PDF(Pubmed)
Abstract：
Epilepsy constitutes the most common paroxysmal manifestation of glucose transporter type 1 deficiency (G1D) and is generally considered medication-refractory. It can also prove therapeutic diet-resistant. We examined acetazolamide effects in G1D motivated by several longstanding and recent observations: First, the electrographic spike-waves characteristic of absence seizures often resemble those of G1D and, since the 1950s, they have occasionally been treated successfully with acetazolamide, well before G1D was segregated from absence epilepsy as a distinct syndrome. Second, synaptic inhibitory neuron failure characterizes G1D and, in other experimental models, this can be ameliorated by drugs that modify cellular chloride gradient such as acetazolamide. Third, acetazolamide potently stimulates model cell glucose transport in vitro. Seventeen antiepileptic drug or therapeutic diet-refractory individuals with G1D treated with acetazolamide were thus identified via medical record review complemented by worldwide individual survey. Acetazolamide was tolerated and decreased seizures in 76% of them, with 58% of all persons studied experiencing seizure reductions by more than one-half, including those who first manifested myoclonic-astatic epilepsy or infantile spams. Eighty-eight percent of individuals with G1D continued taking acetazolamide for over 6 months, indicating sustained tolerability and efficacy. The results provide a novel avenue for the treatment and mechanistic investigation of G1D.
摘要：
癫痫是1型葡萄糖转运蛋白缺乏症（G1D）最常见的阵发性表现，通常被认为是药物难治性。它还可以证明具有治疗性饮食抗性。我们研究了乙酰唑胺在G1D中的作用，这是由一些长期和最近的观察结果引起的：首先，失神发作的心电图尖峰波特征通常类似于G1D，自1940年代以来，他们偶尔用乙酰唑胺成功治疗，早在G1D与失神癫痫作为一种独特的综合征分离之前。第二,突触抑制性神经元衰竭表征G1D和，在其他实验模型中，这可以通过改变细胞氯化物梯度的药物如乙酰唑胺来改善。第三，乙酰唑胺在体外有效刺激模型细胞葡萄糖转运。因此，通过医疗记录审查并辅以全球个人调查，确定了17名用乙酰唑胺治疗G1D的抗癫痫药或治疗性饮食难治性个体。乙酰唑胺是可以忍受的，并且减少了其中76％的癫痫发作，58%的研究人员癫痫发作减少了一半以上，包括那些首先表现为肌阵挛性癫痫或婴儿垃圾的人。88%的G1D患者持续服用乙酰唑胺超过6个月，表明持续的耐受性和疗效。该结果为G1D的治疗和机理研究提供了新的途径。
