Wolters Eric Ch, van der Werf Ysbrand D, van den Heuvel Odile A
Dept. of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
J Neurol. 2008 Sep;255 Suppl 5:48-56. doi: 10.1007/s00415-008-5010-5.
In Parkinson's disease (PD), there is increasing evidence for disorders in the impulsive-compulsive spectrum, related to the disease itself, to the pharmacological management of this disease or to both. These disorders comprise dopamine deficiency syndrome (with immediate reward seeking behaviour), dopamine dependency syndrome (with addictive behaviour), dopamine dysregulation syndrome (with both addictive behaviour and stereotyped behaviour) and impulse control disorders (such as pathological gambling, compulsive shopping, binge eating and hypersexuality). These disorders are especially seen in PD patients with young age of onset, higher doses of antiparkinsonian drugs, pre-existent or current depression, pre-existing recreational drug or alcohol use, and high novelty seeking personality traits.Dopamine is not only implicated in voluntary movement control but also plays a significant role in the brain's reward system and the modulation of behaviours. Therefore, most if not all drugnaïve PD patients will suffer dysphoria, leading to mild immediate reward seeking behaviour as a consequence of the striatal dopaminergic denervation. In some of these patients, during treatment, this may even lead to the intake of increasing quantities of levodopa, above those required to adequately treat motor parkinsonism, with all characteristics of a dopamine dependence syndrome. These patients may develop plastic changes in the striatal matrix leading to hyperkinesia, caused by extracellular striatal dopaminergic fluctuations due to pulsatile dopamine replacement therapy. As soon as these changes are also seen in the striatal striosomes, in the framework of a dopamine dysregulation syndrome, stereotyped behaviours (punding) may occur (supposedly due to dorsal versus ventral striatal overactivity). Finally, impulse control disorders are suggested as being pure adverse side-effects of dopamine replacement therapy. Obsessive-compulsive behaviour (caused by ventral to dorsal overactivity) so far has not been described in PD patients.Treatment of impulse control disorders is related to the underlying pathology. In the case of an intrinsic dopamine deficiency syndrome, treatment with dopamine replacement therapy, especially levodopa, will help. In the multifactorial (intrinsic and extrinsic) dopamine dependency and dysregulation syndromes, addictive behaviour might best be helped by psychosocial strategies, and punding by continuous dopaminergic receptor stimulation (or amantadine), hypothesized to reduce the plastic changes-induced hypersensitization. The extrinsic impulse control disorders might be best treated by reducing or replacing dopamine receptor agonists.
在帕金森病（PD）中，越来越多的证据表明，冲动控制谱系障碍与疾病本身、该疾病的药物治疗或两者都有关系。这些障碍包括多巴胺缺乏综合征（伴有即时奖赏寻求行为）、多巴胺依赖综合征（伴有成瘾行为）、多巴胺调节障碍综合征（伴有成瘾行为和刻板行为）以及冲动控制障碍（如病理性赌博、强迫性购物、暴饮暴食和性欲亢进）。这些障碍在发病年龄较轻、抗帕金森病药物剂量较高、既往或当前患有抑郁症、既往有使用消遣性药物或酒精史以及具有高寻求新奇人格特质的PD患者中尤为常见。多巴胺不仅参与自主运动控制，还在大脑奖赏系统和行为调节中发挥重要作用。因此，大多数（如果不是全部）未经药物治疗的PD患者会出现烦躁不安，由于纹状体多巴胺能去神经支配，导致轻微的即时奖赏寻求行为。在其中一些患者的治疗过程中，这甚至可能导致左旋多巴摄入量增加，超过充分治疗运动性帕金森病所需的量，呈现出多巴胺依赖综合征的所有特征。这些患者可能会在纹状体基质中发生可塑性变化，导致运动障碍，这是由脉冲式多巴胺替代疗法引起的细胞外纹状体多巴胺能波动所致。一旦在纹状体纹状体内也出现这些变化，在多巴胺调节障碍综合征的框架下，可能会出现刻板行为（反复做固定动作）（据推测是由于背侧与腹侧纹状体活动过度）。最后，冲动控制障碍被认为是多巴胺替代疗法的纯粹不良副作用。迄今为止，尚未在PD患者中描述过强迫行为（由腹侧到背侧活动过度引起）。冲动控制障碍的治疗与潜在病理相关。对于内在性多巴胺缺乏综合征，使用多巴胺替代疗法，尤其是左旋多巴进行治疗会有帮助。在多因素（内在和外在）多巴胺依赖和调节障碍综合征中，成瘾行为可能最好通过社会心理策略来帮助改善，而反复做固定动作则通过持续的多巴胺能受体刺激（或金刚烷胺）来改善，据推测这可以减少可塑性变化引起的超敏反应。外在性冲动控制障碍可能最好通过减少或替代多巴胺受体激动剂来治疗。
