cottrell DA, Davies NP, Gibson A, Gorman GS, Hammans S, Jackson AP, Khan A, Lane R, McConville J, McEntagart M, Al-Memar A, Nixon J, Panicker J, Parton M, Petty R, Price CJ, Rakowicz W, Ray P, Schapira AH, Swingler R, Turner C, Wagner KR, Maddison P, Shaw PJ, Straub V, Bushby K, Lochmüller H (2013) ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Hum Mutat 34:1111–1118
Schwartz M, Hertz JM, Sveen ML, Vissing J (2005) LGMD2I presenting with a characteristic Duchenne or Becker muscular dystrophy phenotype. Neurology 64:1635–1637
Senderek J, Müller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hübner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmüller H (2011) Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am J Hum Genet 88:162–172
Servián-Morilla E, Takeuchi H, Lee TV, Clarimon J, Mavillard F, Area-Gómez E, Rivas E, Nieto-González JL, Rivero MC, Cabrera-Serrano M, Gómez-Sánchez L, Martínez-López JA, Estrada B, Márquez C, Morgado Y, Suárez-Calvet X, Pita G, Bigot A, Gallardo E, Fernández-Chacón R, Hirano M, Haltiwanger RS, Jafar-Nejad H, Paradas C (2016) A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss. EMBO Mol Med 8:1289–1309
Starling A, Kok F, Passos-Bueno MR, Vainzof M, Zatz M (2004) A new form of autosomal dominant limb-girdle muscular dystrophy (LGMD1G) with progressive fingers and toes flexion limitation maps to chromosome 4p21. Eur J Hum Genet 12:1033–1040
Sussman J (2016) Thymectomy: the more you know, the more you know you don’t know. Pract Neurol 16:426–427
Tolosa E, Litvan I, Höglinger GU, Burn D, Lees A, Andrés MV, Gómez-Carrillo B, León T, Del Ser T, Investigators T (2014) A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord 29:470–478
Van De Vlekkert J, Maas M, Hoogendijk JE, De Visser M, Van Schaik IN (2015) Combining MRI and muscle biopsy improves diagnostic accuracy in subacute-onset idiopathic inflammatory myopathy. Muscle Nerve 51:253–258
van der Kooi AJ, Ten Dam L, Frankhuizen WS, Straathof CS, van Doorn PA, de Visser M, Ginjaar IB (2013) ANO5 mutations in the Dutch limb girdle muscular dystrophy population. Neuromuscul Disord 23:456–460
Vieira NM, Naslavsky MS, Licinio L, Kok F, Schlesinger D, Vainzof M, Sanchez N, Kitajima JP, Gal L, Cavaçana N, Serafini PR, Chuartzman S, Vasquez C, Mimbacas A, Nigro V, Pavanello RC, Schuldiner M, Kunkel LM, Zatz M (2014) A defect in the RNA-processing protein HNRPDL causes limb-girdle muscular dystrophy 1G (LGMD1G). Hum Mol Genet 23:4103–4110
Watanabe Y, Suzuki S, Nishimura H, Murata KY, Kurashige T, Ikawa M, Asahi M, Konishi H, Mitsuma S, Kawabata S, Suzuki N, Nishino I (2015) Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan. Medicine (Baltimore) 94:e416
Werner JL, Christopher-Stine L, Ghazarian SR, Pak KS, Kus JE, Daya NR, Lloyd TE, Mammen AL (2012) Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Arthritis Rheum 64:4087–4093
Willcocks RJ, Rooney WD, Triplett WT, Forbes SC, Lott DJ, Senesac CR, Daniels MJ, Wang DJ, Harrington AT, Tennekoon GI, Russman BS, Finanger EL, Byrne BJ, Finkel RS, Walter GA, Sweeney HL, Vandenborne K (2016) Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort. Ann Neurol 79:535–547
Wolfe GI, Kaminski HJ, Cutter GR (2016) Randomized trial of thymectomy in myasthenia gravis. N Engl J Med 375:2006–2007
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
JW reports no disclosures. SB received a travel bursary from Sanofi-Genzyme in 2016.
Rights and permissions
About this article
Cite this article
Witherick, J., Brady, S. Update on muscle disease. J Neurol 265, 1717–1725 (2018). https://doi.org/10.1007/s00415-018-8856-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-018-8856-1