探讨大剂量吡哆醇联合5-磷酸吡哆醛(P5P)治疗遗传性糖基磷脂酰肌醇(GPI)缺乏症相关癫痫的近期疗效和安全性。
经遗传证实的GPI缺乏症的参与者在商定的临床治疗方案中口服吡哆醇或P5P作为同情使用。使用吡哆醇(20-30mg/kg/天)3个月。基线评估包括4周的前瞻性癫痫发作数据和一个视频脑电图(EEG)。每天捕获癫痫发作频率。在达到最大剂量的吡哆醇后重复EEG。如果治疗3个月后癫痫发作负担无变化,则将吡哆醇转换为P5P(20-30mg/kg/天)。在P5P治疗3个月后进行另一次EEG。主要结果指标是减少癫痫发作频率和改善脑电图。
7名参与者(1名女性,6名男性;年龄范围5-23岁;平均年龄11岁10个月,包括SD5年2个月)。遗传性GPI缺乏症的遗传原因是磷脂酰肌醇N-乙酰氨基葡萄糖转移酶亚基A/T/V缺乏症。所有患者均患有耐药性癫痫和神经发育障碍。我们观察到7人中有2人的癫痫发作频率减少了50%以上,另外7人中有3人的癫痫发作频率减少了50%以下。没有参与者达到癫痫发作的自由。在比较基线和随访EEG时,在7名接受吡哆醇或P5P治疗的参与者中,有6名未观察到电生理发现的显着变化。
我们观察到治疗期间没有持久的电生理改善,但吡哆醇可以减少遗传性GPI缺乏症的癫痫发作频率或负担。
遗传性糖基磷脂酰肌醇(GPI)缺乏常引起早发性和耐药性癫痫。维生素B6是一种潜在的疾病特异性治疗;然而,疗效和安全性尚不明确。吡哆醇可降低遗传性GPI缺乏症的癫痫发作频率或负担。吡哆醇和P5P可能被证明是一些遗传性GPI缺乏症和癫痫患者的有用治疗方法。
To investigate the short-term efficacy and safety of high-dose pyridoxine and pyridoxal 5-phosphate (P5P) in the treatment of inherited glycosylphosphatidylinositol (GPI) deficiency-associated epilepsy.
Participants with genetically confirmed GPI deficiency were treated with oral pyridoxine or P5P as compassionate use in an agreed-upon clinical regimen. Pyridoxine (20-30 mg/kg/day) was used for 3 months. Baseline evaluation included 4 weeks of prospective seizure data and one video electroencephalogram (EEG). Seizure frequency was captured daily. The EEG was repeated after reaching maximum dosage of pyridoxine. Pyridoxine was switched to P5P (20-30 mg/kg/day) if seizure burden was unchanged after 3 months\' treatment. Another EEG was done after 3 months of P5P treatment. Primary outcome measures were reduction of seizure frequency and EEG improvements.
Seven participants (one female, six males; age range 5-23 year; mean age 11 years 10 months, SD 5 year 2 months) were included. The genetic causes of inherited GPI deficiency were phosphatidylinositol N-acetylglucosaminyltransferase subunit A/T/V deficiency. All had drug-resistant epilepsy and neurodevelopmental impairment. We observed more than 50% seizure frequency reduction in 2 out of 7 and less than 50% reduction in another 3 out of 7 participants. No participants reached seizure freedom. No remarkable changes in electrophysiological findings were observed in 6 out of 7 participants treated with pyridoxine or P5P when comparing the baseline and follow-up EEGs.
We observed no long-lasting electrophysiological improvements during treatment but pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency.
Inherited glycosylphosphatidylinositol (GPI) deficiency often causes early-onset and drug-resistant epilepsy. Vitamin B6 is a potential disease-specific treatment; however, efficacy and safety are ill-defined. Pyridoxine may reduce seizure frequency or burden in inherited GPI deficiency. Pyridoxine and P5P could prove to be a useful treatment in some individuals with inherited GPI deficiency and epilepsy.