Perampanel effect on sleep architecture in patients with epilepsy.

Perampanel 对癫痫患者睡眠结构的影响。

  • 影响因子:2.77
  • DOI:10.1016/j.seizure.2020.01.021
  • 作者列表:"Rocamora R","Álvarez I","Chavarría B","Principe A
  • 发表时间:2020-02-10

PURPOSE:Among patients with epilepsy, sleep disturbances can worsen seizure control. This prospective open-label study determined the effect of the antiepileptic drug perampanel on sleep architecture in patients with refractory epilepsy. METHODS:Adult patients with refractory epilepsy received add-on perampanel, starting at 2 mg/day at bedtime, increased by 2 mg after 2 weeks and then monthly until the target dose of 4-8 mg/day was reached. The median dose of perampanel used was 6 mg (SD 1.2). Polysomnographic (PSG) recordings were scheduled 1 week before starting perampanel and the control PSG after 12 weeks under perampanel treatment and at least 4 weeks on stable perampanel dose; patients completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. The main endpoints were change from baseline in the ESS and PSQI scores, and PSG variables. RESULTS:Of 25 patients included (aged 18-65 years, 56 % female) only 17 completed the study. Perampanel caused a modest decrease from baseline in mean ESS score (n = 13 patients; p = 0.126) and PSQI score (n = 12 patients; p = 0.127). Treatment significantly improved sleep parameters (n = 17 patients) including total sleep time (p = 0.037), sleep latency (p = 0.022), sleep efficiency (p = 0.015), sleep maintenance index (p = 0.005), wake time after sleep onset (p = 0.015), and duration of N3 sleep stage (p = 0.026). Patients with altered sleep efficiency parameters at baseline showed a significant increase in sleep maintenance index (p = 0.015), and 77.8 % achieved sleep efficiency >85 % (p = 0.016 vs baseline). CONCLUSION:Perampanel improved sleep architecture in patients with focal refractory epilepsy without worsening daytime sleepiness.


目的: 在癫痫患者中,睡眠障碍可使癫痫发作控制恶化。这项前瞻性开放标签研究确定了抗癫痫药物 perampanel 对难治性癫痫患者睡眠结构的影响。 方法: 成人难治性癫痫患者接受添加 perampanel,睡前开始 2 mg/天, 2 周后增加 2 mg,然后每月增加,直到达到 4-8 mg/天的目标剂量。使用 perampanel 的中位剂量为 6 mg (SD 1.2)。在开始 perampanel 前 1 周安排多导睡眠图 (PSG) 记录,在 perampanel 治疗下 12 周后安排对照 PSG,在稳定 perampanel 剂量下至少 4 周; 患者完成 Epworth 嗜睡量表 (ESS) 和匹兹堡睡眠质量指数 (PSQI) 问卷。主要终点是 ESS 和 PSQI 评分与基线相比的变化,以及 PSG 变量。 结果: 在纳入的 25 例患者 (年龄 18-65 岁,56% 为女性) 中,只有 17 例完成了研究。Perampanel 导致平均 ESS 评分 (n = 13 例患者; p = 0.126) 和 PSQI 评分 (n = 12 例患者; p = 0.127) 较基线略有下降。治疗显著改善了 17 例患者的睡眠参数,包括总睡眠时间 (p = 0.037) 、睡眠潜伏期 (p = 0.022), 睡眠效率 (p = 0.015) 、睡眠维持指数 (p = 0.005) 、睡眠后觉醒时间 (p = 0.015) 、和 N3 睡眠阶段的持续时间 (p = 0.026)。基线时睡眠效率参数改变的患者睡眠维持指数显著增加 (p = 0.015),77.8% 的患者达到睡眠效率> 85% (p = 0.016 vs 基线)。 结论: Perampanel 改善了局灶性难治性癫痫患者的睡眠结构,无白天嗜睡恶化。



作者列表:["Garabadu D","Singh D"]

METHODS::Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.

来源期刊:Experimental neurology
作者列表:["Bertrand SJ","Zhang Z","Patel R","O'Ferrell C","Punjabi NM","Kudchadkar SR","Kannan S"]

METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

翻译标题与摘要 下载文献
来源期刊:World neurosurgery
作者列表:["Middlebrooks EH","Lin C","Okromelidze L","Lu CQ","Tatum WO","Wharen RE Jr","Grewal SS"]

METHODS:BACKGROUND:Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level dependent (BOLD) MRI and present the brain activation pattern associated with ANT DBS. METHODS:Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30 second blocks. The scanner was triggered utilizing surface electrophysiological recording to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS:Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS:Utilizing block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown suggesting that these nodes may modulate the effect of seizure control with ANT DBS.

翻译标题与摘要 下载文献