The McCasland Family Comprehensive Headache Center, Ochsner Neuroscience Institute, Ochsner Clinic Foundation, New Orleans, LA, USA.
The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA, USA.
Headache. 2020 Jan;60(1):291-297. doi: 10.1111/head.13696. Epub 2019 Nov 14.
This basic review is intended to summarize the current knowledge of methemoglobinemia as an important cause of secondary headache with the hope of generating a growing interest in studying this phenomenon.
We describe the pathological underpinnings of headaches generated by hypoxia. Possible mechanisms include cerebral vasodilation-associated stretching of the vessel nociceptors, sensitization of perivascular nociceptors mediated by nitric oxide, cerebral calcitonin gene-related peptide, activation of the cyclic adenosine monophosphate pathway, cortical spreading depression, disruption of the blood-brain barrier, and neurogenic inflammation. We review the clinical features, pathophysiology, and management of methemoglobinemia. We conducted a literature review of reports of symptomatic methemoglobinemia with headache. In addition, we describe a case report of a patient who presented with an acute onset of severe holocranial headache associated with rapidly progressive perioral paresthesia, cyanosis in lips and hands, nausea, and mild dyspnea on exertion. These features can be misinterpreted as an acute attack of migraine with pain-related hyperventilation syndrome and anxiety leading to clinically detrimental delay in the management of the progressive hypoxia. Her symptoms resolved following treatment with methylene blue. The complex relationship of migraine and hypoxia-related headaches is also reviewed. We propose that methemoglobinemia-associated headaches are possibly generated by stretching of the nociceptor nerve endings during cerebral vasodilation and hypoxia-mediated oxidative stress.
The case highlights the need to broaden the formulated differential diagnosis of an acute onset severe holocranial headache and pay careful attention to other signs and symptoms that may provide hints on potential mechanism(s) for secondary headaches. We provide justification for the need to incorporate "Headache attributed to Methemoglobinemia" as a subtype under the section "Headache attributed to hypoxia and/or hypercapnia" of the International Classification of Headache Disorders to support clinical decision making.
本篇基础综述旨在总结高铁血红蛋白血症引起继发性头痛这一重要病因的现有知识，以期引起人们对该现象研究的兴趣。
我们描述了由缺氧引起的头痛的病理基础。可能的机制包括血管痛觉感受器的扩张相关的拉伸、一氧化氮介导的血管周围痛觉感受器的敏化、环磷酸腺苷通路的激活、皮质扩散性抑制、血脑屏障破坏和神经源性炎症。我们综述了高铁血红蛋白血症的临床特征、病理生理学和治疗方法。我们对伴有头痛的症状性高铁血红蛋白血症的报告进行了文献回顾。此外，我们还描述了一例患者的病例报告，该患者表现为急性发作的严重全颅头痛，伴有快速进展的口周感觉异常、口唇和手部发绀、恶心和轻度运动时呼吸困难。这些特征可能被误诊为伴有疼痛相关过度通气综合征和焦虑的偏头痛急性发作，导致对进行性缺氧的管理产生临床上不利的延误。她的症状在接受亚甲蓝治疗后得到缓解。偏头痛和缺氧相关性头痛的复杂关系也进行了综述。我们提出，高铁血红蛋白血症相关头痛可能是由脑扩张期间痛觉感受器神经末梢的拉伸和缺氧介导的氧化应激引起的。
该病例强调了需要拓宽急性发作严重全颅头痛的制定鉴别诊断，并仔细注意其他可能提示继发性头痛潜在机制的体征和症状。我们为将“归因于高铁血红蛋白血症的头痛”作为《国际头痛疾病分类》“归因于缺氧和/或高碳酸血症”章节下的一个亚型纳入提供了理由，以支持临床决策。
