Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy.
Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy.
Clin Neurophysiol. 2021 May;132(5):1049-1056. doi: 10.1016/j.clinph.2020.12.030. Epub 2021 Feb 20.
Wedesignedalongitudinalcohortstudyon People with Epilepsy (PwE) with the aimofassessingthe effect of Perampanel (PER) oncortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-corticalprojections(early HFOs) and intracortical GABAergic synapses (late HFOs), thus they could be used to study the anti-glutamatergic action of PER, a selective antagonist of the AMPA receptor.
15 PwE eligible for PER add-on therapy, were enrolled prospectively. Subjects underwent SEPs recording from the dominant hand at two times: PwE (baseline, before PER titration) and PwE (therapeutic dose of 4 mg). HFOs were obtained by filtering N20 scalp response in the 400-800 Hz range. Patients were compared with a normative population of 15 healthy controls (HC) matched for age and sex.
We found a significant reduction ofTotal HFOs and mostly early HFOs area between PwE and PwE (p = 0.05 and p = 0.045 respectively) and between HC and PwE (p = 0.01). Furthermore, we found a significant reduction of P24/N24 Amplitude between PwE and HC and between PwE and PwE (p = 0.006 and p = 0.032, respectively).
Introduction of PER as add-on therapy reduced the area of total HFOs, acting mainly on the early burst, related to thalamo-cortical pathways. Furthermore P24/N24 amplitude, which seems to reflect a form of cortico-subcortical integration, resulted increased in PwE at T0 and normalized at T1.
Our findings suggest that PER acts on cortico-subcortical excitability. This could explain the broad spectrum of PER and its success in forms of epilepsy characterized by thalamo-cortical hyperexcitability.
我们设计了一项针对癫痫患者（PwE）的纵向队列研究，旨在评估吡仑帕奈（PER）对皮质-皮质下网络的影响，通过体感诱发电位（SEP-HFOs）的高频振荡来测量。SEP-HFOs 测量丘脑皮质投射（早期 HFOs）和皮质内 GABA 能突触（晚期 HFOs）的兴奋性，因此可用于研究 PER 的抗谷氨酸能作用，PER 是 AMPA 受体的选择性拮抗剂。
15 名符合 PER 附加治疗条件的 PwE 前瞻性入组。受试者在两次时进行从优势手记录 SEP：PwE（基线，PER 滴定前）和 PwE（治疗剂量 4mg）。通过在 400-800Hz 范围内过滤 N20 头皮反应获得 HFOs。患者与年龄和性别匹配的 15 名健康对照者（HC）进行比较。
我们发现 PwE 与 PwE（p=0.05 和 p=0.045）以及 HC 与 PwE（p=0.01）之间总 HFOs 和早期 HFOs 面积均显著减少。此外，我们发现 P24/N24 振幅在 PwE 与 HC 之间以及 PwE 与 PwE 之间均显著降低（p=0.006 和 p=0.032）。
PER 作为附加治疗药物的引入减少了总 HFOs 的面积，主要作用于与丘脑皮质通路相关的早期爆发。此外，P24/N24 振幅似乎反映了一种皮质-皮质下整合形式，在 T0 时 PwE 增加，在 T1 时恢复正常。
我们的研究结果表明 PER 作用于皮质-皮质下兴奋性。这可以解释 PER 的广谱作用及其在以丘脑皮质过度兴奋为特征的各种癫痫形式中的成功。
