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


  • Potential conflict of interest: Dr. Heinen, Dr. Berweck, Dr. Borggraefe and Dr. Schroeder report having been paid lecture fees by Allergan, Inc., Merz Pharma, and Ipsen, Ltd., the manufacturers of the available Botulinum toxin preparations Botox®, Xeomin® and Dysport®, respectively. Dr. Heinen reports having received grant support from Allergan, Inc. and Merz Pharma in form of unrestricted educational grants. Dr. Heinen reports having received consulting fees from Allergan, Inc., Merz Pharma, and Ipsen, Ltd.


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