The Effects of Testosterone and Transcutaneous Muscle Stimulation on Strength and Muscle Mass in Myotonic Dystrophy

Authors

  • Salman Bhai, MD Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX; Neuromuscular Center, Institute for Exercise and Environmental Medicine,Texas Health Presbyterian, Dallas, TX https://orcid.org/0000-0003-4702-9380
  • Alexis Lizarraga, MD Department of Neurology, University of Rochester, Rochester, NY https://orcid.org/0000-0003-1418-9775
  • Morgan McCreary, PhD Neuromuscular Center, Institute for Exercise and Environmental Medicine,Texas Health Presbyterian, Dallas, TX https://orcid.org/0000-0002-8378-460X
  • Seth Kolkin, MD Department of Neurology, University of Rochester, Rochester, NY
  • John Kissel, MD
  • Richard J. Barohn, MD Department of Neurology, University of Missouri, Kansas City, MO https://orcid.org/0000-0002-0383-6845

DOI:

https://doi.org/10.17161/rrnmf.v3i4.18396

Keywords:

myotonic dystrophy, testosterone, transcutaneous muscle stimulation, muscle strength

Abstract

         In myotonic dystrophy type 1 (DM1) quadriceps weakness often results in severe functional limitations and genu recurvatum. To improve quadriceps strength the effects of isometric tetanic contractions using transcutaneous muscle stimulation (TMS) and testosterone enanthate (TE) were assessed. Ten DM1 subjects underwent unilateral TMS 6 hours per day for 14 days. The stimulated leg was randomly assigned and sham stimulation was done on the opposite leg by transcutaneous nerve stimulation. Muscle mass was estimated by cross-sectional area computed tomography and strength was measured by Cybex ergometry. Following the initial TMS period, 8 of 10 subjects were given a 12-week course of TE (3 mg/kg/wk) followed by 14 days of TMS. Neither TMS nor TE improved strength.  Following 12 weeks of TE, there was an average increase in muscle mass of at least 8.7 +/- 1.6 cm2. These findings are consistent with the TE—increased muscle mass in DM1 as measured by creatinine clearance and total body potassium. The dissociation of mass and strength following TE and the failure of exercise to improve strength may have significance in characterizing the muscle defect in DM1.

Metrics

Metrics Loading ...

Downloads

Download data is not yet available.

References

Griggs RC, Jozefowicz R, Kingston W, Nair KS, Herr BE, Halliday D. Mechanism of muscle wasting in myotonic dystrophy. Ann Neurol. 1990 May;27(5):505–12.

Goldberg AL, Etlinger JD, Goldspink DF, Jablecki C. Mechanism of work-induced hypertrophy of skeletal muscle. Med Sci Sports. 1975;7(3):185–98.

Griggs RC, Halliday D, Kingston W, Moxley RT. Effect of testosterone on muscle protein synthesis in myotonic dystrophy. Ann Neurol. 1986 Nov;20(5):590–6.

Gould N, Donnermeyer D, Pope M, Ashikaga T. Transcutaneous muscle stimulation as a method to retard disuse atrophy. Clin Orthop. 1982 Apr;(164):215–20.

Williams JG, Street M. Sequential faradism in quadriceps rehabilitation. Physiotherapy. 1976 Aug;62(8):252–4.

Eriksson E, Häggmark T. Comparison of isometric muscle training and electrical stimulation supplementing isometric muscle training in the recovery after major knee ligament surgery. A preliminary report. Am J Sports Med. 1979 Jun;7(3):169–71.

Fossati B, Sansone V, Panzeri MC, Zanolini A, De Ambroggi G, Cappato R, et al. Tolerability and safety of mexiletine in patients with myotonic dystrophy type 1 over time. J Neurol. 2009;256(SUPPL. 2):S128–9.

Sansone V, Panzeri M, Zanolini A, Fossati B, Meola G, Testa M, et al. Effects of mexiletine on cardiac parameters, muscle strength and myotonia in myotonic dystrophy type 1. Med Genet. 2009;21(3):435–6.

Logigian EL, Martens WB, Dilek N, Barbieri CA, Annis CL, Thornton CA, et al. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology. 2010;74(18):1441–8.

Heatwole C, Luebbe E, Rosero S, Eichinger K, Martens W, Hilbert J, et al. Mexiletine for myotonic dystrophy type 1 (DM1): Results from a randomized, placebo controlled, clinical efficacy trial. Muscle Nerve. 2018;58(Supplement 1):S3.

Heatwole C, Luebbe E, Rosero S, Eichinger K, Martens W, Hilbert J, et al. Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial. Neurology. 2021;96(2):e228–40.

Gascon GG, Staton RD, Patterson BD, Konewko PJ, Wilson H, Carlson KM, et al. A pilot controlled study of the use of imipramine to reduce myotonia. Am J Phys Med Rehabil. 1989;68(5):215–20.

Schneider-Gold C, Beck M, Wessig C, George A, Reiners K, Toyka KV, et al. Creatine monohydrate in DM2/PROMM: A double-blind placebo-controlled clinical study. Neurology. 2003;60(3):500–2.

Tarnopolsky M, Mahoney D, Thompson T, Naylor H, Doherty TJ. Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Muscle Nerve. 2004;29(1):51–8.

Walter MC, Reilich P, Lochmuller H, Kohnen R, Schlotter B, Hautmann H, et al. Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. J Neurol. 2002;249(12):1717–22.

Orndahl G, Sellden U, Hallin S. Myotonic dystrophy treated with selenium and vitamin E. Acta Med Scand. 1986;219(4):407–14.

Orndahl G, Rindby A, Selin E. Selenium therapy of myotonic dystrophy. Acta Med Scand. 1983;213(3):237–9.

Orndahl G, Grimby G, Grimby A, Johansson G, Wilhelmsen L. Functional deterioration and selenium-vitamin E treatment in myotonic dystrophy. A placebo-controlled study. J Intern Med. 1994;235(3):205–10.

Unlu Z. Myotonic dystrophy. Meandros Med Dent J. 2019;20(2):186–90.

Cudia P, Weis L, Baba A, Kiper P, Marcante A, Rossi S, et al. Effects of Functional Electrical Stimulation Lower Extremity Training in Myotonic Dystrophy Type I: A Pilot Controlled Study. Am J Phys Med Rehabil. 2016;95(11):809–17.

Roussel MP, Morin M, Gagnon C, Duchesne E. What is known about the effects of exercise or training to reduce skeletal muscle impairments of patients with myotonic dystrophy type 1? A scoping review. BMC Musculoskelet Disord. 2019;20(1):101.

Roussel MP, Morin M, Girardin M, Fortin AM, Leone M, Mathieu J, et al. Training program-induced skeletal muscle adaptations in two men with myotonic dystrophy type 1. BMC Res Notes. 2019;12(1):526.

Yoon SH, Baek JH, Leem J. Improved grip myotonia in a patient with myotonic dystrophy type 1 following electroacupuncture therapy: A CARE-compliant case report. Medicine (Baltimore). 2020;99(37):e21845.

Brady LI, MacNeil LG, Tarnopolsky MA. Impact of habitual exercise on the strength of individuals with myotonic dystrophy type 1. Am J Phys Med Rehabil. 2014;93(9):739–8.

Cudia P, Weis L, Baba A, Kiper P, Marcante A, Rossi S, et al. Effects of Functional Electrical Stimulation Lower Extremity Training in Myotonic Dystrophy Type I: A Pilot Controlled Study. Am J Phys Med Rehabil. 2016;95(11):809–17.

Nakazora H, Kurihara T. The effect of dehydroepiandrosterone sulfate (DHEAS) on myotonia: intracellular studies. Intern Med Tokyo Jpn. 2005;44(12):1247–51.

Moxley RT 3rd. Potential for growth factor treatment of muscle disease. Curr Opin Neurol. 1994;7(5):427–34.

Heatwole CR, Eichinger KJ, Friedman DI, Hilbert JE, Jackson CE, Logigian EL, et al. Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1. Arch Neurol. 2011;68(1):37–44.

Vlachopapadopoulou E, Zachwieja JJ, Gertner JM, Manzione D, Bier DM, Matthews DE, et al. Metabolic and clinical response to recombinant human insulin-like growth factor I in myotonic dystrophy--a clinical research center study. J Clin Endocrinol Metab. 1995;80(12):3715–23.

Penisson-Besnier I, Devillers M, Porcher R, Orlikowski D, Doppler V, Desnuelle C, et al. Dehydroepiandrosterone for myotonic dystrophy type 1. Neurology. 2008;71(6):407–12.

Sugino M, Ohsawa N, Ito T, Ishida S, Yamasaki H, Kimura F, et al. A pilot study of dehydroepiandrosterone sulfate in myotonic dystrophy. Neurology. 1998;51(2):586–9.

Griggs RC, Kingston W, Herr BE, Forbes G, Moxley RT 3rd. Lack of relationship of hypogonadism to muscle wasting in myotonic dystrophy. Arch Neurol. 1985;42(9):881–5.

Al-Harbi TM, Bainbridge LJ, McQueen MJ, Tarnopolsky MA. Hypogonadism is common in men with myopathies. J Clin Neuromuscul Dis. 2008;9(4):397–401.

Griggs RC, Pandya S, Florence JM, Brooke MH, Kingston W, Miller JP, et al. Randomized controlled trial of testosterone in myotonic dystrophy. Neurology. 1989;39(2 Pt 1):219–22.

R Core Team. R: A Language and Environment for Statistical Computing. Vienna; 2021.

Wickham H. ggplot2: Elegant Graphics for Data Analysis. New York: Spring-Verlag; 2016.

Kuznetsova A, Brockhoff PB, Christensen RHB. lmerTest Package: Tests in Linear Mixed Effects Models. J Stat Softw [Internet]. 2017 [cited 2022 Jun 4];82(13). Available from: http://www.jstatsoft.org/v82/i13/

Griggs RC, Kingston W, Herr BE, Forbes G, Moxley RT. Myotonic dystrophy: effect of testosterone on total body potassium and on creatinine excretion. Neurology. 1985 Jul;35(7):1035–40.

Haupt HA, Rovere GD. Anabolic steroids: a review of the literature. Am J Sports Med. 1984 Dec;12(6):469–84.

Buckley DC, Kudsk KA, Rose B, Koetting CA, Schlatter M, Miller CA. Transcutaneous muscle stimulation promotes muscle growth in immobilized patients. JPEN J Parenter Enteral Nutr. 1987 Dec;11(6):547–51.

Voet NB, van der Kooi EL, van Engelen BG, Geurts AC. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2019;12(100909747):CD003907.

Milner-Brown HS, Miller RG. Muscle strengthening through high-resistance weight training in patients with neuromuscular disorders. Arch Phys Med Rehabil. 1988;69(1):14–9.

Gianola S, Pecoraro V, Lambiase S, Gatti R, Banfi G, Moja L. Efficacy of Muscle Exercise in Patients with Muscular Dystrophy: A Systematic Review Showing a Missed Opportunity to Improve Outcomes. PLoS ONE. 2013;8(6):e65414.

Missaoui B, Rakotovao E, Bendaya S, Mane M, Pichon B, Faucher M, et al. Posture and gait abilities in patients with myotonic dystrophy (Steinert disease). Evaluation on the short-term of a rehabilitation program. Ann Phys Rehabil Med. 2010;53(6–7):387–98.

Gianola S, Castellini G, Pecoraro V, Monticone M, Banfi G, Moja L. Effect of Muscular Exercise on Patients With Muscular Dystrophy: A Systematic Review and Meta-Analysis of the Literature. Front Neurol. 2020;11(101546899):958.

Hebert L, Roussel M, Gagnon C, Duchesne E. P.26Strength training in myotonic dystrophy type 1: a promising therapeutic strategy. Neuromuscul Disord. 2019;29(Supplement 1):S49.

Voet NB, van der Kooi EL, Riphagen II, Lindeman E, van Engelen BG, Geurts AC. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2010;(1):CD003907.

Jauvin D, Chretien J, Pandey SK, Martineau L, Revillod L, Bassez G, et al. Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice. Mol Ther Nucleic Acids. 2017;7(101581621):465–74.

Bisset DR, Zavaljevski M, Stoltzman C, Chamberlain JR. AAV6-mediated systemic administration of MIR30-based RNAI hairpins impacts muscle disease in the hsalr myotonic dystrophy mouse model. Mol Ther. 2013;21(SUPPL. 1):S173–4.

Bassez G, Audureau E, Hogrel JY, Arrouasse R, Baghdoyan S, Bhugaloo H, et al. Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. Brain J Neurol. 2018;141(10):2855–65.

Bargiela A, Sabater-Arcis M, Espinosa-Espinosa J, Zulaica M, Lopez de Munain A, Artero R. Increased Muscleblind levels by chloroquine treatment improve myotonic dystrophy type 1 phenotypes in in vitro and in vivo models. Proc Natl Acad Sci U S A. 2019;116(50):25203–13.

Greene E, Thonhoff J, John BS, Rosenfield DB, Helekar SA. Multifocal Noninvasive Magnetic Stimulation of the Primary Motor Cortex in Type 1 Myotonic Dystrophy -A Proof of Concept Pilot Study. J Neuromuscul Dis. 2021;8(6):963–72.

Portaro S, Naro A, Leo A, Cimino V, Balletta T, Buda A, et al. Overground exoskeletons may boost neuroplasticity in myotonic dystrophy type 1 rehabilitation: A case report. Medicine (Baltimore). 2019;98(46):e17582.

Downloads

Published

2023-02-07

Issue

Section

New Discoveries/New Stuff (Original Research)

How to Cite

Bhai, S., Lizarraga, A., McCreary, M., Kolkin, S., Kissel, J., & Barohn, R. (2023). The Effects of Testosterone and Transcutaneous Muscle Stimulation on Strength and Muscle Mass in Myotonic Dystrophy . RRNMF Neuromuscular Journal, 4(1), 20-26. https://doi.org/10.17161/rrnmf.v3i4.18396