Study of levodopa response in Parkinson's disease: Observations on rates of motor progression.

INTRODUCTION: It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment. METHODS: The methods for this study comprised prospective defined off state measurements of the levodopa response at 3-year intervals over a mean 13.3-year period in 34 patients enrolled before treatment initiation. RESULTS: Despite worsening of on and off scores, the magnitude of the l-dopa short-duration response is maintained as the disease progresses. A linear mixed-effects regression analysis of off phase motor scores showed a yearly deterioration of 2.3% of the maximum disability score. Greater motor disability at the commencement of treatment was an independent predictor of faster progression. Demented patients had worse motor function than those without dementia (P = 0.02), and motor deficit appeared to accelerate toward the end of the disease course in patients who had died. CONCLUSIONS: These observations should inform clinical trial design for drugs with possible neuroprotective properties.

Disturbances of automatic gait control mechanisms in higher level gait disorder.

The underlying mechanisms responsible for the gait changes in frontal gait disorder (FGD), a form of higher level gait disorders, are poorly understood. We investigated the relationship between stride length and cadence (SLCrel) in people with FGD (n=15) in comparison to healthy older adults (n=21) to improve our understanding of the changes to gait in FGD. Gait data was captured using an electronic walkway system as participants walked at five self-selected speed conditions: preferred, very slow, slow, fast and very fast. Linear regression was used to determine the strength of the relationship (R(2)), slope and intercept. In the FGD group 9 participants had a strong SLCrel (linear group) (R(2)>0.8) and 6 a weak relationship (R(2)<0.8) (nonlinear group). The linear FGD group did not differ to healthy control for slope (p>0.05) but did have a lower intercept (p<0.001). The linear FGD group modulated gait speed by adjusting stride length and cadence similar to controls whereas the nonlinear FGD participants adjusted stride length but not cadence similar to controls. The non-linear FGD group had greater disturbance to their gait, poorer postural control and greater fear of falling compared to the linear FGD group. Investigation of the SLCrel resulted in new insights into the underlying mechanisms responsible for the gait changes found in FGD. The findings suggest stride length regulation was disrupted in milder FGD but as the disorder worsened, cadence control also became disordered resulting in a break down in the relationship between stride length and cadence.