在伴有耐药性癫痫的全脑畸形中观察到苯并二氮杂卓受体的急剧下调

Kousuke Nakamura , Sayaka Ishii , Kei Tamaru , Takeshi Inukai , Masao Aihara , Yoshimi Kaga
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摘要

背景颅脑发育不全(HPE)是一种中枢神经系统畸形,由发育过程中大脑半球分离缺陷引起,与耐药性癫痫有关。有关 HPE 的动物实验表明,HPE 与大脑皮层抑制性中间神经元发育不良有关;然而,在 HPE 患者中还没有这种关联的报道。在本研究中,我们利用 123I-iomazenil 单光子发射计算机断层扫描(SPECT)对三名 HPE 患儿的苯二氮卓受体(抑制系统受体)分布情况进行了检查。为了评估致痫性,他们接受了99m锝半胱氨酸乙二酯(ECD)SPECT和123I-碘马泽尼SPECT检查。99mTc 乙半胱氨酸二聚体(ECD)SPECT 显示患者只有全身性脑灌注不足,而 123I-iomazenil SPECT 则显示大脑、丘脑和脑干存在广泛的苯并二氮杂卓受体抑制。尽管包括氯硝西泮、氯巴泮和劳拉西泮在内的苯二氮卓类药物对癫痫发作的影响有限,但加入左乙拉西坦后,三名患者的癫痫发作频率均有所降低。因此,可以推断增强抑制性神经元机制的传统抗癫痫药物效果较差。具有其他作用机制的药物可能有助于治疗难治性癫痫。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dramatic benzodiazepine receptor downregulation observed in holoprosencephaly with drug-resistant epilepsy

Background

Holoprosencephaly (HPE), a central nervous system malformation caused by a defect in the separation of cerebral hemispheres during development, is associated with drug-resistant epilepsy. Animal studies on HPE have suggested its association with dysplasia of the inhibitory interneurons in the cerebral cortex; however, this association has not been reported in patients with HPE. In this study, we presented cases of three children with HPE who were examined for the distribution of benzodiazepine receptors, which are receptors of the inhibitory system, using 123I-iomazenil single-photon emission computed tomography (SPECT).

Case presentation

All three children had drug-resistant epilepsy with frequent daily seizures. 99mTc ethyl cysteinate dimer (ECD) SPECT and 123I-iomazenil SPECT were performed to evaluate the epileptogenicity. 99mTc ECD SPECT showed generalized only cerebral hypoperfusion, and 123I-iomazenil SPECT showed widespread benzodiazepine receptor depression in the cerebrum, thalamus, and brainstem. Although, benzodiazepines, including clonazepam, clobazam, and lorazepam have limited effects on epileptic seizures, the addition of levetiracetam led to the reduction in seizure frequency in all three patients.

Conclusion

The SPECT findings in children with HPE suggested a defect in the development of GABAergic-benzodiazepinergic inhibitory neurons, especially in the thalamus and brainstem. Therefore, it is inferred that conventional antiepileptic drugs that potentiate the mechanisms of inhibitory neurons are less effective. Agents, with alternative mechanisms of action may be useful for the treatment of refractory epilepsy.

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