1Quantification 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°, 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 (≥8) activation. Work required per unit displacement was calculated. 2Specificity: 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. 3Validation 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. 4Sensitivity 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, ≤6 h) was delayed, compatible with a gastrointestinal anti‐muscarinic action and the subjects' ages. 5Reliability (Fleiss's criterion) was shown to be good in 30 untreated parkinsonians.

London WC1 lAX 1 We have used gait analysis to investigate the efficacy of maintenance therapy with a levodopa/carbidopa combination in patients with idiopathic Parkinsonism, who do not have overt fluctuations in control in relation to administration of medication. 2 Fourteen patients (aged 64 to 88 years) receiving maintenance therapy with levodopa and carbidopa (Sinemet Plus) entered a placebo-controlled, randomised cross-over study of the effect of omission of a morning dose of active treatment on distance/time parameters of gait. Measurements made 2, 4 and 6 h after the morning treatment were standardised by taking the pre-treatment measurement on that day as baseline. 3 The mean increase in stride length (7%) and decrease in double support time (20%) on active treatment were small but statistically significant (P < 0.0001, in each case), there being no significant placebo effect on either gait parameter (P = 0.69 and 0.08 respectively). Neither active nor placebo treatments had any significant (P > 0.45 in each case) effect on the lying, standing or postural fall in mean arterial pressure, measurements being made in the same temporal relation to the treatments as was gait. 4 In a generalised linear model, after allowing for the effect (P < 0.0001) of intrinsic variability in pre-treatment speed as well as for structure of the study, nature of treatment had an effect on stride length over the whole walk, significant at P = 0.002. 5 Pre-treatment postural fall in mean arterial pressure was nearly as significant (P = 0.003) as the nature of treatment in the context of such a model: the greater the fall, the greater the increment in stride length seen following active or placebo treatment. This was probably explained by an acquired tolerance to the fall as the day progressed. 6 The major determinant (P < 0.0001) of the change in double support time over the whole walk, after allowing for the structure of the study, appeared to be the post treatment mean arterial standing blood pressure. The lower the pressure, the shorter the double support time, and hence, the greater the tendency to a hurried gait. 7 Nature of treatment, when added into the models described in summary points 5 and 6, had no significant effect (P > 0.25, in each case). 8 In elderly patients without overt fluctuations in performance in relation to medication, the effect of intrinsic variability in mean arterial pressure on gait, may confound the interpretation of an apparent treatment effect on stride length and, to an even greater extent, on double support time.

Work on the causation of idiopathic parkinsonism is limited by relying on gross clinical definition and lack of studies in the old. A prognostic index for parkinsonism, based on hypo/bradykinesia of gait, had considerably higher values in spouses of 20 aged suffers, who had been cohabiting for about half a century, than in 40 controls. Postural abnormality, measured by standing sway and foot separation during walking, was also greater in these spouses. Marked differences remained after correction for relevant covariates. A blinded rigidity rating was greater in the spouses of sufferers, tremor rating was not. The differences found are difficult to explain by selective mating, learned or reactive behaviour. This suggests that environmental causative influences operate in adult life.

Reaction time was studied in 103 subjects with idiopathic parkinsonism and 144 without. Central processing time, as measured by the response to a warning, had a component which could be explained by the presence or absence of parkinsonism, but not by the ageing process, a mental test score, or consumption of exogenous substances. Depression did not influence the efficiency of response. Cigarette smoking and anti-parkinsonian medication were associated with greater efficiency.