title: Muscle structure and stiffness assessment after botulinum toxin type A injection. A systematic review.
abstract: BACKGROUND
  Botulinum toxin type A manages spasticity disorders in neurological central diseases. Some studies have reported that it might induce muscle changes.
  
  
  METHODS
  We present a literature review abiding by the PRISMA statement guidelines. The purpose was to explore the structural and passive biomechanical muscle properties after botulinum toxin type A injections in healthy and spastic limb muscles, on animals and humans, as well as methods for evaluating these properties. We searched the PubMed and Cochrane Library databases using the following keywords: "Botulinum toxin" AND ("muscle structure" OR "muscle atrophy") and, "Botulinum toxin" AND "muscle elasticity".
  
  
  RESULTS
  From the 228 initially identified articles, 21 articles were included. Histological analyses were performed, especially on animals. A neurogenic atrophy systematically occurred. In humans, one year after a single injection, the histological recovery remained incomplete. Furthermore, 2D ultrasound analyses showed a reduction of the gastrocnemius thickness and pennation angle. MRI volumetric analysis evidenced muscular atrophy six months or one year after a single injection. Passive muscle stiffness depends on these structural changes. On the short term, the biomechanical analysis showed an elastic modulus increase in animals whereas no change was recorded in humans. On the short term, ultrasound elastography imaging showed a decreased elastic modulus.
  
  
  CONCLUSIONS
  To date, few data are available, but all show a structural and mechanical muscle impact post injections, specifically muscle atrophy which can linger over time. Further studies are necessary to validate this element, and the possibility of change must be taken into account particularly with repeated injections. Thus, in clinical practice, 2D ultrasound and ultrasound elastography are two non-invasive techniques that will help physicians to develop an efficient long term monitoring.
authors.affiliation: Service de médecine physique et de réadaptation, laboratoire de physiologie de l'exercice, université Jean-Monnet, CHU de Saint-Étienne, Saint-Étienne, France. Electronic address: Laure.mathevon@laposte.net.
authors.forename: L
authors.initials: L
authors.lastname: Mathevon
authors.affiliation: Service de médecine physique et de réadaptation, université de Franche-Comté, CHU de Besançon, Besançon, France.
authors.forename: F
authors.initials: F
authors.lastname: Michel
authors.affiliation: Service de médecine physique et de réadaptation, université de Franche-Comté, CHU de Besançon, Besançon, France.
authors.forename: P
authors.initials: P
authors.lastname: Decavel
authors.affiliation: Service de médecine physique et de réadaptation, laboratoire de physiologie de l'exercice, université Jean-Monnet, CHU de Saint-Étienne, Saint-Étienne, France.
authors.forename: B
authors.initials: B
authors.lastname: Fernandez
authors.affiliation: Service de médecine physique et de réadaptation, laboratoire d'anatomie, université de Franche-Comté, CHU de Besançon, Besançon, France.
authors.forename: B
authors.initials: B
authors.lastname: Parratte
authors.affiliation: Service de médecine physique et de réadaptation, laboratoire de physiologie de l'exercice, université Jean-Monnet, CHU de Saint-Étienne, Saint-Étienne, France.
authors.forename: P
authors.initials: P
authors.lastname: Calmels
mesh_terms: D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000000981:diagnostic imaging; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects*; D055119:Elastic Modulus / Q000187:drug effects*; D054459:Elasticity Imaging Techniques; D006801:Humans; D007273:Injections, Intramuscular; D008279:Magnetic Resonance Imaging; D009128:Muscle Spasticity / Q000188:drug therapy; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A
keywords: Atrophy; Botulinum toxin; Literature review; Spastic muscle; Stiffness