Therapeutic effects of anti-spastic medication on neuromuscular abnormalities in SCI: A system identification approach

Previous attempts to investigate the effects of antispastic medications are limited to clinical studies using that use clinical evaluations to assess. Since these measures are neither objective nor quantitative, the therapeutic effects of such medications on neuromuscular properties have not been fully evaluated. In this study, as a first attempt, we examined the effect of tizanidine, an anti-spastic medication, on modification of the neuromuscular properties of patients with chronic incomplete spinal cord injury (SCI). Each patient was administered 2 mg of tizanidine four times per day for four weeks. The spastic ankle of each patient was evaluated at baseline (prior to any medication, and then 1, 2, and 4 weeks after the start of medication. The ankle was perturbed with a small-amplitude Pseudo-Random Binary Sequence (PRBS) perturbation at various positions over the ankle range-of-motion. A parallel-cascade system identification technique, which provides an objective and quantitative measure of neuromuscular properties, was used to calculate the intrinsic and reflex stiffness. The stiffness vs. joint angle trends were then calculated for each evaluation; these curves were compared across the intervention time to determine the recovery pattern (i.e. change over time) due to the tizanidine intervention. All patients exhibited decreases in reflex stiffness (which abnormally increase after SCI) due to the medication; however, patients were observed to exhibit multiple recovery patterns. For some patients, the reflex stiffness continuously reduced over the four-week intervention period, while for other patients, the decrease during the first week (i.e. between the baseline and 1-Week evaluations) was most pronounced. Also, some patients presented a significant decrease with time, while others presented no improvement in the intrinsic stiffness. These findings suggest that tizanidine may be effective in reducing not only reflex stiffness, but also the subject's intrinsic stiffness for certain patients. Future work remains to identify predictors which can objectively determine which patients are likely to exhibit maximal benefit from the tizanidine prior to being prescribed with the medication.