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†

Department of Pediatric Surgery, Dr. von Hauner’s Children’s Hospital, University of Munich, Munich, GermanyAbstract: Despite numerous clinical and experimental stud-ies on botulinum toxin type A (BoNT/A), long-term altera-tions of muscle texture and fine structure following BoNT/Atreatment have thus far not been studied in normal humanskeletal muscle. After obtaining institutional review boardapproval, we performed a prospective, placebo-controlled,double-blinded follow-up study on two healthy adults usingmagnetic resonance imaging (MRI) and muscle biopsy to vis-ualize long-term alterations after a single BoNT/A injectioninto the lateral head of the gastrocnemius muscle. MRI dis-closed a high-signal-intensity pattern in short tau inversionrecovery sequences, and a reduction of the cross-sectionalarea in the BoNT/A-injected, but not in the saline-injectedcontralateral 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, confirmedneurogenic atrophy of muscle fibers only in the BoNT/A-injected muscle. Electron microscopy revealed additional de-generative changes at the neuromuscular junction. The dataconfirm that MRI is a suitable tool to monitor the long-termeffect of BoNT/A on skeletal muscle. Neurogenic muscle at-rophy following a single BoNT/A injection should be takeninto consideration when repeated BoNT/A injections into thesame muscles are proposed. 2009 Movement Disorder So-cietyKey words: botulinum toxin type A (BoNT/A) injection;muscle MRI; high signal intensity pattern; muscle biopsy,long-term neurogenic atrophy; neuromuscular junction