Muscle biopsy substantiates long‐term MRI alterations one year after a single dose of botulinum toxin injected into the lateral gastrocnemius muscle of healthy volunteers

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. © 2009 Movement Disorder Society