Clinical, neuropathological and neuroimaging research suggests that pathological changes in Parkinson’s disease (PD) start many years before the emergence of motor signs. Since disease-modifying treatments are likely to be most effective when initiated early in the disease process, there has been significant interest in characterizing prodromal PD. Some people with PD describe autonomic symptoms at the time of diagnosis suggesting that autonomic dysfunction is a common feature of prodromal PD. Furthermore, subtle motor signs may be present and emerge prior to the time of diagnosis. We present a series of patients who, in the prodromal phase of PD, experienced the emergence of tremor initially only while yawning or straining at stool and discuss how early involvement of autonomic brainstem nuclei could lead to these previously unreported phenomena. The hypothalamic paraventricular nucleus (PVN) plays a central role in autonomic control including bowel/bladder function, cardiovascular homeostasis and yawning and innervates multiple brainstem nuclei involved in autonomic functions (including brainstem reticular formation, locus ceruleus, dorsal raphe nucleus and motor nucleus of the vagus). The PVN is affected in PD and evidence from related phenomena suggest that the PVN could increase tremor either by increasing downstream cholinergic activity on brainstem nuclei such as the reticular formation or by stimulating the locus ceruleus to activate the cerebellothalamocortical network via the ventrolateral nucleus of the thalamus. Aberrant cholinergic/noradrenergic transmission between these brainstem nuclei early in PD couldlead to tremor before the emergence of other parkinsonian signs, representing an early clinical clue to prodromal PD.

中文翻译：

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前驱帕金森病震颤的出现

临床、神经病理学和神经影像学研究表明，帕金森病 (PD) 的病理变化在运动症状出现前多年就开始了。由于在疾病过程的早期开始改善疾病的治疗可能最有效，因此人们对表征前驱 PD 产生了浓厚的兴趣。一些 PD 患者在诊断时描述自主神经症状，表明自主神经功能障碍是前驱 PD 的常见特征。此外，在诊断之前，可能存在和出现细微的运动体征。我们介绍了一系列患者，他们在 PD 的前驱期，最初仅在打哈欠或大便时出现震颤，并讨论了自主脑干核的早期受累如何导致这些以前未报告的现象。下丘脑室旁核 (PVN) 在自主控制中起核心作用，包括肠/膀胱功能、心血管稳态和打哈欠，并支配与自主功能有关的多个脑干核（包括脑干网状结构、蓝斑、中缝背核和运动神经核）。迷走神经）。PVN 在 PD 中受到影响，相关现象的证据表明 PVN 可以通过增加脑干核（如网状结构）的下游胆碱能活动或通过刺激蓝斑通过丘脑腹外侧核激活小脑丘脑皮质网络来增加震颤. PD 早期这些脑干核之间的异常胆碱能/去甲肾上腺素能传递可能导致其他帕金森症状出现之前的震颤，