Despite numerous clinical and experimental studies on
botulinum toxin type A (
BoNT/A), long-term alterations of muscle texture and fine structure following
BoNT/A treatment have thus far not been studied in normal human skeletal muscle. After obtaining institutional review board approval, we performed a prospective, placebo-controlled, double-blinded follow-up study on two healthy adults using magnetic resonance imaging (MRI) and muscle biopsy to visualize long-term alterations after a single
BoNT/A injection into the lateral head of the gastrocnemius muscle. MRI disclosed a high-signal-intensity pattern in short tau inversion recovery sequences, and a reduction of the cross-sectional area in the
BoNT/A-injected, but not in the saline-injected contralateral control muscle (at 6 to 9 months in volunteer A: 73%, in B: 62%; at 12 months in A: 88%, and in B: 78%).
Enzyme histochemistry, 12 months after injection, confirmed neurogenic
atrophy of muscle fibers only in the
BoNT/A-injected muscle. Electron microscopy revealed additional degenerative changes at the neuromuscular junction. The data confirm that MRI is a suitable tool to monitor the long-term effect of
BoNT/A on skeletal muscle. Neurogenic
muscle atrophy following a single
BoNT/A injection should be taken into consideration when repeated
BoNT/A injections into the same muscles are proposed.