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 2weeks (T1), within 4–6weeks (T2), and within 3–5months 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.
Highlights
Spasticity is a common movement disorder after neurologic injury of cerebral and spinal origin such as stroke, traumatic brain injury, brain tumor, cerebral palsy, spinal cord injury, and multiple sclerosis
The shortening may predominate in muscles with large myofascial expansions (Stecco, 2015) such as the pectoralis major, the biceps brachii, and pronator teres, connecting them together and leading to posturing of the upper limb in a typical flexor synergy pattern characterized by shoulder internal rotation, elbow flexion, and forearm pronation
The dose of intramuscular hyaluronidase was determined according to each patient's pattern and extent of muscle stiffness, but the maximum dose used in this cohort was 600 IU, with no N75 IU injected into a single site
Summary
Spasticity is a common movement disorder after neurologic injury of cerebral and spinal origin such as stroke, traumatic brain injury, brain tumor, cerebral palsy, spinal cord injury, and multiple sclerosis. Muscle stiffness adds further insult to the underlying weakness It both prevents full passive movement (leading to abnormal posturing that can become fixed over time) and makes active movement more difficult in patients who are already weak from the neurologic injury. P. Raghavan et al / EBioMedicine 9 (2016) 306–313 which hydrolyzes hyaluronan, and is available for off-label clinical use, increases both passive and active joint movement, and reduces muscle stiffness in individuals with upper limb spasticity. Raghavan et al / EBioMedicine 9 (2016) 306–313 which hydrolyzes hyaluronan, and is available for off-label clinical use, increases both passive and active joint movement, and reduces muscle stiffness in individuals with upper limb spasticity These results fill a critical gap in the understanding of muscle stiffness, and present a promising treatment for a vexing and widespread problem
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