Shimura Masaru, Yamada Hikari, Takahashi Hidekuni, Yamada Naoto, Go Soken, Yamanaka Gaku, Kawashima Hisashi
Department of Pediatrics, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami-machi, Inashiki-gun, Ibaraki, 300-0395, Japan.
Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
J Med Case Rep. 2019 Aug 12;13(1):250. doi: 10.1186/s13256-019-2188-3.
Various antiepileptic drugs can potentially cause psychiatric side effects in patients with epilepsy, but the precise mechanism of these actions remains unknown. In recent years, the common polymorphism C677T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has attracted attention for its role in the onset of psychiatric diseases. MTHFR and several vitamins (as cofactors) are crucial for remethylation of homocysteine via folate and homocysteine metabolism. We report a case of a Japanese patient who presented with reversible schizophrenia-like symptoms during antiepileptic drug therapy.
Our patient had frontal lobe epilepsy and had been treated with several antiepileptic drugs since the age of 13 years. He developed auditory hallucinations and multiple personalities at 17 years of age, several months after the initiation of phenytoin and phenobarbital, despite these antiepileptic drugs being used within the therapeutic ranges. Genetic analysis revealed that he was homozygous for the C677T polymorphism of MTHFR. Hyperhomocysteinemia, hypomethionemia, and multiple vitamin deficiencies, including folate, riboflavin, and pyridoxal, were identified at the age of 23 years. Vitamin supplementation and alteration of the antiepileptic drugs improved his psychotic symptoms. Multiple vitamin deficiencies with homozygous MTHFR C677T should be considered in patients presenting with schizophrenia-like symptoms during antiepileptic drug therapy.
To the best of our knowledge, this is the first report of antiepileptic drug-induced psychosis associated with homozygous C677T and multiple vitamin deficiencies. Our findings will contribute to the elucidation of the pathogenesis of the psychiatric side effects of antiepileptic drugs and lead to improved medical management for patients with epilepsy.
多种抗癫痫药物可能会在癫痫患者中引发精神方面的副作用，但其确切作用机制尚不清楚。近年来，5,10 - 亚甲基四氢叶酸还原酶（MTHFR）基因的常见多态性C677T因其在精神疾病发病中的作用而受到关注。MTHFR和几种维生素（作为辅助因子）对于通过叶酸和同型半胱氨酸代谢进行同型半胱氨酸的再甲基化至关重要。我们报告一例日本患者，其在抗癫痫药物治疗期间出现了可逆的精神分裂症样症状。
我们的患者患有额叶癫痫，自13岁起就接受了多种抗癫痫药物治疗。他在17岁时，即在开始使用苯妥英钠和苯巴比妥几个月后，出现了幻听和多重人格，尽管这些抗癫痫药物的使用剂量在治疗范围内。基因分析显示他是MTHFR基因C677T多态性的纯合子。在23岁时发现了高同型半胱氨酸血症、低蛋氨酸血症以及多种维生素缺乏，包括叶酸、核黄素和吡哆醛。补充维生素以及调整抗癫痫药物改善了他的精神症状。在抗癫痫药物治疗期间出现精神分裂症样症状的患者中，应考虑存在MTHFR C677T纯合子且伴有多种维生素缺乏的情况。
据我们所知，这是首例与C677T纯合子及多种维生素缺乏相关的抗癫痫药物所致精神病的报告。我们的研究结果将有助于阐明抗癫痫药物精神副作用的发病机制，并改善癫痫患者的医疗管理。
