A concise study of acetazolamide in glucose transporter type 1 deficiency (G1D) epilepsy.
A concise study of acetazolamide in glucose transporter type 1 deficiency (G1D) epilepsy.
复制标题
乙酰唑胺治疗 1 型葡萄糖转运蛋白缺陷 (G1D) 癫痫的简明研究。
DOI：
10.1111/epi.17684
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发表时间：
2023
期刊：
影响因子：
5.6
通讯作者：
Pascual,JuanM
中科院分区：
文献类型：
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作者：
Málaga,Ignacio;Avila,Adrian;Primeaux,Sharon;Park,JasonY;Pascual,JuanM
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。它还可以证明对治疗性饮食有抵抗力。我们研究了乙酰唑胺对G1D的影响，其动机是几个长期和最近的观察结果：首先，失神发作的电描记棘波特征通常与G1D相似，自20世纪50年代以来，在G1D作为一种独特的综合征与失神癫痫分离之前，偶尔用乙酰唑胺成功治疗。其次，突触抑制性神经元衰竭是G1D的特征，在其他实验模型中，这可以通过改变细胞氯梯度的药物（如乙酰唑胺）来改善。第三，乙酰唑胺在体外有效地刺激模型细胞葡萄糖转运。因此，通过病历审查并辅以全球个体调查，确定了17名接受乙酰唑胺治疗的抗癫痫药物或治疗性饮食难治性G1D患者。乙酰唑胺是耐受的，其中76%的人癫痫发作减少，58%的人癫痫发作减少一半以上，包括那些首次表现为肌阵挛性失稳性癫痫或婴儿痉挛的人。88%的G1D患者继续服用乙酰唑胺超过6个月，表明持续的耐受性和疗效。这一结果为G1D的治疗和机制研究提供了新的途径。
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.