Objective measurement of activation of rigidity: diagnostic, pathogenetic and therapeutic implications in parkinsonism.

1. Quantification of the effect on rigidity of its 'activation', by isometric grip, of standardized pressure, of the contralateral hand, was explored. Torque required to move the forearm through a fixed angle of 40 degrees, at a controlled rate of 0.5 Hz, in a horizontal plane about a pivotal axis aligned to the elbow joint, was recorded before (12 'baseline' recordings), during (10), and after (> or = 8) activation. Work required per unit displacement was calculated. 2. Specificity: Pilot serial daytime measurements gave an overall mean ratio, work required on activation over baseline, of 2.94 (95% CI 2.53, 3.42) in two elderly untreated parkinsonians, and 3.19 (2.75, 3.71) in two elderly subjects with isolated, clinically activation phenomenon, compared with 1.90 (1.64, 2.21) in two elderly without (P < 0.001), whilst two young adults did not activate, 0.98 (0.85, 1.14). In elderly subjects, work required under activation decreased during the day in health (-10 (-5, -14)% h-1, P = 0.0002), showed no significant change in those with clinical activation (4 (-1, 9)% h-1), and increased in parkinsonians (6 (0, 12)% h-1, P = 0.05): there appeared to be a transitionary state. 3. Validation of methodology: Quantifying the same work ratio on a single occasion in 20 aged parkinsonians (P), their spouses (Ps), 20 index controls (C) without parkinsonism, matched to (P), and their spouses (Cs) gave corroborative evidence of a pre-clinical state, defined by other measurements, in the spouses of sufferers. Values for C, Cs and Ps, 1.89 (1.42, 2.52), 2.38 (1.79, 3.17) and 2.93 (2.20, 3.90) respectively, were in consecutive positions, from health to (P, 2.96 (2.22, 3.95)) disease (P = 0.001 for Ps c.f. C; P = 0.1 for Ps c.f. Cs). Data on change over the day may enhance discrimination. 4. Sensitivity to medicines was illustrated, in two parkinsonians, by randomised, placebo balanced and controlled challenges: 1 and 2 tablets, Sinemet CR (Du Pont Pharmaceuticals, each levodopa 200 mg/carbidopa 50 mg) and 1 tablet, Sinemet-Plus (levodopa 100 mg/carbidopa 25 mg), then two 2 mg tablets, benzhexol. The dopaminergic effect (P < 0.001) was selective for activation (treatment.test-condition interaction, P = 0.004), and showed the expected time profiles. The effect of benzhexol (P = 0.008) lacked such selectivity. Its onset (> 4, < or = 6 h) was delayed, compatible with a gastrointestinal anti-muscarinic action and the subjects' ages. 5. Reliability (Fleiss's criterion) was shown to be good in 30 untreated parkinsonians.