Background: In patients with advanced Parkinson disease (PD) who are undergoi ng long term treatment with a dopaminergic medication, a down regulation of st riatal dopamine D2 receptor expression has been demonstrated...Background: In patients with advanced Parkinson disease (PD) who are undergoi ng long term treatment with a dopaminergic medication, a down regulation of st riatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. Objective: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who com pletely discontinued dopaminergic therapy (off drug) with that in PD patients wh o continued receiving dopaminergic therapy (on drug) after undergoing subthalami c nucleus stimulation. Main Outcome Measures: The positron emission tomographic data were acquired in off stimulation and, for 12 hours, offmedication conditio ns. Five off drug PD patients, 7 on drug PD patients, and 8 healthy subjects p articipated. Results: In off drug PD patients, the putaminal raclopride C 11 bi nding was 24%higher than in on drug PD patients. The same tendency was noted f or the caudate nucleus, but was not significant (P=.07). Compared with control s ubjects, the putaminal raclopride C 11 binding was increased by 21%in off drug and was normal in on drug PD patients. Compared with controls, the caudate rac lopride C 11 binding was reduced by 23%in on drug and was normal in off drug PD patients. Further analysis using statistical parametric mapping showed a sign ificant increase of binding bilaterally in the caudate nucleus and putamen in of fdrug compared with on drug PD patients (P=.002 at cluster level). Conclusions: The down regulation of dopamine D2 receptors probably relates to the long ter m and intermittent administration of dopaminergic treatments rather than to dise ase progression. This phenomenon is reversed by the complete withdrawal of dopam inergic drugs. Furthermore, an up regu lation of putaminal dopamine D2 recepto rs is demonstrated in late stage PD after dopaminergic drug withdrawal.展开更多
Background: The catechol O methyltransferase inhibitor entacaponeacts by exte nding the elimination half life of levodopaand is currently approved as an adju nct to levodopa for thetreatment of patients with Parkinson...Background: The catechol O methyltransferase inhibitor entacaponeacts by exte nding the elimination half life of levodopaand is currently approved as an adju nct to levodopa for thetreatment of patients with Parkinson disease (PD) with mo torfluctuations. Objective: To determine if the addition of entacapone administr ation provides benefit to levodopa treated PD patients who have a stable respon se to levodopa and do notexperience motor complications. Design: Prospective, do ubleblind,placebo controlled trial. Setting: Outpatient multicenter study. Pati ents: Female and male patients 30 years or older with idiopathic PD receiving st able doses of levodopa or carbidopa with or without other dopaminergic therapies and who did not experience motor fluctuations were eligible for the study. Main Outcome Measures: Parkinsonian function and quality of life. Results: The addit ion of entacapone did not improve motor scores on the Unified Parkinsons Disea se Rating Scale in levodopa treated PD patients who did not experience motor fl uctuations. The mean ±SE adjusted change between baseline and final treatment v isitwas -0.9±0.35 in the entacapone group and -0.8 ±0.35 in the placebo grou p (P = .83). Significant improvement with entacapone treatment was detected in s everal quality of life measures, including the Parkinson Disease Questionnaire 39, the 36 item Short Form Health Survey, the Parkinsons Symptom Inventory, and investigator and subject Clinical Global Assessments. The drug was well tolerated by patients in this population . Conclusions: The catechol Omethyltransferase inhibitor entacapone, used as an adjunct to levodopa in PD patients who do not experience motor fluctuations, doe s not improve Unified Parkinsons Disease Rating Scale motor scores but does im prove a variety of quality of life measures.展开更多
文摘Background: In patients with advanced Parkinson disease (PD) who are undergoi ng long term treatment with a dopaminergic medication, a down regulation of st riatal dopamine D2 receptor expression has been demonstrated and interpreted as a consequence of either the disease itself or dopaminergic drug administration. Objective: To compare, using positron emission tomography, the striatal binding of raclopride carbon C 11, a dopamine D2 receptor ligand, in PD patients who com pletely discontinued dopaminergic therapy (off drug) with that in PD patients wh o continued receiving dopaminergic therapy (on drug) after undergoing subthalami c nucleus stimulation. Main Outcome Measures: The positron emission tomographic data were acquired in off stimulation and, for 12 hours, offmedication conditio ns. Five off drug PD patients, 7 on drug PD patients, and 8 healthy subjects p articipated. Results: In off drug PD patients, the putaminal raclopride C 11 bi nding was 24%higher than in on drug PD patients. The same tendency was noted f or the caudate nucleus, but was not significant (P=.07). Compared with control s ubjects, the putaminal raclopride C 11 binding was increased by 21%in off drug and was normal in on drug PD patients. Compared with controls, the caudate rac lopride C 11 binding was reduced by 23%in on drug and was normal in off drug PD patients. Further analysis using statistical parametric mapping showed a sign ificant increase of binding bilaterally in the caudate nucleus and putamen in of fdrug compared with on drug PD patients (P=.002 at cluster level). Conclusions: The down regulation of dopamine D2 receptors probably relates to the long ter m and intermittent administration of dopaminergic treatments rather than to dise ase progression. This phenomenon is reversed by the complete withdrawal of dopam inergic drugs. Furthermore, an up regu lation of putaminal dopamine D2 recepto rs is demonstrated in late stage PD after dopaminergic drug withdrawal.
文摘Background: The catechol O methyltransferase inhibitor entacaponeacts by exte nding the elimination half life of levodopaand is currently approved as an adju nct to levodopa for thetreatment of patients with Parkinson disease (PD) with mo torfluctuations. Objective: To determine if the addition of entacapone administr ation provides benefit to levodopa treated PD patients who have a stable respon se to levodopa and do notexperience motor complications. Design: Prospective, do ubleblind,placebo controlled trial. Setting: Outpatient multicenter study. Pati ents: Female and male patients 30 years or older with idiopathic PD receiving st able doses of levodopa or carbidopa with or without other dopaminergic therapies and who did not experience motor fluctuations were eligible for the study. Main Outcome Measures: Parkinsonian function and quality of life. Results: The addit ion of entacapone did not improve motor scores on the Unified Parkinsons Disea se Rating Scale in levodopa treated PD patients who did not experience motor fl uctuations. The mean ±SE adjusted change between baseline and final treatment v isitwas -0.9±0.35 in the entacapone group and -0.8 ±0.35 in the placebo grou p (P = .83). Significant improvement with entacapone treatment was detected in s everal quality of life measures, including the Parkinson Disease Questionnaire 39, the 36 item Short Form Health Survey, the Parkinsons Symptom Inventory, and investigator and subject Clinical Global Assessments. The drug was well tolerated by patients in this population . Conclusions: The catechol Omethyltransferase inhibitor entacapone, used as an adjunct to levodopa in PD patients who do not experience motor fluctuations, doe s not improve Unified Parkinsons Disease Rating Scale motor scores but does im prove a variety of quality of life measures.
