Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.
Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations.
复制标题
早发性重症ATP1A2癫痫脑病：临床特征和潜在突变。
DOI：
10.1016/j.yebeh.2020.107732
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Mikati MA
中科院分区：
文献类型：
--
作者：
Moya-Mendez ME;Mueller DM;Pratt M;Bonner M;Elliott C;Hunanyan A;Kucera G;Bock C;Prange L;Jasien J;Keough K;Shashi V;McDonald M;Mikati MA
ATP1A2突变导致偏瘫偏头痛伴或不伴癫痫或急性可逆性脑病。典型的发病是在成年或较大的儿童时期，没有随后严重的长期发育障碍。描述早发性重症ATP1A2相关癫痫脑病及其潜在突变在7名患者队列中的表现。对7名患者队列的回顾图表。通过全球变化评价量表(GRSC)和临床总体印象改善量表(CGI-I)方法评估开放标签美金刚疗法的疗效，该疗法因其NMDA受体拮抗剂作用而在标签外使用。用PYMol程序进行分子模拟。患者(年龄2.5-20岁)在早期(6天-1岁)出现症状。癫痫发作为局灶性或全身性。耐药、反复发作的癫痫持续状态、严重发育迟缓，常伴有头痛、肌张力障碍、偏瘫、癫痫发作、发育减退等急性重症脑病发作。所有人都有预测致病的变异(p.Ile293Met，p.Glu1000Lys，c.1017+5G>；A，p.Leu809Arg，以及3名p.Met813Lys患者)。模型显示突变干扰了ATP1A2离子结合和易位位点。5个人服用美金刚，所有人都能耐受(平均治疗时间：2.3年，6周-4.8年)，所有5个人都有一些改善。我们的观察描述了7个无亲缘关系的先证者的独特临床特征，为ATP1A2基因突变的结构-功能关系提供了洞察力，并支持了NMDAR拮抗剂治疗ATP1A2脑病的进一步研究。
ATP1A2 mutations cause hemiplegic migraine with or without epilepsy or acute reversible encephalopathy. Typical onset is in adulthood or older childhood without subsequent severe long-term developmental impairments. Describe the manifestations of early onset severe ATP1A2-related epileptic encephalopathy and its underlying mutations in a cohort of seven patients. Retrospective chart review of a cohort of seven patients. Response to open label memantine therapy, used off-label due to its NMDA receptor antagonist effects, was assessed by the Global Rating Scale of Change (GRSC) and Clinical Global Impression Scale of Improvement (CGI-I) methodologies. Molecular modeling was performed using PyMol program. Patients (age 2.5-20 years) had symptom onset at an early age (6 days-1 year). Seizures were either focal or generalized. Drug resistance, recurrent status epilepticus, severe developmental delay with episodes of acute severe encephalopathy often with headaches, dystonias, hemiplegias, seizures, and developmental regression were common features. All had variants predicted to be disease causing (p.Ile293Met, p.Glu1000Lys, c.1017+5G>A, p.Leu809Arg, and 3 patients with p.Met813Lys). Modeling revealed that mutations interfered with ATP1A2 ion binding and translocation sites. Memantine, given to five, was tolerated in all (mean treatment: 2.3 years, range 6 weeks-4.8 years) with some improvements reported in all five. Our observations describe a distinctive clinical profile of seven unrelated probands with early onset severe ATP1A2-related epileptic encephalopathy, provide insights into structure-function relationships of ATP1A2 mutations, and support further studies of NMDAR antagonist therapy in ATP1A2-encephalopathy.
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影响因子：
4.6
作者：
Bøttger P;Glerup S;Gesslein B;Illarionova NB;Isaksen TJ;Heuck A;Clausen BH;Füchtbauer EM;Gramsbergen JB;Gunnarson E;Aperia A;Lauritzen M;Lambertsen KL;Nissen P;Lykke-Hartmann K
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Lykke-Hartmann K
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2.6
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影响因子：
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Hunanyan, Arsen S.;Fainberg, Nina A.;Mikati, Mohamad A.
通讯作者：
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影响因子：
5.6
作者：
Deprez, Liesbet;Weckhuysen, Sarah;De Jonghe, Peter
通讯作者：
De Jonghe, Peter
影响因子：
3
作者：
Mewasingh, LD;Sékhara, T;Dan, B
通讯作者：
Dan, B