A Case Report of N2O Abuse-Induced Straight Sinus Thrombosis in a Female Patient Harboring MTHFR C677T Homozygous Mutation

doi:10.3969/j.issn.1673-5765.2025.12.012

Chinese Journal of Stroke ›› 2025, Vol. 20 ›› Issue (12): 1565-1570.DOI: 10.3969/j.issn.1673-5765.2025.12.012

Previous Articles Next Articles

A Case Report of N₂O Abuse-Induced Straight Sinus Thrombosis in a Female Patient Harboring MTHFR C677T Homozygous Mutation

LI Xue¹, SHI Jina¹, LIU Yanjun², LIU Wei²

1 Lanzhou University Second Clinical Medical School, Lanzhou 730030, China
2 Department of Neurology, The Second Hospital, Lanzhou University, Lanzhou 730030, China

Received:2025-06-16 Revised:2025-12-11 Accepted:2025-12-12 Online:2025-12-20 Published:2025-12-20
Contact: LIU Wei, E-mail: ery_liuwer@lzu.edu.cn

N₂O滥用诱发MTHFR C677T纯合突变女性患者直窦血栓形成1例报道

李雪¹，史季娜¹，刘妍君²，刘伟²

1 兰州 730030 兰州大学第二临床医学院
2 兰州大学第二医院神经内科

通讯作者: 刘伟 ery_liuwer@lzu.edu.cn
基金资助:
兰州市科技发展指导性计划项目（2023-ZD-84）
兰州市科技计划项目（2023-4-43）
兰州大学第二医院“萃英科技创新”计划（CY2022-BJ-01）
兰州大学第二医院萃英学子科研培育计划项目（CYXZ2023-52）

Abstract

Abstract: Cerebral venous thrombosis (CVT) is a rare type of stroke pathologically characterized by thrombus formation within the intracranial veins or venous sinuses. This paper reports a case of a patient harboring a homozygous mutation (TT genotype) of methylenetetrahydrofolate reductase (MTHFR) C677T, who developed straight sinus thrombosis following nitrous oxide (N2O) inhalation and hyperhomocysteinemia, with concurrent vitamin B12 deficiency and megaloblastic anemia. After six months of anticoagulation therapy, along with vitamin B12 and folic acid supplementation, the patient’s symptoms improved, and the extent of straight sinus thrombosis significantly decreased. This case suggests that genetic susceptibility (MTHFR 677TT genotype), environmental exposure (N2O abuse), and vitamin B12 deficiency collectively contribute to the pathophysiological process of CVT. This case report enhances clinicians’ awareness of early screening and intervention for high-risk populations, and it also holds significant social significance in advocating public prevention and control of N2O abuse.

Key words: Cerebral venous thrombosis; Hyperhomocysteinemia; Methylenetetrahydrofolate reductase; Gene polymorphism; Nitrous oxide

摘要： 脑静脉血栓形成（cerebral venous thrombosis，CVT）是一种以颅内静脉或静脉窦内血栓形成为病理特征的罕见卒中类型。本文报道1例携带亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）C677T纯合突变（TT基因型）的患者，该患者因一氧化二氮（nitrous oxide，N2O）吸入和高同型半胱氨酸血症诱发直窦血栓形成，同时还合并维生素B12缺乏症及巨幼红细胞贫血，予以抗凝治疗及维生素B12、叶酸补充治疗6个月后，其症状好转，直窦血栓范围明显缩小。本病例提示遗传易感性（MTHFR 677TT基因型）、环境暴露（N2O滥用）及维生素B12缺乏共同参与了CVT的病理生理过程。本病例报道有助于提高临床医师对CVT高危人群的早期筛查与干预意识，同时对倡导全民防控N2O滥用具有重要的社会意义。

关键词: 脑静脉血栓形成; 高同型半胱氨酸血症; 亚甲基四氢叶酸还原酶; 基因多态性; 一氧化二氮

CLC Number:

LI Xue, SHI Jina, LIU Yanjun, LIU Wei. A Case Report of N₂O Abuse-Induced Straight Sinus Thrombosis in a Female Patient Harboring MTHFR C677T Homozygous Mutation[J]. Chinese Journal of Stroke, 2025, 20(12): 1565-1570.

李雪, 史季娜, 刘妍君, 刘伟. N₂O滥用诱发MTHFR C677T纯合突变女性患者直窦血栓形成1例报道[J]. 中国卒中杂志, 2025, 20(12): 1565-1570.

References

[1] ZAFIROVA Z，SHEEHAN C，HOSSEINIAN L. Update on nitrous oxide and its use in anesthesia practice[J]. Best Pract Res Clin Anaesthesiol，2018，32（2）：113-123.
[2] LEW V，MCKAY E，MAZE M. Past，present，and future of nitrous oxide[J]. Br Med Bull，2018，125（1）：103-119.
[3] OULKADI S，PETERS B，VLIEGEN A S. Thromboembolic complications of recreational nitrous oxide（ab）use：a systematic review[J]. J Thromb Thrombolysis，2022，54（4）：686-695.
[4] 中华医学会神经病学分会，中华医学会神经病学分会脑血管病学组. 中国颅内静脉血栓形成诊断和治疗指南2019[J]. 中华神经科杂志，2020，53（9）：648-663.
Chinese Society of Neurology，Chinese Stroke Society. Chinese guidelines for diagnosis and treatment of cerebral venous thrombosis 2019[J]. Chin J Neurol，2020，53（9）：648-663.
[5] STOLZ E，GERRIETS T，BÖDEKER R H，et al. Intracranial venous hemodynamics is a factor related to a favorable outcome in cerebral venous thrombosis[J]. Stroke，2002，33（6）：1645-1650.
[6] MORRIS N，LYNCH K，GREENBERG S A. Severe motor neuropathy or neuronopathy due to nitrous oxide toxicity after correction of vitamin B12 deficiency[J]. Muscle Nerve，2015，51（4）：614-616.
[7] MAZDEH M，KHAZAIE M，OMRANI M D，et al. Association between methylene tetrahydrofolate reductase polymorphisms and risk of ischemic stroke[J]. Int J Neurosci，2021，131（1）：44-48.
[8] HUANG L W，LI L L，LI J，et al. Association of the methylenetetrahydrofolate reductase（MTHFR）gene variant C677T with serum homocysteine levels and the severity of ischaemic stroke：a case-control study in the southwest of China[J/OL]. J Int Med Res，2022，50（2）：3000605221081632[2025-08-15]. https://doi.org/10.1177/03000605221081632.
[9] ZHAO L L，LI T，DANG M J，et al. Association of methylenetetrahydrofolate reductase（MTHFR）
rs1801133（677C>T）gene polymorphism with ischemic stroke risk in different populations：an updated meta-analysis[J/OL]. Front Genet，2023，13：1021423[2025-08-15]. https://doi.org/10.3389/fgene.2022.1021423.
[10] AMES P R J，D’ANDREA G，MAROTTOLI V，et al. Earlier onset of peripheral arterial thrombosis in homozygous MTHFR C677T carriers than in other MTHFR genotypes：a cohort study[J]. Clin Exp Med，2023，23（2）：503-509.
[11] LAURETTA M P，MELOTTI R M，SANGERMANO C，et al. Homocysteine plasmatic concentration in brain-injured neurocritical care patients：systematic review of clinical evidence[J/OL]. J Clin Med，2022，11（2）：394[2025-08-15]. https://doi.org/10.3390/jcm11020394.
[12] SAPOSNIK G，BUSHNELL C，COUTINHO J M，et al. Diagnosis and management of cerebral venous thrombosis：a scientific statement from the American Heart Association[J/OL]. Stroke，2024，55（3）：e77-e90[2025-08-15]. https://doi.org/10.1161/STR.0000000000000456.
[13] ESMAEILI S，ABOLMAALI M，AARABI S，et al. Rivaroxaban for the treatment of cerebral venous thrombosis[J/OL]. BMC Neurol，2021，21（1）：73[2025-08-15]. https://doi.org/10.1186/s12883-021-02091-1.
[14] LIU M，ZHANG J，BU B T. Isolated cortical vein thrombosis after nitrous oxide use in a young woman：a case report[J/OL]. BMC Neurol，2020，20：378[2025-08-15]. https://doi.org/10.1186/s12883-020-01961-4.
[15] PRATT D N，PATTERSON K C，QUIN K. Venous thrombosis after nitrous oxide abuse，a case report[J]. J Thromb Thrombolysis，2020，49（3）：501-503.
[16] HUANG X，BAO H H，DING C C，et al. Optimal folic acid dosage in lowering homocysteine：precision folic acid trial to lower homocysteine（PFAT-Hcy）[J]. Eur J Nutr，2024，63（5）：1513-1528.

A Case Report of N₂O Abuse-Induced Straight Sinus Thrombosis in a Female Patient Harboring MTHFR C677T Homozygous Mutation

N₂O滥用诱发MTHFR C677T纯合突变女性患者直窦血栓形成1例报道

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

[1]	QIAN Yutong, ZHANG Shufan, HAN Zhenxiang, WU Weicheng, HAN Xiang. Residual Metabolic Risk Factors and Stroke in Young Adults [J]. Chinese Journal of Stroke, 2024, 19(12): 1400-1408.
[2]	FAN Yuhua, DANG Chao, YU Jian, CHEN Hongbing, DUAN Jiangang, MO Dapeng, ZHU Wenhao, OUYANG Fubing, WANG Bo, ZENG Jinsheng, the Writing Committee of Chinese Stroke Association Guidelines for Clinical Management of Cerebrovascular Diseases. Chinese Stroke Association Guidelines for Clinical Management of Cerebrovascular Diseases (Second Edition) (Excerpt)——Chapter Seven Clinical Management of Cerebral Venous Thrombosis [J]. Chinese Journal of Stroke, 2023, 18(9): 1030-1035.
[3]	WENG Jiaxu, ZHOU Hongyu, LI Zixiao. DNA Methylation and Hyperhomocysteinemia [J]. Chinese Journal of Stroke, 2023, 18(04): 404-409.
[4]	DENG Qi-Le, WU Jie-Hong, CHEN Ji-Xiang. Progress of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in the Treatment of Ischemic Stroke [J]. Chinese Journal of Stroke, 2021, 16(08): 850-854.
[5]	XU Li, YUAN Dan, GONG Zhong, WANG Ying-Peng, LI Dong-Hua, WANG Hai-Peng. Headache Characteristics of Cerebral Venous Thrombosis Patients with Headache as the Sole Presentation [J]. Chinese Journal of Stroke, 2020, 15(12): 1313-1316.
[6]	ZHENG Hua-Guang, LIU Xiao-Nan, ZHANG Wei-Wei, ZHANG Long-You, WANG Rui-Qing, MENG Qing-Ying,DUAN Yun-Yun, LIU Ya-Ou, WANG Yong-Jun. Association of Hypertension and Hyperhomocysteinemia with Silent Brain Infarction in the Healthy [J]. Chinese Journal of Stroke, 2020, 15(08): 861-868.
[7]	ZHOU Hong-Yu, SUO Yue, CHEN Wei-Qi, WANG Yong-Jun. Progress of Ring Finger Protein 213 Gene-related Cerebrovascular Disease [J]. Chinese Journal of Stroke, 2020, 15(02): 195-201.
[8]	WANG Ming-Yu, ZHANG Li-Hui, ZHOU Hao, ZHAO Yong. Correlation between MTHFR C677T Gene Polymorphism and Cognitive Impairment in Patients with Cerebral Small Vessel Disease [J]. Chinese Journal of Stroke, 2019, 14(11): 1095-1100.
[9]	LU Dong, ZHAO Wei, DU Jing, GENG Jie-Li, WANG Yao, CAO Wen-Wei, YU Ling, ZHI Nan,ZHOU Yan, XU Qun. Study on the Correlation between Blood Homocysteine Level and Cognitive Function in Patients with Cerebrovascular Disease [J]. Chinese Journal of Stroke, 2019, 14(02): 100-105.
[10]	ZHAO Chen-Wei, ZHANG Jun-Fang, WU Yun-Cheng. Research Progress of Hereditary Stroke [J]. Chinese Journal of Stroke, 2019, 14(01): 54-57.
[11]	ZENG Tao, XIAO Xuan-Hao, XU Bang-Lao, LEI Xiu-Xia, LI Ze, ZHOU Jin, HUANG Hui, PAN Xiao-Ping. Association of CYP2C19 Gene Polymorphisms with Risk of Recurrent Stroke in First-ever Ischemic Stroke Patients with Clopidogrel for Secondary Prevention [J]. Chinese Journal of Stroke, 2018, 13(09): 908-914.
[12]	ZHANG Lu, CUI Xiao-Yan, ZHANG Bo-Ai. Analysis of Relationship of Plasma Homocysteine Level and Polymorphism of Methylenetetrahydrofolate Reductase with Ischemic Stroke [J]. Chinese Journal of Stroke, 2017, 12(05): 404-409.
[13]	HUANG Huan, ZHAO Gang. Advances in Relation between Folic Acid and Ischemic Stroke [J]. Chinese Journal of Stroke, 2017, 12(05): 457-461.
[14]	ZHOU-Hao, WEI Shou-Chao, ZHAO Xing-Jun, et al.. Study on the Correlation between Polymorphism of 5,10 Methylenetetrahydrofolate Reductase Gene and Carotid Atherosclerosis in Patients with Cerebral Infarction [J]. Chinese Journal of Stroke, 2017, 12(01): 23-28.
[15]	MO Da-Peng, LUO Gang, WANG Yi-Long, et al.. Primary Analysis of the Multiple Mode of Endovascular Treatments for Progressively Acute Cerebral Venous Sinus Thrombosis [J]. Chinese Journal of Stroke, 2016, 11(09): 764-768.