恩他卡朋添加治疗症状波动的帕金森病的随机、双盲、安慰剂对照临床研究

目的:探讨添加恩他卡朋治疗PD患者剂末现象的疗效和安全性。方法:40例伴有剂末现象的PD患者进行随机、双盲、安慰剂、平行分组临床对照试验。根据患者日记记录的"开"、"关"期时间、UPDRS各部分评分、研究者总体评估变化量表和左旋多巴每日剂量来评定疗效。结果:恩他卡朋治疗12周时能显著延长"开"期时间、缩短"关"期时间,降低UPDRS评分,减少每日左旋多巴用量,研究者主观感觉65%的患者病情好转,与安慰剂组相比差异有显著意义。不良事件的发生率与安慰剂组相比差异无显著意义。结论:添加恩他卡朋治疗伴有剂末现象的PD患者安全、有效。     

Mood fluctuations in Parkinson's disease: a pilot study comparing the effects of intravenous and oral levodopa administration

OBJECTIVES: Parkinson's disease (PD) is associated with motor fluctuations that have been shown to improve when stable plasma levodopa levels are achieved with continuous levodopa infusions. Many patients also develop mood fluctuations. In this pilot study, we gathered preliminary information about the relationship between changing mood states and plasma levodopa levels. METHODS: Six patients with idiopathic PD and histories of motor and mood fluctuations participated in a double-blind levodopa infusion study. Subjects received active oral carbidopa/levodopa and a placebo levodopa infusion on one day and placebo oral carbidopa/levodopa and an active levodopa infusion on the other day, in a randomly determined order. Evaluations included serial plasma levodopa levels and assessments of mood and motor states. RESULTS: Only 4 of the 6 subjects demonstrated mood fluctuations on at least one of the treatment days. All subjects achieved more stable plasma levodopa levels on the active infusion day. Two subjects experienced fewer mood fluctuations on the active infusion day and two experienced fewer on the oral day. Conclusions The results of this pilot study suggest that the relationship between mood state and plasma levodopa level may vary among PD patients.     

Effects of levodopa oral bolus on the kinematics of the pointing movements in Parkinson’s disease patients

We studied the time-course of a levodopa oral bolus effects on the kinematics of patients affected by a mild akinetic–rigid form of idiopathic Parkinson’s disease (PD). Eleven PD patients were evaluated: a) in OFF–state, that is before their first medication or after its withdrawal, b) in ON–state, that is at 1/2, 1, 2, 3, 4, 5, 6, 24, 30 and 48 hours after the administration of 250 mg of levodopa plus 25mg of carbidopa. The main kinematics (i. e.movement time, peak of velocity, peak of acceleration and peak of deceleration) of pointing movements to six target–stimuli placed on the horizontal plane of a table were recorded. Clinical conditions were assessed according to the Motor Examination section of the Unified Parkinson’s Disease Rating Scale. The levopoda bolus had stable clinical effects only within the first six hours from its administration. The decline of the clinical response was marked by the changes of peak acceleration whereas other kinematics (i. e. movement time and the peak of velocity) changed also in the late observations (24, 30 and 48 hours after drug intake). The dissociation between the persistent improvement on movement time on peak velocity and the rapid deterioration of levodopa effects on early kinematics (i. e. peak acceleration) could be accounted for by a progressive decline in movement programming.     

Combining entacapone with levodopa/DDCI improves clinical status and quality of life in Parkinson’s Disease (PD) patients experiencing wearing-off,regardless of the dosing frequency: results of a large multicentre open-label study

Summary. The efficacy of entacapone and its impact on patient quality of life (QOL) was investigated in an open-label study of 899 patients with idiopathic Parkinsons Disease (PD) experiencing wearing-off fluctuations. Patients were divided into 3 groups (3, 4 or 5 doses daily) based on their current levodopa dosage frequency. Patients received 200mg entacapone with each levodopa/dopa-decarboxylase inhibitor (DDCI) dose, while continuing their same levodopa/DDCI dosage regimen for 4 weeks. Primary efficacy measure was the Investigators Clinical Global Impression of Change (CGIC). Patient QoL was assessed using the validated 8-item Parkinsons Disease Questionnaire (PDQ-8). Investigators CGIC revealed that 76.5% of entacapone treated patients experienced an improvement in global status after 4 weeks. Treatment with entacapone was also associated with improvement in patient QoL, with a mean reduction (improvement) in PDQ-8 score of 1.8 from baseline. This study confirms and extends the results of earlier studies demonstrating that, independent of dosing frequency, completing levodopa/DDCI therapy with entacapone provides clinically relevant improvements in global status and QoL in PD patients experiencing wearing-off on their current levodopa dosing frequency.     

Repeated rating improves value of diagnostic dopaminergic challenge tests in Parkinson's disease

Summary. Clinicians use acute challenges with levodopa (LD) and/or apomorphine (A) for diagnostic dopaminergic response tests in Parkinson's disease (PD) patients. We consecutively compared the value of both drugs with performance of repeated ratings and adverse effect recording. Oral administration of 200 mg LD was superior to subcutaneous injection of 4 mg A in terms of tolerability and onset of temporary UPDRS motor score decline ([previously untreated PD patients] LD: 4.02 [mean] ± 2.45 [SD] {significant decrease: p = 1.42E-07} vs. A: 1.58 ± 3.38 {not significant decrease: p = 0.14}, p = 0.0009; [treated PD patients] LD: 7.71 ± 4.35 {significant decrease: p = 2.48E-06} vs. A: 5.19 ± 4.32 {significant decrease: p = 7.83E-05}, p = 0.07). We suggest diagnostic acute challenge test performance with LD as first- and A as second choice due to better tolerability and valuation in combination with repeated scoring procedures to improve sensitivity and specifity. Received December 12, 2002; accepted January 20, 2003 Published online April 7, 2003 Authors' address: Prof. Dr. Th. Müller, Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany, e-mail: thomas.mueller@ruhr-uni-bochum.de     

Duodenal levodopa infusion in Parkinson's disease--long-term experience

Motor fluctuations in parkinsonian patients can be reduced by intraduodenal infusion of levodopa. Between 1991 and 1998 continuous daytime administration of levodopa through a transabdominal port has been used in 28 very advanced patients over a total period of 1045 months. A stable suspension of levodopa and carbidopa (Duodopa) has been developed. Patients were characterized by early onset, long history of disease and levodopa therapy. The reason for infusion was in all cases related to on-off fluctuations. All patients experienced a general improvement after the introduction of continuous treatment. There have been no severe complications. Six patients have taken the decision to curtail their treatment. The mean daily levodopa consumption has been slightly reduced on infusion as compared to oral therapy. Nine of the first group of patients participating in the new therapy have been regularly evaluated by means of rating scales and movement analyses. Short-term results have already been published and a follow-up showing continued positive effect after 4-7 years of continuous duodenal infusion is presented.     

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke – a randomized,double‐blind,placebo‐controlled trial

Lokk J, Salman Roghani R, Delbari A. Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke – a randomized, double‐blind, placebo‐controlled trial.
Acta Neurol Scand: 2011: 123: 266–273.
© 2010 John Wiley & Sons A/S. Objective – Amphetamine‐like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. Material and methods – A randomized, double‐blind, placebo‐controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl‐Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. Results – All participants showed recovery of motor function and ADL during treatment and at 6‐month follow‐up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6‐month follow‐up. Conclusion – Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most.     

Combination of a dopamine agonist, MAO-B inhibitor and levodopa — a new strategy in the treatment of early Parkinson's disease

Abstract– During 3 years'treatment of de novo parkinsonian patients with lisuride in combination with selegiline and levodopa the optimal therapeutic dose of levodopa was significantly lower than that when given alone or together with lisuride. The improvement in parkinsonian disability was equal in all these patient groups, but treatment with an early combination of lisuride and levodopa without or with selegiline resulted in significantly and equally reduced end-of-dose disturbances and dyskinesias than treatment with levodopa alone. This finding, together with the possible retardation of the progression of the disease with selegiline suggests that dopaminergic treatment in early Parkinson's disease should be initiated using a dopamine agonist such as lisuride in combination with selegiline and levodopa.     

Selegiline and levodopa in early or moderately advanced Parkinson's disease: a double-blind controlled short- and long-term study

Abstract– Selegiline 10 mg per day was compared to placebo as an adjunct to levodopa treatment in this double-blind study of early or moderately advanced Parkinson's disease. Thirty-eight patients completed an initial cross-over trial comprising two treatment periods, each of eight weeks, with a four weeks'wash-out period between them. Thirty of the patients continued in a long-term, double-blind parallel trial with a mean duration of 16 months (range 6–30 months). Selegiline treatment allowed a significant reduction of the necessary daily levodopa dose in both parts of the study and of the daily dosing frequency in the long-term investigation. In spite of this reduction of levodopa dose, an improvement was noted in tremor during the short-term selegiline periods. The side-effects were slight and related to dopamine effects and disappeared after reduction of levodopa-dose. The results support the use of selegiline as an early adjunctive treatment in Parkinson's disease.     

Effects of dopaminergic medications on psychosis and motor function in dementia with Lewy bodies

Dopaminergic treatment in dementia with Lewy bodies (DLB) requires balancing risk of worsened psychosis and potential motor benefit. We assessed the effects of increased dopaminergic medication on psychosis and motor function in DLB. We studied 19 subjects fulfilling probable DLB Consensus criteria before and after increased dopaminergic medications. Standard clinical measures included: Thought Disorder score from the Unified Parkinson's disease Rating Scale (UPDRS) Part I, total motor score (UPDRS Part III), and Hoehn–Yahr (H&Y) stage. Motor benefit defined as >10% improvement over baseline UPDRS Part III score, occurred in only one‐third of subjects. In this group, worsened hallucinations or psychosis developed in one‐third. Considering motor benefit without exacerbation of psychosis as our aim, only 4 DLB subjects (22%) achieved this goal. Our results suggest that dopaminergic medications have limited benefit in DLB because of the low likelihood of motor improvement and the risk of psychosis exacerbation. © 2008 Movement Disorder Society