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

Mov Disord. 2009 Jul 30;24(10):1494-503. doi: 10.1002/mds.22661.

Abstract

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-Dyskinesia Agents / pharmacology*
  • Biopsy / methods
  • Botulinum Toxins / pharmacology*
  • Double-Blind Method
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Microscopy, Electron, Transmission / methods
  • Middle Aged
  • Muscle, Skeletal / anatomy & histology*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / ultrastructure
  • Prospective Studies

Substances

  • Anti-Dyskinesia Agents
  • Botulinum Toxins