Sequential intrarectal diazepam and intravenous levetiracetam in treating acute repetitive and prolonged seizures

In this retrospective study of institutionalized patients with mental retardation, we present the efficacy and safety of sequential treatment with intrarectal diazepam (IRD) gel (Diastat) and intravenous levetiracetam (IVL) in comparison with either treatment alone for acute repetitive or prolonged seizures (ARPS). We defined ARPS as ≥3 seizures of any type within 1 h or a single seizure of any type lasting ≥3 min. Eighty‐eight ARPS episodes were treated in 25 patients (14 female, age 21–72 years), with mainly symptomatic generalized epilepsy. There were no adverse events directly attributable to the administration of IRD or IVL. Seizure recurrence within 4 h of treatment, the primary outcome measure, was significantly lower after combined sequential IRD + IVL treatment (3 of 36) compared to IRD alone (6 of 24, p = 0.048) or IVL alone (10 of 28, p = 0.039). There was no statistically significant difference between the individual IRD and IVL treatments (p = 0.604). The estimated odds ratio (OR) indicated that the risk of seizure recurrence was higher after IRD or IVL monotherapy compared to combined IRD + IVL treatment. Subsequent emergency room (ER) transfers following seizure recurrence were least likely after IVL treatment (10%) compared to combined IRD + IVL (67%) or IRD (83%) treatment. These findings suggest that although IRD or IVL monotherapy is efficacious, the combination is superior in controlling ARPS in this special group of institutionalized patients. In addition, we speculate that a more reliable onset of action after IVL treatment results in rapid seizure control and fewer ER transfers, despite seizure recurrence.     

Intravenous levetiracetam for treatment of neonatal seizures

In this case series we report on eight neonates with refractory seizures who received intravenous levetiracetam when seizures did not respond to two or more conventional anticonvulsants. Six of the eight neonates had an excellent response with either cessation, or reduction in seizures by at least 80%. One neonate showed a partial response while one did not have any reduction in seizure frequency. We did not encounter any adverse effects that could be attributable to levetiracetam.     

Response to antiseizure medications in neonates with acute symptomatic seizures

In a prospective cohort of 534 neonates with acute symptomatic seizures, 66% had incomplete response to the initial loading dose of antiseizure medication (ASM). Treatment response did not differ by gestational age, sex, medication, or dose. The risk of incomplete response was highest for seizures due to intracranial hemorrhage and lowest for hypoxic‐ischemic encephalopathy, although the difference was not significant after adjusting for high seizure burden and therapeutic hypothermia treatment. Future trial design may test ASMs in neonates with all acute symptomatic seizure etiologies and could target neonates with seizures refractory to an initial ASM.     

High‐dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy

We review our experience with high‐dose intravenous levetiracetam (IV‐LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures—while on chronic antiepileptic drugs—that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV‐LEV of 150 mg/kg/day or greater, with a mean dose of 228 ± 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure‐free in two, ≥80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV‐LEV was well tolerated in all children without complications.     

左乙拉西坦添加治疗难治性部分性发作癫痫疗效的Meta分析

目的系统评价左乙拉西坦添加治疗难治性部分性发作癫痫的疗效和药物安全性。方法计算机检索1998年1月-2010年12月Cochrane图书馆、MEDLINE、EMbase、社会科学引文索引、维普中文科技期刊、中国知网中国期刊全文数据库和中国生物医学文献数据库,并手工检索相关杂志,由两名研究者独立进行质量评价及数据分析,RevMan5．0统计软件进行Meta分析。结果根据Cochrane5．0．2版随机对照临床试验质量评价标准,纳入11项随机对照临床试验共1981例受试者（左乙拉西坦组1192例、安慰剂对照组789例）。Meta分析结果显示,左乙拉西坦组每周部分性癫痫发作频率减少≥50％的病例数高于对照组（1000mg／d：OR=2．990,P=0．000;2000mg／d：OR=3．870,P=0．000;3000mg／d：OR=3．440,P=0．000）;每周发作频率减少≥75％的病例明显高于对照组（100013mg／d：OR=3．130,P=0．000;2000mg／d：OR：5．060,P=0．000;3000mg／d：OR=4．730,P：0．000）;完全不发作病例明显高于对照组（1000mg／d：OR=5．080,P=0．001;2000mg／d：OR=4．420,P=0．050;3000mg／d：OR=4．150,P=0．000）。左乙拉西坦组失访率与安慰剂对照组之间差异无统计学意义（P〉0．05）。治疗期间常见药物不良反应包括嗜睡、头晕、乏力、鼻咽炎、精神行为异常等,两组精神行为不良反应方面存在异质性（P=0．360,12=8．000％）。结论现有证据显示,左乙拉西坦添加治疗难治性部分性发作癫痫的疗效与安慰剂组相比效果显著,保留率高;药物安全性应注意其所引起的精神行为异常。     

左乙拉西坦添加治疗难治性部分性发作癫痫疗效的Meta分析

目的系统评价左乙拉西坦添加治疗难治性部分性发作癫癎的疗效和药物安全性。方法计算机检索1998年1月-2010年12月Cochrane图书馆、MEDLINE、EMbase、社会科学引文索引、维普中文科技期刊、中国知网中国期刊全文数据库和中国生物医学文献数据库,并手工检索相关杂志,由两名研究者独立进行质量评价及数据分析,RevMan 5.0统计软件进行Meta分析。结果根据Cochrane5.0.2版随机对照临床试验质量评价标准,纳入11项随机对照临床试验共1981例受试者(左乙拉西坦组1192例、安慰剂对照组789例)。Meta分析结果显示,左乙拉西坦组每周部分性癫癎发作频率减少≥50%的病例数高于对照组(1000 mg/d:OR=2.990,P=0.000;2000 mg/d:OR=3.870,P=0.000;3000 mg/d:OR=3.440,P=0.000);每周发作频率减少≥75%的病例明显高于对照组(1000 mg/d:OR=3.130,P=0.000;2000 mg/d:OR=5.060,P=0.000;3000 mg/d:OR=4.730,P=0.000);完全不发作病例明显高于对照组(1000 mg/d:OR=5.080,P=0.001;2000 mg/d:OR=4.420,P=0.050;3000 mg/d:OR=4.150,P=0.000)。左乙拉西坦组失访率与安慰剂对照组之间差异无统计学意义(P>0.05)。治疗期间常见药物不良反应包括嗜睡、头晕、乏力、鼻咽炎、精神行为异常等,两组精神行为不良反应方面存在异质性(P=0.360,I~2=8.000%)。结论现有证据显示,左乙拉西坦添加治疗难治性部分性发作癫癎的疗效与安慰剂组相比效果显著,保留率高;药物安全性应注意其所引起的精神行为异常。     

Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children

Midazolam, a water-soluble benzodiazepine, is usually given intravenously in status epilepticus. The aim of this study was to determine whether intranasal midazolam is as safe and effective as intravenous diazepam in the treatment of acute childhood seizures. Seventy children aged 2 months to 15 years with acute seizures (febrile or afebrile) admitted to the pediatric emergency department of a general hospital during a 14-month period were eligible for inclusion. Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.2 mg/kg were administered after intravenous lines were established. Intranasal midazolam and intravenous diazepam were equally effective. The mean time to control of seizures was 3.58 (SD 1.68) minutes in the midazolam group and 2.94 (SD 2.62) in the diazepam group, not counting the time required to insert the intravenous line. No significant side effects were observed in either group. Although intranasal midazolam was as safe and effective as diazepam, seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam. Intranasal midazolam can possibly be used not only in medical centers, but also in general practice and at home after appropriate instructions are given to families of children with recurrent seizures.     

Use of levetiracetam in hospitalized patients

PURPOSE: The objective of the study was to analyze the short-term efficacy and safety of levetiracetam (LEV) to treat repetitive seizures in hospitalized patients. METHODS: During admission to a tertiary hospital, we retrospectively identified patients with repetitive seizures who were treated for the first time with LEV during a hospital stay. LEV was considered effective if seizure cessation or >75% seizure reduction occurred in the 24 h after starting LEV (compared with the previous 48 h), requiring no further antiepileptic drug (AED) treatment. RESULTS: Thirty patients (12 men, 18 women) were included. Mean age was 59.7 years. Most frequent seizure type was focal motor in 12 (40%) of 30 patients. Most frequent etiology was stroke: nine (30%) of 30 patients. Relevant medical conditions included atrial fibrillation (three) and hepatic disease (three). Concomitant medications included oral anticoagulants (seven), corticosteroids (two), and chemotherapy (two). Four patients received LEV as the only AED. Six patients with focal SE and 20 (66.6%) patients with clusters of seizures but not in SE received LEV as add-on treatment after lack of response to first-line AEDs. Mean LEV dose during first day was 1,119 mg. Mean daily maintenance dose was 1,724 mg. LEV was effective in 24 (80%) patients, all four patients who received it as the only AED, four of six patients with focal SE, and 16 of 20 patients with clusters of seizures. Three (10%) elderly patients with seizures secondary to stroke and chronic obstructive pulmonary disease (COPD) reported moderate/severe somnolence and dizziness, leading to treatment discontinuation in one. On discharge, 20 (66.7%) patients continued on LEV, nine (30%) as the only AED. CONCLUSIONS: LEV is effective and safe to treat repetitive seizures in hospitalized patients, including patients in focal SE.     

Unidirectional cross-tolerance from levetiracetam to carbamazepine in amygdala-kindled seizures

PURPOSE: Tolerance is a potential problem in long-term anticonvulsant therapy of epilepsy, bipolar disorder, and neuropathic pain. The present study was designed to determine whether cross-tolerance occurs between levetiracetam (LEV) and carbamazepine (CBZ) in amygdala-kindled rats. METHODS: Male Sprague-Dawley rats were implanted with an electrode into the left amygdala. While kindling stimulation was started, animals received repeated treatment (i.p.) with saline (n = 7) or LEV (150 mg/kg, n = 8). Saline-injected rats were subsequently challenged with a single dose of 150 mg/kg LEV when full kindling developed (stage > or =4). Both groups of rats were then administered long-term CBZ (5 mg/kg) until rats developed complete tolerance. All CBZ-tolerant rats were subsequently re-exposed to LEV (150 mg/kg) for an additional 10 consecutive days.RESULTS: Repeated LEV treatment significantly suppressed the increase in seizure stage, seizure duration, and afterdischarge duration induced by amygdala stimulation, markedly increasing the number of stimulations to achieve a kindling major motor seizure. The LEV challenge produced a more robust suppression of seizure stage in saline-injected rats compared with LEV-treated animals. CBZ treatment markedly suppressed fully kindled seizures in rats initially injected with saline, and then anticonvulsant tolerance rapidly developed after 3-4 days of repeated treatment. In contrast, rats that had initially received repeated LEV treatment did not show a response to treatment with CBZ (5 mg/kg). When CBZ-tolerant rats were subsequently exposed to LEV (150 mg/kg), noticeable anticonvulsant effects were observed; but these were gradually lost with increasing numbers of LEV exposures. CONCLUSIONS: Whereas LEV shows potent antiepileptogenic and anticonvulsant effects in amygdala-kindled rats, its repeated treatment induces anticonvulsant tolerance and unidirectional cross-tolerance to CBZ. In contrast, anticonvulsant tolerance to CBZ does not transfer to LEV. The mechanistic implications of the present results for clinical therapeutics remain to be evaluated.     

Neurobehavioral anomalies in neonates with seizures

Neurobehavioral evaluation of the high-risk neonate represents an important advance in early detection of behavioral anomalies which may give rise to later neuropsychological sequelae. In the present study neonates comprising three diagnostic categories (i.e., respiratory distressed, seizure-disordered, normals) were evaluated with the Brazelton Neonatal Behavior Assessment Scale (BNBAS) to determine the extent to which differences in neurobehavioral organization could be detected with the scale, and how they were related to diagnostic classification. Average conceptional age at testing for the three groups was within the range usually considered full term: e.g., 38.81 weeks (respiratory distressed), 40.18 weeks (normal healthy) and 42.54 weeks (seizure disorder). Infants who had been diagnosed with neonatal seizures exhibited consistently less optimal behavior than did either of the other two groups. Infants with respiratory distress and normal controls did not differ significantly on most summary measures of neurobehavioral organization scored with the BNBAS. The study offers support for the discriminative validity of the BNBAS and its potential usefulness in the assessment of clinically ill newborns.     

neurobehavioral anomalies in neonates with seizures

Abstract

Neurobehavioral evaluation of the high-risk neonate represents an important advance in early detection of behavioral anomalies which may give rise to later neuropsychological sequelae. In the present study neonates comprising three diagnostic categories (i.e, respiratory distressed, seizure-disordered, normals) were evaluated with the Brazelton Neonatal Behavior Assessment Scale (BNBAS) to determine the extent to which differences in neurobehavioral organization could be detected with the scale, and how they were related to diagnostic classification. Average conceptional age at testing for the three groups was within the range usually considered full term: e.g., 38.81 weeks (respiratory distressed), 40.18 weeks (normal healthy) and 42.54 weeks (seizure disorder). Infants who had been diagnosed with neonatal seizures exhibited consistently less optimal behavior than did either of the other two groups. Infants with respiratory distress and normal controls did not differ significantly on most summary measures of neurobehavioral organization scored with the BNBAS. The study offers support for the discriminitive validity of the BNBAS and its potential usefulness in the assessment of clinically ill newborns.     

左乙拉西坦联合用药在成人颞叶癫术后早期的应用

目的观察新型抗痫药物左乙拉西坦（LEV）联合治疗对成人颞叶癫痫术后早发性癫痫（APOS）的预防作用。方法选择近1年来进行手术的成人颞叶癫痫患者60例,术后仅服用卡马西平（CBZ）者为对照组和术后应用CBZ联合LEV者为实验组,观察两组APOS例数、白细胞数、意识、精神状态、CBZ药浓度和胃肠道反应。结果对照组8例发生APOS,实验组为2例,有显著性差异,实验组白细胞、血小板、CBZ药浓度明显变化,未见明显胃肠道反应。实验组有5例出现烦躁或夜间睡眠障碍,而对照组仅1例。结论成人颞叶癫痫术后LEV联合CBZ较单药CBZ预防APOS有良好疗效,短期应用未见明显副作用,但可能会出现烦躁或睡眠障碍。     

Intranasal versus intravenous lorazepam for control of acute seizures in children: a randomized open-label study

Purpose: Intravenous lorazepam is considered the drug of first choice for control of acute convulsive seizures. However, resource or personnel constraints necessitate the study of alternative routes and medications. This study compared the efficacy and adverse effects of intranasal versus intravenous lorazepam in children aged 6–14 years who presented with acute seizures. Methods: This was a randomized open‐label study conducted at an Indian hospital from August 2008 to April 2009. One hundred forty‐one consecutive children aged 6–14 years who presented convulsing to the emergency room were included. After stabilization, the children were randomized to receive either intravenous or intranasal lorazepam (0.1 mg/kg, maximum 4 mg). The primary outcome measure was clinical seizure remission within 10 min of drug administration. The study was registered with clinicaltrials.gov (NCT00735527). Key Findings: Seventy patients were randomized to receive intravenous and 71 to receive intranasal lorazepam. The patients in the two groups were comparable at baseline. Clinical seizure remission within 10 min of drug administration was found in 80% of the intravenous group as compared to 83.1% of intranasal group. The lower limit of 95% confidence interval for effect size was approximately −9.7%, with an a priori cutoff for noninferiority of −10%. Significance: Intranasal administration of lorazepam is not found to be inferior to intravenous administration for termination of acute convulsive seizures in children.