Document 0090
 DOCN  M9610090
 TI    Early features of zidovudine-associated myopathy: histopathological
       findings and clinical correlations.
 DT    9601
 AU    Cupler EJ; Danon MJ; Jay C; Hench K; Ropka M; Dalakas MC; Neuromuscular
       Diseases Section, National Institute of; Neurological Disorders and
       Stroke, National Institutes of Health,; Bethesda, MD 20892-1382, USA.
 SO    Acta Neuropathol (Berl). 1995;90(1):1-6. Unique Identifier : AIDSLINE
       MED/96057167
 AB    Zidovudine-induced myopathy is characterized by reversible muscle
       weakness, wasting, myalgia, fatigue, and elevated creatine kinase (CK).
       Some zidovudine-treated patients with normal muscle strength experience
       excessive fatigue, myalgia, or transient mild CK elevations that improve
       when zidovudine is stopped. To determine the cause of these symptoms, we
       studied 13 physically fit, HIV-infected men who developed fatigue,
       myalgia, and reduced endurance, while taking zidovudine for a mean
       period of 20 months (2-39 months), with neurological evaluation and
       muscle biopsy processed for enzyme histochemistry and electron
       microscopy (EM). All subjects had normal muscle strength. In 6 of the 13
       patients, muscle biopsies were normal by enzyme histochemistry. EM,
       however, demonstrated proliferation of normal or abnormal mitochondria,
       and increased amounts of lipid, glycogen, and lipofuscin.
       Electromyographic (EMG) studies (5/5) and serum CK (6/6) were normal.
       The other 7 individuals had signs of moderate to severe mitochondrial
       abnormalities shown by both light microscopy and EM, characterized by
       severe destruction, vacuolization, and rare paracrystalline inclusions.
       Most had elevated CK (4 out of 7) and normal EMG (5 out of 7). The
       severity of morphological abnormalities did not correlate with duration
       of HIV infection, zidovudine therapy, or zidovudine dosage. We conclude
       that in zidovudine-treated patients, symptoms of fatigue, myalgia,
       reduced endurance, and exercise intolerance represent early signs of
       zidovudine-induced mitochondriotoxicity, which causes an energy shortage
       within the muscle fibers even when muscle strength is still normal.
       Zidovudine, a DNA chain terminator, results in overt myopathy when a
       critical threshold of molecular, histological, and biochemical
       dysfunction of mitochondria is crossed, which seems to vary between
       individuals.
 DE    Adult  Biopsy  Electromyography  Electrophysiology  Human  HIV  Middle
       Age  Muscle Fatigue  Muscular Diseases/*PATHOLOGY  Zidovudine/*ADVERSE
       EFFECTS  CLINICAL TRIAL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).