Chavda Vishal, Chaurasia Bipin, Umana Giuseppe E, Tomasi Santino Ottavio, Lu Bingwei, Montemurro Nicola
Department of Pathology, Stanford of School of Medicine, Stanford University Medical Centre, Stanford, Palo Alto, CA 94305, USA.
Department of Neurosurgery, Neurosurgery Clinic, Birgunj 44300, Nepal.
Brain Sci. 2022 Oct 30;12(11):1473. doi: 10.3390/brainsci12111473.
Narcolepsy is a chronic, long-term neurological disorder characterized by a decreased ability to regulate sleep-wake cycles. Some clinical symptoms enter into differential diagnosis with other neurological diseases. Excessive daytime sleepiness and brief involuntary sleep episodes are the main clinical symptoms. The majority of people with narcolepsy experience cataplexy, which is a loss of muscle tone. Many people experience neurological complications such as sleep cycle disruption, hallucinations or sleep paralysis. Because of the associated neurological conditions, the exact pathophysiology of narcolepsy is unknown. The differential diagnosis is essential because relatively clinical symptoms of narcolepsy are easy to diagnose when all symptoms are present, but it becomes much more complicated when sleep attacks are isolated and cataplexy is episodic or absent. Treatment is tailored to the patient's symptoms and clinical diagnosis. To facilitate the diagnosis and treatment of sleep disorders and to better understand the neuropathological mechanisms of this sleep disorder, this review summarizes current knowledge on narcolepsy, in particular, genetic and non-genetic associations of narcolepsy, the pathophysiology up to the inflammatory response, the neuromorphological hallmarks of narcolepsy, and possible links with other diseases, such as diabetes, ischemic stroke and Alzheimer's disease. This review also reports all of the most recent updated research and therapeutic advances in narcolepsy. There have been significant advances in highlighting the pathogenesis of narcolepsy, with substantial evidence for an autoimmune response against hypocretin neurons; however, there are some gaps that need to be filled. To treat narcolepsy, more research should be focused on identifying molecular targets and novel autoantigens. In addition to therapeutic advances, standardized criteria for narcolepsy and diagnostic measures are widely accepted, but they may be reviewed and updated in the future with comprehension. Tailored treatment to the patient's symptoms and clinical diagnosis and future treatment modalities with hypocretin agonists, GABA agonists, histamine receptor antagonists and immunomodulatory drugs should be aimed at addressing the underlying cause of narcolepsy.
发作性睡病是一种慢性、长期的神经系统疾病，其特征是调节睡眠 - 觉醒周期的能力下降。一些临床症状会与其他神经系统疾病进行鉴别诊断。白天过度嗜睡和短暂的非自愿睡眠发作是主要临床症状。大多数发作性睡病患者会经历猝倒，即肌肉张力丧失。许多人还会出现神经并发症，如睡眠周期紊乱、幻觉或睡眠麻痹。由于相关的神经状况，发作性睡病的确切病理生理学尚不清楚。鉴别诊断至关重要，因为当所有症状都出现时，发作性睡病相对明显的临床症状很容易诊断，但当仅出现睡眠发作且猝倒为发作性或不存在时，诊断就会变得复杂得多。治疗是根据患者的症状和临床诊断量身定制的。为了促进睡眠障碍的诊断和治疗，并更好地理解这种睡眠障碍的神经病理机制，本综述总结了关于发作性睡病的当前知识，特别是发作性睡病的遗传和非遗传关联、直至炎症反应的病理生理学、发作性睡病的神经形态学特征，以及与其他疾病（如糖尿病、缺血性中风和阿尔茨海默病）的可能联系。本综述还报告了发作性睡病的所有最新研究和治疗进展。在突出发作性睡病的发病机制方面已经取得了重大进展，有大量证据表明存在针对下丘脑分泌素神经元的自身免疫反应；然而，仍有一些空白需要填补。为了治疗发作性睡病，更多的研究应集中在确定分子靶点和新型自身抗原上。除了治疗进展外，发作性睡病的标准化标准和诊断措施已被广泛接受，但未来可能会根据理解进行审查和更新。根据患者的症状和临床诊断进行量身定制的治疗，以及未来使用下丘脑分泌素激动剂、GABA激动剂、组胺受体拮抗剂和免疫调节药物的治疗方式，应旨在解决发作性睡病的根本原因。
