Highlights
- •The accumulation of hyaluronan within muscles contributes to the development of muscle stiffness after neurologic injury.
- •Intramuscular injection of hyaluronidase reduces muscle stiffness and increases passive and active movement.
- •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.
Abstract
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.
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