一些帕金森患者可能受益于非多巴胺能治疗
Some Parkinson’s Patients May Benefit from Non-dopaminergic Treatments
March 6, 2018 by Iqra Mumal In News.
Non-dopaminergic treatments might be beneficial for Parkinson’s disease patients whose tremor is associated with a dysfunction of the serotonergic system, an area of the brain directly connected to serotonin interactions.
A study with that finding, “Progression of tremor in early stages of Parkinson’s disease: a clinical and neuroimaging study,” was published in the journal Brain.
The pathological hallmark of Parkinson’s disease is degeneration of a part of the brain called the substantia nigra, which contains dopaminergic neurons (nerve cells responsible for releasing the neurotransmitter dopamine that acts as a central power-driver for brain activity).
Dysfunction of dopaminergic neurons can lead to tremors, which can be clinically classified as rest (occurring when the muscle is relaxed and the most common in Parkinson’s), postural (occurring when a person maintains a position against gravity, such as holding the arms outstretched), or kinetic (associated with any voluntary movement, such as moving the wrists up and down or closing and opening the eyes).
The mechanism behind the occurrence of rest tremors in Parkinson’s disease remains poorly understood. It is known, however, that rest tremors often are less responsive to dopamine replacement therapy, suggesting that dopamine deficiency alone does not determine tremor severity.
The serotonergic system, which originates from an area of the brain called the brainstem raphe nuclei, is known to be disrupted in Parkinson’s disease. Nerve cells that make up the serotonergic system, and can be found within the raphe nuclei, have serotonin transporters, which are small proteins responsible for the transport of the neurotransmitter serotonin and the correct communication between nerve cells.
Dysfunction of these molecules is known to increase the severity of rest tremor in Parkinson’s patients.
In this study, researchers used clinical and imaging data from the Parkinson’s Progressive Markers Initiative database to assess for the prevalence and progression of resting tremor, postural tremor, and kinetic tremor during early Parkinson’s disease.
Clinical analysis of tremors was conducted on 378 patients: 87.8% presented with tremor at baseline; rest tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up. Postural and kinetic tremors occurred in about 50% of patients at both baseline and follow-up.
Data revealed that, as disease progressed, dysfunction of both the serotonergic system and the dopaminergic system could contribute to the occurrence of rest tremors. In fact, patients with fewer available serotonin transporters had more severe resting tremors. Additionally, severity of the tremors also was higher in patients with higher raphe nuclei dysfunction and connected to a poorer response to dopaminergic therapy.
Based on this clinical data, the authors believe that non-dopaminergic treatments might be beneficial for patients whose tremor is associated with a dysfunction of the serotonergic system, in particular that associated with a raphe-predominant dysfunction.
非多巴胺能治疗可能有益于帕金森病患者, 其震颤与血清素系统功能障碍有关, 大脑区域直接与血清素相互作用有关。
一项研究发现, "帕金森病早期震颤的进展: 临床和神经影像学研究" 发表在《 脑 》上。.
帕金森病的病理特征是大脑的一部分被称为黑质,含有多巴胺能神经元 (神经细胞负责释放神经递质多巴胺, 充当中枢大脑活动的动力驱动程序)。
多巴胺能神经元功能障碍可导致震颤, 这可以临床归类为休息 (发生时肌肉放松和最常见的帕金森氏), 体位 (发生时, 一个人保持一个立场反对重力, 如伸出双臂), 或运动 (与任何自愿运动有关, 如移动手腕向上和向下或关闭和睁开眼睛)。
帕金森病患者静止震颤发生的机制仍不清楚。然而, 众所周知, 静止的震颤往往对多巴胺替代疗法反应较少, 表明多巴胺缺乏本身并不决定震颤的严重性。
血清素系统, 起源于大脑中称为脑干中缝核的区域, 它被称为帕金森病的干扰。神经细胞组成的血清素系统, 并可以发现在中缝核, 有血清素转运蛋白, 这是小蛋白质负责运输的神经递质血清素和正确的沟通神经细胞之间。
众所周知, 这些分子的功能障碍会增加帕金森患者的静止震颤的严重性。
在这项研究中, 研究人员使用了来自帕金森进步标记倡议数据库的临床和影像数据来评估早期帕金森患者的静止震颤、体位性震颤和动态震颤的患病率和进展情况。疾病.
对378例患者进行了震颤的临床分析: 87.8% 为基线震颤;69.6% 例患者在基线时出现静止震颤;和67.9% 的后续行动。在基线和随访中大约50% 的患者出现体位和运动性震颤。
数据显示, 随着疾病的进展, 血清素系统和多巴胺能系统的功能失调会导致静止震颤的发生。事实上, 使用较少的血清素转运蛋白的患者有更严重的静止震颤。此外, 高的中缝核功能障碍患者的震颤程度也较高, 与多巴胺能疗法的反应较差有关。
根据这一临床数据, 作者认为, 非多巴胺能治疗对震颤与血清素系统功能障碍相关的患者是有益的, 尤其是与中缝主要功能障碍有关的病人。
