Human Recombinant Hyaluronidase Injections For Upper Limb Muscle Stiffness in Individuals With Cerebral Injury: A Case Series

EBioMedicine. 2016 Jul:9:306-313. doi: 10.1016/j.ebiom.2016.05.014. Epub 2016 May 13.


Spasticity, muscle stiffness and contracture cause severe disability after central nervous system injury. However, current treatment options for spasticity produce muscle weakness which can impede movement, and do not directly address muscle stiffness. Here we propose that the accumulation of hyaluronan within muscles promotes the development of muscle stiffness, and report that treatment with the enzyme hyaluronidase increases upper limb movement and reduces muscle stiffness without producing weakness. 20 patients with unilateral upper limb spasticity received multiple intramuscular injections of human recombinant hyaluronidase with saline at a single visit. The safety and efficacy of the injections, passive and active movement, and muscle stiffness at eight upper limb joints were assessed at four time points: pre-injection (T0), within 2 weeks (T1), within 4–6 weeks (T2), and within 3–5 months post-injection (T3). There were no clinically significant adverse effects from the injections. Passive movement at all joints, and active movement at most joints increased at T1, and persisted at T2 and T3 for most joints. The modified Ashworth scores also declined significantly over time post-injection. Hyaluronidase injections offer a safe and potentially efficacious treatment for muscle stiffness in neurologically impaired individuals. These results warrant confirmation in placebo-controlled clinical trials.

  1. The accumulation of hyaluronan within muscles contributes to the development of muscle stiffness after neurologic injury.

  2. Intramuscular injection of hyaluronidase reduces muscle stiffness and increases passive and active movement.

  3. The injections did not produce weakness or clinically significant adverse effects in the reported case series.

Muscle stiffness contributes to disability after neurologic injury. However both the cause of the muscle stiffness and its treatment remain to be established. We propose that the accumulation of hyaluronan within muscles promotes the development of muscle stiffness. We report that the enzyme hyaluronidase, which hydrolyzes hyaluronan, reduces muscle stiffness and increases both passive and active movement in individuals with spastic paralysis after cerebral injury. The treatment takes effect within days to 2 weeks, lasts for at least three months, does not produce weakness, and is safe without clinically significant adverse effects. These results present a promising treatment for a widespread problem.

Keywords: Case series; Connective tissue; Fascia; Hyaluronidase; Hypertonia; Motor control; Spasticity; Stroke.

Publication types

  • Case Reports
  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Injuries / drug therapy*
  • Brain Injuries / pathology
  • Child
  • Exercise
  • Female
  • Humans
  • Hyaluronoglucosaminidase / genetics
  • Hyaluronoglucosaminidase / metabolism
  • Hyaluronoglucosaminidase / therapeutic use*
  • Joints / physiology
  • Male
  • Middle Aged
  • Muscle, Skeletal / physiology*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome
  • Upper Extremity / physiology*
  • Young Adult


  • Recombinant Proteins
  • Hyaluronoglucosaminidase