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OBJECTIVE To compare the efficacy and safety of lacosamide （LCM） and carbamazepine （CAR） as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis， 84 adult patients with newly diagnosed epilepsy， were admitted to the Department of Neurology， Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022， were divided into the control group （40 cases， receiving CAR treatment） and the observation group （44 cases， receiving LCM treatment） according to different medication regimens. Total response rate， epilepsy seizure frequency， blood lipid levels， and the occurrence of adverse events （AEs） of patients were compared between the 2 groups. RESULTS In the first month after treatment， there was no statistically significant difference in the total response rate between the observation group （63.64%） and the control group （55.00%， P＞0.05）； the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment （P＜0.05）， but there was no statistically significant difference between 2 groups （P＞0.05）. In the third month after treatment， the total response rate of the observation group （90.91%） was significantly higher than control group （67.50%， P＜0.05）； the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment， and the observation group was significantly lower than the control group （P＜0.05）. In the third month after treatment， the levels of total cholesterol （TC）， triglyceride （TG） and low-density lipoprotein cholestrol （LDL-C） in the control group and the level of LDL-C in the observation group were significantly higher than before treatment， and the levels of TC， TG and LDL-C in the observation group were significantly lower than those in the control group （P＜0.05）. There was no statistically significant difference in the incidence of AEs between the observation group （15.91%） and the control group （17.50%， P＞0.05）. CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults， which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile， LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults， and its impact on the patient’s blood lipid is smaller than CAR.
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OBJECTIVE To establish a method for simultaneous determination of two third-generation anti-epileptic medicines such as lacosamide and perampanel in human plasma and apply this method in clinical practice. METHODS Using clozapine as internal standard， the concentrations of lacosamide and perampanel of plasma samples in 10 epileptic patients were determined by LC-MS/MS after protein precipitation with acetonitrile and dilution with acetonitrile-water （20∶80，V/V）， and the plasma minimum concentrations were obtained by dilution of multiple. The determination was performed on Welch Ultimate XB-C18 column， with mobile phase A consisted of 10 mmol/L ammonium formate and mobile phase B consisted of methanol-acetonitrile-isopropanol （0.2% formic acid） mixed solution （7∶1.5∶1.5， V/V/V） for gradient elution at the flow rate of 0.4 mL/min. The column temperature was set at 40 ℃ ， and the sample size was 5 μL. The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning. The ion pair used for quantitative analysis of lacosamide， perampanel and internal standard were m/z 251.2→ 144.1， m/z 350.2→219.2 and m/z 327.2→270.0， respectively. RESULTS The linear ranges of lacosamide and perampanel were 0.001 25-0.125 μg/mL（r＞0.99）， 0.037 5-3.75 ng/mL （r＞0.99）； the limits of quantification were 0.001 25 μg/mL and 0.037 5 ng/mL， respectively. The precision and accuracy within and between batches， extraction recovery rate， matrix effect， and stability all met relevant requirements. The minimum concentrations of lacosamide in No. 1-5 patients were 5.3-12.2 μg/mL， and the minimum concentrations of perampanel in No.6-10 patients were 208-510 ng/mL， respectively. CONCLUSIONS The established method is simple， rapid and suitable for the therapeutic drug monitoring of lacosamide and perampanel.
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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.
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A 36-year-old female with serum anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD) on carbamazepine (CBZ) therapy for paroxysmal tonic spasms (PTS) developed Type 1 respiratory failure. High-resolution computed tomography chest showed diffuse ground-glass opacities in both lungs predominantly in bilateral perihilar region sparing subpleural regions and predominantly upper lobes with a smooth interlobular septal thickening. A transbronchial lung biopsy was consistent with hypersensitivity pneumonitis and following withdrawal of the CBZ and treatment with steroids her respiratory symptoms resolved. After stopping CBZ, PTS recurred, which was successfully treated with lacosamide. This is the first described biopsy-proven case of CBZ-induced hypersensitivity pneumonitis in the NMOSD patient.
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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).
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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.
Subject(s)
Heart Rate Determination , Long Term Adverse Effects , Lacosamide , AnticonvulsantsABSTRACT
BACKGROUND AND PURPOSE: Lacosamide (LCM) is an antiepileptic drug that enhances the slow inactivation of sodium channels and modulates collapsin response mediator protein-2. LCM was recently demonstrated to exert a neuroprotective effect in a murine model of traumatic brain injury and status epilepticus. Assuming the same underlying excitotoxicity-related brain injury mechanism, we hypothesized that LCM would have a neuroprotective effect in hypoxic-ischemic brain injury. METHODS: We divided rats into three groups at each testing session: pre- or postfed with LCM, fed with normal saline, and sham. A hypoxic-ischemic brain injury was induced by subjecting 7-day-old rats to right carotid artery coagulation followed by 2.5 h of exposure to 8% oxygen. The animals were killed on postnatal day 12 to evaluate the severity of brain damage. Open field testing was also performed between week 2 and week 6, and the Morris water maze test was performed in week 7 after hypoxia-ischemia. RESULTS: The incidence of liquefactive cerebral infarction was lower in rats prefed with LCM at 100 mg/kg/dose, with the mortality rate being higher at higher doses (200 and 300 mg/kg/dose). The infarct areas were smaller in LCM-prefed rats in several brain regions including the hemisphere, hippocampus, cortex, and striatum. Spatial learning and memory function were better in LCM-prefed rats (p<0.05). No effect was observed in postfed rats. CONCLUSIONS: This study suggests that LCM pretreatment exerts a neuroprotective effect on hypoxia-ischemia in neonatal rats. The obtained results suggest that LCM pretreatment could be used as an effective neuroprotective method for neonates under hypoxic-ischemic conditions including heart surgery.
Subject(s)
Animals , Humans , Infant, Newborn , Rats , Brain Injuries , Brain , Carotid Arteries , Cerebral Infarction , Hippocampus , Incidence , Memory , Methods , Mortality , Neuroprotection , Neuroprotective Agents , Oxygen , Semaphorin-3A , Sodium Channels , Spatial Learning , Status Epilepticus , Thoracic Surgery , WaterABSTRACT
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.