Effect of levetiracetam on ocular perfusion measure with optical coherence tomography angiography / Efeito do levetiracetam na medição da pressão de perfusão ocular com angiotomografia de coerência óptica

ABSTRACT Purpose: To evaluate using optical coherence tomography angiography the macular and optic nerve head blood flow in pediatric patients with epilepsy treated with levetiracetam for at least 12 months. Methods: This study included 33 pediatric patients with epilepsy and 30 sex- and age-matched healthy volunteer children were included in the study. Optical coherence tomography angiography was used to evaluate the optic nerve head and macular perfusion changes. The mean ocular perfusion pressures were also calculated. Patients who were using multiple antiepileptic drugs or had a prior history of using different drugs were excluded. Results: The choriocapillaris flow area was significantly lower in the Study Group than in the Control Group (p=0.006). However, the foveal avascular zone and vessel densities of the macula in the superficial capillary plexus, deep capillary plexus, and optic nerve head of the study group were not significantly different from those of the control group (p>0.05). Moreover, no significant difference in means of mean ocular perfusion pressure was found between the two groups (p=0.211). No obvious correlation was found between treatment duration and optical coherence tomography angiography parameters or mean ocular perfusion pressure. Conclusion: Choroidal perfusion was reduced in children taking levetiracetam compared with that in the control group, whereas retinal perfusion was not affected in this optical coherence tomography angiography study.

RESUMO Objetivo: Avaliar através de angiotomografia de coerência óptica o fluxo sanguíneo macular e da cabeça do nervo óptico em pacientes pediátricos com epilepsia tratados com levetiracetam por pelo menos 12 meses. Método: Trinta e três pacientes pediátricos com epilepsia e 30 crianças voluntárias saudáveis pareadas por sexo e idade foram incluídos no estudo. A angiotomografia de coerência óptica foi utilizada para avaliar as alterações da perfusão da cabeça do nervo óptico e da macular. As médias das pressões de perfusão ocular também foram calculadas. Pacientes em uso de múltiplas drogas antiepilépticas ou com história prévia de uso de diferentes drogas foram excluídos do estudo. Resultado: A área do fluxo coriocapilar foi significativamente menor no Grupo Estudo do que no Grupo Controle (p=0,006). Entretanto, a zona avascular foveal e as densidades vasculares no plexo capilar superficial e profundo da região macular e na cabeça do nervo óptico não foram significativamente diferentes daquelas de olhos saudáveis (p>0,05). Também não houve diferença significativa entre os dois grupos em relação às médias da pressão de perfusão ocular (p=0,211). Nenhuma correlação aparente foi encontrada entre a duração do tratamento e os parâmetros da angiotomografia de coerência óptica ou a média da pressão de perfusão ocular. Conclusão: Em crianças usando levetiracetam, a perfusão coroidal mostrou-se reduzida em comparação ao grupo controle, enquanto a perfusão retiniana não foi afetada neste estudo com angiotomografia de coerência óptica.

Research progress in therapy drug monitoring of levetiracetam / 中国药房

Levetiracetam （LEV） is the second generation of broad-spectrum anti-epileptic drug. LEV has the advantages of rapid absorption， short half-life， precise efficacy， good tolerance and few drug interactions. In order to improve the clinical efficacy of LEV， and reduce the occurrence of adverse reactions， children， pregnant women， the elderly， and patients with renal insufficiency should receive therapeutic drug monitoring （TDM）. Clinically， the samples are usually plasma or serum， and the TDM methods are mostly immunoassay or chromatography. There is currently no consensus on the effective concentration range of LEV， and the correlation between plasma concentration and adverse reactions is also unclear. The main factors affecting LEV plasma concentration include age， pregnancy， and patient compliance. How to interpret TDM results and adjust dosage based on the results will be the focus of future work.

Mioclonías positivas y negativas en paciente con enfermedad renal crónica / Positive and negative myoclonus in a patient with end stage renal disease

Introducción: Las mioclonías son contracciones musculares paroxísticas de corta duración o pérdida abrupta del tono muscular, denominadas mioclonías positivas y negativas, respectivamente. Se presenta un caso clínico de mioclonías positivas y negativas generalizadas y se pretende describir los múltiples mecanismos fisiopatológicos y etiologías que lo desencadenan. Presentación del caso: Hombre de 35 años, con diabetes mellitus tipo 1 complicada con enfermedad renal diabética en hemodiálisis, desarrolló una bacteriemia asociada a catéter por Staphylococcus aureus y presentó mioclonías positivas y negativas. Se identificaron como posibles desencadenantes la uremia, la infección y los fármacos con potencial promioclónico; el hallazgo incidental de una lesión isquémica en núcleo caudado no explicaba la semiología encontrada en el paciente. Se hizo el control y retiro de todos los factores promioclónicos enunciados, junto a manejo farmacológico con levetiracetam, y con ello se logró el control de los síntomas. Discusión: Los pacientes con enfermedad renal crónica son susceptibles a la acumulación de productos tóxicos de tipo guanidinas, que tienen potencial para producir mioclonías. Además, las infecciones, el uso de fármacos con potencial promioclónico y lesiones estructurales como las isquemias corticales son etiologías que deben considerarse en el diagnóstico diferencial. El mayor impacto en los síntomas se observa con el control del factor desencadenante, y, en caso de persistir, la terapia farmacológica proporciona buenos resultados. Conclusión: Las mioclonías son trastornos del movimiento relativamente comunes en la enfermedad renal crónica. La identificación del desencadenante es crucial para su manejo junto al uso de fármacos con actividad antimioclónica.

Introduction: Myoclonus are paroxysmal muscle contractions of short duration or abrupt loss of muscle tone, called positive and negative myoclonus respectively. A clinical case of generalized positive and negative myoclonus is presented and the aim is to describe the multiple pathophysiological mechanisms and etiologies that trigger it. Case presentation: A 35-year-old man with type 1 diabetes mellitus complicated by diabetic kidney disease on hemodialysis developed catheter-associated bacteremia due to Staphylococcus aureus and presented positive and negative myoclonus. Uremia, infection, and drugs with pro-myoclonic potential were identified as possible triggers; The incidental finding of an ischemic lesion in the caudate nucleus did not explain the semiology found in the patient. The control and removal of all the pro-myoclonic factors mentioned was carried out, along with pharmacological management with levetiracetam, thus achieving control of the symptoms. Discussion: Patients with chronic kidney disease are susceptible to the accumulation of guanidine-type toxic products, which have the potential to produce myoclonus. Furthermore, infections, the use of drugs with pro-myoclonic potential and structural lesions such as cortical ischemia are etiologies that should be considered in the differential diagnosis. The greatest impact on symptoms is observed with the control of the triggering factor and if it persists, pharmacological therapy provides good results. Conclusion: Myoclonus are relatively common movement disorders in chronic kidney disease. Identification of the trigger is crucial for its management along with the use of drugs with anti-myoclonic activity.

Treatment of Seizures in the Neonate: Special Report From the ILAE Task Force on Neonatal Seizures, 2022

The International League Against Epilepsy (ILAE) task force on neonatal seizures has recently published draft guidelines and consensusbased recommendations on the treatment of neonatal seizures. This update provides a summary of the recommendations and the changes in management compared to the previous WHO ILAE guidelines, published in 2011, with emphasis on practical decision making requirements for a pediatrician.

A Rare Case Report of “Torsades De Pointes” Induced by Fluconazole-Levetiracetam Combined Therapy

Drugs used to treat cardiovascular disease as well as those used in the treatment of multiple other conditions can occasionally produce exaggerated prolongation of the QT interval on the surface electrocardiogram and the morphologically distinctive polymorphic ventricular tachycardia that results is known as «torsade de pointe». «Torsade de pointe» (TDP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface electrocardiogram by QT interval prolongation. It typically occurs in self-limiting bursts, causing dizziness and syncope, but may occasionally progress to ventricular fibrillation and sudden death. This rare case report showed the potential higher risk of the occurrences of «Tdp» when levetiracetam (KEPPRA) was used in combination therapy with fluconazole, which is already a known medication with the risk of causing polymorphic ventricular arrhythmia.

Efficacy and safety of levetiracetam versus valproic acid in the treatment of pediatric epilepsy：a meta analysis / 中国药房

OBJECTIVE To compare the efficacy and safety of levetiracetam versus valproic acid in the treatment of pediatric epilepsy， and to provide evidence-based reference. METHODS The databases including CNKI， VIP， China Biomedical Literature Database， Wanfang data， PubMed， Embase and Cochrane Library were searched for the RCTs about levetiracetam （trial group） and valproic acid （control group） were collected from the inception to October 1st， 2021. After literature screening and data extraction， the quality of included literature was evaluated using the bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0 and RevMan 5.3 software were used for meta-analysis， sensitivity analysis and bias risk analysis. RESULTS A total of 33 RCTs were included， involving 3 116 patients in total. The results of the meta-analysis showed that the effective rate of trial group was significantly higher than control group [RR＝1.06， 95%CI （1.02， 1.11）， P＝0.003]. The subgroup analysis according to different courses of treatment showed that there was no statistical significance in the effective rate between 2 groups after 1 and 3 months of treatment （P＞0.05）； after 6 months of treatment， the effective rate of trial group was significantly higher than that of control group （P＜0.05）. The incidence of adverse drug reaction in trial group was significantly lower than control group [RR＝0.50， 95%CI （0.41， 0.61）， P＜0.000 01]； among specific adverse drug reactions， the incidence of nausea and vomiting in trial group was significantly lower than control group （P＜0.05）； but there was no statistical significance in the incidence of rash， drowsiness， abnormal mood， loss of appetite， dizziness or headache （P＞0.05）. Results of sensitivity analysis showed that study results were stable and reliable. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS The short-term efficacy （1， 3 months） of LEV is similar to that of VPA in the treatment of pediatric epilepsy， but long-term efficacy （6 months） of LEV is better than that of VPA； moreover， LEV shows better safety in digestive system.

Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy

Abstract The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.

Síndrome de reacción a medicamento con eosinofilia y síntomas sistémicos (DRESS) asociado a levetiracetam: Reporte de caso

El síndrome de hipersensibilidad a medicamentos, con eosinofilia y síntomas sistémicos (DRESS de sus siglas en inglés) es un síndrome muy infrecuente que se caracteriza por erupción dérmica, eosinofilia y compromiso sistémico. Inicialmente fue descrito asociado a medicamentos anticrisis (antiepilépticos), pero posteriormente ha sido descrito en asociación a otros medicamentos. Entre los medicamentos anticrisis, se ha descrito predominantemente su asociación a fármacos aromáticos o con estructura similar: fenitoína, carbamazepina, fenobarbital, oxcarbazepina y lamotrigina. Entre los medicamentos anticrisis no aromáticos, se ha descrito su presentación en algunos pacientes expuestos a gabapentina, zonisamida, valproato, rufinamida y raramente a levetiracetam. La severidad del síndrome se relaciona al tiempo de exposición al fármaco, por lo que su detección precoz es de vital importancia. Describimos el primer caso en nuestro país, de un paciente con DRESS inducido por levetiracetam y revisamos los infrecuentes reportes de DRESS en pacientes expuestos a levetiracetam descritos en la literatura.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a very rare syndrome characterized by skin rash, eosinophilia and systemic compromise. This was initially described in association with antiseizures drugs, but later it was described in association with other drugs. Among antiseizure drugs, it has been described association with aromatic drugs as phenytoin, carbamazepine, phenobarbital, oxcarbazepine and lamotrigine; and non-aromatic antiseizure drugs as gabapentin, zonisamide, valproate, rufinamide and rarely to levetiracetam. The severity of the syndrome is related to the time of exposure to the drug, so early detection is of vital importance. We describe the first case in our country, of a patient with DRESS induced by levetiracetam, and we review the infrequent scientific reports of DRESS in patients exposed to levetiracetam.

Placement of Oral Formulations of Brivaracetam in Various Patient Profiles: An Indian Perspective

Brivaracetam (BRV), an analog of levetiracetam (LEV), lowers seizure frequency through a unique mechanism. Although BRV is approved for focal epilepsy in patients aged >1 month (by the US Food and Drug Administration) or >16 years (in India), clinical studies have suggested its potential role in other indications such as generalized seizures, secondarily generalized tonic-clonic seizures, and drug-resistant focal epilepsy, and in certain special populations. Here, we discuss the potential role of BRV in different patient populations and present expert opinions for positioning the pre-existing and newly available oral formulations of BRV to aid both clinicians and diverse patient groupswith a simple and easy dosing and titration-based treatment, including safe and effective switching from LEV to BRV.

Effects of levetiracetam combined with low-dose topiramate on bone and lipid metabolism in children with epilepsy / 中国基层医药

Objective:To investigate the efficacy of levetiracetam combined with low-dose topiramate on epilepsy and its effects on bone metabolism and lipid metabolism in children.Methods:A total of 108 children with epilepsy who received treatment in the First People's Hospital of Yongkang from August 2016 to December 2019 were included in this study. They were randomly allocated to study and control groups ( n = 54/group). The study group was treated with levetiracetam combined with low-dose topiramate. The control group was treated with carbamazepine combined with low-dose topiramate. Before treatment and half a year after treatment, serum alkaline phosphatase (ALP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels, blood Ca 2+ and P 3- concentrations, and bone mineral density (BMD) were determined. Clinical efficacy was evaluated in each group. Results:Half a year after treatment, blood Ca 2+ concentration, blood P 3- concentration, and BMD in the study group were (2.41 ± 0.35) mmol/L, (1.57 ± 0.26) mmol/L, and (2.21 ± 0.52) g/cm2, respectively, which were significantly greater than those in the control group [(2.19 ± 0.27) mmol/L, (1.18 ± 0.15) mmol/L, (1.81 ± 0.38) g/cm, tca2+ = 4.20, tbloodP3- = 5.73, tBMD = 6.42, all P < 0.05). ALP level was significantly lower in the study group than in the control group [(129.78 ± 25.63) U/L vs. (181.55 ± 21.94) U/L, t = 15.39, P < 0.05). Half a year after treatment, TC, TG, and LDL-C levels in the study group were (4.38 ± 0.64) mmol/L, (1.71 ± 0.42) mmol/L, and (1.65 ± 0.32) mmol/L, respectively, which were significantly lower than those in the control group [(4.76 ± 0.83) mmol/L, (1.96 ± 0.45) mmol/L, (1.98 ± 0.34) mmol/L, tTC = 3.81, tTG = 4.14, tLDL-C = 5.58, all P < 0.05]. HDL-C level in the study group was significantly higher than that in the control group [(1.96 ± 0.38) mmol/L vs. (1.63 ± 0.27) mmol/L, tHDL-C = 7.39, P < 0.05]. Half a year after medication, clinical efficacy was significantly higher in the study group than that in the control group (94.44% vs. 81.48%, χ2 = 6.29, P < 0.05). Conclusion:Low-dose topiramate combined with levetiracetam is highly effective on epilepsy in children. The combined therapy has less impact on the levels of bone and lipid metabolism indicators and is suitable for clinical application.

Efficacy and safety of switching from brand-name to domestic generic levetiracetam in children with epilepsy / 中国当代儿科杂志

OBJECTIVES@#To study the efficacy and safety of domestic generic levetiracetam in replacement of brand-name levetiracetam in the treatment of children with epilepsy.@*METHODS@#A retrospective analysis was performed on the medical data of 154 children with epilepsy who received domestic generic levetiracetam in the inpatient or outpatient service of Guangdong Provincial People's Hospital from May 2019 to December 2020. Domestic generic levetiracetam and brand-name levetiracetam were compared in terms of efficacy and safety.@*RESULTS@#For these 154 children, the epilepsy control rate was 77.3% (119/154) at baseline. At 6 months after switching to domestic generic levetiracetam, the epilepsy control rate reached 83.8% (129/154), which showed a significant increase (P<0.05). There was no significant change in the frequency of seizures from baseline to 6 months after switching (P>0.05). The incidence of refractory epilepsy in children with no response after switching treatment was significantly higher than that in children with response (P<0.05). Before switching, only 1 child (0.6%) experienced somnolence, while after switching, 3 children (1.9%) experienced mild adverse drug reactions, including dizziness, somnolence, irritability, and bad temper.@*CONCLUSIONS@#Switching from brand-name to generic levetiracetam is safe and effective and holds promise for clinical application, but more prospective randomized controlled trials are required in future.

Establishment of the method for simultaneous determination of levetiracetam and carbamazepine in human plasma / 中国药房

OBJECT IVE To e stablish the method for simultaneous determination of levetiracetam and carbamazepine concentrations in human plasma. METHODS After plasma samples were precipitated with methanol ，using carbamazepine-D 10 as the internal standard ，the concentrations of levetiracetam and carbamazepine were determined by high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. The determination was performed on XBridge BEH C 18 column with methanol-0.1％ formic acid as mobile phase （gradient elution ）at the flow rate of 0.35 mL/min. The column temperature was set at 40℃，and sample size was 2 μL. With electrospray ion source，a multiple reaction monitoring mode was used for positive ion scanning；the detected ion pairs for quantitative analysis were m/z 171.3→126.3（levetiracetam），m/z 237.1→194.1（carbamazepine）， 247.1→204.1（internal standard ）. RESULTS The linear range of the concentrations of levetiracetam and carbamazepine were 0.5-50 and 0.2-20 μg/mL（r＝0.997 3 and 0.998 5），respectively；the lower quantitative limits were 0.5 and 0.2 μg/mL，respectively. RSDs of intra-day and inter-day were all no more than 10.00％. RE of intra-day and inter-day were within ±4.00％；the average extraction recoveries rate were 95.60％-105.00％；the average internal standard correction matrix factors were 98.40％-110.00％； RSDs of stability tests were all not higher than 5.60％. The concentrations of levetiracetam and carbamazepine in the plasma of 22 patients measured by this method were 3.36-40.90 and 3.64-9.93 μg/mL，respectively. CONCLUSIONS The established method for determining the concentration of levetiracetam and carbamazepine in human plasma is f ast，sensitive，accurate and stable ，and can be used for the monitoring of plasma concentration and pharmacokinetic study in epilepsy patients.

A description of sodium valproate, lamotrigine and levetiracetam consumption in the Western Cape public sector

The rational use of medicine is fundamental to ensure effective and safe patient medicine treatment, and hence, should be monitored. Undisputable evidence exists for the teratogenic risk factors associated with sodium valproate. Consequently, the Western Cape Department of Health introduced a policy (2019) recommending alternatives for valproate in women of childbearing age, including lamotrigine or levetiracetam as alternatives for patients on antiretrovirals. This study aimed to describe the change in the consumption of valproate, lamotrigine and levetiracetam after a policy implementation in public sector health facilities of the Western Cape, South Africa. Methods: This observational study followed a quasi-experimental design. Consumption data from the Cape Medical Depot over the period 01 April 2018 to 31 March 2020 were analysed retrospectively. Consumption was presented as a defined daily dose (DDD) per 1000 population per quarter for sodium valproate, levetiracetam and lamotrigine for the Western Cape province, urban and rural areas. Consumption 12 months before was compared with consumption 12 months after policy implementation. Results: Post-policy implementation, valproate consumption remained unchanged provincially (3.3%; p = 0.255), in urban (7.8%; p = 0.255) and rural (1.5%; p = 0.701) areas. Lamotrigine consumption increased significantly provincially (30.7%; p = 0.020) and in urban areas (54.5%; p = 0.002); however, rural (26.1%; p = 0.108) areas did not show significant change. Provincially, valproate consumption remained substantially higher (209 DDDs/1000 population per quarter) compared with lamotrigine consumption (32.22 DDDs/1000 population per quarter). Conclusion: In the Western Cape public sector, the consumption of sodium valproate remained unchanged 12 months after policy implementation. Although there were significant increases in lamotrigine and levetiracetam consumption, the consumption was considerably less compared with sodium valproate consumption.

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy / Eficácia e segurança do levetiracetam como terapia adjunta na epilepsia focal refratária

ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.

Relief of HHV-6 Encephalomyelitis-induced Electric Shock-like Pain with Levetiracetam after Blood Stem Cell Transplantation

We encountered a case of HHV-6 encephalomyelitis following blood stem cell transplantation. A woman in her 30’s suffered from paroxysmal electric shock-like pain, itching, tremor of lower limbs and excessive sweating on the 15th day after cord blood transplantation. Urinary retention also occurred. Pregabalin and opioid administration was started, and foscarnet was administered after a finding of HHV-6DNA positive in cerebrospinal fluid. Combined use of levetiracetam 1000 mg per day decreased both frequency and intensity of the electric shock-like pain. In a week before the negative results of HHV-6 amplification, she became excessively drowsy. With withdrawal of levetiracetam, her consciousness returned to be clear. The main symptoms on discharge were pain and itching with numbness around the anus, and were well controlled with oxycodone 15 mg, pregabalin 225 mg, and lorazepam 0.5 mg per day. In our case of HHV-6 encephalomyelitis after cord blood transplantation, levetiracetam was effective in suppressing electric shock-like pain.

Progress in pharmacogenomics and efficacy prediction of levetiracetam / 中华神经科杂志

Levetiracetam (LEV) is the second generation of broad-spectrum antiepileptic drugs. Compared with other antiepileptic drugs, LEV has unique antiepileptic mechanism, good efficacy and tolerance, and its target is synaptic vesicle protein 2A. With the widespread use of LEV, more and more adverse reactions have been reported, especially mental related adverse reactions. This paper reviewed the research progress of LEV pharmacogenomics related targets, metabolism, adverse reaction related genetic variation and efficacy prediction, so as to provide decision-making for the application of LEV individualized treatment in clinical practice, improve the quality of life of epileptic patients and reduce the disease burden of patients with epilepsy.

Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation / 药学学报

The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.

Phenobarbitone versus levetiracetam in neonatal seizures

Background: There is increasing evidence that neonatal seizures have an adverse effect on neurodevelopmental progression and it may predispose to cognitive, behavioral or epileptic complications later in life. The objective of this study was to compare the efficacy of phenobarbitone and levetiracetam for the treatment of neonatal seizures in term and late preterm neonates. The study was aimed to know the efficacy of phenobarbitone (PB) in comparison with levetiracetam (LEV) in controlling neonatal seizures.Methods: This was a randomized controlled trial where data of the babies with seizures weighing more than 2 kg who were admitted in NICU of Muzaffarnagar Medical College was collected and analysed for intervention to either phenobarbitone or levetiracetam.Results: Clinically apparent seizures were controlled in only 65.38% neonates assigned to receive levetiracetam as compared to 76.92% neonates assigned to receive phenobarbitone.Conclusions: LEV although lesser effective than PB with very fewer side effects is found to be a good alternative in controlling neonatal seizures.

Efficacy and Safety of Subcutaneous Levetiracetam Injection for Terminally-ill Cancer Patients: A Case Report

Introduction: Antiepileptic drugs were occasionally administered to manage seizures in terminally-ill cancer patients. When enteral route is no longer feasible due to dysphagia or depressed level of consciousness, subcutaneous route could be an option. We reported three cases of terminally cancer patients who received subcutaneous levetiracetam (LEV) due to an inability to administer via intravenous route. Cases: The age of 3 cases was 83, 75, 82 years, respectively. In all cases, the prognosis prediction at the start of subcutaneous LEV was about 1 month. In all cases, the route of administration of LEV was changed from intravenous to subcutaneous. No exacerbation of convulsions, or injection site reaction was confirmed after subcutaneous LEV administration. Discussion: We believe that subcutaneous LEV administration may be one of the treatment options for seizures in patients with terminal cancer for whom intravenous administration of LEV is no longer feasible.

Observation of Therapeutic Efficacy of Oxcarbazepine Combined with Levetiracetam in the Treatment of Cognitive Dysfunction in Adult Patients with Temporal Lobe Epilepsy / 中国药房

OBJECTIVE：To observe therapuetic effica cy of oxcarbazepine combined with levetiracetam in the treatment of cognitive dysfunction in adult patients with temporal lobe epilepsy. METHODS ：According to inclusion and exclusion criteria ，83 adult patients with temporal lobe epilepsy were collected from neurology department of the First Affiliated Hospital of Kunming Medical University during January 2018 to October 2019，and then divided into control group （39 cases）and observation group （44 cases）. Control group was given Oxcarbazepine tablet with initial dose of 8-10 mg/（kg·d），morning and night ，increased by 5-10 mg/（kg·d）each week according to patient ’s condition ，the maximal dose was 45 mg/（kg·d），lasting for 3 months with the lowest effective treatment dose. Based on treatment of control group ，observation group was additionally given Levetiracetam tablet with initial dose of 5-10 mg/（kg·d），morning and night ，increased by 5-10 mg/（kg·d）each week according to the severity of disease，the total dose was not more than 2 000 mg/d，lasting for 3 months with the lowest effective treatment dose. The event-related potential P 300 at Pz site in 2 groups was measured before and after treatment （including the incubation period of N 1， P2，N2 and P 3 waves，amplitude of P 3 wave）. Webster ’s Adult Intelligence Scale [WAIS-RC ，including verbal IQ （VIQ）， performance IQ （PIQ），full scale IQ （FIQ）scores] and Clinical Memory Scale [CMS ，converting to memory quotient （MQ） score] were adopted. The occurrence of ADR was recorded. RESULTS ：Totally 5 patients of control group and 7 patients of observation group fell off. Finally ，a total of 71 patients participated in the entire study （34 cases in control group and 37 cases in observation group ）. Before treatment ，there was no statistical significance in P 300 at Pz site ，WAIS-RC and CMS between 2 groups （P＞0.05）. Compared with before treatment ，incubation period of N 2 and P 3 waves was shortenedsignificantly in 2 groups，and amplitude of P 3 wave wasincreased significantly after treatment （P＜0.05）；VIQ，FIQ and MQ scores were increased significantly （P＜0.05）. The incubation pe riod of P 2 wave was shortened significantly，and PIQ score was increased significantly in observation group （P＜ 0.05）. Compared with control group ，the shortening degree of incubation period of P 2，P3 waves，rising degree of amplitude of P 3 wave and rising degree of VIQ ，PIQ，FIQ，MQ scores were more bigger after treatment in observation （P＜0.05）. In the control group，there was 1 case of slight rash ，1 case of conscious asthenia ；in the observation group ，there was 1 case of nausea and vomiting，1 case of conscious asthenia ，and 1 case of emotional instability ；no serious ADR was found in 2 groups. CONCLUSIONS：Oxcarbazepine combined with levetiracetam can improve cognitive dysfunction in adult patients with temporal lobe epilepsy ，and the treatment effect is significantly better than oxcarbazepine monotherapy.