Acute Quadriplegic Myopathy: An Acquired “Myosinopathy”

  • Lars Larsson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 642)


Acquired neuromuscular disorders have been shown to be very common in critically ill patients receiving prolonged mechanical ventilation in the intensive care unit (ICU). Acute Quadriplegic Myopathy (AQM) is a specific acquired myopathy in ICU patients. Patients with AQM are characterized by severe muscle weakness and atrophy of spinal nerve innervated limb and trunk muscles, while cranial nerve innervated craniofacial muscles, sensory and cognitive functions are spared or less affected. The muscle weakness is associated with altered muscle membrane properties and a preferential loss of the motor protein myosin and myosin-associated thick filament proteins. Prolonged mechanical ventilation, muscle unloading, postsynaptic block of neuromuscular transmission, sepsis and systemic corticosteroid hormone treatment have been suggested as important triggering factors in AQM. However, the exact mechanisms underlying the loss of thick filament proteins are not known, though enhanced myofibrillar protein degradation in combination with a downregulation of protein synthesis at the transcriptional level play important roles.


Inclusion Body Myositis Prolonged Mechanical Ventilation Status Asthmaticus Critical Illness Polyneuropathy Intensive Care Unit Treatment 
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  1. 1.
    MacFarlane IA, Rosenthal FD. Severe myopathy after status asthmaticus. Lancet 1977; 2(8038):615.PubMedCrossRefGoogle Scholar
  2. 2.
    Lacomis D, Zochodne DW, Bird SJ. Critical illness myopathy. Muscle Nerve 2000; 23(12):1785–1788.PubMedCrossRefGoogle Scholar
  3. 3.
    Rich MM, Teener JW, Raps EC et al. Muscle inexcitability in patients with reversible paralysis following steroids and neuromuscular blockade. Muscle Nerve 1998; 21(9):1231–1232.PubMedCrossRefGoogle Scholar
  4. 4.
    Rich MM, Raps EC, Bird SJ. Distinction between acute myopathy syndrome and critical illness polyneuropathy. Mayo Clin Proc 1995; 70(2):198–200.PubMedGoogle Scholar
  5. 5.
    Rich MM, Pinter MJ, Kraner SD et al. Loss of electrical excitability in an animal model of acute quadriplegic myopathy. Ann Neurol 1998; 43(2):171–179.PubMedCrossRefGoogle Scholar
  6. 6.
    Rich MM, Teener JW, Raps EC et al. Muscle is electrically inexcitable in acute quadriplegic myopathy. Neurology 1996; 46(3):731–736.PubMedGoogle Scholar
  7. 7.
    Rich MM, Bird SJ, Raps EC et al. Direct muscle stimulation in acute quadriplegic myopathy. Muscle Nerve 1997; 20(6):665–673.PubMedCrossRefGoogle Scholar
  8. 8.
    De Jonghe B, Sharshar T, Lefaucheur JP et al. Paresis acquired in the intensive care unit: A prospective multicenter study. JAMA 2002; 288(22):2859–2867.PubMedCrossRefGoogle Scholar
  9. 9.
    Leijten FS, Harinck-de Weerd JE, Poortvliet DC et al. The role of polyneuropathy in motor convalescence after prolonged mechanical ventilation. JAMA 1995; 274(15):1221–1225.PubMedCrossRefGoogle Scholar
  10. 10.
    Friedrich O, Fink RH, Hund E. Understanding critical illness myopathy: approaching the pathomechanism. J Nutr 2005; 135(7):1813S–1817S.PubMedGoogle Scholar
  11. 11.
    Rudis MI, Guslits BJ, Peterson EL et al. Economic impact of prolonged motor weakness complicating neuromuscular blockade in the intensive care unit. Crit Care Med 1996; 24(10):1749–1756.PubMedCrossRefGoogle Scholar
  12. 12.
    Seneff MG, Wagner D, Thompson D et al. The impact of long-term acute-care facilities on the out-come and cost of care for patients undergoing prolonged mechanical ventilation. Crit Care Med 2000; 28(2):342–350.PubMedCrossRefGoogle Scholar
  13. 13.
    Cheung AM, Tansey CM, Tomlinson G et al. 2-Year outcomes, health care use and costs in survivors of ARDS. Am J Respir Crit Care Med 2006; 174(5):528–544.CrossRefGoogle Scholar
  14. 14.
    Herridge MS, Cheung AM, Tansey CM et al. One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348(8):683–693.PubMedCrossRefGoogle Scholar
  15. 15.
    Visser LH. Critical illness polyneuropathy and myopathy: Clinical features, risk factors and prognosis. Eur J Neurol 2006; 13(11):1203–1212.PubMedCrossRefGoogle Scholar
  16. 16.
    al-Lozi MT, Pestronk A, Yee WC et al. Rapidly evolving myopathy with myosin-deficient muscle fibers. Ann Neurol 1994; 35(3):273–279.PubMedCrossRefGoogle Scholar
  17. 17.
    Danon MJ, Carpenter S. Myopathy with thick filament (myosin) loss following prolonged paralysis with vecuro nium during steroid treatment. Muscle Nerve 1991; 14(11):1131–1139.PubMedCrossRefGoogle Scholar
  18. 18.
    Larsson L, Li X, Edstrom L et al. Acute quadriplegia and loss of muscle myosin in patients treated with nondepolarizing neuromuscular blocking agents and corticosteroids: Mechanisms at the cellular and molecular levels [see comments]. Crit Care Med 2000; 28(1):34–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Matsumoto N, Nakamura T, Yasui Y et al. Analysis of muscle proteins in acute quadriplegic myopathy. Muscle Nerve 2000; 23(8):1270–1276.PubMedCrossRefGoogle Scholar
  20. 20.
    Ochala J, Larsson L. Effects of myosin heavy chain loss on the regulation of Ca2+-activation in single human skeletal muscle fibres. Submitted for publication 2007.Google Scholar
  21. 21.
    Banduseela V, Ochala J, Lamberg K et al. Muscle paralysis and myosin loss in a patient with cancer cachexia. Acta Myologica. In press, 2007.Google Scholar
  22. 22.
    Hund E. Neurological complications of sepsis: Critical illness polyneuropathy and myopathy. J Neurol 2001; 248(11):929–934.PubMedCrossRefGoogle Scholar
  23. 23.
    Druschky A, Herkert M, Radespiel-Troger M et al. Critical illness polyneuropathy: Clinical findings and cell culture assay of neurotoxicity assessed by a prospective study. Intensive Care Med 2001; 27(4):686–693.PubMedCrossRefGoogle Scholar
  24. 24.
    Di Giovanni S, Knoblach SM, Brandoli C et al. Gene profiling in spinal cord injury shows role of cell cycle in neuronal death. Ann Neurol 2003; 53(4):454–468.PubMedCrossRefGoogle Scholar
  25. 25.
    Showalter CJ, Engel AG. Acute quadriplegic myopathy: Analysis of myosin isoforms and evidence for calpain-mediated proteolysis. Muscle Nerve 1997; 20(3):316–322.PubMedCrossRefGoogle Scholar
  26. 26.
    Helliwell TR, Wilkinson A, Griffiths RD et al. Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin. Neuropathol Appl Neurobiol 1998; 24(6):507–517.PubMedCrossRefGoogle Scholar
  27. 27.
    Di Giovanni S, Molon A, Broccolini A et al. Constitutive activation of MAPK cascade in acute quadriplegic myopathy. Ann Neurol 2004; 55(2):195–206.PubMedCrossRefGoogle Scholar
  28. 28.
    Norman H, Hedström Y, Andersson P et al. Changes in myofibrillar protein and mRNA expression in patients with acute quadriplegic myopathy during recovery. In review, 2007.Google Scholar
  29. 29.
    Thomason DB, Biggs RB, Booth FW. Protein metabolism and beta-myosin heavy-chain mRNA in unweighted soleus muscle. Am J Physiol 1989; 257(2 Pt 2):R300–305.PubMedGoogle Scholar
  30. 30.
    Thomason DB, Booth FW. Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol 1990; 68(1):1–12.PubMedCrossRefGoogle Scholar
  31. 31.
    Shanely RA, Van Gammeren D, Deruisseau KC et al. Mechanical ventilation depresses protein synthesis in the rat diaphragm. Am J Respir Crit Care Med 2004; 170(9):994–999.PubMedCrossRefGoogle Scholar
  32. 32.
    Giger JM, Haddad F, Qin AX et al. Effect of unloading on type I myosin heavy chain gene regulation in rat soleus muscle. J Appl Physiol 2005; 98(4):1185–1194.PubMedCrossRefGoogle Scholar
  33. 33.
    Huey KA, Roy RR, Haddad F et al. Transcriptional regulation of the type I myosin heavy chain promoter in inactive rat soleus. Am J Physiol Cell Physiol 2002; 282(3):C528–537.PubMedGoogle Scholar
  34. 34.
    Nates JL, Cooper DJ, Day B et al. Acute weakness syndromes in critically ill patients—A reappraisal. Anaesth Intensive Care 1997; 25(5):502–513.PubMedGoogle Scholar
  35. 35.
    Larsson L, Roland A. Drug induced tetraparesis and loss of myosin. Mild types are probably overlooked. Lakartidningen 1996; 93(23):2249–2254.PubMedGoogle Scholar
  36. 36.
    Larsson L. Experimental animal models of muscle wasting in intensive care unit patients. Crit Care Med 2007; 35(9 Suppl):484–487.CrossRefGoogle Scholar
  37. 37.
    Rich MM, Pinter MJ. Crucial role of sodium channel fast inactivation in muscle fibre inexcitability in a rat model of critical illness myopathy. J Physiol 2003; 547(Pt 2):555–566.PubMedCrossRefGoogle Scholar
  38. 38.
    Rich MM, Pinter MJ. Sodium channel inactivation in an animal model of acute quadriplegic myopathy. Ann Neurol 2001; 50(1):26–33.PubMedCrossRefGoogle Scholar
  39. 39.
    Norman H, Nordquist J, Andersson P et al. Impact of postsynaptic block of neuromuscular transmission, muscle unloading and mechanical ventilation on skeletal muscle protein and mRNA expression. Pflugers Arch 2006; I10:1007/s00424-006-0110-5.Google Scholar
  40. 40.
    Nordquist J, Höglund AS, Norman H et al. Transcription factors in muscle atrophy caused by postsynaptic block of neuromuscular transmission and muscle unloading in rats. Mol Med 2007; 13(9–10):461–70.PubMedGoogle Scholar
  41. 41.
    Norman H, Kandala K, Kolluri R et al. A porcine model of acute quadriplegic myopathy: A feasability study. Acta Anaesthesiol Scand 2006; 50(9):1058–67.PubMedCrossRefGoogle Scholar
  42. 42.
    Ochala J, Bandusela V, Norman H et al. Triggering factors and mechanisms underlying muscle weakness in AQM, experimental studies in a porcine AQM model. In preparation 2007.Google Scholar
  43. 43.
    Dworkin BR, Dworkin S. Learning of physiological responses: I. Habituation, sensitization and classical conditioning. Behav Neurosci 1990; 104(2):298–319.PubMedCrossRefGoogle Scholar
  44. 44.
    Dworkin BR, Dworkin S. Baroreflexes of the rat. III. Open-loop gain and electroencephalographic arousal. Am J Physiol Regul Integr Comp Physiol 2004; 286(3):R597–605.PubMedGoogle Scholar
  45. 45.
    Dworkin BR, Dworkin S, Tang X. Carotid and aortic baro reflexes of the rat: I. Open-loop steady-state properties and blood pressure variability. Am J Physiol Regul Integr Comp Physiol 2000; 279(5): R1910–1921.PubMedGoogle Scholar
  46. 46.
    Dworkin BR, Tang X, Snyder AJ et al. Carotid and aortic baroreflexes of the rat: II. Open-loop frequency response and the blood pressure spectrum. Am J Physiol Regul Integr Comp Physiol 2000; 279(5): R1922–1933.PubMedGoogle Scholar
  47. 47.
    Nordqvist J, Höglund AS, Norman H et al. Transcription factors in muscle atrophycaused by postsynaptic block of neuromuscular transmission and muscle unloading in rats. Molecular Medicine 2007; In review.Google Scholar
  48. 48.
    Norman H, Nordquist J, Andersson P et al. Impact of postsynaptic block of neuromuscular transmission, muscle unloading and mechanical ventilation on skeletal muscle protein and mRNA expression. Pflugers Arch 2006; 453(1):53–66.PubMedCrossRefGoogle Scholar
  49. 49.
    Griffiths RD, Jones C, Palmer TE. Outcome of nutrition therapies in the intensive care unit. Nutrition 1995; 11(2 Suppl):224–228.PubMedGoogle Scholar
  50. 50.
    Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997; 13(4):295–302.PubMedGoogle Scholar
  51. 51.
    Griffiths RD, Palmer TE, Jones C. Parenteral glutamine supply in intensive care patients. Nutrition 1996; 12(11–12 Suppl):s73–75.CrossRefGoogle Scholar
  52. 52.
    Jones C, Palmer TE, Griffiths RD. Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 1999; 15(2):108–115.PubMedCrossRefGoogle Scholar
  53. 53.
    Griffiths RD, Palmer TE, Helliwell T et al. Effect of passive stretching on the wasting of muscle in the critically ill. Nutrition 1995; 11(5):428–432.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Lars Larsson
    • 1
  1. 1.Department of Clinical NeurophysiologyUppsala UniversityUppsalaSweden

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