Post-stroke spasticity develops a result of CNS injury, but secondary non-neural changes can contribute to upper limb muscle stiffness. The hylauronan hypothesis postulates that an increase in the concentration of hyaluronan, a glycosaminoglycan (GAG) in the extra-cellular matrix (ECM) of muscles, may contribute to muscle stiffness in spastic patients. This study sought to provide imaging evidence of the hyaluronan hypothesis.

Five post-stroke patients (3 males, 2 females, age=46±15) and five healthy control subjects (3 males, 2 females, age=27±2) underwent Dixon based water-fat imaging and 3D-T1rho relaxation mapping of upper arm muscles were used to determine intramuscular GAG content. The MRI was study was conducted on a 3T clinical scanner (Prisma, Siemens Healthcare, Germany). Following the MRI, the patients underwent off-label intramuscular hyaluronidase injections (Hylenex, Halozyme Therapeutics, Inc.) for clinical treatment. Post-injection MRIs were conducted approximately two weeks after the treatment. Two tailed student t-tests were used for comparing the groups. A paired t-test was used for the pre- and post-injection comparison.

Following the hyaluronidase injections patients reported significant relief from muscle stiffness and showed increased arm movement. The hyaluronan concentration in the biceps and triceps was significantly higher in patients pre-injection, and was reduced post-injection. Note the change in muscle shape from triangular to more circular as in controls post-injection in the patient.

3D T1ρ mapping of the muscle can be used to detect intramuscular GAG content (hyaluronan) non-invasively. The muscle micro-environment can contribute to muscle stiffness, and injections of the enzyme hyaluronidase can be used to restore normal muscle microenvironment and reduce muscle stiffness post-stroke.