Przuntek H, Welzel D, Schwarzmann D, Letzel H, Kraus P H
Neurological Clinic, Ruhr University Bochum, St.-Josef-Hospital, FRG.
Eur Neurol. 1992;32 Suppl 1:36-45. doi: 10.1159/000116868.
The aim of this multicenter randomized prospective study in patients with early Parkinson's disease is to differentiate over a 4-year period between levodopa/benserazide monotherapy and the corresponding combination with bromocriptine by the assessment of motorial side effects, therapeutical benefit and fine motorial skills. Although there is circumstantial evidence, that partial substitution of levodopa by bromocriptine carries benefit in preventing late levodopa-specific side effects and delaying the declining therapeutical benefit, so far no knowledge has been available how levodopa and the corresponding combination with bromocriptine would compare on a long-term basis. Such study appears all the more important since there are experimental findings consistent with a neurotoxic effect of levodopa on the one hand and some 'protective' impact of bromocriptine on the other. As to the practical procedure of the comparison, all patients were first treated with a levodopa monotherapy for 3 months. This was a platform for the consecutive randomized splitting of the patients into two groups receiving either continuing levodopa therapy or combination therapy, based upon at least 40 +/- 10% substitution of levodopa by bromocriptine. The investigation methods included, besides the usual clinical rating scales (Webster, Zung, Hoehn and Yahr), an apparative test series, the so-called 'MLS', which allowed a sensitive and reliable assessment of fine motorial skills. The results of the first 3 months of treatment with levodopa monotherapy before the consecutive splitting into the two treatment regimens demonstrate that the randomization was successful and that there were no significant differences, that potentially might interfere with the drug-specific evaluation afterwards. The results of the substitution phase show that combined treatment permitted a mean reduction of the levodopa dosage by 40%, without deterioration of therapeutic response. In addition, feasibility of the overall approach based upon a sophisticated interplay between the practising neurologists (101) and the centers (27) was demonstrated.
这项针对早期帕金森病患者的多中心随机前瞻性研究的目的是，通过评估运动副作用、治疗效果和精细运动技能，在4年时间里区分左旋多巴/苄丝肼单一疗法以及与溴隐亭的相应联合疗法。虽然有间接证据表明，用溴隐亭部分替代左旋多巴在预防晚期左旋多巴特异性副作用和延缓治疗效果下降方面有益，但到目前为止，尚不清楚左旋多巴以及与溴隐亭的相应联合疗法在长期使用时如何进行比较。鉴于一方面有实验结果表明左旋多巴具有神经毒性作用，另一方面溴隐亭有一些“保护”作用，这样的研究显得尤为重要。关于比较的实际操作过程，所有患者首先接受3个月的左旋多巴单一疗法治疗。这为随后将患者连续随机分为两组奠定了基础，一组继续接受左旋多巴治疗，另一组接受联合治疗，联合治疗中溴隐亭至少替代40±10%的左旋多巴。除了常用的临床评定量表（韦伯斯特、zung、霍恩和雅尔）外，研究方法还包括一系列仪器测试，即所谓的“MLS”，它能够对精细运动技能进行灵敏且可靠的评估。在连续分为两种治疗方案之前，左旋多巴单一疗法治疗的前3个月结果表明随机分组是成功的，并且不存在可能干扰后续药物特异性评估的显著差异。替代阶段的结果显示，联合治疗使左旋多巴剂量平均减少了40%，而治疗反应并未恶化。此外，还证明了基于执业神经科医生（101名）和各中心（27个）之间复杂相互作用的整体方法的可行性。
