Levetiracetam Treatment Research Articles

左乙拉西坦和奥卡西平治疗伴中央颞区棘波儿童良性癫痫的对比研究

目的：为明确左乙拉西坦(Levetiracetam, LEV)单药治疗首发伴中央颞区儿童良性癫痫(benign child-hood epilepsy with centro-temporal spikes, BECT)患儿的疗效及对认知的影响，采用奥卡西平(Oxcar- bazepine, OXC)作为对照进行开放性、平行性研究。方法：在来我院门诊就诊符合BECT诊断标准的患儿中选取104例，随机分为2组。OXC组51例，LEV组53例。以实验前3个月的每月平均发作次数为基线发作水平，每2~4周电话或门诊回访，记录临床发作次数。服药前、服药后3个月、6个月、12个月进行认知功能评定(4~6岁采用韦氏学龄前及小学智力量表，6~16岁采用韦氏儿童智力量表)。结果：1) 疗效比较：3次回访二组有效率、各组组内不同回访时间有效率比较无差异。2) 认知功能比较：基线时及12个月治疗后两组儿童比较无统计学差异。两组患儿用药后自身对照比较均显示多项分测验得分有增高趋势，OXC组治疗前后得分改变无统计学意义，LEV组的词汇及数字广度分测验得分的提高幅度与治疗前相比有统计学意义。结论：首选LEV治疗儿童BECT疗效与OXC相似，对BECT患儿的认知无不良影响。Objective: To clarify the therapeutic effect and the cognitive improvement of Levetiracetam (LEV) monotherapy on the first BECT (benign childhood epilepsy with centro-temporal spikes, BECT) compared with Oxcarbazepine (OXC) in an open and parallel study. Methods: 104 patients who were admitted in our hospital and conformed to the BECT diagnostic criteria were divided into two groups randomly: OXC therapy group (51 cases) and LEV therapy group (53 cases). The monthly average seizure times of the 3 months before the beginning of the study were taken as the baseline seizure level, while the seizures times were recorded after telephone follow-up or clinical return visits per 2 - 4 weeks. Evaluations on cognitive functions were conducted before the treatment and 3 months, 6 months and 12 months after the treatment (Wechslet preschool and primary scale of intelligence were applied to the patients at the age of 4 - 6, and Wechsler intelligence scale for children were applied to those at the age of 6 - 16). Results: 1) Comparison of curative effects: The curative effect difference between the LEV group and OXC group and the difference during the different period of each group were both not significant. 2) Comparison of cognitive function: There is no statistical difference between the two groups before and after treatment. Both the two groups showed an increasing trend of intelligence test scores after treatment. There was no statistical significance between scores before and after OXC treatment, while the scores difference of words and digit span before and after the treatment of LEV had statistical significance. Conclusions: The curative effect of LEV on the first BECT patients is similar to OXC without adverse influence on cognition.

Acute Mania Associated With Levetiracetam Treatment

Acute Mania Associated With Levetiracetam Treatment

Early‐onset absence epilepsy aggravated by valproic acid: a video‐EEG report

Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

Hair loss with levetiracetam in five patients with epilepsy

PurposeTo report cases of hair loss with levetiracetam (LEV) in epilepsy patient and summarise their demographic and clinical features. MethodAll patients reported attended the epilepsy outpatient clinic of the West China Hospital, Sichuan University. Demographic and clinical information was obtained from medical records and by interview. All the patients were under regular follow up. ResultsFive epilepsy patients (4 females and 1 male) are reported. All developed hair loss within two months of starting LEV treatment. Three had idiopathic epilepsy, two symptomatic epilepsy. Three patients received LEV monotherapy, two combination treatment. None decided to switch away from LEV to another drug after developing hair loss, although the dose of LEV was reduced in one patient. ConclusionHair loss may be a rare side effect of LEV treatment in patients with epilepsy. LEV-related hair loss appears reversible if the dose is reduced or treatment is stopped.

Efficacy of Levetiracetam in Electrical Status Epilepticus During Sleep of Children: A Multicenter Experience

BackgroundElectrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep. MethodsA multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response. ResultsAfter a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects. ConclusionsLevetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects.

Continuation rates of levetiracetam in children from the EULEVp cohort study

BackgroundSince indication extension to children data regarding the effectiveness of levetiracetam in paediatric patients remains limited. AimsInvestigate the real-life effectiveness of levetiracetam in paediatric patients. MethodsEpileptic children (<16 years) who had initiated levetiracetam between the 1 October 2006 and the 31 March 2007 were included and followed for 1 year by hospital or non-hospital neurologists practising in France. ResultsAmong the 156 identified children, 147 were analysed: 51.7% were female, and mean (SD) age was 9.2 years (4.2). Most patients had either partial symptomatic (30.6%) or partial cryptogenic (26.5%) epilepsy, 92.5% experienced seizures during the 6 months preceding levetiracetam initiation, and 19.2% were on levetiracetam alone at initiation. One-year levetiracetam continuation rate was estimated to be 72.0% (95%CI [63.8; 78.6]). Of the 104 children continuing levetiracetam treatment at end of study, 31.7% were seizure-free during the last six months of follow-up, and 23.1% on levetiracetam alone. Discontinuation of levetiracetam (n = 41) was mainly for insufficient efficacy (58.5% of those concerned). ConclusionsIn real-life clinical practice important treatment retention and non-negligible reduction of seizure frequency may be expected.

P25 – 2072 Diagnostic clues and difficulties in Dravet syndrome starting from 34 Dravet patients analysis within Romanian Research Group for Rare Genetic Epilepsies

Objectives: Antiepileptic drugs, such as carbamazepine, often increase the serum concentrations of serum lipids. Studies evaluating the effect of levetiracetam (LEV), a newer broad spectrum antiepileptic agent, on serum lipid levels are very limited. The aim of this study was to investigate prospectively the effect of LEV monotherapy on serum lipid profile in children with epilepsy. Material and methods: The study population consisted of 20 children (8 males, 12 females, aged 2 to 15 years old, mean age 6.5±4.16 years) with epilepsy treated with LEV monotherapy. None of the children were receiving any form of AED medication prior to LEV initiation. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), apolipoprotein AI (apo A-I), apolipoprotein B (apo B) and lipoprotein (a) [Lp(a)] were evaluated in all children, before and at 2 and 6 months of LEV monotherapy. Results: TC and HDL-C were significantly increased at 6 (p=0.011 and p=0.012, respectively) months of LEV treatment. There were no significant alterations in LDL-C, TGs, apo A-I, apo B and Lp(a) levels during the study. Conclusions: LEV monotherapy may cause significant alterations in TC, and HDL-C levels in children with epilepsy, occurring early in the course of treatment. Long-term, large, prospective studies are required to clarify the possible effect of LEV on serum lipid profile, the underlying mechanisms involved and its clinical significance.

The Beneficial Effects of Levetiracetam on Polyneuropathy in the Early Stage of Sepsis in Rats: Electrophysiological and Biochemical Evidence

ABSTRACTCritical illness polyneuropathy (CIP) is a common complication in long (≥1 week) critical/intensive care hospitalizations. Rapidly progressing atrophy and weakness of the limb, trunk and, particularly, respiratory muscles may lead to severe morbidity or mortality. The aim of the present study was to investigate the protective effects of levetiracetam (LEV) on CIP in the early stage of sepsis in rats. We simulated CIP by a surgically induced sepsis model and verified it by lower-limb lectromyography (EMG) (amplitude and duration of CMAP, and distal latency). We evaluated the effects of various doses of LEV treatment (300, 600, and 1200 mg/kg i.p.) on CIP by performing electrophysiology, and determining plasma tumor necrosis factor (TNF)-α, lipid peroxides (malondialdehyde, MDA) levels, and total antioxidant capacity (TAC). Our data showed: (1) significant suppression of CMAP amplitude and prolongation of distal latency in the saline-treated sepsis group, and distal latency as well as CMAP amplitudes benefiting best from the 600 mg/kg LEV treatment; (2) significant rise in plasma TNF-α and MDA levels in the saline-treated sepsis group, but significant ameliorations by the 600 and 1200 mg/kg LEV treatment; (3) highly significant suppression of TAC in the saline-treated group, but profound reversals in all LEV-treated groups. We conclude that 300, 600, and 1200 mg/kg i.p. doses of post-septic treatment by LEV has possibly acted in a dose-dependent manner to both protect and restore the affected peripheral nerves’ axon and myelin following surgical disturbance of the cecum to induce sepsis and consequent polyneuropathy.

Effects of antiepileptic drugs on reproductive endocrine function, sexual function and sperm parameters in Chinese Han men with epilepsy

The effects of the antiepileptic drugs sodium valproate (VPA) and levetiracetam (LEV) on reproductive endocrine function, sexual function, and spermatozoa were explored, together with their possible etiological mechanisms, in Chinese Han men with epilepsy. Following VPA treatment (n=32), luteinizing hormone and follicle-stimulating hormone levels were significantly lower than in controls (n=30). The bioactive testosterone/luteinizing hormone ratio and the prolactin level were significantly elevated in the VPA treatment group. There were no significant differences in these hormones between the LEV treatment (n=20) and control groups. The rates of sperm morphologic abnormality (head, body, and tail) were significantly higher in the VPA treatment group than the control group but did not differ significantly between the LEV treatment and control groups. The sperm motility rate was significantly lower in the VPA treatment group (grade A sperm motility rate <25%, grade A+B sperm motility rate <50%) than in controls, as well as in the LEV treatment group (grade A sperm motility rate <25%). Patients in the VPA and LEV treatment groups had lower scores on questions 1, 2 and 3 of a simplified International Index of Erectile Function Scale than controls, but no significant difference on questions 4 or 5. The total International Index of Erectile Function Scale scores were significantly lower in the VPA and LEV treatment groups. We conclude that treatment with VPA adversely affects reproductive endocrine function, sperm parameters and sexual function to varying degrees in Chinese men with epilepsy.

Acute Mania Associated With Levetiracetam Treatment

Levetiracetamisanovelantiepilepticdrugusedfor the treatment of partial and generalized epilepsy. Its mechanism of action is unclear, though it is thought to bind to a presynaptic vesicle protein that ultimately reduces the synaptic release of glutamate, impeding conduction of epileptic action potentials across the synapse. 1 Levetiracetam is frequently used owing to its ease of oral administration, excellent bioavailability, and low rate of drug interactions as it is not metabolized by the liver or bound significantly to serum proteins. 2,3 Adverse cognitive effects are atypical; however, adverse effects in the central nervous system (CNS) are relatively common, with behavioral symptoms occurring in up to 16% of patients in randomized controlled trials. 4 Frequently reported behavioral symptoms include depression, hostility, agitation, emotional lability, anger, nervousness, and depersonalization. Nonbehavioral CNS effects include sedation,headache,andasthenia. 5 Psychosisisinfrequently associated with levetiracetam, occurring in approximately 1% of patients, but well described in multiple case reports. 6,7 Researchers have explored the use of levetiracetam as a mood stabilizer for treatment of both depressive and manic phases of bipolar disorder with mixed results. 8–10 Despite the known association between levetiracetam and aggression and irritability, there are no reported cases in the literature of levetiracetam precipitating manic symptoms. In the following case report, we describe the acute onset of mania after levetiracetam therapy in a woman with no history of mania or hypomania.

Levetiracetam Treatment Does Not Result in Broken Bones

Levetiracetam Treatment Does Not Result in Broken Bones

Insomnia symptoms in South Florida military veterans with epilepsy

BackgroundDespite the high prevalence of insomnia in veterans with epilepsy, it remains understudied. Our aim was to identify the associations of insomnia with epilepsy, comorbidities, and treatment-related variables in South Florida veterans. MethodsWe performed a cross-sectional analysis of veterans attending an epilepsy clinic over 18months. Participants completed standardized assessments of seizure and sleep. Insomnia was defined as 1) difficulty with sleep onset, maintenance, or premature awakenings with daytime consequences or 2) sedative-hypnotic use on most nights of the previous month. ResultsOne hundred sixty-five veterans (87% male, age 56±15years) were included: 66 reporting insomnia (40%). In logistic regression analysis, insomnia was significantly associated with post-traumatic seizure etiology, lamotrigine prescription, and mood and psychotic disorders. Female gender and levetiracetam treatment were associated with lower odds for insomnia. ConclusionInsomnia was associated with post-traumatic epilepsy, mood/psychotic comorbidities, and antiepileptic regimen. Insomnia represents an under-recognized opportunity to improve comprehensive epilepsy care.

Effects of levetiracetam, an antiepileptic drug, on memory impairments associated with aging and Alzheimer’s disease in mice

Emerging evidence suggests that elevated hippocampal activation may be important for disrupting cognitive functions in aged subjects as well as patients with Alzheimer’s disease (AD). Therefore, reducing deleterious overactivity of the hippocampus may have therapeutic benefits. This study was designed to compare the effects of levetiracetam, an antiepileptic drug, on memory deficits associated with normal aging and AD in mouse models. Pretraining administration of levetiracetam ameliorated memory impairments of aged C57BL/6 mice (17–20months of age) in the contextual fear conditioning paradigm. Acute levetiracetam immediately after training was also efficacious in rescuing contextual memory decline in aged mice, whereas administration at a later posttraining interval (3h) had no effect. These results suggest that suppressing overexcitation with acute levetiracetam around the time of acquisition or early consolidation may be sufficient to reverse memory decline associated with aging. In contrast, pretraining administration of levetiracetam was not able to rescue memory deficits in 5XFAD transgenic mice harboring amyloid plaque pathologies at moderate (6–8months old) or massive (12–15months old) levels, differentiating between normal aging- and AD-related memory impairments in the responsiveness to acute levetiracetam treatment.

A cost-effectiveness analysis of valproate and levetiracetam treatment in Chinese children with newly diagnosed epilepsy

Objective To analyze the cost-effectiveness of valproate(VPA) or levetiracetam(LEV) for the first choice in children with newly diagnosed epilepsy, and to understand the pharmacoeconomics choice for anti-epileptic drugs in individual patient. Methods The differences were observed during 6 months treatment process in Chinese children with newly diagnosed epilepsy treated with VPA as the first line drug or LEV as the first line drug by decision tree model.The curative efficacy was evaluated for the first time at the end of 3 months in patients treated with LEV or VPA as monotherapy, and then the treatment strategy was adjusted according to the efficacy evaluation and adverse effects (the first drug continued, added or replaced with VPA or LEV). The second curative efficacy was evaluated after another 3 months of treatment.The effect and cost of 2 kinds of treatment strategies were compared by the incremental cost-effectiveness ratio (ICER), that was, the additional cost of pay for one more seizure-free case was compared between a kind of treatment and another treatment. Results For a Chinese child with median weight, additional 4981.858 Yuan(RMB) was needed for the increase of each seizure-free case treated with LEV as the first line treatment drug compared with VPA as the first line treatment drug within 6 months.If patients were to pay 4000 Yuan within 6 months treatment, the cost-effectiveness of LEV as the first line treatment was probably better than that of VPA.If patients were to pay 25 000 Yuan within 6 months treatment, there could be 90% possibility of the former cost-effectiveness with LEV as the first line treatment. Conclusions If patients are unlikely to pay more, VPA as the first line treatment is better in cost-effectiveness than that of LEV.If patients are willing to pay, LEV as first line treatment drug is better in cost-effectiveness.Pharmacoeconomics factors, as well as other factors, should be considered in guiding the drug choice by the individual patient. Key words: Epilepsy; Cost-effectiveness; Valproate; Levetiracetam; Child

Prospects of Levetiracetam as a Neuroprotective Drug Against Status Epilepticus, Traumatic Brain Injury, and Stroke

Levetiracetam (LEV) is an anti-epileptic drug commonly used for the treatment of partial onset and generalized seizures. In addition to its neuromodulatory and neuroinhibitory effects via its binding to the synaptic vesicle protein SV2A, multiple studies have suggested neuroprotective properties for LEV in both epileptic and non-epileptic conditions. The purpose of this review is to discuss the extent of LEV-mediated protection seen in different neurological conditions, the potential of LEV for easing epileptogenesis, and the possible mechanisms that underlie the protective properties of LEV. LEV has been found to be particularly beneficial for restraining seizures in animal models of spontaneous epilepsy, acute seizures, and status epilepticus (SE). However, its ability for easing epileptogenesis and cognitive dysfunction following SE remains controversial with some studies implying favorable outcomes and others reporting no beneficial effects. Efficacy of LEV as a neuroprotective drug against traumatic brain injury (TBI) has received much attention. While animal studies in TBI models have showed significant neuroprotection and improvements in motor and memory performance with LEV treatment, clinical studies suggest that LEV has similar efficacy as phenytoin in terms of its ability to prevent post-traumatic epilepsy. LEV treatment for TBI is also reported to have fewer adverse effects and monitoring considerations but electroencephalographic recordings suggest the presence of increased seizure tendency. Studies on stroke imply that LEV is a useful alternative to carbamazepine for preventing post-stroke seizures in terms of efficacy and safety. Thus, LEV treatment has promise for restraining SE-, TBI-, or stroke-induced chronic epilepsy. Nevertheless, additional studies are needed to ascertain the most apt dose, timing of intervention, and duration of treatment after the initial precipitating injury and the mechanisms underlying LEV-mediated beneficial effects.

The Role of Levetiracetam in Treatment of Seizures in Brain Tumor Patients

Levetiracetam, trade name Keppra, is a new second generation antiepileptic drug that is being increasingly used in brain tumor patients. In patients suffering with brain tumors, seizures are one of the leading neurologic complications being seen in more than 30% of patients. Unlike other antiepileptic drugs, levetiracetam is proposed to bind to a synaptic vesicle protein inhibiting calcium release. Brain tumor patients are frequently on chemotherapy or other drugs that induce cytochrome P450, causing significant drug interactions. However, levetiracetam does not induce the P450 system and does not exhibit any relevant drug interactions. Intravenous delivery is as bioavailable as the oral medication allowing it to be used in emergency situations. Levetiracetam is an attractive option for brain tumor patients suffering from seizures, but also can be used prophylactically in patients with brain tumors, or patients undergoing neurological surgery. Emerging studies have also demonstrated that levetiracetam can increase the sensitivity of Glioblastoma tumors to the chemotherapy drug temozolomide. Levetiracetam is a safe alternative to conventional antiepileptic drugs and an emerging tool for brain tumor patients combating seizures.

The Honeymoon Effect in Adult Patients with Refractory Partial-Onset Epilepsy Under Levetiracetam Add-on Treatment

Objectives: Resistance to antiepileptic drugs has occurres in some patients. The aim of this study was to evaluate the patients with refractory partial epilepsy who initially responded to levetiracetam (LEV) add-on therapy and who had the seizure frequency return to their baseline after a honeymoon period. Methods: Seven patients with refractory epilepsy, who had transient seizure control with LEV add-on therapy, were included in this study. Age, sex, detailed medical history, epilepsy duration, seizure frequency, concomitant AEDs, time to seizure occurrence after the initiation of LEV, side effects of LEV, cranial magnetic resonance imaging (MRI) and electroencephalography (EEG) data were collected for each patient. Results: Mean age was 26.14±5.14 years. Three patients were male and the other four were female. Mean seizure frequency before LEV treatment was 8.71±5.25 /month. The seizure-free days with levetiracetam add-on therapy was 51-82 days. After the honeymoon effect, seizure frequency returned to the baseline level and did not changed despite an increase in dosage. Cranial MRI was normal in two patients, while interictal EEG was normal in two patients. Conclusion: The resistance to LEV add-on treatment in patients with refractory partial onset seizures may develop, but the honeymoon effect of LEV was longer in our patients when compared to the drug’s literature.

Acute Liver Failure Associated with Levetiracetam and Lacosamide Combination Treatment for Unspecified Epileptic Disorder

Background and Aim. Levetiracetam is a second-generation antiepileptic drug. It is approved as an adjunctive treatment of partial onset seizures with or without secondary generalization. It is considered safe with less than 1% of patients with transient elevations of liver enzymes. Methods. We report a case of acute liver failure secondary to Levetiracetam in combination with Lacosamide documented with a liver biopsy. Results. Liver biopsy demonstrated acute liver injury with a predominant submassive necrosis pattern and features of a drug-induced hepatitis. Conclusions. This is the first published case of acute liver failure due to antiepileptic therapy with Levetiracetam in combination with Lacosamide.

Apparent dose-dependent levetiracetam-induced de novo major depression with suicidal behavior

Levetiracetam (LEV) is a novel antiepileptic drug (AED) approved for the adjunctive treatment of generalized and partial seizures. LEV has no clinically significant drug interactions and has limited adverse effects. The psychiatric adverse effects of LEV include de novo psychosis, affective disorder, and aggression. LEV-induced suicidal behavior has been reported infrequently with a past history of affective disorders. The authors report an apparent dose/concentration-dependent LEV-induced de novo major depression with near fatal suicide attempt in a patient without prior history of affective disorder. Psychiatric evaluation with emphasis on historic/current affective disorders, impulsive–aggressive behaviors, and assessment of risk factors for suicidal behaviors is indicated in treating patients with epilepsy with LEV. Clinicians should consider therapeutic drug monitoring to optimize therapeutic LEV treatment.

Loss of the initial efficacy of levetiracetam in patients with refractory epilepsy

PurposeThe efficacy and safety of the anti-convulsive drug levetiracetam (LEV) has been well documented but few clinical studies have investigated tolerance to LEV. The aim of this study was to evaluate the loss of the initial efficacy of LEV in adult patients with refractory partial-onset seizures. MethodsWe enrolled patients with refractory partial epilepsy who were started on add-on LEV treatment. The efficacy of LEV was evaluated every three months and the seizure frequency was decided by the average number of monthly seizures. A responder was defined as a patient with a ≥50% reduction in seizure frequency from the baseline. Seizure freedom was defined as a seizure-free status from the beginning of LEV treatment to the evaluation period. Loss of the initial efficacy was defined as a shift from responder status during the first three months of LEV treatment to non-responder status during the follow-up period. ResultsA total of 95 epilepsy patients were analyzed. During the first three months of LEV treatment, 50 (52.6%) of the 95 patients were responders with a ≥50% seizure reduction. Nine patients (18.0%) showed a loss of initial efficacy during the second three-month period. In contrast, only two (4.0%) of the non-responders during the first three months became responders during the next three months. However, this difference did not reach statistical significance (P=0.054). Based on Kaplan–Meier survival estimates, 49.2% of the patients who initially responded to LEV treatment during the first three months were predicted to lose this response at 42 months. Loss of the initial efficacy of LEV treatment occurred mostly within 18 months. ConclusionThis study suggests that the occurrence of tolerance is more common than late gain of efficacy of treatment although larger prospective studies would have to be carried out to prove this observation.