Neurological Disorders in Critical Illness

Česká verzia

Authors: prof. MUDr. Josef Bednařík, CSc.
Authors place of work: LF MU a FN Brno ; Ne urologická klinika
Published in the journal: Cesk Slov Neurol N 2008; 71/104(5): 511-529
Category: Minimonography

Poděkování: a utor děkuje prof. MUDr. Zdeňku Lukášovi, CSc., za poskytnutí histopatologických nálezů.

Summary

Critical illness is usu ally defined as a conditi on characterised by failure of one or more organs or systems as a result of a seri o us dise ase or tra uma and usu ally accompani ed by systemic inflammatory response syndrome. Among ca uses of critical illness are infecti ons, usu ally respiratory ones, tra umas, burns, gre at surgery or primary failure of one organ including central nervo us system or ne uromuscular failure. Original concept of sepsis as an inappropri ate mobilizati on of defence mechanisms against virulent infecti on was modifi ed by a concept of systemic inflammatory response syndrome as uncontrolled wide inflammatory response against not only infecti on and le ading into multiple organ failure. Failure of cerebral functi ons in the form of diffuse encephalopathy – encephalopathy in critical illness – is usu ally an integral part of multiple organ failure. Among key signs are decre ased level of consci o usness and disordered cognitive functi ons (especi ally attenti on, cogniti on and ori entati on). Most scoring systems of multiple organ failure use the Glasgow coma scale to score the central nervo us system failure. The aeti ology of encephalopathy in critical illness is probably multi- factori al and overlaps with that of eti ologically unspecific syndrome of deliri um. Encephalopathy in critical illness sho uld be differenti ated from infecti o us encephalitis and acute para- infecti o us a uto immune encephalopathi es. Ne uromuscular disorders in critically ill pati ents demonstrate especi ally as a new we akness (“critical illness we akness”). Beside exacerbati on of pre- existing ne uromuscular disorder and persistent pharmacological blockade of ne uromuscular transmissi on ca used by non‑depolarising muscle blocking agents, there exists the newly recognised ca use called polyne uropathy and myopathy of critical illness. These disorders affect to some extend at le ast half of critically ill pati ents. Aeti ology is probably multi- factori al. Systemic inflammatory response syndrome and multiple organ failure are probably among important eti ological factors. In critical illness myopathy, “functi onal denervati on” ca used by non‑depolarising muscle blocking agents and high doses of corticostero ids have additi onal effect. Both conditi ons are frequently associ ated in the same pati ent – critical illness polyne uromyopathy. In contrast to original concept of complicati ons of critical illness these conditi ons seem to be an integral part of multiple organ failure – a ne uromuscular failure – analogical to the failure of other organs and systems. Critical illness polyne uropathy and myopathy are important risk factors of prolonged morbidity and mortality in critically ill pati ents. Current state of art in the are a of aeti ology and pathogenesis of critical illness doesn’t enable the use of effective preventi on and tre atment of ne uromuscular disorders.

Key words:
critical illness – sepsis – multiple organ failure – encephalopathy – polyne uropathy – myopathy

Zdroje

1. Mahidhara R, Billi ar TR. Apoptosis in sepsis. Crit Care Med 2000; 28 (Suppl 4): N105– N113.

2. Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunni on RE et al. Septic shock in humans. Advances in the understanding of pathogenesis, cardi ovascular dysfuncti on, and therapy. Ann Intern Med 1990; 113(3): 227– 242.

3. Bone RC, Sprung CL, Sibbald WJ. Definiti ons for sepsis and organ failure. Crit Care Med 1992; 20(6): 724– 726.

4. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med 1996; 24(7): 1125– 1128.

5. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in pati ents with the sepsis syndrome. Ann Intern Med 1993; 119(8): 771– 778.

6. Marano MA, Fong Y, Moldawer LL, Wei H, Calvano SE, Tracey KJ et al. Serum cachectin/ tumor necrosis factor in critically ill pati ents with burns correlates with infecti on and mortality. Surg Gynecol Obstet 1990; 170(1): 32– 38.

7. Kna us WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of dise ase classificati on system. Crit Care Med 1985; 13(10): 818– 829.

8. Kna us WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG et al. The APACHE III prognostic system. Risk predicti on of hospital mortality for critically ill hospitalized adults. Chest 1991; 100(6): 1619– 1636.

9. Vincent JL, Moreno R, Takala J, Willatts S,de Mendonca A, Bruining H et al. The SOFA (Sepsis‑related Organ Failure Assessment) score to describe organ dysfuncti on/ failure. On behalf of the Working Gro up on Sepsis- Related Problems of the Europe an Soci ety of Intensive Care Medicine. Intensive Care Med 1996; 22(7): 707– 710.

10. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM et al. Use of the SOFA score to assess the incidence of organ dysfuncti on/ failure in intensive care units: results of a multicenter, prospective study. Working gro up on „sepsis‑related problems“ of the Europe an Soci ety of Intensive Care Medicine. Crit Care Med 1998; 26(11): 1793– 1800.

11. Moreno R, Vincent JL, Matos R, de Mendonca A, Cantraine F, Thijs L et al. The use of maximum SOFA score to qu antify organ dysfuncti on/ failure in intensive care. Results of a prospective, multicentre study. Working Gro up on Sepsis related Problems of the ESICM. Intensive Care Med 1999; 25(7): 686– 696.

12. Janssens U, Graf C, Graf J, Radke PW, Königs B, Koch KC et al. Evalu ati on of the SOFA score: a single‑center experi ence of a medical intensive care unit in 303 consecutive pati ents with predominantly cardi ovascular disorders. Sequenti al Organ Failure Assessment. Intensive Care Med 2000; 26(8): 1037– 1045.

13. Bednarik J, Vondracek P, Dusek L, Moravcova E, Cundrle I. Risk factors for critical illness polyne uromyopathy. J Ne urol 2005; 252(3): 343– 351.

14. Bolton CF, Yo ung GB, Zochodne DW. The ne urological complicati ons of sepsis. Ann Ne urol 1993; 33(1): 94– 100.

15. Chadwick J, Mann WN. Epidemics, Bo ok III. The medical works of Hippocrates. Oxford: Blackwell Sci entific Publicati ons 1950.

16. Eggers V, Schilling A, Kox WJ, Spi es C. Septic encephalopathy. Di agnosis und therapy. Anaesthesist 2003; 52(4): 294– 303.

17. Eidelman LA, Putterman D, Putterman C, Sprung CL. The spectrum of septic encephalopathy. Definiti ons, eti ologi es, and mortaliti es. JAMA 1996; 275(6): 470– 473.

18. Yo ung GB, Bolton CF, Austin TW, Archibald YM, Gonder J, Wells GA. The encephalopathy associ ated with septicillness. Clin Invest Med 1990; 13(6): 297– 304.

19. Davi es NW, Shari ef MK, Howard RS. Infecti on‑associ ated encephalopathi es: their investigati on, di agnosis, and tre atment. J Ne urol 2006; 253(7): 833– 845.

20. Yo ung GB, Bolton CF, Archibald YM, Austin TW, Wells GA. The electroencephalogram in sepsis‑associ ated encephalopathy. J Clin Ne urophysi ol 1992; 9(1): 145– 152.

21. Za uner C, Gendo A, Kramer L, Funk GC, Ba uer E, Schenk P et al. Impaired subcortical and cortical sensory evoked potenti al pathways in septic pati ents. Crit Care Med 2002; 30(5): 1136– 1139.

22. Bednařík J. Deliri um: nová výzva pro ne urologii? Cesk Slov Ne urol N 2006; 69/ 102(1): 18– 26.

23. Kostalova M, Bednarik J, Haluzova A, Badurova R, Vohanka S, Urbanek I. Deliri um in stroke pati ents: epidemi ology and risk factors. J Ne urol 2007; 254 (Suppl 3): 115.

24. Papadopo ulos MC, Lamb FJ, Moss RF, Davi es DC, Tighe D, Bennett ED. Faecal peritonitis ca uses oedema and ne uronal injury in pig cerebral cortex. Clin Sci (Lond) 1999; 96(5): 461– 466.

25. Dantzer R. Cytokine‑induced sickness behavi or: mechanisms and implicati ons. Ann N Y Acad Sci 2001; 933: 222– 234.

26. Dafny N, Pri eto- Gomez B, Dong WQ, Reyes- Vazquez C. Interferon modulates ne uronal activity recorded from the hypothalamus, thalamus, hippocampus, amygdala and the somatosensory cortex. Brain Res 1996; 734(1– 2): 269– 274.

27. Huynh HK, Dorovini‑Zis K. Effects of interferon- gamma on primary cultures of human brain microvessel endotheli al cells. Am J Pathol 1993; 142(4): 1265– 1278.

28. Papadopo ulos MC, Davi es DC, Moss RF, Tighe D, Bennett ED. Pathophysi ology of septic encephalopathy: a revi ew. Crit Care Med 2000; 28(8): 3019– 3024.

29. Ino uye SK, Viscoli CM, Horwitz RI, Hurst LD, Tinetti ME. A predictive model for deliri um in hospitalized elderly medical pati ents based on admissi on characteristics. Ann Intern Med 1993; 119(6): 474– 481.

30. Marcantoni o ER, Goldman L, Mangi one CM, Ludwig LE, Muraca B, Hasla uer CM et al. A clinical predicti on rule for deliri um after elective noncardi ac surgery. JAMA 1994; 271(2): 134– 139.

31. Eli e M, Cole MG, Prime a u FJ, Bellavance F. Deliri um risk factors in elderly hospitalized pati ents. J Gen Intern Med 1998; 13(3): 204– 212.

32. Ino uye SK. Deliri um in older persons. N Engl J Med 2006: 354(11): 1157– 1165.

33. Marcantoni o ER, Rudolph JL, Culley D,Crosby G, Alsop D, Ino uye SK. Serum bi omarkers for deliri um. J Gerontol A Bi ol Sci Med Sci 2006; 61(12): 1281– 1286.

34. Han L, McCusker J, Cole M, Abrahamowicz M, Prime a u F, Eli e M. Use of medicati ons with anticholinergic effect predicts clinical severity of deliri um symptoms in older medical inpati ents. Arch Intern Med 2001; 161(8): 1099– 1105.

35. Flacker JM, Lipsitz LA. Serum anticholinergic activity changes with acute illness in elderly medical pati ents. J Gerontol A Bi ol Sci Med Sci 1999; 54(1): M12– M16.

36. Flacker JM, Lipsitz LA. Ne ural mechanisms of deliri um: current hypotheses and evolving concepts. J Gerontol A Bi ol Sci Med Sci 1999; 54(6): B239– B246.

37. Visvanathan K, Sundararajan V, Pugach P, Zabriski e JB. Postoperative cognitive decline: associ ati on with preoperative tumor necrosis factor‑alpha levels. J Am Geri atr Soc 2003; 51(11): 1673– 1674.

38. Anzueto A. Muscle dysfuncti on in the intensive care unit. Clin Chest Med 1999; 20(2): 435– 452.

39. Hopkins IJ. A new syndrome: poli omyelitis‑like illness associ ated with acute asthma in childho od. Aust Paedi atr J 1974; 10(5): 273– 276.

40. Bednařík J, Vondráček P. Ne uromuskulární komplikace kritického stavu. Ne urol pro praxi 2001; 2: 67– 72.

41. Ambler Z. Diferenci ální di agnóza svalové slabosti u kriticky nemocných. Ne urol pro praxi 2001; 2: 63– 66.

42. Bizzarri- Schmid ND, Desai SP. Prolonged ne uromuscular blockade with atracuri um. Can Anaesth Soc J 1986; 33: 209– 212.

43. Pascuzzi RM. Evalu ati on and tre atment of pati ents with ne uromuscular juncti on disorders. In: American Academy of Ne urology (ed). 2000 Syllabi- on- CD- ROM. Northfi eld: Marathon Multimedi a 2000.

44. Adamus M, Bělohlávek R. Automatické dávkování svalových relaxanci í u náročných ne urochirurgických výkonů. Cesk Slov Ne urol N 2006; 69/ 102(6): 447– 451.

45. Bednarik J. Critical illness polyne uropathy, myopathy or polyne uromyopathy: future directi ons. Int J Intens Care 2005; 12(1): 38– 46.

46. Mertens HG. Di e dissemini erte ne uropathi e nach koma. Nervenarzt 1961; 32: 71– 79.

47. Henderson B, Koepke GH, Feller I. Peripheral polyne uropathy among pati ents with burns. Arch Phys Med Rehabil 1971; 52(4): 149– 151.

48. Bolton CF, Brown JD, Sibbald WJ. The electrophysi ological investigati on of respiratory paralysis in critically ill pati ents. Ne urology 1983; 33 (Suppl 2): 186.

49. Roelofs RI, Cerra F, Bi elka N. Prolonged respiratory insuffici ency due to acute motor ne uropathy: a new syndrome. Ne urology 1983; 33 (Suppl 2): 240.

50. Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ. Polyne uropathy in critically ill pati ents. J Ne urol Ne urosurg Psychi atry 1984; 47(11): 1223– 1231.

51. Hund EF. Ne uromuscular complicati ons in the ICU: the spectrum of critical illness‑related conditi ons ca using muscular we akness and we aning failure. J Ne urol Sci 1996; 136(1– 2): 10– 16.

52. Lopez Messa JB, García A. Acute polyne uropathy in critically ill pati ents. Intensive Care Med 1990; 16(3): 159– 162.

53. Witt NJ, Zochodne DW, Bolton CF, Grand‘Maison F, Wells G, Yo ung GB et al. Peripheral nerve functi on in sepsis and multiple organ failure. Chest 1991; 99(1): 176– 184.

54. Zochodne DW, Bolton CF, Wells GA, Gilbert JJ, Hahn AF, Brown JD et al. Critical illness polyne uropathy: a complicati on of sepsis and multiple organ failure. Brain 1987; 110 (Pt 4): 819– 841.

55. Vondráček P, Bednařík J. Polyne uromyopati e kriticky nemocných – pilotní studi e. Cesk Slov Ne urol N 2000; 69/ 96(4): 226– 233.

56. Tran DD, Groeneveld AB, van der Me ulen J, Na uta JJ, Strack van Schijndel RJ, Thijs LG. Age, chronic dise ase, sepsis, organ system failure, and mortality in a medical intensive care unit. Crit Care Med 1990; 18(5): 474– 479.

57. Petersen B, Schneider C, Strassburg HM, Schrod L. Critical illness ne uropathy in pedi atric intensive care pati ents. Pedi atr Ne urol 1999; 21(4): 749– 753.

58. Vondracek P, Bednarik J. Clinical and electrophysi ological findings and long‑term o utcomes in paedi atric pati ents with critical illness polyne uromyopathy. Eur J Paedi atr Ne urol 2006, 10(4): 176– 181.

59. De Jonghe B, Sharshar T, Lefa uche ur JP, Authi er FJ, Durand- Zaleski I, Bo ussarsar M et al. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002; 288(22): 2859– 2867.

60. Wilmshurst PT, Tre acher DF, Lantos PL, Wiles CM. Critical illness polyne uropathy following severe hyperpyrexi a. QJM 1995; 88(5): 351– 355.

61. Gla user MP, Zanetti G, Ba umgartner JD, Cohen J. Septic shock: pathogenesis. Lancet 1991; 338(8769): 732– 736.

62. Low PA, Tuck RR, Take uchi M. Nerve microenvironment in di abetic polyne uropathy. In: Dyck PJ, Thomas PK, Asbury AK et al (eds). Di abetic Ne uropathy. Philadelphi a: WB Sa unders 1987: 268– 277.

63. Hund EF, Fogel W, Kri eger D, DeGeorgi a M, Hacke W. Critical illness polyne uropathy: clinical findings and o utcomes of a frequent ca use of ne uromuscular we aning failure. Crit Care Med 1996; 24(8): 1282– 1283.

64. Gorson KC, Ropper AH. Acute respiratory failure ne uropathy: a vari ant of critical illness polyne uropathy. Crit Care Med 1993; 21(2): 267– 271.

65. Wijdicks EF, Litchy WJ, Harrison BA, Gracey DR. The clinical spectrum of critical illness polyne uropathy. Mayo Clin Proc 1994; 69(10): 955– 959.

66. Co akley JH, Nagendran K, Yarwo od GD, Honavar M, Hinds CJ. Patterns of ne urophysi ological abnormality in prolonged critical illness. Intensive Care Med 1998; 24(8): 801– 817.

67. Schwarz J, Planck J, Bri egel J, Stra ube A. Single‑fiber electromyography, nerve conducti on studi es, and conventi onal electromyography in pati ents with critical- illness polyne uropathy: evidence for a lesi on of terminal motor axons. Muscle Nerve 1997; 20(6): 696– 701.

68. Bednarik J, Vondracek P, Kadanka Z.Electrophysi ological differenti ati on between critical illness ne uropathy and myopathy: prospective case seri es study. Ne urology 2000; 54 (Suppl 3): A: 377.

69. Rich MM, Pinter MJ, Kraner SD, Barchi RL. Loss of electrical excitability in an animal model of acute qu adriplegic myopathy. Ann Ne urol 1998; 43(2): 171– 179.

70. Rich MM, Teener JW, Raps EC, Schotland DL, Bird SJ. Muscle is electrically inexcitable in acute qu adriplegic myopathy. Ne urology 1996; 46(3): 731– 736.

71. Rich MM, Bird SJ, Raps EC, McCluskey LF, Teener JW. Direct muscle stimulati on in acute qu adriplegic myopathy. Muscle Nerve 1997; 20(6): 665– 673.

72. Bednařík J, Vondráček P, Lukáš Z, Dvořák K,Moravcová E, Adamová B et al. Polyne uromyopati e kritického stavu. I. Di agnostika. Cesk Slov Ne urol N 2002; 65/ 98(4): 386– 394.

73. Bednarik J, Lukas Z, Vondracek P. Critical illness polyne uromyopathy: the electrophysi ological components of a complex entity. Intensive Care Med 2003; 29(9): 1505– 1514.

74. Zifko UA. Long‑term o utcome of critical illness polyne uropathy. Muscle Nerve 2000; 23 (Suppl 9): S49– S52.

75. Abraham E, Wunderink R, Silverman H,Perl TM, Nasraway S, Levy H et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in pati ents with sepsis syndrome. A randomized, controlled, do uble- blind, multicenter clinical tri al. TNF‑alpha MAb Sepsis Study Gro up. JAMA 1995; 273(12): 934– 941.

76. Fisher CJ jr, Dhaina ut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ et al. Recombinant human interle ukin 1 receptor antagonist in the tre atment of pati ents with sepsis syndrome. Results from a randomized, do uble- blind, placebo- controlled tri al. Phase III rhIL‑1ra Sepsis Syndrome Study Gro up. JAMA 1994; 271(23): 1836– 1843.

77. Zi egler EJ, Fisher CJ Jr, Sprung CL, Stra ube RC, Sadoff JC, Fo ulke GE et al.Tre atment of gram- negative bacteremi a and septic shock with HA- 1A human monoclonal antibody against endotoxin. A randomized, do uble- blind, placebo- controlled tri al. The HA- 1A Sepsis Study Gro up. N Engl J Med 1991; 324(7): 429– 436.

78. Döcke WD, Randow F, Syrbe U, Kra usch D,Asadullah K, Reinke P et al. Monocyte de activati on in septic pati ents: restorati on by IFN- gamma tre atment. Nat Med 1997; 3(6): 678– 681.

79. La upland KB, Kirkpatrick AW, Delaney A.Polyclonal intraveno us immunoglobulin for the tre atment of severe sepsis and septic shock in critically ill adults: A systematic revi ew and meta‑analysis. Crit Care Med 2007 Oct 23. [Epub ahe ad of print].

80. MacFarlane IA, Rosenthal FD. Severe myopathy after status asthmaticus. Lancet 1977; 2(8038): 615– 620.

81. De Smet Y, Jaminet M, Jaeger U, Jacob J,Ne uray H, Ha us G et al. Acute corticostero id myopathy following status asthmaticus. Rev Ne urol (Paris) 1991; 147(10): 682– 685.

82. Do uglass JA, Tuxen DV, Horne M, Scheinkestel CD, Weinmann M, Czarny D et al. Myopathy in severe asthma. Am Rev Respir Dis 1992; 146(2): 517– 519.

83. Hirano M, Ott BR, Raps EC, Minetti C, Lennihan L, Libbey NP et al. Acute qu adriplegic myopathy: a complicati on of tre atment with stero ids, nondepolarizing blocking agents, or both. Ne urology 1992; 42(11): 2082– 2087.

84. Lacomis D, Smith TW, Chad DA. Acute myopathy and ne uropathy in status asthmaticus: case report and literature revi ew. Muscle Nerve 1993; 16(1): 84– 90.

85. Shapiro JM, Condos R, Cole RP. Myopathy in status asthmaticus: relati on to ne uromuscular blockade and corticostero id administrati on. J Intensive Care Med 1993; 8: 144– 152.

86. Barohn RJ, Jackson CE, Rogers SJ, Ridings LW, McVey AL. Prolonged paralysis due to non‑depolarizing ne uromuscular blocking agents and corticostero ids. Muscle Nerve 1994; 17(6): 647– 654.

87. Van Marle W, Wo ods KL. Acute hydrocortisone myopathy. Br Med J 1980; 281(6235): 271– 272.

88. Helliwell TR, Co akley JH, Wagenmakers AJ, Griffiths RD, Campbell IT, Green CJ et al. Necrotizing myopathy of critically- ill pati ents. J Pathol 1991; 164(4): 307– 314.

89. Ramsay DA, Zochodne DW, Robertson DM, Nag S, Ludwin SK. A syndrome of acute severe muscle necrosis in intensive care unit pati ents. J Ne uropathol Exp Ne urol 1993; 52(4): 387– 398.

90. Zochodne DW, Ramsay DA, Saly V, Shelley S, Moffatt S. Acute necrotizing myopathy of intensive care: electrophysi ological studi es. Muscle Nerve 1994; 17(3): 285– 292.

91. al- Lozi MT, Pestronk A, Yee WC, Flairs N,Co oper J. Rapidly evolving myopathy with myosin defici ent muscle fibers. Ann Ne urol 1994; 35(3): 273– 279.

92. Sher JH, Shafiq SA, Schutta HS. Acute myopathy with selective lysis of myosin filaments. Ne urology 1979; 29(1): 100– 106.

93. Gorson KC, Ropper AH. Generalized paralysis in the intensive care unit: emphasis on the complicati ons of ne uromuscular blocking agents and corticostero ids. J Int Care Med 1996; 11: 219– 231.

94. Hund EF. Myopathy in critically ill pati ents. Crit Care Med 1999; 27: 2544– 2547.

95. Deconinck N, Van Parijs V, Beckers--Ble ukx G, Van den Bergh P. Critical illness myopathy unrelated to corticostero ids or ne uromuscular blocking agents. Ne uromusc Disord 1998; 8: 186– 192.

96. Helliwell TR, Wilkinson A, Griffiths RD, McClelland P, Palmer TE, Bone JM. Muscle fibre atrophy in critically ill pati ents is associ ated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin. Ne uropathol Appl Ne urobi ol 1998; 24: 507– 517.

97. De Letter MA, van Do orn PA, Savelko ul HF, Laman JD, Schmitz PI, Op de Co ul AA et al. Critical illness polyne uropathy and myopathy (CIPNM): evidence for local immune activati on by cytokine- expressi on in the muscle tissue. J Ne uro immunol 2000; 106: 206– 213.

98. Lacomis D, Petrella JT, Gi uli ani MJ. Ca uses of ne uromuscular we akness inthe intensive care unit: a study of ninety- two pati ents. Muscle Nerve 1998; 21: 610– 617.

99. Latronico N, Fenzi F, Recupero D, Gu arneri B, Tomelleri G, Tonin P et al. Critical illness myopathy and ne uropathy. Lancet 1996; 347: 1579– 1582.

100. Ruff RL. Acute illness myopathy. Ne urology 1996; 46: 600– 601.

101. DuBo is DC, Almon RR. A possible role for glucocortico ids in denervati on atrophy. Muscle Nerve 1981; 4: 370– 373.

102. Ro ule a u G, Karpati G, Carpenter S, Soza M, Prescott S, Holland P. Glucocortico id excess induces preferenti al depleti on of myosin in denervated skeletal muscle fibers. Muscle Nerve 1987; 10: 428– 438.

103. Wing SS, Goldberg AL. Glucocortico ids activate the ATP- ubiquitin‑dependent proteolytic system in skeletal muscle during fasting. Am J Physi ol 1993; 264: 668– 676.

104. Showalter CJ, Engel AG. Acute qu adriplegic myopathy: analysis of myosin isoforms and evidence of calpain‑medi ated proteolysis. Muscle Nerve 1997; 20: 316– 322.

105. Raps EC, Bird SJ, Hansen- Flaschen JH. Prolonged muscle we akness after ne uromuscular blockade in the intensive care unit. Crit Care Clinics 1994; 10: 799– 813.

106. Waclawik AJ, Sufit RL, Beinlich BR, Schutta HS. Acute myopathy with selective degenerati on of myosin filaments following status asthmaticus tre ated with methylprednisolone and vecuroni um. Ne uromusc Disord 1992; 2: 19– 26.

107. Kupfer Y, Okrent DG, Twersky RA, Tessler S. Disuse atrophy in a ventilated pati ent with status asthmaticus receiving ne uromuscular blockade. Crit Care Med 1987; 15: 795– 796.

108. Meyer KC, Pri elipp RC, Grossman JE, Co ursin DB. Prolonged we akness after infusi on of atracuri um in two intensive care unit pati ents. Anesth Analg 1994; 78: 772– 774.

109. Bolton CF. Sepsis and the systemic inflammatory response syndrome: Ne uromuscular manifestati ons. Crit Care Med 1996; 24: 1408– 1416.

110. Clowes GHA, George BC, Villee CA. Muscle proteolysis induced by a circulating peptide in pati ents with sepsis or tra uma. N Engl J Med 1983; 308: 545– 552.

111. Apte- Kakade F. Rehabilitati on of pati ents with qu adriparesis after tre atment of status asthmaticus with ne uromuscular blocking agents and high dose corticostero ids. Arch Phys Med Rehabil 1991; 72: 1024– 1028.

112. Sitwell LD, Weinshenker BG, Monpetit V, Reid D. Complete ophthalmoplegi a as a complicati on of acute corticostero id and pancuroni um associ ated myopathy. Ne urology 1991; 41: 921– 922.

113. Campellone JV, Lacomis D, Kramer DJ, van Cott AC, Gi uli ani MJ. Acute myopathy after liver transplantati on. Ne urology 1998; 50: 46– 53.

114. Lacomis D, Gi uli ani MJ, Van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Ne urol 1996; 40: 645– 654.

115. Yarom R, Sphira Y. Myosin degenerati on in a congenital myopathy. Arch Ne urol 1977; 34: 114– 115.

116. Bazzi P, Moggi o M, Prelle A, Sci acco M,Messina S, Barbi eri S et al. Critically ill pati ents: immunological evidence of inflammati on in muscle bi opsy. Clin Ne uropathol 1999; 18:23– 30.

117. Lacomis D, Zochodne DW, Bird SJ. Critical illness myopathy. Muscle Nerve 2000; 23: 1785– 1788.

118. Co akley J. Sho uld ICU pati ents receive muscle relaxants? Schweiz Med Wochenschr 1996; 126: 1644– 1648.

119. Op de Co ul AAW, Lambregts PCLA, Koeman J, van Puyenbroek PJ, Ter Laak HJ, Gabreels- Festen AA. Ne uromuscular complicati ons in pati ents give Pavulon (pancuroni um bromide) during artifici al ventilati on. Clin Ne urol Ne urosurg 1985; 87: 17– 22.

120. Op de Co ul AA, Verhe ul GA, Leyten AC, Schellens RL, Teepen JL. Critical illness polyne uromyopathy after artifici al respirati on. Clin Ne urol Ne urosurg 1991; 93: 27– 33.

121. Latronico N, Bertolini G, Gu arneri B, Botteri M, Peli E, Andreoletti S et al. Simplifi ed electrophysi ological evalu ati on of peripheral nerves in critically ill pati ents: the Itali an multi- centre CRIMYNE study. Crit Care 2007; 11: R11.

122. Trojaborg W, Weimer LH, Hays AP. Electrophysi ologic studi es in critical illness associ ated we akness: myopathy or ne uropathy – a re appraisal. Clin Ne urophysi ol 2001; 112: 1568– 1593.

123. Latronico N. Ne uromuscular alterati ons in the critically ill pati ent: critical illness myopathy, critical illness ne uropathy, or both? Intensive Care Med 2003; 29: 1411– 1413.

124. De Letter MA, Schmitz PI, Visser LH, Verhe ul FA, Schellens RL, Op de Co ul DA et al. Risk factors for the development of polyne uropathy and myopathy in critically ill pati ents. Crit Care Med 2001; 29: 2281– 2286.