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“光敏模型”也是一种局灶性(部分性)癫痫发作的模型。

The 'Photosensitivity Model' is (also) a model for focal (partial) seizures.

作者信息

Kasteleijn-Nolst Trenite Dorothee, Genton Pierre, Brandt Christian, Reed Ronald C

机构信息

University Medical Center Utrecht, Utrecht, The Netherlands; Sapienza University, Rome, Italy.

Centre St. Paul, Marseille, France.

出版信息

Epilepsy Res. 2017 Jul;133:113-120. doi: 10.1016/j.eplepsyres.2016.11.012. Epub 2016 Dec 2.

Abstract

The 'Photosensitivity Model' uses a standardized stimulation protocol of repeated intermittent photic stimulation (IPS) over a three-day period, with administration of a single dose of an investigational antiepileptic drug (AED) after a baseline IPS day in photosensitive patients, followed by a third IPS day to determine duration of effect. This 'Photosensitivity Model' has shown its value in the development of new AEDs. Levetiracetam (LEV), currently a first-line AED in new-onset focal epilepsies, was not effective in classical animal models, but showed dose-dependent efficacy in the human 'Photosensitivity Model'. Nevertheless, concerns have been expressed that AEDs selectively suppressing focal seizures might not suppress generalized photoparoxysmal EEG responses (PPR), the pharmacodynamic outcome measure in the Model. Herein, the following questions have been addressed: I. Can patients with generalized epileptiform discharges, evoked by IPS, so-called PPR, have focal epilepsy (focal seizures)? II. Are the photosensitive patients with focal epilepsy, who have participated in the photosensitivity trials, non-responsive to a new AED under investigation, as compared to those with generalized epilepsies? III. Are "focal epilepsy" AEDs effective both in the 'Photosensitivity Model' and in real life in photosensitive patients? We performed a systematic literature review of PPR in focal seizures and focal epilepsy and we analyzed data (published and unpublished) from 20 different potential AEDs studied prospectively in the 'Photosensitivity Model'. Finally, the PPR effects of Na channel-blocking AEDs (considered as the most typical AEDs for focal epilepsy) are discussed with unequivocal examples given of the focal nature of a patient's PPR. Based on the entire data evidence, we conclude that: 1. PPRs certainly exist in focal epilepsy (17% on average); 2. Clinical signs and symptoms of PPRs can be focal and 3. PPRs can definitely be used to identify or to prove efficacy of new AEDs for patients with focal epilepsy.

摘要

“光敏性模型”采用标准化刺激方案,在三天时间内进行重复间歇性光刺激(IPS),在光敏患者基线IPS日之后给予单剂量研究性抗癫痫药物(AED),随后进行第三天的IPS以确定疗效持续时间。这种“光敏性模型”已在新型AED的研发中显示出其价值。左乙拉西坦(LEV)目前是新发性局灶性癫痫的一线AED,在经典动物模型中无效,但在人类“光敏性模型”中显示出剂量依赖性疗效。然而,有人担心选择性抑制局灶性癫痫发作的AED可能无法抑制全身性光阵发性脑电图反应(PPR),这是该模型中的药效学结果指标。在此,探讨了以下问题:I. 由IPS诱发全身性癫痫样放电(即所谓的PPR)的患者会患有局灶性癫痫(局灶性发作)吗?II. 与全身性癫痫患者相比,参与光敏性试验的局灶性癫痫光敏患者对正在研究的新型AED无反应吗?III. “局灶性癫痫”AED在“光敏性模型”和光敏患者的实际生活中都有效吗?我们对PPR在局灶性发作和局灶性癫痫中的情况进行了系统的文献综述,并分析了在“光敏性模型”中前瞻性研究的20种不同潜在AED的已发表和未发表数据。最后,讨论了钠通道阻滞剂AED(被认为是局灶性癫痫最典型的AED)的PPR效应,并给出了患者PPR局灶性特征的确切示例。基于全部数据证据,我们得出以下结论:1. PPR肯定存在于局灶性癫痫中(平均为17%);2. PPR的临床体征和症状可以是局灶性的;3. PPR肯定可用于识别或证明新型AED对局灶性癫痫患者的疗效。

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