帕金森病及其胃肠道神经胃肠动力效应的当前治疗方法。
Parkinson's Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects.
作者信息
Ramprasad Chethan, Douglas Jane Yellowlees, Moshiree Baharak
机构信息
Internal Medicine Residency, New York University School of Medicine, New York City, NY, USA.
Carolinas Healthcare-Charlotte, UNC School of Medicine, Charlotte Campus, 1025 Morehead Medical Dr. Suite 300, Charlotte, NC, 28204, USA.
出版信息
Curr Treat Options Gastroenterol. 2018 Dec;16(4):489-510. doi: 10.1007/s11938-018-0201-3.
Gastrointestinal disturbances are seen in nearly all patients with Parkinson's disease and lead to impaired quality of life, affect drug pharmacodynamics, and potentially worsen patient's existing motor fluctuations, leading to further disability. Recent evidence links abnormal accumulations of α-synuclein aggregates in the periphery (gut) as seen in the cortex which causes dysfunctions impacting every level of the gastrointestinal tract from the esophagus, to the stomach, small bowel, colon, and rectum and can even predate the onset of the central neurologic disorder itself. Many treatments exist for the clinical phenotypes that result from the autonomic dysfunction and neuropathy involved in this neurodegenerative disorder. The treatments for the gut dysfunction seen in Parkinson's disease (PD) depend on the specific area of the gastrointestinal tract affected. For dysphagia, behavioral therapies with speech pathology, neuromuscular electrical stimulation, or botulinum toxin injection may be helpful. For gastroparesis, domperidone may serve as an antiemetic while also blunting the hypotensive potential of Levodopa while new treatments such as ghrelin agonists may prove beneficial to help appetite, satiety, gastric emptying in those with constipation, and even improve constipation. Antibiotics such as rifaximin with poor systemic absorption may be used to treat small bacterial overgrowth also found in those with PD while the benefits of probiotics is yet to be determined. Finally, constipation in PD can be a reflection of pelvic floor dyssynergia, slow transit constipation, or both, thus treatments targeting the specific anorectal dysfunction is necessary for better outcomes.
几乎所有帕金森病患者都会出现胃肠道功能紊乱,这会导致生活质量下降,影响药物药效学,并可能使患者现有的运动波动恶化,导致进一步的残疾。最近的证据表明,在外周(肠道)中异常积累的α-突触核蛋白聚集体,就像在大脑皮层中看到的那样,会导致功能障碍,影响从食道到胃、小肠、结肠和直肠的胃肠道各个层面,甚至可能早于中枢神经系统疾病本身的发作。对于这种神经退行性疾病中涉及的自主神经功能障碍和神经病变所导致的临床表型,有许多治疗方法。帕金森病(PD)中出现的肠道功能障碍的治疗方法取决于受影响的胃肠道的特定区域。对于吞咽困难,言语病理学行为疗法、神经肌肉电刺激或肉毒杆菌毒素注射可能会有所帮助。对于胃轻瘫,多潘立酮可作为止吐药,同时也可减弱左旋多巴的降压作用,而诸如胃饥饿素激动剂等新疗法可能被证明有助于改善便秘患者的食欲、饱腹感、胃排空,甚至改善便秘。全身吸收差的抗生素如利福昔明可用于治疗帕金森病患者中也存在的小肠细菌过度生长,而益生菌的益处尚未确定。最后,帕金森病中的便秘可能是盆底协同失调、慢传输型便秘或两者兼有的反映,因此针对特定肛门直肠功能障碍的治疗对于获得更好的效果是必要的。