1360 - Effects of Hyaluronidase on the force generation capacity of upper extremity muscles in patients with post-stroke muscle stiffness

Friday, February 24, 2023

11:45 AM – 1:15 PM PST

Presenting Author(s)

Paria Arfa Fatollahkhani, MD, MSc

Research Postdoctoral Fellow
Johns Hopkins University
Baltimore, Maryland, United States

Co-Author(s)

MB

Matthew Bird, MS

Senior Research Assistant
Johns Hopkins University
Baltimore, Maryland, United States
LM

Layla J. Murray, BA

Research Program Coordinator
Johns Hopkins University
Baltimore, Maryland, United States
Pablo Celnik, MD

Professor
Johns Hopkins University
Baltimore, Maryland, United States

Corresponding Author(s)

Preeti Raghavan, MBBS

Associate Professor
Johns Hopkins
Baltimore, Maryland, United States

Objectives: The cause of muscle stiffness in post-stroke people, may be due to neural reflex-induced muscle overactivity, or non-neural adhesions of the extracellular matrix of the muscle due to accumulation of hyaluronan. We tested the hypothesis that the muscle stiffness leads to reduced force generation capacity due to accumulation of hyaluronan, and that human recombinant hyaluronidase injections will increase force generation capacity during isometric muscle strength testing.

Design:

Eight patients with post-stroke upper limb muscle stiffness, were enrolled in this double-blind, randomized, placebo-controlled, Phase II trial of human recombinant hyaluronidase injections. This trial included three evaluation and two injection visits of the hyaluronidase and placebo. The maximum voluntary contraction (MVC) of the elbow flexors (medial biceps, lateral biceps, brachialis, and brachioradialis) and extensors (medial, lateral and long head of triceps) were analyzed across the testing visits. The MVC was calculated based on the root mean square (RMS) of the electromyogram (EMG) signal recorded during isometric elbow extension and flexion. The co-contraction index (CCI) was also computed to assess the resistance from the antagonist muscles in generating force by the agonist muscles.

Results:

At baseline, the MVC was decreased in the elbow flexor and extensor muscles on the affected side compared to the unaffected side. The MVC increased in all subjects after treatment with hyaluronidase on the affected side compared to the baseline visit. There was an increase in MVC for both extensor and flexor muscles in 4 subjects, for only extensors in 3 subjects and for only flexors in 1 subject. The increase in the MVC EMG amplitude was associated with a decrease in CCI in all the subjects.

Conclusions:

These findings suggest that the accumulation of hyaluronan in muscle can reduce force generation capacity, which may be increased by human recombinant hyaluronidase injections in individuals with post-stroke muscle stiffness.