title: 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.
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.
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, Dr. von Hauner's Children's Hospital, University of Munich, Munich, Germany. sebastian.schroeder@med.uni-muenchen.de
authors.forename: A Sebastian
authors.initials: AS
authors.lastname: Schroeder
authors.forename: Birgit
authors.initials: B
authors.lastname: Ertl-Wagner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Britsch
authors.forename: J Michael
authors.initials: JM
authors.lastname: Schröder
authors.forename: Stefan
authors.initials: S
authors.lastname: Nikolin
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Müller-Felber
authors.forename: Inga
authors.initials: I
authors.lastname: Koerte
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stehr
authors.forename: Steffen
authors.initials: S
authors.lastname: Berweck
authors.forename: Ingo
authors.initials: I
authors.lastname: Borggraefe
authors.forename: Florian
authors.initials: F
authors.lastname: Heinen
mesh_terms: D000328:Adult; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology*; D001706:Biopsy / Q000379:methods; D001905:Botulinum Toxins / Q000494:pharmacology*; D004311:Double-Blind Method; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000187:drug effects* / Q000648:ultrastructure; D011446:Prospective Studies
chemical_list: D018726:Anti-Dyskinesia Agents; D001905:Botulinum Toxins