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1996-01-30
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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).