摘要
BACKGROUND: Despite the known benefit of levodopa in reducing the symptoms of Parkinson’s disease, concern has been expressed that its use might hasten neu rodegeneration. This study assessed the effect of levodopa on the rate of progre ssion of Parkinson s disease. METHODS: In this randomized, double blind, pla cebocontrolled trial, we evaluated 361 patients with early Parkinson s disease who were assigned to receive carbidopa levodopa at a daily dose of 37.5 and 1 50 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson s Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamin e transporter density with the use of iodine 123 labeled 2 β carboxy methoxy 3 β (4 io dophe nyl) tropane ([123I]/β CIT) uptake. R ESULTS: The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the meandifference between the total score o n the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those re ceiving 300 mg daily, and 1.4 in those receiving 600 mg daily (P < 0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [123I] β CIT uptake was significantly greater with levodopa than placebo ( 6 percent among those receiving levodopa at 150 mg daily, 4 percent in those receiving it at 300 mg daily, and 7.2 percent among those receiving it at 600 mg daily, as compared with 1.4 percent among those recei ving placebo; 19 patients with no dopaminergic deficits on the baseline scans we re excluded from the analysis) (P=0.036). The subjects receiving the highest dos e of levodopa had significantly more dyskinesia,hypertonia, infection, headache, and nausea than those receiving placebo. CONCLUSIONS: The clinical data suggest that levodopa either slows the progression of Parkinson s disease or has a pr olonged effect on the symptoms of the disease. In contrast, the neuroimaging dat a suggest either that levodopa accelerates the loss of nigrostriatal dopamine ne rve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long term effects of levodopa on Parkinson s disease remain u ncertain.
BACKGROUND: Despite the known benefit of levodopa in reducing the symptoms of Parkinson's disease, concern has been expressed that its use might hasten neu rodegeneration. This study assessed the effect of levodopa on the rate of progre ssion of Parkinson s disease. METHODS: In this randomized, double blind, pla cebocontrolled trial, we evaluated 361 patients with early Parkinson s disease who were assigned to receive carbidopa levodopa at a daily dose of 37.5 and 1 50 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson s Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamin e transporter density with the use of iodine 123 labeled 2 β carboxy methoxy 3 β (4 io dophe nyl) tropane ([123I]/β CIT) uptake. R ESULTS: The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the meandifference between the total score o n the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those re ceiving 300 mg daily, and 1.4 in those receiving 600 mg daily (P < 0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [123I] β CIT uptake was significantly greater with levodopa than placebo ( 6 percent among those receiving levodopa at 150 mg daily, 4 percent in those receiving it at 300 mg daily, and 7.2 percent among those receiving it at 600 mg daily, as compared with 1.4 percent among those recei ving placebo; 19 patients with no dopaminergic deficits on the baseline scans we re excluded from the analysis) (P=0.036). The subjects receiving the highest dos e of levodopa had significantly more dyskinesia,hypertonia, infection, headache, and nausea than those receiving placebo. CONCLUSIONS: The clinical data suggest that levodopa either slows the progression of Parkinson s disease or has a pr olonged effect on the symptoms of the disease. In contrast, the neuroimaging dat a suggest either that levodopa accelerates the loss of nigrostriatal dopamine ne rve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long term effects of levodopa on Parkinson s disease remain u ncertain.
出处
《世界核心医学期刊文摘（神经病学分册）》
2005年第5期9-10,共2页
Digest of the World Core Medical Journals:Clinical Neurology
