Brain Pathology Case of the Month - February 1999



The patient was initally treated with corticosteroids and the cholesterol lowering agents discontinued. He gradually improved with resolution of his creatine kinase to normal. The corticosteroids were tapered and discontinued after the biopsy results were known. The role of corticosteroid treatment in non-inflammatory myopathy is uncertain. In experimental models, it may in fact make the situation significantly worse (1).

EMG findings in necrotizing myopathy typically consist of fibrillation potentials and short, polyphasic motor unit potentials. However, the extent and rapidity of the process allows for a wide variation in EMG findings including normal studies. The florid nature of EMG findings in this case correlate well with his acute clinical presentation.

Several drugs may cause toxic rhabdomyolysis (Table 1) Rhabdomyolysis secondary to HMG-CoA reductase inhibitors such as lovastatin occurs in approximately 0.1% of treated patients (2). The incidence may be much higher in association with cyclosporine, macrolide antibiotics, or gemfibrozil use (3). Rhabdomyolysis has been reported once with lovastatin and nicotinic acid (4). Three cases of very mild isolated nicotinic acid myopathy without rhabdomyolysis have also been reported (5).

The etiology of HMG-CoA reductase inhibitor myopathy is not known. Experimental work in rats has suggested that type II fibres are most sensitive to the toxic effects of lovastatin, but that all fibre types are affected eventually (6). Work with a rabbit model of simvastatin-induced myopathy has suggested that the muscle membrane is affected resulting in electromyographic myotonia (7). Others have speculated based on experimental evidence that blocking HMG-CoA reductase results in reduced ubiquinone levels and respiratory chain dysfunction implying an acquired mitochondrial myopathy (8).

In 1990, clinical experience with more than one million patients taking lovastatin was available.2 That number is almost certainly higher now. In addition, lovastatin has been recently investigated as an antineoplastic agent in several experimental models (9, 10). As trials progress to involve human subjects, oncologists will also have to be alert to the possibility of drug induced myopathy. The potential number of patients involved is huge. Fortunately, early recognition of symptoms and prompt evaluation of the serum creatine kinase may prevent serious sequellae and even death from renal failure, making awareness of the clinical syndrome of crucial importance.


  1. Patterson RE, Haut MJ, Montgomery CA, et al. Natural history of potassium-deficiency myopathy in the dog: role of adrenocorticosteroid in rhabdomyolysis. J Lab Clin Med 1983;102: 565-576
  2. Tobert JA, Shear CL Chremos AN et al., Clinical experience with lovastatin. Am J Cardiol 1990; 65(suppl):23F-26F
  3. Tobert JA., Efficacy and long-term adverse effect pattern of lovastatin. Am J Cardiol 1988; 62:28J-34J
  4. Reaven P, Wiutztum JL., Lovastatin, nicotinic acid and rhabdomyolysis.(letter) Ann Int Med 1988; 109:597-598
  5. Litin SC, Anderson CF., Nicotinic acid associated myopathy: a report of three cases. Am J Med 1989; 86:481-483
  6. Waclawik AJ, Lindal S, Engel AG., Experimental lovastatin myopathy. J Neuropath Exp Neurol 1993; 52(5):542-549
  7. Nakahara K, Kuriyama M, Yoshidome H et al., Experimental simvastatin-induced myopathy in rabbits. J Neurol Sci 1992; 113:114-117
  8. Walravens PA, Greene C, Frerman FE., Lovastatin, isoprenes, and myopathy (letter). Lancet 1989; 2(8671):1097-1098
  9. Dimitroulakos J, Yeger H., HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets p-glycoprotein-expressing cells. Nature Medicine 1996; 2(3):326-333
  10. Morris TJ, Palm SL, Furcht LL, Buchwald H., Effect of lovastatin alone and as an adjuvant chemotherapeutic agent on hepatoma tissue culture-4 cell growth. Annals Surg Onc 1995; 2(3):266-274

Contributed by Michael D. Hill, MD and Juan M. Bilbao, MD

International Society of Neuropathology