原发性遗传性神经递质代谢紊乱相关癫痫的发病机制及临床诊治进展

The pathogenesis of epilepsy related to primary inherited neurotransmitter disorders and advance in its diagnosis and treatment

遗传性神经递质病是一组罕见的神经系统疾病, 多在儿童时期起病, 是由神经递质或其合成过程中必需的辅助因子合成、分解或转运缺陷引起, 分为原发性和继发性疾病。原发性遗传性神经递质病临床表型包括发育迟缓、运动障碍、精神分裂症和癫痫等, 其中癫痫是其主要临床表型。γ氨基丁酸、谷氨酸、乙酰胆碱、生物胺等神经递质均参与了癫痫的发生。原发性遗传性神经递质代谢紊乱相关癫痫表型多样, 从轻微表型到严重的早发性癫痫性脑病不等。如果癫痫患儿有以下特征, 应怀疑遗传性神经递质病:(1)早发性癫痫性脑病伴发育障碍、自主神经功能障碍或运动障碍;(2)频繁出现特殊的脑电图模式, 包括暴发抑制、高度节律失调、弥漫性、局灶性或多灶性放电;(3)头颅影像学提示代谢毒性的疾病特征;(4)脑脊液中检测到特异性的生物标志物。对于遗传性神经递质病的早期识别与诊治, 在降低发病率、死亡率及改善预后方面有重大意义。

Inherited neurotransmitter disorders are a group of rare nervous system diseases frequently diagnosed in children.The disorders are caused by biosynthesis,breakdown or transport detects of neurotransmitters or cofactors essential in their biosynthesis.They can be classified as primary and secondary disorders.The clinical phenotypes of primary inherited neurotransmitter disorders include developmental delay,dyskinesia,schizophrenia,and epilepsy.Among them,epilepsy is the main clinical phenotype.Gamma-aminobutyric acid,glutamate,acetylcholine,biogenic amine and other neurotransmitters are involved in the epileptogenesis.The epilepsy related to primary inherited neurotransmitter disorders has diverse phenotypes,from mild seizures to severe early onset epileptic encephalopathy.An inherited neurotransmitter disorder should be suspected in children with epilepsy if the following features are present:(1)early onset epileptic encephalopathies associated with developmental impairment,autonomic dysfunctions or movement disorders;(2)frequent occurrence of such peculiar electroencephalogram patterns as burst suppression,hypsarrhythmia,and diffused/focal/multifocal electroencephalogram abnormalities;(3)neuroradiological signs of metabolic intoxication;(4)detection of specific cerebrospinal fluid biomarkers.Early identification,diagnosis and treatment is of great significance in reducing the incidence,lowering the mortality rate,and improving the prognosis of patients with epilepsy related to primary inherited neurotransmitter disorders.