Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Centre of Expertise for Parkinson and Movement Disorders, Nijmegen, Netherlands.
Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA.
Lancet. 2021 Jun 12;397(10291):2284-2303. doi: 10.1016/S0140-6736(21)00218-X. Epub 2021 Apr 10.
Parkinson's disease is a recognisable clinical syndrome with a range of causes and clinical presentations. Parkinson's disease represents a fast-growing neurodegenerative condition; the rising prevalence worldwide resembles the many characteristics typically observed during a pandemic, except for an infectious cause. In most populations, 3-5% of Parkinson's disease is explained by genetic causes linked to known Parkinson's disease genes, thus representing monogenic Parkinson's disease, whereas 90 genetic risk variants collectively explain 16-36% of the heritable risk of non-monogenic Parkinson's disease. Additional causal associations include having a relative with Parkinson's disease or tremor, constipation, and being a non-smoker, each at least doubling the risk of Parkinson's disease. The diagnosis is clinically based; ancillary testing is reserved for people with an atypical presentation. Current criteria define Parkinson's disease as the presence of bradykinesia combined with either rest tremor, rigidity, or both. However, the clinical presentation is multifaceted and includes many non-motor symptoms. Prognostic counselling is guided by awareness of disease subtypes. Clinically manifest Parkinson's disease is preceded by a potentially long prodromal period. Presently, establishment of prodromal symptoms has no clinical implications other than symptom suppression, although recognition of prodromal parkinsonism will probably have consequences when disease-modifying treatments become available. Treatment goals vary from person to person, emphasising the need for personalised management. There is no reason to postpone symptomatic treatment in people developing disability due to Parkinson's disease. Levodopa is the most common medication used as first-line therapy. Optimal management should start at diagnosis and requires a multidisciplinary team approach, including a growing repertoire of non-pharmacological interventions. At present, no therapy can slow down or arrest the progression of Parkinson's disease, but informed by new insights in genetic causes and mechanisms of neuronal death, several promising strategies are being tested for disease-modifying potential. With the perspective of people with Parkinson's disease as a so-called red thread throughout this Seminar, we will show how personalised management of Parkinson's disease can be optimised.
帕金森病是一种可识别的临床综合征,其病因和临床表现多种多样。帕金森病代表着一种快速发展的神经退行性疾病;全球患病率的上升与大流行期间观察到的许多特征相似,只是没有传染性病因。在大多数人群中,3-5%的帕金森病是由与已知帕金森病基因相关的遗传原因引起的,因此代表单基因帕金森病,而 90 个遗传风险变异共同解释了非单基因帕金森病可遗传风险的 16-36%。其他因果关联包括有帕金森病或震颤的亲属、便秘和不吸烟,这些因素至少使帕金森病的风险增加一倍。诊断基于临床;辅助检查保留给表现不典型的人。目前的标准将帕金森病定义为存在运动迟缓,伴有静止性震颤、僵硬或两者兼有。然而,临床表现是多方面的,包括许多非运动症状。预后咨询取决于对疾病亚型的认识。有临床症状的帕金森病之前可能有一个潜在的较长前驱期。目前,除了抑制症状外,前驱期症状的确定对临床没有影响,尽管当出现可改变疾病进程的治疗方法时,前驱性帕金森病的识别可能会产生后果。治疗目标因人而异,强调需要个性化管理。对于因帕金森病而出现残疾的人,没有理由推迟对症治疗。左旋多巴是最常用的一线治疗药物。最佳治疗应从诊断开始,并需要多学科团队的方法,包括越来越多的非药物干预措施。目前,没有任何治疗方法可以减缓或阻止帕金森病的进展,但基于对遗传原因和神经元死亡机制的新认识,正在测试几种有前途的策略来改变疾病进程。以帕金森病患者的视角为贯穿整个研讨会的一条红线,我们将展示如何优化帕金森病的个性化管理。
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