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A Neuromuscular Approach to Statin-Related Myotoxicity

Published online by Cambridge University Press:  02 December 2014

Steven K. Baker
Affiliation:
The Department of Medicine, Neuromuscular Disease Clinic, McMaster University, Hamilton, Ontario, Canada
Imtiaz A. Samjoo
Affiliation:
The Department of Medicine, Neuromuscular Disease Clinic, McMaster University, Hamilton, Ontario, Canada
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Abstract

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Approximately 95% of statin-treated patients tolerate this form of cholesterol management without any adverse effects. However, given their efficacy in reducing low density lipoproteins and cardiovascular events large numbers of patients are selected for statin therapy. Therefore muscle complications are, in fact, quite common. Limited understanding of the underlying pathophysiology has hampered physicians' ability to identify patients at risk for developing statin myotoxicity. A growing number of published case reports/series have implicated statins in the exacerbation of both acquired and genetic myopathies. A clinical management algorithm is presented which outlines a variety of co-morbidities which can potentiate the adverse effects of statins on muscle. In addition, a rational approach to the selection of those patients most likely to benefit from skeletal muscle biopsy is discussed. Ongoing work will define the extent to which statin-intolerant patients represent carriers of recessive metabolic myopathies or pre-symptomatic acquired myopathies. The expanding importance of pharmacogenomics will undoubtedly be realized in the field of statin myopathy research within the next few years. Such critical information is needed to establish more definitive management and diagnostic strategies.

Résumé:

RÉSUMÉ:

Près de 95% des patients qui reçoivent une statine tolèrent bien ce traitement hypocholestérolémiant, sans réactions indésirables. Cependant, les complications musculaires sont relativement fréquentes parce qu'un grand nombre de patients reçoivent ce traitement à cause de son efficacité pour abaisser le taux de lipoprotéines de faible densité et pour diminuer l'incidence d'événements cardiovasculaires. Comme on connaîmal leur pathophysiologie, il est difficile d'identifier les patients à risque de développer une myotoxicité sous statine. Il y a de plus en plus de cas ou de séries de cas rapportés qui impliquent les statines dans l'exacerbation de myopathies tant acquises que génétiques. Nous présentons un algorithme concernant la conduite à tenir le cas échéant, qui énumère différentes co-morbidités pouvant potentialiser les effets indésirables des statines sur le muscle. De plus, nous discutons d'une démarche rationnelle pour identifier les patients qui sont les plus susceptibles de bénéficier d'une biopsie musculaire. Les travaux en cours permettront de défmir dans quelle mesure les patients qui sont intolérants aux statines sont porteurs de myopathies métaboliques récessives ou de myopathies acquises pré-symptomatiques. L'importance croissante de la pharmacogénomique jouera sans doute un rôle dans le domaine de la recherche sur la myopathie due aux statines dans les prochaines années. Cette information est d'une grande importance pour établir des stratégies de diagnostic et de traitement.

Type
Review Article
Copyright
Copyright © The Canadian Journal of Neurological 2008

References

1. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001; 285: 2486–97.CrossRefGoogle Scholar
2. Mitka, M. Expanding statin use to help more at-risk patients is causing financial heartburn. JAMA. 2003; 290: 2243–5.Google ScholarPubMed
3. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344: 1383–9.Google Scholar
4. Sacks, FM, Pfeffer, MA, Moye, LA, Rouleau, JL, Rutherford, JD, Cole, TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators. N Engl J Med. 1996; 335: 1001–9.CrossRefGoogle ScholarPubMed
5. Shepherd, J, Cobbe, SM, Ford, I, Isles, CG, Lorimer, AR, MacFarlane, PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995; 333: 1301–7.CrossRefGoogle ScholarPubMed
6. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 722.Google Scholar
7. Nissen, SE, Nicholls, SJ, Sipahi, I, Libby, P, Raichlen, JS, Ballantyne, CM, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006; 295: 155665.CrossRefGoogle Scholar
8. Amarenco, P, Bogousslavsky, J, Callahan, A, 3rd, Goldstein, LB, Hennerici, M, Rudolph, AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006; 355: 54959.Google ScholarPubMed
9. Rashid, S. Should cholesterol-lowering medications be available in Canada without a prescription? Can J Cardiol. 2007; 23: 18993.CrossRefGoogle ScholarPubMed
10. Vladutiu, GD, Simmons, Z, Isackson, PJ, Tarnopolsky, M, Peltier, WL, Barboi, AC, et al. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve. 2006; 34: 15362.CrossRefGoogle ScholarPubMed
11. Corsini, A, Maggi, FM, Catapano, AL. Pharmacology of competitive inhibitors of HMG-CoA reductase. Pharmacol Res. 1995; 31: 927.CrossRefGoogle ScholarPubMed
12. Sabia, H, Prasad, P, Smith, HT, Stoltz, RR, Rothenberg, P. Safety, tolerability, and pharmacokinetics of an extended-release formulation of fluvastatin administered once daily to patients with primary hypercholesterolemia. J Cardiovasc Pharmacol. 2001; 37: 50211.CrossRefGoogle ScholarPubMed
13. Corsini, A, Bellosta, S, Baetta, R, Fumagalli, R, Paoletti, R, Bernini, F. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther. 1999; 84: 41328.CrossRefGoogle ScholarPubMed
14. Kitazawa, E, Tamura, N, Iwabuchi, H, Uchiyama, M, Muramatsu, S, Takahagi, H, et al. Biotransformation of pravastatin sodium (I). Mechanisms of enzymic transformation and epimerization of an allylic hydroxy group of pravastatin sodium. Biochem Biophys Res Commun. 1993; 192: 597602.CrossRefGoogle ScholarPubMed
15. White, CM. A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin. J Clin Pharmacol. 2002; 42: 96370.CrossRefGoogle ScholarPubMed
16. Ejendal, KF, Hrycyna, CA. Differential sensitivities of the human ATP-binding cassette transporters ABCG2 and P-glycoprotein to cyclosporin A. Mol Pharmacol. 2005; 67: 90211.CrossRefGoogle ScholarPubMed
17. Kajosaari, LI, Niemi, M, Neuvonen, M, Laitila, J, Neuvonen, PJ, Backman, JT. Cyclosporine markedly raises the plasma concentrations of repaglinide. Clin Pharmacol Ther. 2005; 78: 38899.CrossRefGoogle ScholarPubMed
18. Shitara, Y, Itoh, T, Sato, H, Li, AP, Sugiyama, Y. Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. J Pharmacol Exp Ther. 2003; 304: 6106.CrossRefGoogle ScholarPubMed
19. Hsiang, B, Zhu, Y, Wang, Z, Wu, Y, Sasseville, V, Yang, WP, et al. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999; 274: 371618.CrossRefGoogle ScholarPubMed
20. Brown, CD, Windass, AS, Bleasby, K, Lauffart, B. Rosuvastatin is a high affinity substrate of hepatic organic anion transporter OATP-C [abstr]. Atheroscler Suppl. 2001; 2: 90.CrossRefGoogle Scholar
21. Pasternak, RC, Smith, SC Jr., Bairey-Merz, CN, Grundy, SM, Cleeman, JI, Lenfant, C. ACC/AHA/NHLBI Clinical advisory on the use and safety of statins. Stroke. 2002; 33: 233741.Google ScholarPubMed
22. Jacobson, TA. Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol. 2004; 94: 11406.CrossRefGoogle ScholarPubMed
23. Baker, SK, Goodwin, S, Sur, M, Tarnopolsky, MA. Cytoskeletal myotoxicity from simvastatin and colchicine. Muscle Nerve. 2004; 30: 799802.CrossRefGoogle ScholarPubMed
24. Zuccaro, P, Mombelli, G, Calabresi, L, Baldassarre, D, Palmi, I, Sirtori, CR. Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin. Pharmacol Res. 2007.Google Scholar
25. Staffa, JA, Chang, J, Green, L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med. 2002; 346: 53940.CrossRefGoogle ScholarPubMed
26. Chang, JT, Staffa, JA, Parks, M, Green, L. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol Drug Saf. 2004; 13: 41726.CrossRefGoogle ScholarPubMed
27. Backman, JT, Kyrklund, C, Kivisto, KT, Wang, JS, Neuvonen, PJ. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther. 2000; 68: 1229.CrossRefGoogle ScholarPubMed
28. Bergman, AJ, Murphy, G, Burke, J, Zhao, JJ, Valesky, R, Liu, L, et al. Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. J Clin Pharmacol. 2004; 44: 105462.CrossRefGoogle Scholar
29. Martin, PD, Dane, AL, Schneck, DW, Warwick, MJ. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther. 2003; 25: 45971.CrossRefGoogle ScholarPubMed
30. Graham, DJ, Staffa, JA, Shatin, D, Andrade, SE, Schech, SD, La Grenade, L, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004; 292: 258590.CrossRefGoogle ScholarPubMed
31. Jacob, SS, Jacob, S, Williams, C, Deeg, MA. Simvastatin, fenofibrate, and rhabdomyolysis. Diabetes Care. 2005; 28: 1258.CrossRefGoogle ScholarPubMed
32. Jones, PH, Davidson, MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol. 2005; 95: 1202.CrossRefGoogle ScholarPubMed
33. Melli, G, Chaudhry, V, Cornblath, DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore). 2005; 84: 37785.CrossRefGoogle ScholarPubMed
34. Tokinaga, K, Oeda, T, Suzuki, Y, Matsushima, Y. HMG-CoA reductase inhibitors (statins) might cause high elevations of creatine phosphokinase (CK) in patients with unnoticed hypothyroidism. Endocr J. 2006; 53: 4015.CrossRefGoogle ScholarPubMed
35. Shek, A, Ferrill, MJ. Statin-fibrate combination therapy. Ann Pharmacother. 2001; 35: 90817.CrossRefGoogle ScholarPubMed
36. Choi, JW, Choi, HS. The regulatory effects of thyroid hormone on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Endocr Res. 2000; 26: 121.CrossRefGoogle ScholarPubMed
37. Hekimsoy, Z, Oktem, IK. Serum creatine kinase levels in overt and subclinical hypothyroidism. Endocr Res. 2005; 31: 1715.CrossRefGoogle ScholarPubMed
38. Kisch, E, Segall, HS. Interaction between simvastatin and L-thyroxine. Ann Intern Med. 2005; 143: 547.CrossRefGoogle ScholarPubMed
39. Sinclair, C, Gilchrist, JM, Hennessey, JV, Kandula, M. Muscle carnitine in hypo- and hyperthyroidism. Muscle Nerve. 2005; 32: 3579.CrossRefGoogle ScholarPubMed
40. Galland, S, Georges, B, Le Borgne, F, Conductier, G, Dias, JV, Demarquoy, J. Thyroid hormone controls carnitine status through modifications of gamma-butyrobetaine hydroxylase activity and gene expression. Cell Mol Life Sci. 2002; 59: 5405.CrossRefGoogle ScholarPubMed
41. Thompson, PD, Zmuda, JM, Domalik, LJ, Zimet, RJ, Staggers, J, Guyton, JR. Lovastatin increases exercise-induced skeletal muscle injury. Metabolism. 1997; 46: 120610.CrossRefGoogle ScholarPubMed
42. Sinzinger, H, O’Grady, J. Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems. Br J Clin Pharmacol. 2004; 57: 5258.CrossRefGoogle ScholarPubMed
43. Clarkson, PM, Kearns, AK, Rouzier, P, Rubin, R, Thompson, PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med Sci Sports Exerc. 2006; 38: 6237.CrossRefGoogle ScholarPubMed
44. Graves, JE, Clarkson, PM, Litchfield, P, Kirwan, JP, Norton, JP. Serum creatine kinase activity following repeated bouts of isometric exercise with different muscle groups. Eur J Appl Physiol Occup Physiol. 1987; 56: 65761.CrossRefGoogle ScholarPubMed
45. Clarkson, PM, Byrnes, WC, Gillisson, E, Harper, E. Adaptation to exercise-induced muscle damage. Clin Sci (Lond). 1987; 73: 3836.CrossRefGoogle ScholarPubMed
46. Skenderi, KP, Kavouras, SA, Anastasiou, CA, Yiannakouris, N, Matalas, AL. Exertional Rhabdomyolysis during a 246-km continuous running race. Med Sci Sports Exerc. 2006; 38: 10547.CrossRefGoogle ScholarPubMed
47. Neumayr, G, Pfister, R, Hoertnagl, H, Mitterbauer, G, Getzner, W, Ulmer, H, et al. The effect of marathon cycling on renal function. Int J Sports Med. 2003; 24: 1317.CrossRefGoogle ScholarPubMed
48. Armstrong, RB. Muscle damage and endurance events. Sports Med. 1986; 3: 37081.CrossRefGoogle ScholarPubMed
49. Schwane, JA, Buckley, RT, Dipaolo, DP, Atkinson, MA, Shepherd, JR. Plasma creatine kinase responses of 18- to 30-yr-old African-American men to eccentric exercise. Med Sci Sports Exerc. 2000; 32: 3708.CrossRefGoogle ScholarPubMed
50. Streichenberger, N, Meyronet, D, Fiere, V, Pellissier, JF, Petiot, P. Focal myositis associated with S-1 radiculopathy: report of two cases. Muscle Nerve. 2004; 29: 4436.CrossRefGoogle ScholarPubMed
51. Lima, AF, Evangelista, T, de Carvalho, M. Increased creatine kinase and spontaneous activity on electromyography, in amyotrophic lateral sclerosis. Electromyogr Clin Neurophysiol. 2003; 43: 18992.Google ScholarPubMed
52. Lee, E, Ryan, S, Birmingham, B, Zalikowski, J, March, R, Ambrose, H, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005; 78: 33041.CrossRefGoogle ScholarPubMed
53. Fernandez, C, de Paula, AM, Figarella-Branger, D, Krahn, M, Giorgi, R, Chabrol, B, et al. Diagnostic evaluation of clinically normal subjects with chronic hyperCKemia. Neurology. 2006; 66: 15857.CrossRefGoogle ScholarPubMed
54. Finsterer, J, Neuhuber, W, Mittendorfer, B. Reconsidering idiopathic CK-elevation. Int J Neurosci. 2004; 114: 133342.CrossRefGoogle ScholarPubMed
55. Prelle, A, Tancredi, L, Sciacco, M, Chiveri, L, Comi, GP, Battistel, A, et al. Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels. J Neurol. 2002; 249: 30511.CrossRefGoogle ScholarPubMed
56. Simmons, Z, Peterlin, BL, Boyer, PJ, Towfighi, J. Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels. Muscle Nerve. 2003; 27: 2424.CrossRefGoogle ScholarPubMed
57. Capasso, M, De Angelis, MV, Di Muzio, A, Scarciolla, O, Pace, M, Stuppia, L, et al. Familial idiopathic hyper-CK-emia: an underrecognized condition. Muscle Nerve. 2006; 33: 7605.CrossRefGoogle ScholarPubMed
58. Phillips, PS, Haas, RH, Bannykh, S, Hathaway, S, Gray, NL, Kimura, BJ, et al. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med. 2002; 137: 5815.CrossRefGoogle ScholarPubMed
59. Troseid, M, Henriksen, OA, Lindal, S. Statin-associated myopathy with normal creatine kinase levels. Case report from a Norwegian family. APMIS. 2005; 113: 6357.CrossRefGoogle ScholarPubMed
60. Thompson, PD, Clarkson, PM, Rosenson, RS. An assessment of statin safety by muscle experts. Am J Cardiol. 2006; 97: 69C76C.CrossRefGoogle ScholarPubMed
61. Bakris, GL, Weir, MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000; 160: 68593.CrossRefGoogle Scholar
62. Chazerain, P, Hayem, G, Hamza, S, Best, C, Ziza, JM. Four cases of tendinopathy in patients on statin therapy. Joint Bone Spine. 2001; 68: 4303.CrossRefGoogle ScholarPubMed
63. Beattie, MS, Lane, NE, Hung, YY, Nevitt, MC. Association of statin use and development and progression of hip osteoarthritis in elderly women. J Rheumatol. 2005; 32: 10610.Google ScholarPubMed
64. Harada, K, Tsuruoka, S, Fujimura, A. Shoulder stiffness: a common adverse effect of HMG-CoA reductase inhibitors in women? Intern Med. 2001; 40: 8178.CrossRefGoogle ScholarPubMed
65. Noel, B, Panizzon, RG. Lupus-like syndrome associated with statin therapy. Dermatology. 2004; 208: 2767.CrossRefGoogle ScholarPubMed
66. Graziadei, IW, Obermoser, GE, Sepp, NT, Erhart, KH, Vogel, W. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus. 2003; 12: 40912.CrossRefGoogle ScholarPubMed
67. Hanson, J, Bossingham, D. Lupus-like syndrome associated with simvastatin. Lancet. 1998; 352: 1070.CrossRefGoogle ScholarPubMed
68. Chong, PH, Boskovich, A, Stevkovic, N, Bartt, RE. Statin-associated peripheral neuropathy: review of the literature. Pharmacotherapy. 2004; 24: 1194203.CrossRefGoogle ScholarPubMed
69. Lo, YL, Leoh, TH, Loh, LM, Tan, CE. Statin therapy and small fibre neuropathy: a serial electrophysiological study. J Neurol Sci. 2003; 208: 1058.CrossRefGoogle ScholarPubMed
70. Vaughan, TB, Bell, DS. Statin neuropathy masquerading as diabetic autoimmune polyneuropathy. Diabetes Care. 2005; 28: 2082.CrossRefGoogle ScholarPubMed
71. McPherson, R, Frohlich, J, Fodor, G, Genest, J. Canadian Cardiovascular Society position statement-recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol. 2006; 22: 91327.CrossRefGoogle ScholarPubMed
72. Genest, J, Frohlich, J, Fodor, G, McPherson, R. Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease: summary of the 2003 update. CMAJ. 2003; 169: 9214.Google ScholarPubMed
73. Golomb, BA. Implications of statin adverse effects in the elderly. Expert Opin Drug Saf. 2005; 4: 38997.CrossRefGoogle ScholarPubMed
74. Golomb, G, Yang, E, Denenberg, J, Criqui, M. Statin-associated adverse effects. Circulation. 2003; 107: e70289.Google Scholar
75. Garcia-Calvo, M, Lisnock, J, Bull, HG, Hawes, BE, Burnett, DA, Braun, MP, et al. The target of ezetimibe is Niemann-Pick C1- Like 1 (NPC1L1). Proc Natl Acad Sci USA. 2005; 102: 81327.CrossRefGoogle ScholarPubMed
76. Altmann, SW, Davis, HR Jr., Zhu, LJ, Yao, X, Hoos, LM, Tetzloff, G, et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004; 303: 12014.CrossRefGoogle ScholarPubMed
77. Davis, HR Jr., Zhu, LJ, Hoos, LM, Tetzloff, G, Maguire, M, Liu, J, et al. Niemann-Pick C1 Like 1 (NPC1L1) is the intestinal phytosterol and cholesterol transporter and a key modulator of whole-body cholesterol homeostasis. J Biol Chem. 2004; 279: 3358692.CrossRefGoogle Scholar
78. Davidson, MH, Maccubbin, D, Stepanavage, M, Strony, J, Musliner, T. Striated muscle safety of ezetimibe/simvastatin (Vytorin). Am J Cardiol. 2006; 97: 2238.CrossRefGoogle ScholarPubMed
79. Fux, R, Morike, K, Gundel, UF, Hartmann, R, Gleiter, CH. Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004; 140: 6712.CrossRefGoogle ScholarPubMed
80. Phillips, PS. Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004; 141: 649.CrossRefGoogle ScholarPubMed
81. Perez-Calvo, J, Civeira-Murillo, F, Cabello, A. Worsening myopathy associated with ezetimibe in a patient with McArdle disease. Q J Med. 2005; 98: 4612.CrossRefGoogle Scholar
82. Cziraky, MJ, Willey, VJ, McKenney, JM, Kamat, SA, Fisher, MD, Guyton, JR, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol. 2006; 97: 61C68C.CrossRefGoogle ScholarPubMed
83. Franc, S, Bruckert, E, Giral, P, Turpin, G. [Rhabdomyolysis in patients with preexisting myopathy, treated with antilipemic agents]. Presse Med. 1997; 26: 18558.Google ScholarPubMed
84. Phillips, P, Gray, N, McDonald, F, Blaszcak, M, Wolfson, T, Sullivan, M. Colesevelam HCL is safe and effective in patients with statin myotoxicity. Atheroscler Thromb Vasc Biol Online Journal. 2005; 25: e97.Google Scholar
85. Castano, G, Fernandez, L, Mas, R, Illnait, J, Gamez, R, Mendoza, S, et al. Effects of addition of policosanol to omega-3 fatty acid therapy on the lipid profile of patients with type II hypercholesterolaemia. Drugs R D. 2005; 6: 20719.CrossRefGoogle Scholar
86. Mas, R, Castano, G, Fernandez, J, Gamez, R, Illnait, J, Fernandez, L, et al. Long-term effects of policosanol on obese patients with Type II Hypercholesterolemia. Asia Pac J Clin Nutr. 2004; 13: S102.Google Scholar
87. Castano, G, Mas, R, Fernandez, JC, Fernandez, L, Illnait, J, Lopez, E. Effects of policosanol on older patients with hypertension and type II hypercholesterolaemia. Drugs R D. 2002; 3: 15972.CrossRefGoogle ScholarPubMed
88. Castano, G, Menendez, R, Mas, R, Amor, A, Fernandez, JL, Gonzalez, RL, et al. Effects of policosanol and lovastatin on lipid profile and lipid peroxidation in patients with dyslipidemia associated with type 2 diabetes mellitus. Int J Clin Pharmacol Res. 2002; 22: 8999.Google ScholarPubMed
89. Berthold, HK, Unverdorben, S, Degenhardt, R, Bulitta, M, Gouni-Berthold, I. Effect of policosanol on lipid levels among patients with hypercholesterolemia or combined hyperlipidemia: a randomized controlled trial. JAMA. 2006; 295: 22629.CrossRefGoogle ScholarPubMed
90. Greyling, A, De Witt, C, Oosthuizen, W, Jerling, JC. Effects of a policosanol supplement on serum lipid concentrations in hypercholesterolaemic and heterozygous familial hyper-cholesterolaemic subjects. Br J Nutr. 2006; 95: 96875.CrossRefGoogle Scholar
91. Davidson, MH, Dugan, LD, Burns, JH, Bova, J, Story, K, Drennan, KB. The hypocholesterolemic effects of beta-glucan in oatmeal and oat bran. A dose-controlled study. JAMA. 1991; 265: 18339.CrossRefGoogle Scholar
92. Brown, L, Rosner, B, Willett, WW, Sacks, FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999; 69: 3042.CrossRefGoogle ScholarPubMed
93. Laaksonen, R, Jokelainen, K, Laakso, J, Sahi, T, Harkonen, M, Tikkanen, MJ, et al. The effect of simvastatin treatment on natural antioxidants in low-density lipoproteins and high-energy phosphates and ubiquinone in skeletal muscle. Am J Cardiol. 1996; 77: 8514.CrossRefGoogle ScholarPubMed
94. Chariot, P, Abadia, R, Agnus, D, Danan, C, Charpentier, C, Gherardi, RK. Simvastatin-induced rhabdomyolysis followed by a MELAS syndrome. Am J Med. 1993; 94: 10910.CrossRefGoogle ScholarPubMed
95. De Pinieux, G, Chariot, P, Ammi-Said, M, Louarn, F, Lejonc, JL, Astier, A, et al. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol. 1996; 42: 3337.CrossRefGoogle ScholarPubMed
96. Elmberger, PG, Kalen, A, Lund, E, Reihner, E, Eriksson, M, Berglund, L, et al. Effects of pravastatin and cholestyramine on products of the mevalonate pathway in familial hypercholesterolemia. J Lipid Res. 1991; 32: 93540.CrossRefGoogle ScholarPubMed
97. Folkers, K, Langsjoen, P, Willis, R, Richardson, P, Xia, LJ, Ye, CQ, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA. 1990; 87: 89314.CrossRefGoogle ScholarPubMed
98. Willis, RA, Folkers, K, Tucker, JL, Ye, CQ, Xia, LJ, Tamagawa, H. Lovastatin decreases coenzyme Q levels in rats. Proc Natl Acad Sci USA. 1990; 87: 892830.CrossRefGoogle ScholarPubMed
99. Ghirlanda, G, Oradei, A, Manto, A, Lippa, S, Uccioli, L, Caputo, S, et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol. 1993; 33: 2269.CrossRefGoogle ScholarPubMed
100. Laaksonen, R, Jokelainen, K, Sahi, T, Tikkanen, MJ, Himberg, JJ. Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. Clin Pharmacol Ther. 1995; 57: 626.CrossRefGoogle Scholar
101. Schaefer, WH, Lawrence, JW, Loughlin, AF, Stoffregen, DA, Mixson, LA, Dean, DC, et al. Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats. Toxicol Appl Pharmacol. 2004; 194: 1023.CrossRefGoogle ScholarPubMed
102. Walravens, PA, Greene, C, Frerman, FE. Lovastatin, isoprenes, and myopathy. Lancet. 1989; 2: 10978.CrossRefGoogle ScholarPubMed
103. Strey, CH, Young, JM, Molyneux, SL, George, PM, Florkowski, CM, Scott, RS, et al. Endothelium-ameliorating effects of statin therapy and coenzyme Q10 reductions in chronic heart failure. Atherosclerosis. 2005; 179: 2016.CrossRefGoogle ScholarPubMed
104. Stocker, R, Pollicino, C, Gay, CA, Nestel, P, Colquhoun, D, Whiting, M, et al. Neither plasma coenzyme Q10 concentration, nor its decline during pravastatin therapy, is linked to recurrent cardiovascular disease events: a prospective case-control study from the LIPID study. Atherosclerosis. 2006; 187: 198204.CrossRefGoogle ScholarPubMed
105. Berthold, HK, Naini, A, Di Mauro, S, Hallikainen, M, Gylling, H, Krone, W, et al. Effect of ezetimibe and/or simvastatin on coenzyme Q10 levels in plasma : a randomised trial. Drug Saf. 2006; 29: 70312.CrossRefGoogle ScholarPubMed
106. Mabuchi, H, Higashikata, T, Kawashiri, M, Katsuda, S, Mizuno, M, Nohara, A, et al. Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients. J Atheroscler Thromb. 2005; 12: 1119.CrossRefGoogle ScholarPubMed
107. Lamperti, C, Naini, AB, Lucchini, V, Prelle, A, Bresolin, N, Moggio, M, et al. Muscle coenzyme Q10 level in statin-related myopathy. Arch Neurol. 2005; 62: 170912.CrossRefGoogle ScholarPubMed
108. Colquhoun, DM, Jackson, R, Walters, M, Hicks, BJ, Goldsmith, J, Young, P, et al. Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. Eur J Clin Invest. 2005; 35: 2518.CrossRefGoogle ScholarPubMed
109. Mabuchi, H, Haba, T, Tatami, R, Miyamoto, S, Sakai, Y, Wakasugi, T, et al. Effects of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase on serum lipoproteins and ubiquinone-10 levels in patients with familial hypercholesterolemia. 1981. Atheroscler Suppl. 2004; 5: 515.CrossRefGoogle Scholar
110. Rundek, T, Naini, A, Sacco, R, Coates, K, DiMauro, S. Atorvastatin decreases the coenzyme Q10 level in the blood of patients at risk for cardiovascular disease and stroke. Arch Neurol. 2004; 61: 88992.CrossRefGoogle ScholarPubMed
111. Päivä, H, Thelen, KM, Van Coster, R, Smet, J, De Paepe, B, Mattila, KM, et al. High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther. 2005; 78: 608.CrossRefGoogle ScholarPubMed
112. Kelly, P, Vaso, S, Gelato, M, McNurlan, M, Lawson, W. Coenzyme Q10 improves myopathic pain in statin treated patients [abstract]. J Am Coll Cardiol. 2005; 45 (3 Suppl A):3A.Google Scholar
113. Inui, D, Fukuta, Y, Oto, J, Miki, T, Suzue, A, Kawahito, S, et al. [Six cases of rhabdomyolysis induced by dehydration]. Masui. 2005; 54: 10246.Google ScholarPubMed
114. Kodama, K, Ikeda, K, Kawamura, S, Oyama, T, Fujita, S, Kobayashi, Y. A case of severe dehydration with marked rhabdomyolysis. Jpn J Med. 1985; 24: 1504.CrossRefGoogle ScholarPubMed
115. Baker, SK, Tarnopolsky, MA. Sporadic Rippling muscle disease unmasked by simvastatin. Muscle Nerve. 2006. Oct;34(4): 38790.CrossRefGoogle ScholarPubMed
116. Krivosic-Horber, R, Depret, T, Wagner, JM, Maurage, CA. Malignant hyperthermia susceptibility revealed by increased serum creatine kinase concentrations during statin treatment. Eur J Anaesthesiol. 2004; 21: 5724.CrossRefGoogle ScholarPubMed
117. Parmar, B, Francis, PJ, Ragge, NK. Statins, fibrates, and ocular myasthenia. Lancet. 2002; 360: 717.CrossRefGoogle ScholarPubMed
118. Cartwright, MS, Jeffery, DR, Nuss, GR, Donofrio, PD. Statin-associated exacerbation of myasthenia gravis. Neurology. 2004; 63: 2188.CrossRefGoogle ScholarPubMed
119. Guis, S, Bendahan, D, Kozak-Ribbens, G, Figarella-Branger, D, Mattei, JP, Pellissier, JF, et al. Rhabdomyolysis and myalgia associated with anticholesterolemic treatment as potential signs of malignant hyperthermia susceptibility. Arthritis Rheum. 2003; 49: 2378.CrossRefGoogle ScholarPubMed
120. Delgado-Lopez, F, Bautista-Lorite, J, Villamil-Fernandez, F. [Worsening for using statin in carnitine palmityol transferase deficiency myopathy]. Rev Neurol. 2004; 38: 1095.Google ScholarPubMed
121. Livingstone, C, Al Riyami, S, Wilkins, P, Ferns, GA. McArdle’s disease diagnosed following statin-induced myositis. Ann Clin Biochem. 2004; 41: 33840.CrossRefGoogle ScholarPubMed
122. Baker, SK, Vladutiu, GD, Tarnopolsky, MA. McArdle disease unmasked by statin exposure. Muscle Nerve. 2003; S734.Google Scholar
123. Vasconcelos, OM, Campbell, WW. Dermatomyositis-like syndrome and HMG-CoA reductase inhibitor (statin) intake. Muscle Nerve. 2004; 30: 8037.CrossRefGoogle ScholarPubMed
124. Huynh, T, Cordato, D, Yang, F, Choy, T, Johnstone, K, Bagnall, F, et al. HMG CoA reductase-inhibitor-related myopathy and the influence of drug interactions. Intern Med J. 2002; 32: 48690.CrossRefGoogle ScholarPubMed
125. Giordano, N, Senesi, M, Mattii, G, Battisti, E, Villanova, M, Gennari, C. Polymyositis associated with simvastatin. Lancet. 1997; 349: 16001.CrossRefGoogle ScholarPubMed
126. Hill, C, Zeitz, C, Kirkham, B. Dermatomyositis with lung involvement in a patient treated with simvastatin. Aust N Z J Med. 1995; 25: 7456.CrossRefGoogle Scholar
127. Khattak, FH, Morris, IM, Branford, WA. Simvastatin-associated dermatomyositis. Br J Rheumatol. 1994; 33: 199.CrossRefGoogle ScholarPubMed
128. Rodriguez-Garcia, JL, Serrano Commino M. Lovastatin-associated dermatomyositis. Postgrad Med J. 1996; 72: 694.CrossRefGoogle ScholarPubMed
129. Voermans, NC, Lammens, M, Wevers, RA, Hermus, AR, van Engelen, BG. Statin-disclosed acid maltase deficiency. J Intern Med. 2005; 258: 1967.CrossRefGoogle ScholarPubMed
130. Tsivgoulis, G, Spengos, K, Karandreas, N, Panas, M, Kladi, A, Manta, P. Presymptomatic neuromuscular disorders disclosed following statin treatment. Arch Intern Med. 2006; 166: 151924.CrossRefGoogle ScholarPubMed
131. Edwards, IR, Star, K, Kiuru, A. Statins, neuromuscular degenerative disease and an amyotrophic lateral sclerosis-like syndrome: an analysis of individual case safety reports from vigibase. Drug Saf. 2007: 51525.CrossRefGoogle Scholar
132. Dalakas, MC. Therapeutic approaches in patients with inflammatory myopathies. Semin Neurol. 2003; 23: 199206.Google ScholarPubMed
133. Dalakas, MC. Molecular pathogenesis of inflammatory myopathies and future therapeutic strategies. Suppl Clin Neurophysiol. 2004; 57: 288303.CrossRefGoogle ScholarPubMed
134. Dalakas, MC. Inflammatory disorders of muscle: progress in polymyositis, dermatomyositis and inclusion body myositis. Curr Opin Neurol. 2004; 17: 5617.CrossRefGoogle ScholarPubMed
135. Dalakas, MC. Update on the molecular pathogenesis of inflammatory myopathies. Autoimmun Rev. 2004; 3 Suppl 1:S379.Google ScholarPubMed
136. Griggs, RC, Mendell, JR, Brooke, MH, Fenichel, GM, Miller, JP, Province, M, et al. Clinical investigation in Duchenne dystrophy: V. Use of creatine kinase and pyruvate kinase in carrier detection. Muscle Nerve. 1985; 8: 607.CrossRefGoogle ScholarPubMed
137. Youssef, S, Stuve, O, Patarroyo, JC, Ruiz, PJ, Radosevich, JL, Hur, EM, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002; 420: 7884.CrossRefGoogle ScholarPubMed
138. Krendel, DA, Sanders, DB, Massey, JM. Single fiber electromyography in chronic progressive external ophthalmoplegia. Muscle Nerve. 1987; 10: 299302.CrossRefGoogle ScholarPubMed
139. Dai, Z, Luo, X, Xie, H, Peng, HB. The actin-driven movement and formation of acetylcholine receptor clusters. J Cell Biol. 2000; 150: 132134.CrossRefGoogle ScholarPubMed
140. Bloch, RJ. Acetylcholine receptor clustering in rat myotubes: requirement for CA2+ and effects of drugs which depolymerize microtubules. J Neurosci. 1983; 3: 267080.CrossRefGoogle ScholarPubMed
141. Bifulco, M, Laezza, C, Aloj, SM, Garbi, C. Mevalonate controls cytoskeleton organization and cell morphology in thyroid epithelial cells. J Cell Physiol. 1993; 155: 3408.CrossRefGoogle ScholarPubMed
142. Thomas, JE, Lee, N, Thompson, PD. Statins Provoking MELAS Syndrome. A Case Report. Eur Neurol. 2007; 57: 2325.CrossRefGoogle ScholarPubMed
143. Estornell, E, Fato, R, Castelluccio, C, Cavazzoni, M, Parenti, Castelli G, Lenaz, G. Saturation kinetics of coenzyme Q in NADH and succinate oxidation in beef heart mitochondria. FEBS Lett. 1992; 311: 1079.CrossRefGoogle ScholarPubMed
144. Oh, J, Ban, MR, Miskie, BA, Pollex, RL, Hegele, RA. Genetic determinants of statin intolerance. Lipids Health Dis. 2007; 6: 7.CrossRefGoogle ScholarPubMed
145. Bhuiyan, J, Seccombe, DW. The effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition on tissue levels of carnitine and carnitine acyltransferase activity in the rabbit. Lipids. 1996; 31: 86770.CrossRefGoogle Scholar
146. Kaufmann, P, Torok, M, Zahno, A, Waldhauser, KM, Brecht, K, Krahenbuhl, S. Toxicity of statins on rat skeletal muscle mitochondria. Cell Mol Life Sci. 2006; 63: 241525.CrossRefGoogle ScholarPubMed
147. Sirvent, P, Mercier, J, Vassort, G, Lacampagne, A. Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle. Biochem Biophys Res Commun. 2005; 329: 106775.CrossRefGoogle ScholarPubMed
148. Guis, S, Figarella-Branger, D, Mattei, JP, Nicoli, F, Le Fur, Y, Kozak-Ribbens, G, et al. In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects. Arthritis Rheum. 2006; 55: 5517.CrossRefGoogle ScholarPubMed
149. Lamb, GD. Rippling muscle disease may be caused by “silent” action potentials in the tubular system of skeletal muscle fibers. Muscle Nerve. 2005; 31: 6528.CrossRefGoogle ScholarPubMed
150. Minetti, C, Sotgia, F, Bruno, C, Scartezzini, P, Broda, P, Bado, M, et al. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nat Genet. 1998; 18: 3658.CrossRefGoogle ScholarPubMed
151. Pol, A, Martin, S, Fernandez, MA, Ingelmo-Torres, M, Ferguson, C, Enrich, C, et al. Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies. Mol Biol Cell. 2005; 16: 2091105.CrossRefGoogle ScholarPubMed
152. Weis, M, Heeschen, C, Glassford, AJ, Cooke, JP. Statins have biphasic effects on angiogenesis. Circulation. 2002; 105: 73945.CrossRefGoogle ScholarPubMed
153. Tsao, CY, Mendell, JR. Combined partial deficiencies of carnitine palmitoyltransferase II and mitochondrial complex I presenting as increased serum creatine kinase level. J Child Neurol. 2002; 17: 3046.CrossRefGoogle ScholarPubMed
154. Aguilera, I, Garcia-Lozano, JR, Munoz, A, Arenas, J, Campos, Y, Chinchon, I, et al. Mitochondrial DNA point mutation in the COI gene in a patient with McArdle’s disease. J Neurol Sci. 2001; 192: 814.CrossRefGoogle Scholar
155. Baker, SK, Tarnopolsky, MA. Statin myopathies: pathophysiologic and clinical perspectives. Clin Invest Med. 2001; 24: 25872.Google ScholarPubMed
156. Mazzuca, M, Lesage, F, Lazdunski, M. Ion channels and epilepsy. Epileptic Disord. 2006; 8 Suppl 1:116.Google Scholar
157. Sherer, Y, Livneh, A, Levy, Y, Shoenfeld, Y, Langevitz, P. Dermatomyositis and polymyositis associated with the antiphospholipid syndrome-a novel overlap syndrome. Lupus. 2000; 9: 426.CrossRefGoogle ScholarPubMed
158. Sonoda, Y, Gotow, T, Kuriyama, M, Nakahara, K, Arimura, K, Osame, M. Electrical myotonia of rabbit skeletal muscles by HMG-CoA reductase inhibitors. Muscle Nerve. 1994; 17: 8917.CrossRefGoogle ScholarPubMed
159. Pierno, S, De Luca, A, Tricarico, D, Ferrannini, E, Conte, T, D’Alo, G, et al. Experimental evaluation of the effects of pravastatin on electrophysiological parameters of rat skeletal muscle. Pharmacol Toxicol. 1992; 71: 3259.CrossRefGoogle ScholarPubMed
160. Pierno, S, De Luca, A, Tricarico, D, Roselli, A, Natuzzi, F, Ferrannini, E, et al. Potential risk of myopathy by HMG-CoA reductase inhibitors: a comparison of pravastatin and simvastatin effects on membrane electrical properties of rat skeletal muscle fibers. J Pharmacol Exp Ther. 1995; 275: 14906.Google ScholarPubMed
161. Nakahara, K, Kuriyama, M, Sonoda, Y, Yoshidome, H, Nakagawa, H, Fujiyama, J, et al. Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study. Toxicol Appl Pharmacol. 1998; 152: 99106.CrossRefGoogle Scholar
162. Riggs, JE, Schochet, SS Jr. Myotonia associated with sarcoidosis: marked exacerbation with pravastatin. Clin Neuropharmacol. 1999; 22: 1801.Google ScholarPubMed
163. Campbell, WW. Statin myopathy: the iceberg or its tip? Muscle Nerve. 2006; 34: 38790.CrossRefGoogle ScholarPubMed
164. Dirks, AJ, Jones, KM. Statin-induced apoptosis and skeletal myopathy. Am J Physiol Cell Physiol. 2006; 291: C120812.CrossRefGoogle ScholarPubMed
165. Holtzman, CW, Wiggins, BS, Spinler, SA. Role of P-glycoprotein in statin drug interactions. Pharmacotherapy. 2006; 26: 16017.CrossRefGoogle ScholarPubMed
166. Bellosta, S, Paoletti, R, Corsini, A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004; 109: III507.CrossRefGoogle ScholarPubMed
167. Reijneveld, JC, Notermans, NC, Linssen, WH, Bar, PR, Wokke, JH. Hyper-CK-aemia revisited. Neuromuscul Disord. 2001; 11: 1634.CrossRefGoogle ScholarPubMed
168. Fee, DB, So, YT, Barraza, C, Figueroa, KP, Pulst, SM. Phenotypic variability associated with Arg26Gln mutation in caveolin3. Muscle Nerve. 2004; 30: 3758.CrossRefGoogle ScholarPubMed
169. Galassi, G, Rowland, LP, Hays, AP, Hopkins, LC, DiMauro, S. High serum levels of creatine kinase: asymptomatic prelude to distal myopathy. Muscle Nerve. 1987; 10: 34650.CrossRefGoogle ScholarPubMed
170. Merlini, L, Sabatelli, P, Columbaro, M, Bonifazi, E, Pisani, V, Massa, R, et al. Hyper-CK-emia as the sole manifestation of myotonic dystrophy type 2. Muscle Nerve. 2005; 31: 7647.CrossRefGoogle ScholarPubMed
171. Nevins, MA, Saran, M, Bright, M, Lyon, LJ. Pitfalls in interpreting serum creatine phosphokinase activity. JAMA. 1973; 224: 13827.CrossRefGoogle ScholarPubMed
172. Monsieurs, KG, Van Broeckhoven, C, Martin, JJ, Van Hoof, VO, Heytens, L. Gly341Arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity. J Neurol Sci. 1998; 154: 625.CrossRefGoogle ScholarPubMed
173. Sunohara, N, Takagi, A, Nonaka, I, Sugita, H, Satoyoshi, E. Idiopathic hyperCKemia. Neurology. 1984; 34: 5447.CrossRefGoogle ScholarPubMed
174. Weglinski, MR, Wedel, DJ, Engel, AG. Malignant hyperthermia testing in patients with persistently increased serum creatine kinase levels. Anesth Analg. 1997; 84: 103841.CrossRefGoogle ScholarPubMed
175. Brewster, LM, de Visser, M. Persistent hyperCKemia: fourteen patients studied in retrospect. Acta Neurol Scand. 1988; 77: 603.CrossRefGoogle ScholarPubMed
176. Shane, E, McClane, KA, Olarte, MR, Bilezikian, JP. Hypoparathyroidism and elevated muscle enzymes. Neurology. 1980; 30: 1925.CrossRefGoogle ScholarPubMed
177. Osborn, LA, Rossum, A, Standefer, J, Jackson, J, Skipper, B, Beeson, C, et al. Evaluation of CK and CK-MB in alcohol abuse subjects with recent heavy consumption. Cardiology. 1995; 86: 1304.CrossRefGoogle ScholarPubMed
178. Prelle, A, Rigoletto, C, Moggio, M, Sciacco, M, Comi, GP, Ciscato, P, et al. Asymptomatic familial hyperCKemia associated with desmin accumulation in skeletal muscle. J Neurol Sci. 1996; 140: 1326.CrossRefGoogle ScholarPubMed