In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0-014 and 0'004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually. (9 Neurol Neurosurg Psychiatry 1994;57: 1355-1359 Tizanidine (SirdaludO) is a centrally active a, adrenergic receptor agonist with potent myotonolytic action.l The substance was shown to suppress selectively polysynaptic spinal reflexes while sparing the monosynaptic reflexes.5 Clinical investigations have consistently shown an antispastic effect of tizanidine that was associated with little undue muscle weakness,69 sometimes associated with an improvement in paresis.10 There is, however, little information on the correlation between the antispastic effect and plasma concentrations of tizanidine. ' We report data on the correlations between single doses, plasma concentrations, and antispastic action of tizanidine in patients with spasticity due to multiple sclerosis, by means of an objective quantitative method and a clinical scale for the assessment of spasticity. Methods PATIENT SELECTIONSeventeen patients were entered into the study, but one patient was excluded from further analysis because the baseline severity of spasticity decreased during the study to below that stipulated in the protocol. There were 13 women and four men, mean age 43 (range 24-58) years. All patients had definite multiple sclerosis, diagnosed by clinical criteria and paraclinical investigations. Spasticity had been present for a mean of 70 (range 12-180) months and had been stable for a mean of 17 (range 2-48) months. Extensor spasticity reaching a minimum score of 2 on the Ashworth scale in at least one leg and remaining stable for at least one month was required as an entry criterion. All patients had a baseline score of either 2 or 3 on knee extensors, none had a score of 4, and none of them were bedridden. Patients receiving any drugs with antispastic action, those with significant systemic diseases, local complications, an exacerbation of the disease, or abnormalities in laboratory tests ...

The Wartenberg pendulum test is an objective quantitative method for the assessment of muscle tone. We have compared the results of measurements of muscle tone using this method with traditional clinical assessments graded on the Ashworth scale. Two indices ( R 1 and R 2 ) were measured from the Wartenberg test. Both were related to readings from the Ashworth scale. The ratio R 2 (the ratio of the amplitude of the first swing to the difference in angle between the start and finish positions), however, showed a linear relationship throughout the range of spasticity tested in contrast to the curvilinear relationship shown by R 1 (the ratio of the amplitude of the first swing to the difference between the rebound angle and the start angle). Significant changes in the ratio R 2 without any corresponding change in the Ashworth grading were observed. It is concluded that the Wartenberg ratio R 2 and the Ashworth scale assess similar features of the muscle and/or its motor control, but that the pendulum test provides a more finely graded observerindependent measurement.