Torres O A, Miller V S, Buist N M, Hyland K
Division of Pediatric Neurology, University of Texas Southwestern Medical Center, Dallas, USA.
J Child Neurol. 1999 Aug;14(8):529-32. doi: 10.1177/088307389901400809.
We report three cases of folinic acid-responsive intractable neonatal seizures. All patients were born at term following normal gestation and delivery. In the first infant, seizures began on the 5th day of life and were unresponsive to phenobarbital, pyridoxine, and valproate, but stopped within 24 hours of initiation of folinic acid treatment at the age of 6 months. Her sibling had died at age 6 months with intractable seizures. In the second infant, seizures began in the 2nd hour of life. These were initially controlled with phenobarbital; however, at 3 months of age she developed status epilepticus refractory to anticonvulsants, steroids, and pyridoxine and she required repeated induction of pentobarbital coma. Seizures stopped within 24 hours of starting folinic acid. Seizures and encephalopathy were noted in the third infant on the 2nd day of life. These were controlled with phenobarbital, but at 8 weeks of age seizures recurred and were difficult to control despite the addition of phenytoin. Immediately after folinic acid was initiated the seizures stopped. Breakthrough seizures in all patients have responded to increases in folinic acid; two of the three remain on standard anticonvulsants. All patients have global developmental delay. Cranial magnetic resonance imaging in the second patient shows diffuse atrophy, and in the third patient shows increased signal on T2 images in the white matter of the frontal and parietal lobes. Analysis of cerebrospinal fluid from these patients using high-performance liquid chromatography with electrochemical detection has consistently revealed an as-yet unidentified compound, which can be used as a marker for this condition. We suggest that cerebrospinal fluid be analyzed for the presence of this compound and a trial of folinic acid be considered in neonates with unexplained early onset intractable seizures.
我们报告了三例对亚叶酸敏感的难治性新生儿癫痫病例。所有患者均足月出生，孕期和分娩过程正常。首例婴儿在出生后第5天开始出现癫痫发作，对苯巴比妥、维生素B6和丙戊酸盐均无反应，但在6个月大开始使用亚叶酸治疗后24小时内癫痫发作停止。她的同胞在6个月大时死于难治性癫痫发作。第二例婴儿在出生后第2小时开始出现癫痫发作。最初用苯巴比妥控制；然而，在3个月大时，她出现了对抗惊厥药、类固醇和维生素B6难治的癫痫持续状态，需要反复诱导戊巴比妥昏迷。开始使用亚叶酸后24小时内癫痫发作停止。第三例婴儿在出生后第2天出现癫痫发作和脑病。这些症状用苯巴比妥控制，但在8周大时癫痫复发，尽管加用了苯妥英钠仍难以控制。开始使用亚叶酸后癫痫立即停止。所有患者均有全面发育迟缓。第二例患者的头颅磁共振成像显示弥漫性萎缩，第三例患者的头颅磁共振成像显示额叶和顶叶白质T2加权像信号增强。使用高效液相色谱-电化学检测法对这些患者的脑脊液进行分析，始终发现一种尚未鉴定的化合物，可作为这种疾病的标志物。我们建议对脑脊液进行该化合物检测，并考虑对不明原因早发性难治性癫痫的新生儿进行亚叶酸试验。
