National Hospital for Neurology and Neurosurgery, London, UK.
University College London Hospitals NHS Foundation Trust, London, UK.
BMC Neurol. 2023 Apr 26;23(1):167. doi: 10.1186/s12883-023-03197-4.
Severely elevated serum homocysteine is a rare cause of ischaemic stroke and extra-cranial arterial and venous thrombosis. Several factors can lead to mild elevation of homocysteine including dietary folate and B12 deficiency, and genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. The use of Anabolic androgenic steroid (AAS) is under-reported, but increasingly linked to ischaemic stroke and can raise homocysteine levels.
We present a case of a man in his 40s with a large left middle cerebral artery (MCA) territory ischaemic stroke and combined multifocal, extracranial venous, and arterial thrombosis. His past medical history was significant for Crohn's disease and covert use of AAS. A young stroke screen was negative except for a severely elevated total homocysteine concentration, folate and B12 deficiencies. Further tests revealed he was homozygous for the methylenetetrahydrofolate reductase enzyme thermolabile variant (MTHFR c.667 C > T). The etiology of this stroke was a hypercoagulable state induced by raised plasma homocysteine. Raised homocysteine in this case was likely multifactorial and related to chronic AAS use in combination with the homozygous MTHFR c.677 C > T thermolabile variant, folate deficiency and, vitamin B12 deficiency.
In summary, hyperhomocysteinemia is an important potential cause of ischaemic stroke and may result from genetic, dietary, and social factors. Anabolic androgenic steroid use is an important risk factor for clinicians to consider, particularly in cases of young stroke with elevated serum homocysteine. Testing for MFTHR variants in stroke patients with raised homocysteine may be useful to guide secondary stroke prevention through adequate vitamin supplementation. Further studies looking into primary and secondary stroke prevention in the high-risk MTHFR variant cohort are necessary.
同型半胱氨酸水平显著升高是缺血性卒中以及颅外动脉和静脉血栓形成的罕见病因。多种因素可导致同型半胱氨酸轻度升高，包括饮食叶酸和维生素 B12 缺乏以及亚甲基四氢叶酸还原酶（MTHFR）酶的遗传变异。合成代谢雄激素（AAS）的使用报告较少，但与缺血性卒中的关系日益密切，并可升高同型半胱氨酸水平。
我们报告了一例 40 多岁男性，患有左大脑中动脉（MCA）大面积缺血性卒中以及多灶性颅外静脉和动脉血栓形成。他的既往病史包括克罗恩病和隐匿性 AAS 使用。年轻卒中筛查除了总同型半胱氨酸浓度、叶酸和维生素 B12 缺乏严重升高外，结果均为阴性。进一步的检查显示他是亚甲基四氢叶酸还原酶酶不耐热变异（MTHFR c.667 C > T）的纯合子。该卒中的病因是由升高的血浆同型半胱氨酸引起的高凝状态。该病例中同型半胱氨酸升高可能是多因素的，与慢性 AAS 使用以及纯合子 MTHFR c.677 C > T 不耐热变异、叶酸缺乏和维生素 B12 缺乏有关。
总之，高同型半胱氨酸血症是缺血性卒中的一个重要潜在病因，可能由遗传、饮食和社会因素引起。AAS 使用是临床医生需要考虑的一个重要危险因素，特别是在血清同型半胱氨酸升高的年轻卒中患者中。在同型半胱氨酸升高的卒中患者中检测 MTHFR 变异可能有助于通过适当的维生素补充来指导二级卒中预防。需要进一步研究高危 MTHFR 变异人群中的一级和二级卒中预防。
