RESUMO

Abstract Background Lacosamide (LCM) is a third-generation anti-seizure drug approved in Europe and the United States, either as a monotherapy or adjunctive therapy, to treat partial-onset seizures in adults, adolescents, and children. In Brazil, LCM is licensed for treatment only in patients older than 16 years of age. Objective To evaluate a cohort of children presenting with refractory epilepsy who received LCM as an add-on therapy and observe the response and tolerability to the LCM treatment. Methods A retrospective cohort study conducted in a tertiary health care facility, which included 26 children, aged up to 16 years, who presented with refractory epilepsy and received LCM as an add-on treatment. The follow-up visits were scheduled every 3 months until 9 months of treatment with LCM. Results After 3 months of LCM administration, in 73.1% of the children, there was a reduction of > 50% in the frequency of seizures, and this clinical improvement was maintained in most patients (73.9%) for the following 9 months. Mild (such as, somnolence and behavioral changes) or severe (seizure worsening) adverse effects were observed in two and three children respectively. Among responders to LCM, there was a higher prevalence of males, fewer concomitant anti-seizure drugs, and lower percentage of patients using sodium channel blockers. Conclusions Lacosamide should be considered as an early treatment option in pediatric patients with refractory epilepsy, mainly focal seizures.

Resumo Antecedentes Lacosamida (LCM) é um fármaco anticrise de terceira geração aprovado na Europa e nos Estados Unidos, utilizado como monoterapia ou terapia adjuvante para tratar crises epilépticas focais em adultos, adolescentes e crianças. No Brasil, a LCM só é aprovada para tratamento em pacientes com mais de 16 anos de idade. Objetivo Avaliar uma coorte de crianças com epilepsia refratária que receberam LCM como terapia adjuvante e observar a resposta e tolerabilidade ao tratamento. Métodos Um estudo de coorte retrospectivo conduzido em uma unidade terciária de saúde, que incluiu 26 crianças de até 16 anos de idade que apresentavam epilepsia refratária e receberam um tratamento complementar com LCM. As visitas de acompanhamento foram agendadas a cada 3 meses, até 9 meses de tratamento com LCM. Resultados Após 3 meses de administração de LCM, em 73,1% das crianças, a frequência das crises teve uma redução maior do que 50%, e essa melhora clínica foi mantida na maioria dos pacientes (73,9%) pelos 9 meses seguintes. Efeitos adversos leves (como, sonolência e alterações comportamentais) ou graves (agravamento das crises) foram observados em duas e três crianças, respectivamente. Entre as crianças que responderam ao tratamento com LCM, houve uma maior prevalência do sexo masculino, o uso de um menor número de medicações anticrise associadas e o uso de bloqueadores dos canais de sódio. Conclusões A LCM deve ser considerada uma opção de tratamento precoce em pacientes pediátricos com epilepsia refratária, principalmente aqueles que apresentam crises focais.

RESUMO

This study evaluated the effect of lacosamide (LCM) on biochemical and mitochondrial parameters after PTZ kindling in mice. Male mice were treated on alternative days for a period of 11 days with LCM (20, 30, or 40 mg/kg), saline, or diazepam (2 mg/kg), before PTZ administration (50 mg/kg). The hippocampi were collected to evaluate free radicals, the activities of superoxide dismutase (SOD), catalase (CAT), and the mitochondrial complexes I-III, II, and II-III, as well as Bcl-2 and cyclo-oxygenase-2 (COX-2) expressions. Hippocampi, blood, and bone marrow were collected for genotoxic and mutagenic evaluations. LCM 40 mg/kg increased latency and decreased percentage of seizures, only on the 3rd day of observation. The dose of 30 mg/kg only showed positive effects on the percentage of seizures on the 2nd day of observation. LCM decreased free radicals and SOD activity and the dose of 40 mg/kg were able to increase CAT activity. LCM 30 and 40 mg/kg improved the enzymatic mitochondrial activity of the complex I-III and LCM 30 mg/kg improved the activity of the complex II. In the comet assay, the damage induced by PTZ administration was reduced by LCM 20 and 30 mg/kg. The dose of 20 mg/kg increased COX-2 expression while the highest dose used, 40 mg/kg, was able to reduce this expression when compared to the group treated with LCM 20 mg/kg. Although LCM did not produce the antiepileptogenic effect in vivo, it showed the neuroprotective effect against oxidative stress, bioenergetic dysfunction, and DNA damage induced by the repeated PTZ administration.

Assuntos

RESUMO

SUMMARY Ultrasonic velocity, density and viscosity of Lacosamide were measured in various alcohols at 298.15 K. From these measured experimental data, various acoustical parameters such as Specific acoustical impedance (Z), Adiabatic compressibility (k s), Intermolecular free path length (L f ), Rao's molar sound function (R m), Molar compressibility (W), van der Waals constant (b), Solvation number (S n ), Thermal conductivity (K bm), Relaxation strength (r) have been calculated for understanding the molecular interactions occurring in the solution.

RESUMEN Se midieron la velocidad ultrasónica, la densidad y la viscosidad de soluciones de lacosamida en varios alcoholes a 298,15 K. A partir de estos datos experimentales, se calcularon varios parámetros acústicos para comprender las interacciones moleculares que ocurren en la solución, tales como la impedancia acústica específica (Z), la compresibilidad adiabática (k s), la longitud del camino libre intermolecular (L f), la función molar de sonido de Rao (R m), la compresibilidad molar ( W), la constante de van der Waals (b), el número de solvatación (Sn), la conductividad térmica (K bm), y la fuerza de relajación (r).

RESUMO

RESUMEN Se presenta el caso de una paciente de 84 años de edad, con antecedentes de hipertensión arterial, dislipemia, insuficiencia venosa crónica y osteoartrosis, que -debido a una neuralgia del trigémino- había recibido tratamiento con varios fármacos, sin lograr control del dolor neuropático, por lo que se inició tratamiento con lacosamida en monoterapia, con incremento de dosis hasta lograr el objetivo terapéutico; pero la paciente presentó manifestaciones clínicas y alteraciones electrocardiográficas compatibles con disfunción sinusal, que se resolvieron tras la reducción de la dosis del fármaco.

ABSTRACT The case of an 84-year-old female patient is presented, with a history of high blood pressure, dyslipidemia, chronic venous failure and osteoarthritis, which -due to trigeminal neuralgia- had received treatment with several drugs, without achieving neuropathic pain control; that was why the treatment with lacosamide was started in monotherapy, with an increase in dose until the therapeutic objective was achieved; but the patient presented clinical manifestations and electrocardiographic alterations compatible with sinus dysfunction, which were solved after reducing the dose of the drug.

Assuntos

RESUMO

Objetivo: presentar la evidencia publicada hasta el momento acerca de la utilidad de la lacosamida en población pediátrica con epilepsia refractaria. Métodos: se realizaron búsquedas en las bases de datos electrónicas PubMed, Embase, Cochrane y Scielo, encontrando un total de 18 artículos que cumplieron los criterios de búsqueda. Hallazgos principales : lacosamida, uno de los fármacos anticonvulsivantes nuevos, ha sido aprobado como terapia adjunta en epilepsias de inicio focal y epilepsias refractarias en pacientes mayores de 16 años, pero existe creciente evidencia de su eficacia y seguridad en población pediátrica desde los 4 años. Los efectos adversos no difieren en gran medida de los demás anticonvulsivantes y su tasa de éxito es de aproximadamente el 8-40% de control total de crisis. Sin embargo, los estudios no tienen un seguimiento a largo plazo que demuestre que se mantiene este mismo control de crisis en el transcurso del tiempo. Adicionalmente, la lacosamida ofrece mejoría clínica independientemente del control de las crisis en cuanto al patrón motor y comportamental. Conclusiones: Los estudios muestran que la lacosamida es una opción segura indicada para la epilepsia de inicio focal y epilepsia refractaria en la población pediátrica como terapia adjunta, debido a su efectividad en el control de crisis, perfil de seguridad, baja tasa de efectos adversos e interacción con otros medicamentos; no obstante, se requieren estudios con mayor número de pacientes y con seguimientos más prolongados.

Objetive: to present the evidence published about the usefulness of lacosamide in pediatric patients with refractory epilepsy, in order to explain its use in this population. Methods: we conducted search in PubMed, Embase, Cochrane library and Scielo and found 18 articles that fulfilled the inclusion criteria. Findings: lacosamide, is one of the newer AED (Antiepileptic Drugs) approved for focal refractory and focal onset epilepsies as an add on treatment in patients older than 16 years. However there is growing evidence of its use, security and efficacy in pediatric population from 4 years and above. Adverse effects do not differ from others found in others AED with success seizure free rates between 8 and 40%. Studies revisited had major issues on long term following. In addition, lacosamide improves behavioral and motor skills in children despite seizure control. Conclusions: Studies shows lacosamide as a safe option in pediatric patients with focal onset and refractory epilepsies as an add on therapy given its seizure control, safety profile, low rate of adverse effects and interaction between others medications, however larger and long term studies are needed.

Assuntos