Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?
Motor co-activation in siblings of patients with juvenile myoclonic epilepsy: an imaging endophenotype?
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DOI：
10.1093/brain/awu175
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
Koepp MJ
中科院分区：
文献类型：
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作者：
Wandschneider B;Centeno M;Vollmar C;Symms M;Thompson PJ;Duncan JS;Koepp MJ
在青少年肌阵挛性癫痫（JME）中，肌阵挛性抽搐通常由认知努力触发。Wandschneider等人报告了未受影响的兄弟姐妹的运动和前额叶认知网络的共同激活，与之前在患者自身中报告的相似。这种共激活可以构成一个遗传标记，为进一步的遗传研究JME。青少年肌阵挛性癫痫是一种可遗传的特发性全身性癫痫综合征，以肌阵挛性抽搐为特征，常由认知活动触发。据报道，青少年肌阵挛性癫痫患者及其未受影响的同胞额叶认知功能受损。在最近的功能磁共振成像研究中，我们报告了运动皮层的异常共激活，以及在工作记忆范式中运动系统和前额叶认知网络之间的功能连接增加，为认知触发的抽搐提供了潜在机制。在这项研究中，我们在15名未受影响的兄弟姐妹中使用了相同的任务（10名女性;年龄范围18-65岁，中位数40）的11名青少年肌阵挛性癫痫患者（6名女性;年龄范围22-54岁，中位数35），并将功能性磁共振成像激活与20名年龄和性别匹配的健康对照受试者进行比较（12名女性;年龄范围23-46岁，中位数30.5）。未受影响的兄弟姐妹表现出异常的初级运动皮层和辅助运动区共激活，随着认知负荷的增加，以及运动和前额叶认知网络之间的任务相关功能连接增加，与患者相似（P < 0.001未校正; 20体素阈值范围）。在未受影响的兄弟姐妹中的这一发现表明，运动系统激活和功能连接的改变与药物或癫痫无关，但代表了患者和兄弟姐妹额叶功能受损的潜在潜在机制，因此构成了青少年肌阵挛性癫痫的内表型。
In juvenile myoclonic epilepsy (JME), myoclonic jerks are often triggered by cognitive effort. Wandschneider et al. report co-activation of the motor and prefrontal cognitive networks in unaffected siblings, similar to that previously reported in patients themselves. This co-activation could constitute a heritable marker for further genetic studies of JME. Juvenile myoclonic epilepsy is a heritable idiopathic generalized epilepsy syndrome, characterized by myoclonic jerks and frequently triggered by cognitive effort. Impairment of frontal lobe cognitive functions has been reported in patients with juvenile myoclonic epilepsy and their unaffected siblings. In a recent functional magnetic resonance imaging study we reported abnormal co-activation of the motor cortex and increased functional connectivity between the motor system and prefrontal cognitive networks during a working memory paradigm, providing an underlying mechanism for cognitively triggered jerks. In this study, we used the same task in 15 unaffected siblings (10 female; age range 18–65 years, median 40) of 11 of those patients with juvenile myoclonic epilepsy (six female; age range 22–54 years, median 35) and compared functional magnetic resonance imaging activations with 20 age- and gender-matched healthy control subjects (12 female; age range 23–46 years, median 30.5). Unaffected siblings showed abnormal primary motor cortex and supplementary motor area co-activation with increasing cognitive load, as well as increased task-related functional connectivity between motor and prefrontal cognitive networks, with a similar pattern to patients (P < 0.001 uncorrected; 20-voxel threshold extent). This finding in unaffected siblings suggests that altered motor system activation and functional connectivity is not medication- or seizure-related, but represents a potential underlying mechanism for impairment of frontal lobe functions in both patients and siblings, and so constitutes an endophenotype of juvenile myoclonic epilepsy.