1319 - Effects of Hyaluronidase Injections on Muscle Stiffness, Spasticity, Upper Limb Motor Impairment and Mood After Cerebral Injury

Objectives: Muscle stiffness and spasticity cause severe disability in approximately 12 million people after neurologic injury of cerebral or spinal origin. We hypothesized that non-neural alterations in the composition of the extracellular matrix of the muscle due to the accumulation of hyaluronan can produce muscle stiffness and may contribute to spasticity as well as upper limb motor impairment, which may be treated using intramuscular hyaluronidase injections.

Design: 24 individuals with upper limb muscle stiffness after cerebral injury completed a single-center, double-blind, randomized, placebo-controlled, Phase II trial of human recombinant hyaluronidase injections. All subjects received both human recombinant hyaluronidase and placebo injections in a random order in multiple upper limb muscles and were evaluated at baseline and 1-2 weeks after each injection visit. Resistance to passive movement was assessed using the modified Ashworth Scale (MAS), and reflex-induced muscle activity was measured using surface EMG from the medial biceps during tendon tap using an electronic hammer. Motor impairment was evaluated using the upper limb Fugl-Meyer Assessment (FMA). The patient health questionnaire-9 (PHQ9) was used to evaluate mood.

Results: Analysis on 17 subjects showed that at baseline, the reflex EMG amplitude to tendon tap (mean ± SD) was 7.67±10.43 mV on the affected side vs. 1.65±2.17 mV on the contralateral side. On the last post-injection visit, the muscle reflex EMG amplitude decreased by 4.06±10.37 mV (47%) on the affected side, and the MAS score for elbow extension decreased by 0.59±0.57. The total upper limb FMA increased by 6.59±5.15, whereas the PHQ9 showed a score reduction of 1 ±2.33.

Conclusions: The results suggest that peripheral modulation of muscle stiffness using hyaluronidase injections can reduce resistance to passive movement, hyperreflexia, and motor impairment after cerebral injury, which can also improve mood. These findings suggest that secondary changes in muscle composition contribute to these phenomena.