Cost-Effectiveness and Cost-Utility of Early Levodopa in Parkinson's Disease

Background: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40 weeks followed by levodopa/carbidopa 100/25 mg three times per day for 40 weeks (delayed-start).Objective: This paper reports the results of the economic evaluation performed alongside the LEAP-study.Methods: Early-start treatment was evaluated versus delayed-start treatment, in which the cost-effectiveness analysis (CEA) and the cost-utility analysis (CUA) were performed from the societal perspective, including health care costs among providers, non-reimbursable out-of-pocket expenses of patients, employer costs of sick leave, and lowered productivity while at work. The outcome measure for the CEA was the extra cost per unit decrease on the Unified Parkinson's Disease Rating Scale 80 weeks after baseline. The outcome measure for the CUA was the extra costs per additional quality adjusted life year (QALY) during follow-up.Results: 212 patients in the early-start and 219 patients in the delayed-start group reported use of health care resources. With savings of D 59 per patient (BCa 95% CI: -829, 788) in the early-start compared to the delayed-start group, societal costs were balanced. The early-start group showed a mean of 1.30 QALYs (BCa 95% CI: 1.26, 1.33) versus 1.30 QALYs (BCa 95% CI: 1.27, 1.33) for the delayed-start group. Because of this negligible difference, incremental cost-effectiveness and cost-utility ratios were not calculated.Conclusion: From an economic point of view, this study suggests that early treatment with levodopa is not more expensive than delayed treatment with levodopa.Neurological Motor Disorder

Responsiveness to botulinum toxin type A in muscles of complex regional pain patients with tonic dystonia

Tonic dystonia of the limbs in complex regional pain syndrome (CRPS) is associated with considerable disability. Treatment options are scarce. Botulinum toxin (BoNT) is sometimes used, but the effect is often said to be disappointing. However, this notion stems from case reports and clinicians' opinions but has never been formally studied. We therefore investigated responsiveness to BoNT in CRPS patients with tonic dystonia. We injected the extensor digitorum brevis (EDB) muscle with BoNT-A in 17 patients with CRPS and tonic dystonia to compare the response between affected and unaffected legs. We also investigated the right legs of 17 healthy controls. Responsiveness was defined as a decrease of the amplitude of the compound muscle action potential (CMAP) of >20 % from baseline 2 weeks after BoNT-A injection. We controlled for a temperature effect on BoNT efficacy by measuring skin temperature hourly directly above the EDB muscle in the first 2 weeks. CMAP amplitude decreased >20 % after injection on the affected side in 16 of 17 CRPS patients, similar to the response in unaffected legs (12/13) or legs of controls (17/17). The degree of CMAP reduction was significantly smaller in patients than in controls (56.0 ± 22.3 vs. 70.6 ± 14.6 %; p = 0.031). This may be due to a lower physical activity level and a greater difficulty to localize the EDB muscle properly in affected legs. The decrease in CMAP amplitude was not related to skin temperature. Contrary to the prevailing opinion, BoNT-A has a normal, although perhaps slightly lower efficacy in CRPS patients with dystoni

Cerebral activation during motor imagery in complex regional pain syndrome type 1 with dystonia

The pathogenesis of dystonia in Complex Regional Pain Syndrome type 1 (CRPS-1) is unclear. In primary dystonia, functional magnetic resonance imaging (fMRI) has revealed changes in cerebral networks during execution of movement. The aim of this study was to determine cerebral network function in CRPS-1 patients with dystonic postures. Cerebral processing related to both execution and imagining of hand movements in patients and controls was assessed with fMRI. Eight CRPS-1 patients with dystonic postures of the right upper extremity and 17 age-matched healthy controls were studied. Compared with controls, imaginary movement of the affected hand in patients showed reduced activation ipsilaterally in the premotor and adjacent prefrontal cortex, and in a cluster comprising frontal operculum, the anterior part of the insular cortex and the superior temporal gyrus. Contralaterally, reduced activation was seen in the inferior parietal and adjacent primary sensory cortex. There were no differences between patients and controls when they executed movements, nor when they imagined moving their unaffected hand. The altered cerebral activation pattern in patients with CRPS-I linked dystonia most likely reflects an interface between pain-associated circuitry and higher order motor control, which points at a specific mechanistic pathophysiology of this type of dystonia. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved

გოჩა ბაბუნაშვილი

გოჩა ბაბუნაშვილი - თბილისის საკრებულოს წევრ

Levodopa Response in Patients with Early Parkinson Disease: Further Observations of the LEAP Study

Background and Objectives: The Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease. Methods: The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations. Results: A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early-and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was-0.33 for bradykinesia,-0.29 for rigidity, and-0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively,-0.49,-0.36, and-0.44 (small to medium effect); and from baseline to week 40, respectively,-0.32,-0.19, and-0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01). Discussion: In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. Classification of Evidence: This study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment. Trial Registration Information: ISRCTN30518857, EudraCT number 2011-000678-72

Mitochondrial haplogroups and cognitive progression in Parkinson's disease

International audienceMitochondria are a culprit in the onset of Parkinson's disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson's disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P = 2.42 × 10-6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56-0.81) and P = 2.46 × 10-5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson's disease over time