Response of levetiracetam in neonatal seizures

AIM: To review the clinical response to levetiracetam(LEV) in neonatal seizure management in intensive care unit.METHODS: Medical records of neonates who received LEV from January 2009 to August 2014 were reviewed. Their demographic data, clinical characteristics, etiology, seizures, electroencephalograms, response to treatment and outcome were noted. Literature review of use of LEV in neonates were also performed via Pub Med and EMBASE with keywords- "neonates", "seizures", "epilepsy" and "LEV" up to Sep 2014 and retrieved the publications. The response rate to LEV was compared.RESULTS: Twelve neonates were identified during the study period. All patients received phenobarbitone loading prior to consideration of LEV. Seven(58%) and nine(75%) achieved seizure freedom 24 h and 72 h after LEV was added, both clinically and electrographically. No serious adverse effects were associated with LEV use. From the literature, there are total 144 neonates reported to have used LEV. The overall results suggested that LEV could control up to 90% of neonatal seizures.CONCLUSION: LEV was found to be relatively safe and efficacious in treating neonatal seizures, but might not work well in the most severe hypoxic ischemic encephalopathy.

Acute liver failure following levetiracetam therapy for seizure prophylaxis in traumatic brain injury

This case report investigates an uncommon occurrence of drug induced acute liver injury directly associated with the administration of levetiracetam in a patient following traumatic brain injury.

Levetiracetam induces tyrosine kinase receptor B expression in SH-SY5Y cells

Tyrosine kinase receptor B （TrkB） plays an important role in long-term potentiation and memory formation.The present study used all-trans retinoic acid to induce TrkB expression in SH-SY5Y cells,and observed the effects of levetiracetam （LEV） on TrkB expression.Following exposure to 10,50,and 100 μg/mL LEV,the number of TrkB-positive cells,and average absorbance value were increased.Results demonstrated that LEV can induce TrkB expression in SH-SY5Y cells.

Levetiracetam-Associated Acute Kidney Injury and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome

DRESS syndrome is a severe drug induced reaction. Acute kidney injury (AKI) is sometimes present in the form of an acute interstitial nephritis. We present the case of a 75-year-old man with glioblastoma who developed a DRESS two months after starting levetiracetam and a few days after stopping dexamethasone. His skin and kidneys improved after removing levetiracetam and introducing again corticosteroids. DRESS has been reported more frequently with other antiepileptics, rarely with levetiracetam. Clinicians should add this drug to the list of potential causes of AKI.

Influence of adjuvant levetiracetam therapy on serum nerve cytokines and apoptosis molecules in patients with refractory partial epileptic seizure

Objective:To study the influence of adjuvant levetiracetam therapy on serum nerve cytokines and apoptosis molecules in patients with refractory partial epileptic seizure.Methods: A total of 92 patients with refractory partial epileptic seizure treated in our hospital between July 2012 and January 2016 were divided into control group (n=46) and observation group (n=46) according to random number table. Patients in the control group were treated with routine treatment, those in observation group were treated with routine treatment plus adjuvant levetiracetam therapy, and the treatment lasted for 20 weeks. Serum contents of nerve cytokines and apoptosis molecules were compared between two groups before and after treatment.Results:Before treatment, differences in serum levels of nerve injury indexes, nerve protection indexes, monoamine neurotransmitters and apoptosis molecules were not statistically significant between two groups of patients. After treatment, serum contents of nerve injury indexes S-100β, GFAP, NSE and MBP in both groups were significantly lower than those before treatment, contents of nerve protection indexes BDNF and IGF-1 were significantly higher than those before treatment, contents of monoamine neurotransmitters DA, 5-HT and NE were significantly higher than those before treatment, contents of apoptosis molecules Bcl-2, Fas and FasL were significantly lower than those before treatment, and the changes in contents of above indexes in observation group were larger than those in control group.Conclusion:The adjunctive therapy of levetiracetam can reduce the nerve injury in patients with refractory partial epileptic seizure and exert active cerebral protective effect.

Acute Kidney Injury with Levetiracetam in Patient with Epilepsy: A Case Report

Epilepsy is a common neurological disorder in neurology clinic. Levetiracetam is considered as one of common antiepileptic drugs used to manage epilepsy with good efficacy and tolerability profile. It is renally excreted and not depending on the cytochrome p450. It has adverse effects reported as somnolence, headaches, dizziness, depression and anxiety. Also, it was reported that levetiracetam can cause Acute kidney injury (AKI), renal profile disturbance, that may be related to its way of excretion and possible nephrotoxicity especially with high loading dose. We are reporting a young female patient with epilepsy presented to hospital with status epileptcus and started on loading dose of levetiracetam 3 grams and then maintenance dose of 1 gram twice daily seizure were controlled but she developed acute kidney injury that improved after discontinue leveriracetam and medical management without renal dialysis and discharged home in stable condition. Physician and health care providers should be aware of such rare adverse reaction and available management options for better patient care and outcome.

Effects of sodium valproate combined with levetiracetam in treatment of children epilepsy and its influences on serum S-100βand high mobility group box-1

Objective:To explore the effects of sodium valproate combined with levetiracetam in the treatment of children epilepsy,and its influences on serum S-100βand high mobility group box-1(HMGB-1)in children with epilepsy.Methods:A total of 160 children who were diagnosed as epilepsy in Baogang Hospital of Inner Mongolia from July 2016 to October 2018 were selected as research objects.They were randomly divided into the study group(n=80)and the control group(n=80)by the random number table method,i.e.,they were treated with sodium valproate combined with levetiracetam and sodium valproate alone,respectively.After 16 weeks of treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge were evaluated,and chi-square test was used for statistical comparison.The related indicators,including serum tumor necrosis factor-(TNF-α),hypersensitive C-reactive protein(hs-CRP),homocysteine(Hcy),haematocrit(HCT),erythrocyte sedimentation rate(ESR),serum S-100βand HMGB-1,were measured before and after treatment.Paired t-test was used for the comparison in the above indicators within a group before and after treatment;group t-test was used for the comparison between two groups.Chi-square test was used for the comparison in the rate of adverse reactions during treatment between two groups.The study was approved by Ethics Committee of Baogang Hospital(Approval No.:BG201606073),and all children’s guardians were required to sign informed consent forms for clinical study.There were no statistically significant differences between two groups in general clinical data(p>0.05),such as sex constituent ratio,age,the course of disease,the frequency of epileptic seizure per year before treatment,the incidence of epileptiform discharge before treatment and the constituent ratio of types of epileptic seizure,etc.Results:1)After treatment,the effective rates of epileptic seizure treatment and the improvement of epileptiform discharge in the study group were 92.5%(74/80)and 85.0%(68/80)respectively,which were both significantly higher than those in the control group[68.8%(55/80)and 58.8%(47/80)],and the differences were statistically significant(Х^(2)=14.444,13.635;p<0.001).2)In the study group,the levels of serum TNF-α,hs-CRP and Hcy,as well as HCT and ESR after treatment were(53.1±14.0)pg/ml,(5.0±2.5)mg/L,(12.5±3.1)μmol/L,(38.1±5.1)%and(3.0±0.5)mm/h respectively,which were all significantly lower than those[(107.9±17.8)pg/ml,(10.1±2.5)mg/L,(42.2±5.8)μmol/L,(45.3±4.5)%and(5.2±0.6)mm/h]before treatment,and all the differences were statistically significant(t=21.644,12.902,40.393,9.468,25.194;p<0.001).In the control group,the levels of serum TNF-α,hs-CRP and Hcy,as well as HCT and ESR after treatment were(60.6±17.8)pg/ml,(8.2±2.2)mg/L,(15.2±3.1)μmol/L,(40.2±3.4)%and(4.5±0.6)mm/h respectively,which were all significantly lower than those[(112.4±14.3)pg/ml,(9.3±3.8)mg/L,(41.1±2.8)μmol/L,(44.6±5.5)%and(5.4±0.8)mm/h]before treatment,and all the differences were statistically significant(t=20.292,2.241,55.456,3.320,8.050;p<0.05).After treatment,the above indicators in the study group were all significantly lower than those in the control group,and all the differences were statistically significant(t=2.962,8.595,5.508,3.064,17.178;p<0.05).3)In the study group,the levels of serum S-100βand HMGB-1 after treatment were(0.65±0.38)μg/L and(5.3±2.4)μg/L respectively,which were significantly lower than those[(0.91±0.32)μg/L and(8.1±2.0)μg/L]before treatment,and the differences were statistically significant(t=4.681,8.020;p<0.001).In the control group,the levels of serum S-100βand HMGB-1 after treatment were(0.78±0.27)μg/L and(6.4±2.2)μg/L respectively,which were significantly lower than those[(0.88±0.25)μg/L and(7.9±1.7)μg/L]before treatment,and the differences were statistically significant(t=2.431,p=.016;t=4.826,p<0.001).After treatment,the levels of serum S-100βand HMGB-1 in the study group were significantly lower than those in the control group,and the differences were statistically significant(t=2.495,p=.014;t=2.840,p=.005).4)There was no significant difference between two groups in the rate of adverse reactions,such as nausea,vomiting,poor appetite,dizziness,drowsiness,hepatic and renal injury during treatment(p>0.05).Conclusions:The efficacy of sodium valproate combined with levetiracetam is obviously better than that of sodium valproate alone in the treatment of children epilepsy.The children patients’serum S-100βand HMGB-1 are more significantly reduced,resulting in a lower rate of adverse reactions,which has a certain clinical value.

抗惊厥药Levetiracetam

[合成]该化合物可通过用(S)-2-氨基丁酰胺(Ⅰ)与4-溴丁酸乙酯(Ⅱ)在三乙胺存在下于甲苯中反应生成(S)-4-[1-(氨基甲酰基)丙胺]丁酸乙酯(Ⅲ),再用2-羟基吡啶在甲苯中环合得到。化合物(Ⅰ)也能与4-氯丁酰氯(Ⅳ)直接在溴化四丁铵存在下于二氯甲烷中缩合,

Effect of levetiracetam and valproate on late‑onset post‑traumatic seizures

Background To compare the preventive effects of levetiracetam and valproate on late-onset post-traumatic seizures in patients with traumatic brain injury(TBI).Methods A total of 95 patients with TBI were recruited from 2017 to 2020.They were randomized into three groups:levetiracetam(LEV)group(n=30)receiving LEV treatment(500 mg,bid,po);valproate group(n=32)receiving sodium valproate(500 mg/d,once daily,po);and control group(n=33)receiving no anti-seizure medication.LEV and valproate were given to corresponding groups within seven days after TBI,and the administration lasted for one month.The incidence of epilepsy and adverse events were evaluated at 7 days and 12 months post-TBI.Results The cumulative incidences of late post-traumatic seizures at the 12-month follow-up in the LEV,valproate,and control groups were 3.33%,12.50%and 15.63%,respectively.The cumulative incidence of late post-traumatic seizures in the LEV group was significantly lower than those in the valproate and control groups(P<0.05).The cumulative incidence of late post-traumatic seizure in the valproate group was not significantly different from that in the control group(P>0.05).Conclusions LEV can reduce the cumulative incidence of late post-traumatic seizures,whereas valproate can not.

拉考沙胺联合左乙拉西坦治疗癫痫患儿临床疗效及对神经功能相关指标的影响

目的探究拉考沙胺联合左乙拉西坦治疗癫痫患儿的临床疗效及对神经功能相关指标的影响。方法收集2021年1月—2022年7月新疆维吾尔自治区人民医院儿科收治原发性癫痫患儿120例,以随机数字表法分为观察组和对照组,各60例。对照组患儿给予常规支持治疗及左乙拉西坦口服治疗,观察组患儿在对照组治疗基础上联合应用拉考沙胺片,2组均连续治疗6个月。比较2组患儿治疗效果及不良事件发生率,治疗前后神经功能相关指标(MBP、S-100β、HMGB1、GFAP、PGP)及癫痫发作情况变化。结果治疗6个月后,观察组患儿治疗总有效率高于对照组(98.33%vs.90.00%,χ^(2)/P=4.184/0.041),平均癫痫发作次数及癫痫发作持续时间均低于对照组(t/P=13.288/<0.001,2.956/0.002),但2组患儿不良事件发生率比较差异无统计学意义(P>0.05);治疗6个月后,2组患儿血清MBP、S-100β、HMGB1、GFAP及PGP水平低于治疗前,BDNF水平高于治疗前,且观察组低于/高于对照组(t/P=2.858/0.005,4.672/<0.001,2.142/0.034,3.521/<0.001,5.054/<0.001,10.310/<0.001);相关性分析表明治疗后癫痫患儿癫痫发作次数与血清PGP水平呈正相关,与BDNF水平呈负相关(r/P=0.577/<0.001,-0.338/<0.001)。结论拉考沙胺联合左乙拉西坦的治疗方案能显著改善癫痫患儿神经功能相关指标,进而降低癫痫患儿癫痫发作频率、提高治疗有效率,同时临床安全性较好。

左乙拉西坦治疗药物监测的研究进展

左乙拉西坦(LEV)是第二代广谱抗癫痫药物,具有起效快、半衰期短、疗效确切、耐受性好、药物相互作用少等优点。为提高LEV的临床效果,减少不良反应的发生,应对儿童、妊娠期妇女、老年人、肾功能不全等特殊人群予以治疗药物监测(TDM)。临床上LEV监测样本常选择血浆或血清,监测方法多选择免疫分析法或色谱分析法。LEV的有效浓度范围目前尚无统一意见,血药浓度与不良反应的相关性也不明确。影响LEV血药浓度的因素主要有年龄、妊娠及患者用药依从性等。如何解读TDM结果并根据结果调整给药剂量是今后工作的重点。

左乙拉西坦血药浓度监测结果分析及在重症患者中的应用

目的分析左乙拉西坦治疗药物监测(therapeutic drug monitoring,TDM)结果,为重症患者临床合理用药提供参考。方法收集2021年3月—2022年8月左乙拉西坦TDM数据和病历资料,分析左乙拉西坦治疗方案及谷浓度、峰浓度达标情况,探讨左乙拉西坦的血药浓度影响因素。结果共收集64例次左乙拉西坦TDM数据,包括36例谷浓度和28例峰浓度,仅有36.1%患者的谷浓度达标。进行左乙拉西坦TDM的重症患者占52.8%,其中76.9%的重症患者存在肾功能亢进(augmented renal clearance,ARC)现象。1.5每12 h 1次未达标组的重症患者可能存在更加严重的ARC。结论左乙拉西坦的临床血药浓度达标率偏低。对于重症患者,应注意识别ARC,并根据TDM和肌酐清除率(creatinine clearance,Ccr)适当调整左乙拉西坦用药剂量。

丙戊酸钠联合左乙拉西坦治疗对癫痫患儿智力认知水平及脑电图的影响

目的 探讨癫痫患儿采用丙戊酸钠与左乙拉西坦联合治疗对其智力、认知水平及脑电图的影响。方法 选取郑州大学第三附属医院于2022-01-2023-01收治的100例癫痫患儿为研究对象,分为对照组和试验组各50例,对照组采用丙戊酸钠治疗,试验组采用丙戊酸钠联合左乙拉西坦治疗,比较2组患儿疗效、智力、认知水平及脑电图情况。结果 试验组患儿总有效率(92.00%)高于对照组(76.00%,P<0.05)。2组患儿治疗4个月后中国韦氏儿童智力量表(C-WISC)及蒙特利尔认知评估量表(MoCA)评分均较治疗前上升,试验组操作智商(PIQ)、言语智商(VIQ)、总智商(FIQ)、言语理解因子智商、知觉组织因子智商及不分心/记忆因子智商分数及MoCA评分均高于对照组(P<0.05)。2组治疗4个月后θ、α、δ脑电频率均较治疗前稳定,试验组θ、α、δ脑电频率优于对照组(P<0.05)。结论 对癫痫患儿采用丙戊酸钠与左乙拉西坦联合治疗可显著提升疗效、智力及认知水平,控制痫性放电。

HPLC-MS/MS法同时测定微量血浆中甲氨蝶呤、左乙拉西坦、拉莫三嗪浓度及其临床应用

目的 建立HPLC-MS/MS法测定微量血浆中甲氨蝶呤、左乙拉西坦和拉莫三嗪的浓度,同时应用于儿童治疗药物监测。方法 取含药血浆10μl,用蛋白沉淀法对样本进行前处理。色谱柱为Agilent C18(50 mm×2.1 mm,1.8μm),流动相为0.1%甲酸水和甲醇,梯度洗脱;流速为0.4 ml/min。采用电喷雾离子源正离子模式,监测甲氨蝶呤m/z 455.1→308.2,甲氨蝶呤-D3 m/z 458.1→311.1(内标);左乙拉西坦m/z 171.1.4→126.2,左乙拉西坦-D6 m/z177.2→132.2(内标);拉莫三嗪m/z 256.1→211,拉莫三嗪-13C3-D3 m/z 262.1→217.1(内标)。结果 甲氨蝶呤在25~1 500 ng/ml线性关系良好,标准曲线方程:Y=0.251 6X+0.003 4(r=0.998 9),定量下限为25 ng/ml;左乙拉西坦在1~50μg/ml线性关系良好,标准曲线方程:Y=16.687 6X+0.000 2(r=0.991 1),定量下限为1μg/ml;拉莫三嗪在0.5~25.0μg/ml线性关系良好,标准曲线方程:Y=46.369 5X-0.059 9(r=0.999 1),定量下限为0.5μg/ml。样本批内、批间准确度和精密度符合要求、基质效应符合规定。本方法验证后成功用于1 348例临床患儿样本的检测。结论 本方法操作简便、专属性强、灵敏度高,可用于人血浆中甲氨蝶呤、左乙拉西坦及拉莫三嗪的分析,适用于儿童治疗药物监测。