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Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration

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Abstract

To assess the presence and persistence of muscular edema and increased myoplasmic sodium (Na+) concentration in Duchenne muscular dystrophy (DMD). We examined eight DMD patients (mean age 9.5 ± 5.4 years) and eight volunteers (mean age 9.5 ± 3.2 years) with 3-tesla proton (1H) and 23Na density-adapted 3D-radial MR sequences. Seven DMD patients were re-examined about 7 months later without change of therapy. The eighth DMD patient was re-examined after 5 and 11 months under medication with eplerenone. We quantified muscle edema on STIR images with background noise as reference and fatty degeneration on T1-weighted images using subcutaneous fat as reference. Na+ was quantified by a muscular tissue Na+ concentration (TSC) sequence employing a reference containing 51.3 mM Na+ with 5 % agarose. With an inversion-recovery (IR) sequence, we determined mainly the myoplasmic Na+. The normalized muscular 23Na IR signal intensity was higher in DMD than in volunteers (n = 8, 0.75 ± 0.07 vs. 0.50 ± 0.05, p < 0.001) and persisted at second measurement (n = 7, 1st 0.75 ± 0.07, 2nd 0.73 ± 0.06, p = 0.50). When compared to volunteers (25.6 ± 2.0 mmol/l), TSC was markedly increased in DMD (38.0 ± 5.9 mmol/l, p < 0.001) and remained constant (n = 7, 1st 37.9 ± 6.4 mmol/l, 2nd 37.0 ± 4.0 mmol/l, p = 0.49). Muscular edema (15.6 ± 3.5 vs. 6.9 ± 0.7, p < 0.001) and fat content (0.48 ± 0.08 vs. 0.38 ± 0.01, p = 0.003) were elevated in DMD when compared to volunteers. This could also be confirmed during follow-up (n = 7, p = 0.91, p = 0.12). Eplerenone slightly improved muscle strength and reduced muscular sodium and edema. The permanent muscular Na+ overload in all DMD patients is likely osmotically relevant and responsible for the persisting, mainly intracellular muscle edema that may contribute to the progressive muscle degeneration.

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References

  1. Bushby K, Finkel R, Birnkrant DJ et al (2010) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 9:77–93

    Article  PubMed  Google Scholar 

  2. Marden FA, Connolly AM, Siegel MJ, Rubin DA (2005) Compositional analysis of muscle in boys with Duchenne muscular dystrophy using MR imaging. Skeletal Radiol 34:140–148

    Article  PubMed  Google Scholar 

  3. Weber MA, Nagel AM, Jurkat-Rott K, Lehmann-Horn F (2011) Sodium (23Na) MRI detects elevated muscular sodium concentration in Duchenne muscular dystrophy. Neurology 77:2017–2024

    Article  PubMed  CAS  Google Scholar 

  4. Hirn C, Shapovalov G, Petermann O, Roulet E, Ruegg UT (2008) Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell death. J Gen Physiol 132:199–208

    Article  PubMed  CAS  Google Scholar 

  5. Bodensteiner JB, Engel AG (1978) Intracellular calcium accumulation in Duchenne dystrophy and other myopathies: a study of 567,000 muscle fibers in 114 biopsies. Neurology 28:439–446

    Article  PubMed  CAS  Google Scholar 

  6. Nagel AM, Laun FB, Weber MA, Matthies C, Semmler W, Schad LR (2009) Sodium MRI using a density-adapted 3D radial acquisition technique. Magn Reson Med 62:1565–1573

    Article  PubMed  Google Scholar 

  7. Nagel AM, Amarteifio E, Lehmann-Horn F et al (2011) 3 tesla sodium inversion recovery magnetic resonance imaging allows for improved visualization of intracellular sodium content changes in muscular channelopathies. Invest Radiol 46:759–766

    Article  PubMed  CAS  Google Scholar 

  8. Dyck PJ, Boes CJ, Mulder D, Millikan C, Windebank AJ, Espinosa R (2005) History of standard scoring, notation, and summation of neuromuscular signs. A current survey and recommendation. J Peripher Nerv Syst 10:158–173

    Article  PubMed  Google Scholar 

  9. Weber MA, Nielles-Vallespin S, Essig M, Jurkat-Rott K, Kauczor HU, Lehmann-Horn F (2006) Muscle Na+ channelopathies: MRI detects intracellular 23Na accumulation during episodic weakness. Neurology 67:1151–1158

    Article  PubMed  CAS  Google Scholar 

  10. Stobbe R, Beaulieu C (2005) In vivo sodium magnetic resonance imaging of the human brain using soft inversion recovery fluid attenuation. Magn Reson Med 54:1305–1310

    Article  PubMed  CAS  Google Scholar 

  11. Olsen DB, Gideon P, Jeppesen TD, Vissing J (2006) Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI. J Neurol 253:1437–1441

    Article  PubMed  Google Scholar 

  12. Jurkat-Rott K, Weber MA, Fauler M et al (2009) K+-dependent paradoxical membrane depolarization and Na+ overload, major and reversible contributors to weakness by ion channel leaks. Proc Natl Acad Sci USA 106:4036–4041

    Article  PubMed  CAS  Google Scholar 

  13. Jurkat-Rott K, Holzherr B, Fauler M, Lehmann-Horn F (2010) Sodium channelopathies of skeletal muscle result from gain or loss of function. Pflugers Arch 460:239–248

    Article  PubMed  CAS  Google Scholar 

  14. Lansman JB, Franco-Obregón A (2006) Mechanosensitive ion channels in skeletal muscle: a link in the membrane pathology of muscular dystrophy. Clin Exp Pharmacol Physiol 33:649–656

    Article  PubMed  CAS  Google Scholar 

  15. Kirschner J, Schessl J, Schara U et al (2010) Treatment of Duchenne muscular dystrophy with cyclosporin A: a randomised, double-blind, placebo-controlled multicentre trial. Lancet Neurol 9:1053–1059

    Article  PubMed  CAS  Google Scholar 

  16. Manzur AY, Kuntzer T, Pike M, Swan A (2008) Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev 1:CD003725

    PubMed  Google Scholar 

  17. Salinas RA, Alvarez G, Daly F, Ferreira J (2010) Corticosteroids for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 17:CD001942

    Google Scholar 

  18. Yamamoto T, Ohara A, Nishikawa M, Yamamoto G, Saeki Y (2011) Dexamethasone-induced up-regulation of two-pore domain K(+) channel genes, TASK-1 and TWIK-2, in cultured human periodontal ligament fibroblasts. In Vitro Cell Dev Biol Anim 47:273–279

    Article  PubMed  CAS  Google Scholar 

  19. Ouwerkerk R, Bleich KB, Gillen JS, Pomper MG, Bottomley PA (2003) Tissue sodium concentration in human brain tumors as measured with 23Na MR imaging. Radiology 227:529–537

    Article  PubMed  Google Scholar 

  20. Chang G, Wang L, Schweitzer ME, Regatte RR (2010) 3D 23Na MRI of human skeletal muscle at 7 tesla: initial experience. Eur Radiol 20:2039–2046

    Article  PubMed  Google Scholar 

  21. Borthakur A, Hancu I, Boada FE, Shen GX, Shapiro EM, Reddy R (1999) In vivo triple quantum filtered twisted projection sodium MRI of human articular cartilage. J Magn Reson 141:286–290

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by a research grant from the Deutsche Gesellschaft für Muskelkranke e.V. F. Lehmann-Horn is endowed Senior Research Professor of the non-profit Hertie-Foundation. We appreciate the molecular genetics of patient #8 performed by K. Hinderhofer, MD, Institute of Human Genetics, University Hospital, Heidelberg/Germany (Director C.R. Bartram, MD). We also thank A. Behnecke, MD, Institute of Human Genetics, University Hospital, Heidelberg/Germany, H.-M. Meinck, MD, Department of Neurology, University Hospital, Heidelberg/Germany, and M. Sanchez-Albisua, MD, Sozialpädiatrisches Zentrum (SPZ) Tübingen/Germany for referring some patients. We are grateful to the patients and their families for their participation.

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The authors report no conflicts of interest and no disclosures.

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Authors and Affiliations

  1. Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    M.-A. Weber, M. B. Wolf & H.-U. Kauczor

  2. Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    A. M. Nagel & W. Semmler

  3. Division of Neurophysiology, Ulm University, Albert-Einstein-Allee 11, 89069, Ulm, Germany

    K. Jurkat-Rott & F. Lehmann-Horn

  4. Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    M.-A. Weber

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  1. M.-A. Weber
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  2. A. M. Nagel
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  3. M. B. Wolf
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  4. K. Jurkat-Rott
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  5. H.-U. Kauczor
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  6. W. Semmler
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  7. F. Lehmann-Horn
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Correspondence to M.-A. Weber or F. Lehmann-Horn.

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Weber, MA., Nagel, A.M., Wolf, M.B. et al. Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration. J Neurol 259, 2385–2392 (2012). https://doi.org/10.1007/s00415-012-6512-8

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  • DOI: https://doi.org/10.1007/s00415-012-6512-8

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