Neuroscience Campus Amsterdam, Dept. of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S6-12. doi: 10.1016/S1353-8020(09)70770-9.
Clinical symptoms in Parkinson's disease (PD) comprise both motor and non-motor symptoms. In this disease, synucleinopathic-induced, nigral dopamine deficiency-related dysfunction of the basal ganglia is held responsible for the characteristic levodopa-responsive motor signs and symptoms (bradykinesia, hypokinesia, rigidity), known as parkinsonism and essential for clinical diagnosis in PD, as well as subtle motivational and cognitive dysfunctions. Some motor symptoms, such as tremor and postural instability, and most non-motor symptoms, however, are not fully levodopa-responsive, and suggested to manifest extranigral pathology. These symptoms include autonomic, sleep, sensory and neuropsychiatric symptoms, which in some cases may precede the first signs of motor parkinsonism, closely correlating with the progression of Lewy body pathology in PD. The recognition and treatment of these mostly under-recognized and under-treated symptoms is important, as these symptoms might have more impact on the quality of life in PD patients as compared to motor parkinsonism. On top of this, recognition of these manifestations in the prodromal phase of motor PD is critical to early diagnosis and treatment, as disease-modifying drugs, once identified, should be initiated as soon as possible, preferably in this premotor phase of the disease. On top of this, (non)motor extranigral symptoms in PD might also be of iatrogenic origin, whether directly as indirectly. During conventional, oral, dopaminomimetic treatment, the progressive loss of striatal dopaminergic nerve endings with the loss of cerebral dopamine storage capacity, renders the cerebral dopamine level fully dependent of the plasma levodopa levels, thus changing dopaminergic receptor stimulation from continuous to a more pulsatile pattern. Supposedly due to this process, neuroplastic changes in (sub)cortical dopaminergic pathways might cause therapeutic response fluctuations: motor and nonmotor fluctuations with anxiety- and panic-attacks and/or mood swings, dyskinesias and punding. Finally, dopaminomimetic pharmacotherapy may also induce extranigral non-motor drug-related direct adverse effects, such as impulse control disorders. In this article, non-motor signs and symptoms of extranigral PD-related pathology will be discussed, as well as the (suggested) criteria for diagnosis and treatment. Of course, also the recognition of the signs and symptoms of the prodromal (premotor) phase, suggestive for the presence of the PD, will be discussed. Iatrogenic non-motor symptoms, though, will not be further discussed.
帕金森病（PD）的临床症状包括运动症状和非运动症状。在这种疾病中，突触核蛋白诱导的黑质多巴胺缺乏相关的基底节功能障碍被认为是导致特征性左旋多巴反应性运动体征和症状（运动迟缓、运动减少、僵硬）的原因，这些症状被称为帕金森病，是 PD 临床诊断的必要条件，以及微妙的动机和认知功能障碍。然而，一些运动症状，如震颤和姿势不稳，以及大多数非运动症状，并非完全对左旋多巴有反应，并提示表现出额状核外的病理学。这些症状包括自主神经、睡眠、感觉和神经精神症状，在某些情况下，这些症状可能先于运动性帕金森病的第一个迹象出现，与 PD 中路易体病理学的进展密切相关。识别和治疗这些大多未被充分认识和治疗的症状很重要，因为与运动性帕金森病相比，这些症状可能对 PD 患者的生活质量产生更大的影响。除此之外，在运动性 PD 的前驱期识别这些表现对于早期诊断和治疗至关重要，因为一旦确定了可以改变疾病的药物，就应该尽快开始使用，最好在疾病的这个前期阶段开始使用。除此之外，PD 中的（非）运动性额状核外症状也可能具有医源性起源，无论是直接的还是间接的。在常规的、口服的、多巴胺能拟药治疗中，纹状体多巴胺能神经末梢的进行性丧失伴随着大脑多巴胺储存能力的丧失，使得大脑多巴胺水平完全依赖于血浆左旋多巴水平，从而使多巴胺受体刺激从连续模式转变为更脉冲式模式。据推测，由于这个过程，（亚）皮质多巴胺能通路中的神经可塑性变化可能导致治疗反应波动：运动和非运动波动伴焦虑和惊恐发作和/或情绪波动、运动障碍和冲动控制障碍。最后，多巴胺能拟药治疗也可能引起额状核外与药物相关的非运动性直接不良反应，如冲动控制障碍。本文将讨论与 PD 额状核外病理学相关的非运动性体征和症状，以及诊断和治疗的（建议）标准。当然，也将讨论提示 PD 存在的前驱（前期）阶段的体征和症状的识别。医源性非运动症状，虽然，将不再进一步讨论。
