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1.
Ideggyogy Sz ; 73(3-4): 121-127, 2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-32364339

RESUMEN

Background and purpose: To evaluate P-wave dispersion before and after antiepileptic drug (AED) treatment as well as to investigate the risk of ventricular repolarization using the Tpeak-Tend (Tp-e) interval and Tp-e/QT ratio in patients with epileptic disorder. Methods: A total of 63 patients receiving AED therapy and 35 healthy adults were included. ECG recordings were obtained before and 3 months after anti-epileptic treatment among patients with epilepsy. For both groups, Tp-e and Tp-e/QT ratio were measured using a 12-lead ECG device. Results: Tp-e interval, Tpe/QT and Tp-e/QTc ratios were found to be higher in the patient group than in the control group (p<0.05, for all), while QTmax ratio was significantly lower in the patient group. After 3 months of AED therapy, significant increases in QT max, QTc max, QTcd, Tp-e, Tp-e/QT, and Tp-e/QTc were found among the patients (p<0.05). When the arrhythmic effects of the drugs before and after treatment were compared, especially in the valproic acid group, there were significant increases in Tp-e interval, Tp-e/QT and Tp-e/QTc values after three months of treatment (p<0.05). Carbamazepine and levetiracetam groups were not statistically significant in terms of pre- and post-treatment values. Conclusion: It was concluded that an arrhythmogenic environment may be associated with the disease, and patients who received AED monotherapy may need to be followed up more closely for arrhythmia.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Arritmias Cardíacas/diagnóstico , Carbamazepina/uso terapéutico , Epilepsia/tratamiento farmacológico , Sistema de Conducción Cardíaco/efectos de los fármacos , Ventrículos Cardíacos/efectos de los fármacos , Levetiracetam/uso terapéutico , Ácido Valproico/uso terapéutico , Adulto , Arritmias Cardíacas/fisiopatología , Estudios de Casos y Controles , Electrocardiografía/métodos , Sistema de Conducción Cardíaco/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos
2.
Lancet ; 395(10231): 1217-1224, 2020 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-32203691

RESUMEN

BACKGROUND: Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups. METHODS: In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075. FINDINGS: Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group. INTERPRETATION: Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus. FUNDING: National Institute of Neurological Disorders and Stroke, National Institutes of Health.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Levetiracetam/administración & dosificación , Fenitoína/análogos & derivados , Estado Epiléptico/tratamiento farmacológico , Ácido Valproico/administración & dosificación , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Lactante , Levetiracetam/efectos adversos , Masculino , Persona de Mediana Edad , Fenitoína/administración & dosificación , Fenitoína/efectos adversos , Ácido Valproico/efectos adversos , Adulto Joven
7.
J Invest Surg ; 33(3): 252-262, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30204031

RESUMEN

Purpose: Despite advances in spinal biomechanic research, surgical techniques, and rehabilitation processes, no significant improvement has been identified in the treatment of spinal cord injury (SCI) and neurological recovery. Aim of the Study: This study was designed to investigate the potential therapeutic effects of methylprednisolone and levetiracetam on SCI. Materials and Methods: In this study, 42 male Wistar Albino rats, each weighing 300-350 g, were separated into three main groups: control group, acute and subacute stage groups. With the exception of the control group, a T7-8 dorsal laminectomy was performed on the spinal column of the rats. A temporary vascular aneurysm clip was then applied to the spinal cord for 1 min to create SCI and methylprednisolone or levetiracetam was administered intraperitoneally to all except the control and SHAM control groups. The damaged spinal cord was removed for histopathological and biochemical examinations. Results: Both pharmacological agents were determined to have improved the histopathological architecture in damaged neural tissues during the acute period of SCI, but could not sustain this activity in the subacute period. Neither pharmacological agent affected the biochemical data in the acute nor subacute stages. Conclusions: Both pharmacological agents showed histopathological healing effects in injured tissues during the acute phase of SCI in this rat model but these effects could not be sustained in the subacute period. No effect on biochemical data was seen in either the acute or subacute period. There is a need for further advanced studies to determine the effects of levetiracetam on the healing processes in SCI.


Asunto(s)
Fármacos Neuroprotectores , Traumatismos de la Médula Espinal , Animales , Levetiracetam , Masculino , Metilprednisolona , Ratas , Ratas Wistar , Médula Espinal
10.
12.
N Engl J Med ; 381(22): 2103-2113, 2019 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-31774955

RESUMEN

BACKGROUND: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied. METHODS: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death. RESULTS: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant. CONCLUSIONS: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).


Asunto(s)
Anticonvulsivantes/uso terapéutico , Levetiracetam/uso terapéutico , Fenitoína/análogos & derivados , Estado Epiléptico/tratamiento farmacológico , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Anticonvulsivantes/efectos adversos , Benzodiazepinas/uso terapéutico , Niño , Preescolar , Método Doble Ciego , Resistencia a Medicamentos , Femenino , Humanos , Hipotensión/inducido químicamente , Infusiones Intravenosas , Inyecciones Intramusculares , Levetiracetam/efectos adversos , Masculino , Persona de Mediana Edad , Fenitoína/efectos adversos , Fenitoína/uso terapéutico , Ácido Valproico/efectos adversos , Adulto Joven
13.
BMC Neurol ; 19(1): 292, 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31739779

RESUMEN

BACKGROUND: Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported. CASE PRESENTATION: A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs. DISCUSSION AND CONCLUSIONS: To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.


Asunto(s)
Anticonvulsivantes/efectos adversos , Corea/inducido químicamente , Levetiracetam/efectos adversos , Adulto , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/secundario , Femenino , Glioblastoma/complicaciones , Glioblastoma/secundario , Humanos , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Neoplasias de la Médula Espinal/secundario
14.
BMJ ; 367: l5464, 2019 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-31712247

RESUMEN

The studyLyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet 2019;393:2125-34.This trial was funded by the NIHR Health Technology Assessment Programme (project number 12/127/134).To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000790/levetiracetam-vs-phenytoin-in-stopping-childrens-prolonged-epileptic-seizures.


Asunto(s)
Epilepsia , Estado Epiléptico , Niño , Humanos , Levetiracetam , Fenitoína , Convulsiones
16.
Pak J Pharm Sci ; 32(4): 1589-1597, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31608878

RESUMEN

The current study was designed to estimate the effect of υ-radiation on male rats pretreated with Levetiracetam (LEV) and/or Oxcarbazepine (OXC). Poly-treatment of rats with LEV, OXC and υ-radiation showed a significant elevation in the activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and isoenzyme creatinine kinase-MB (CK-MB) along with, an increase in the level of creatinine, urea, cardiac troponin (cTnI) and glutamate. These increases were associated with a decrease in acetylcholine (Ach) and υ-aminobutyric acid (GABA) levels. The data further revealed a significant increase of the apoptotic mediators tumor necrosis factor alpha (TNF-α) and brain caspase3 as well as, alterations in the oxidative stress parameters. The Results of the histopathological examination of liver, kidney, heart and brain tissues indicated coincidence with those recorded by the biochemical analysis. It seems promising to conclude that the exposure to υ-radiation intensified the deleterious and detrimental effect of dual treatment of LEV and OXC in rats.


Asunto(s)
Anticonvulsivantes/farmacología , Rayos gamma/efectos adversos , Levetiracetam/efectos adversos , Oxcarbazepina/efectos adversos , Acetilcolina/metabolismo , Alanina Transaminasa/sangre , Animales , Anticonvulsivantes/efectos adversos , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Encéfalo/efectos de los fármacos , Encéfalo/patología , Encéfalo/efectos de la radiación , Quimioterapia Combinada , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Riñón/efectos de la radiación , Levetiracetam/farmacología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/efectos de la radiación , Masculino , Malondialdehído/metabolismo , Neurotransmisores/metabolismo , Oxcarbazepina/farmacología , Ratas
17.
Medicina (B Aires) ; 79 Suppl 3: 6-9, 2019.
Artículo en Español | MEDLINE | ID: mdl-31603835

RESUMEN

The objective was to describe the frequency, mode of presentation and characteristics of epilepsy in children with congenital hemiparesis (CH). It is a etrospective, descriptive and multicenter study, based on the collection of data from the clinical records of patients from 0 to 19 years with CH secondary to perinatal infarction in different centers of the community of Catalonia. A total of 310 children were included (55% males and 45% females), from a total of 13 centers in Catalonia. Average age of onset of the crises was 2 ± 1 year. Epilepsy was present in 29.5% (n = 76), among which the most frequent vascular subtype was arterial presumed perinatal ischemic stroke (51.3%), followed by neonatal arterial ischemic stroke (18.4%), periventricular venous infarction (15.8%), neonatal hemorrhagic stroke (10.5%) and neonatal cerebral sinovenous thrombosis (3.9%). Semiology of the most frequent seizures was motor focal in 82%, followed by focal motor with secondary bilateralization in 23%, focal discognitive in 13.5%, generalized by 2% and spasms in 6.5%. The 67.3% were controlled with monotherapy and the drugs used were valproate, levetiracetam or carbamazepine. The antecedent of electrical status during sleep was identified in 3 patients, all associated with extensive lesions that included the thalamus. Of the total number of children with epilepsy, 35% began with neonatal seizu res in the first 3 days of life. The 30% of children with perinatal stroke and CH present a risk of epilepsy during childhood. Children with ischemic strock have the highest risk, so they will require a follow-up aimed at detecting prematurely the epilepsy and start a treatment.


Asunto(s)
Epilepsia/etiología , Paresia/congénito , Paresia/etiología , Accidente Cerebrovascular/complicaciones , Adolescente , Anticonvulsivantes/uso terapéutico , Carbamazepina/uso terapéutico , Niño , Preescolar , Epilepsia/tratamiento farmacológico , Femenino , Humanos , Lactante , Recién Nacido , Levetiracetam/uso terapéutico , Masculino , Estudios Retrospectivos , Factores de Riesgo , Convulsiones/etiología , España , Ácido Valproico/uso terapéutico , Adulto Joven
18.
Indian Pediatr ; 56(8): 639-640, 2019 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-31477641
19.
Am J Vet Res ; 80(10): 950-956, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31556719

RESUMEN

OBJECTIVE: To compare pharmacokinetics of levetiracetam in serum and CSF of cats after oral administration of extended-release (ER) levetiracetam. ANIMALS: 9 healthy cats. PROCEDURES: Cats received 1 dose of a commercially available ER levetiracetam product (500 mg, PO). Thirteen blood and 10 CSF samples were collected over a 24-hour period for pharmacokinetic analysis. After 1 week, cats received 1 dose of a compounded ER levetiracetam formulation (500 mg, PO), and samples were obtained at the same times for analysis. RESULTS: CSF concentrations of levetiracetam closely paralleled serum concentrations. There were significant differences between the commercially available product and the compounded formulation for mean ± SD serum maximum concentration (Cmax; 126 ± 33 µg/mL and 169 ± 51 µg/mL, respectively), Cmax corrected for dose (0.83 ± 0.10 µg/mL/mg and 1.10 ± 0.28 µg/mL/mg, respectively), and time to Cmax (5.1 ± 1.6 hours and 3.1 ± 1.5 hours, respectively). Half-life for the commercially available product and compounded formulation of ER levetiracetam was 4.3 ± 2.0 hours and 5.0 ± 1.6 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The commercially available product and compounded formulation of ER levetiracetam both maintained concentrations in healthy cats 12 hours after oral administration that have been found to be therapeutic in humans (ie, 5 µg/mL). Results of this study supported dosing intervals of 12 hours, and potentially 24 hours, for oral administration of ER levetiracetam to cats. Monitoring of serum concentrations of levetiracetam can be used as an accurate representation of levetiracetam concentrations in CSF of cats.


Asunto(s)
Anticonvulsivantes/farmacocinética , Gatos/metabolismo , Levetiracetam/farmacocinética , Administración Oral , Animales , Anticonvulsivantes/sangre , Anticonvulsivantes/líquido cefalorraquídeo , Área Bajo la Curva , Gatos/sangre , Gatos/líquido cefalorraquídeo , Estudios Cruzados , Preparaciones de Acción Retardada/farmacocinética , Semivida , Levetiracetam/administración & dosificación , Levetiracetam/sangre , Levetiracetam/líquido cefalorraquídeo , Estudios Prospectivos
20.
Pediatr Neurol ; 100: 105-106, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31481329
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