Department of Neurology, New York University School of Medicine, 530 First Avenue, Suite 9Q, New York, NY, 10016, USA.
Departament of Neurology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico D.F., Mexico.
Clin Auton Res. 2019 Sep;29(Suppl 1):33-44. doi: 10.1007/s10286-019-00623-x. Epub 2019 Aug 26.
Neurogenic orthostatic hypotension is a prominent and disabling manifestation of autonomic dysfunction in patients with hereditary transthyretin (TTR) amyloidosis affecting an estimated 40-60% of patients, and reducing their quality of life. We reviewed the epidemiology and pathophysiology of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis, summarize non-pharmacologic and pharmacological treatment strategies and discuss the impact of novel disease-modifying treatments such as transthyretin stabilizers (diflunisal, tafamidis) and RNA interference agents (patisiran, inotersen).
Literature review.
Orthostatic hypotension in patients with hereditary transthyretin amyloidosis can be a consequence of heart failure due to amyloid cardiomyopathy or volume depletion due to diarrhea or drug effects. When none of these circumstances are apparent, orthostatic hypotension is usually neurogenic, i.e., caused by impaired norepinephrine release from sympathetic postganglionic neurons, because of neuronal amyloid fibril deposition.
When recognized, neurogenic orthostatic hypotension can be treated. Discontinuation of potentially aggravating medications, patient education and non-pharmacologic approaches should be applied first. Droxidopa (Northera), a synthetic norepinephrine precursor, has shown efficacy in controlled trials of neurogenic orthostatic hypotension in patients with hereditary TTR amyloidosis and is now approved in the US and Asia. Although they may be useful to ameliorate autonomic dysfunction in hereditary TTR amyloidosis, the impact of disease-modifying treatments on neurogenic orthostatic hypotension is still uninvestigated.
神经源性直立性低血压是影响约 40-60%患者的遗传性转甲状腺素蛋白（TTR）淀粉样变性患者自主神经功能障碍的突出和致残表现，降低了他们的生活质量。我们回顾了遗传性 TTR 淀粉样变性患者神经源性直立性低血压的流行病学和病理生理学，总结了非药物和药物治疗策略，并讨论了新型疾病修饰治疗（如转甲状腺素蛋白稳定剂[二氟尼柳、他法米汀]和 RNA 干扰剂[patisiran、inotersen]）对其的影响。
文献回顾。
遗传性转甲状腺素蛋白淀粉样变性患者的直立性低血压可能是由于淀粉样心肌病引起的心力衰竭或腹泻或药物作用引起的容量不足所致。当这些情况都不明显时，直立性低血压通常是神经性的，即由于神经元淀粉样纤维沉积导致交感节后神经元去甲肾上腺素释放受损所致。
当认识到神经源性直立性低血压时，可以进行治疗。首先应停用可能加重病情的药物、对患者进行教育并采取非药物方法。Droxidopa（Northera）是一种合成的去甲肾上腺素前体，在遗传性 TTR 淀粉样变性患者的神经源性直立性低血压对照试验中显示出疗效，现已在美国和亚洲获得批准。尽管它们可能有助于改善遗传性 TTR 淀粉样变性中的自主神经功能障碍，但疾病修饰治疗对神经源性直立性低血压的影响仍有待研究。
