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Anticonvulsivantes , Antineoplásicos Alquilantes , Ifosfamida , Levetiracetam , Humanos , Levetiracetam/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Antineoplásicos Alquilantes/efectos adversos , Ifosfamida/efectos adversos , Piracetam/análogos & derivados , Piracetam/uso terapéutico , Piracetam/efectos adversos , Electroencefalografía , Masculino , Encefalopatías/inducido químicamente , Encefalopatías/diagnóstico por imagen , Encefalopatías/tratamiento farmacológico , FemeninoRESUMEN
Adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are known to be associated with behavioural changes but acute presentation including psychosis and delirium are less common. We report the case of a 42-year-old female patient with a known medical history of hypertension and diabetes mellitus, presenting with acute onset behavioural changes suggestive of psychosis to a tertiary care centre in Muscat, Oman in 2022. Further evaluation revealed an ACTH dependent Cushing's disease with a pituitary microadenoma. The patient was admitted for endoscopic resection of the adenoma. During the peri-operative period, she experienced worsening of psychosis in addition to delirium. She also developed episodes of unresponsiveness, posturing, severe diaphoresis and dyspnoea accompanied by tachycardia and hypertension which were managed with midazolam and levetiracetam. A seizure work-up and computed tomography brain scan were unremarkable. At follow-up, she showed full resolution of symptoms with good blood pressure and glycaemic control.
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Delirio , Trastornos Psicóticos , Humanos , Femenino , Adulto , Trastornos Psicóticos/etiología , Delirio/etiología , Neoplasias Hipofisarias/complicaciones , Omán , Adenoma/complicaciones , Adenoma Hipofisario Secretor de ACTH/complicaciones , Levetiracetam/uso terapéutico , Hormona Adrenocorticotrópica/sangre , Hormona Adrenocorticotrópica/análisisRESUMEN
Epilepsy is a disorder characterized by a predisposition to generate seizures. Levetiracetam (LEV) is an antiseizure drug that has demonstrated oxidant-antioxidant effects during the early stages of epilepsy in several animal models. However, the effect of LEV on oxidant-antioxidant activity during long-term epilepsy has not been studied. Therefore, the objective of the present study was to determine the effects of LEV on the concentrations of five antioxidant enzymes and on the levels of four oxidant stress markers in the hippocampus of rats with temporal lobe epilepsy at 5.7 months after status epilepticus (SE). The results revealed that superoxide dismutase (SOD) activity was significantly greater in the epileptic group (EPI) than in the control (CTRL), CTRL + LEV and EPI + LEV groups. No significant differences were found among the groups' oxidant markers. However, the ratios of SOD/hydrogen peroxide (H2O2), SOD/glutathione peroxidase (GPx) and SOD/GPx + catalase (CAT) were greater in the EPI group than in the CTRL and EPI + LEV groups. Additionally, there was a positive correlation between SOD activity and GPx activity in the EPI + LEV group. LEV-mediated modulation of the antioxidant system appears to be time dependent; at 5.7 months after SE, the role of LEV may be as a stabilizer of the redox state.
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Antioxidantes , Catalasa , Epilepsia del Lóbulo Temporal , Glutatión Peroxidasa , Levetiracetam , Estrés Oxidativo , Superóxido Dismutasa , Animales , Levetiracetam/farmacología , Levetiracetam/uso terapéutico , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/metabolismo , Masculino , Superóxido Dismutasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Catalasa/metabolismo , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Oxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Modelos Animales de Enfermedad , Peróxido de Hidrógeno/metabolismo , Ratas WistarRESUMEN
BACKGROUND AND OBJECTIVES: Systematic screening can help identify antiseizure medication (ASM)-associated adverse events (AEs) that may preclude patients from reaching effective doses or completing adequate trial periods. The Adverse Event Profile (AEP) is a self-completed instrument to identify the frequency of common AEs associated with ASM use. This study aimed to compare the AE profile of commonly used ASMs in adults with newly diagnosed focal epilepsy. METHODS: The Human Epilepsy Project is a prospective, international, observational study investigating markers of treatment response in newly diagnosed focal epilepsy. Participants were enrolled within 4 months of treatment initiation. Adult participants on levetiracetam, lamotrigine, carbamazepine, or oxcarbazepine monotherapy who completed the AEP and Mini International Neuropsychiatric Interview at enrollment were included. Multivariable generalized linear and penalized logistic regression models assessed differences in total and itemized marginal AEP scores and dichotomized responses ("never/rarely" vs "sometimes/always"). RESULTS: A total of 225 adults initiated on levetiracetam (n = 132, 59%), lamotrigine (n = 55, 24%), carbamazepine (n = 19, 8.4%), or oxcarbazepine (n = 19, 8.4%) were included. There were no significant differences in AEP total scores between ASMs. Patients with depression (adjusted marginal score ratio [aMSR] 1.23, 95% CI 1.09-1.39, p = 0.001) and anxiety (aMSR 1.15, 95% CI 1.04-1.26, p = 0.007) had worse AEP total scores than those without. After adjusting for depression and anxiety, levetiracetam users were >3 times more likely to report feelings of aggression (adjusted odds ratio [aOR] 3.38, 95% CI 1.07-10.7, p = 0.038) and almost half as likely to experience unsteadiness (aOR 0.45, 95% CI 0.21-0.99, p = 0.047) than lamotrigine users. Carbamazepine and oxcarbazepine had the highest rates of discontinuation (42.1%, each), followed by levetiracetam (34.8%) and lamotrigine (16.4%). Levetiracetam users had the highest proportion of discontinuations because of AEs alone (18%), and lamotrigine had the lowest (5%). DISCUSSION: Systematic screening for AEs in adults with newly diagnosed focal epilepsy on ASM monotherapy showed that those with comorbid psychiatric conditions report greater AEs overall, irrespective of ASM. Levetiracetam was associated with >3-fold risk of psychiatric AEs and half the risk of experiencing unsteadiness than lamotrigine. Levetiracetam had the highest proportion of discontinuations because of AEs alone, while lamotrigine had the lowest.
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Anticonvulsivantes , Carbamazepina , Epilepsias Parciales , Lamotrigina , Levetiracetam , Oxcarbazepina , Humanos , Femenino , Masculino , Anticonvulsivantes/efectos adversos , Epilepsias Parciales/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Levetiracetam/efectos adversos , Levetiracetam/uso terapéutico , Estudios Prospectivos , Carbamazepina/efectos adversos , Carbamazepina/análogos & derivados , Carbamazepina/uso terapéutico , Oxcarbazepina/efectos adversos , Adulto JovenRESUMEN
PURPOSE: Prenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6-7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy. METHODS: Eligible mother-child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6-7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex. RESULTS: Of 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001). CONCLUSIONS: Consistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.
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Anticonvulsivantes , Carbamazepina , Epilepsia , Lamotrigina , Levetiracetam , Efectos Tardíos de la Exposición Prenatal , Ácido Valproico , Humanos , Femenino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Anticonvulsivantes/efectos adversos , Niño , Embarazo , Masculino , Levetiracetam/efectos adversos , Ácido Valproico/efectos adversos , Lamotrigina/efectos adversos , Lamotrigina/uso terapéutico , Carbamazepina/efectos adversos , Epilepsia/tratamiento farmacológico , Pruebas Neuropsicológicas , Triazinas/efectos adversos , Estudios de Cohortes , Piracetam/análogos & derivados , Piracetam/efectos adversos , Adulto , Cognición/efectos de los fármacos , Estudios Prospectivos , Inteligencia/efectos de los fármacosRESUMEN
Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use is restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk to men's offspring, prompting recommendations to restrict use in everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called a "target trial") using retrospective observational data. The data will be drawn from ~250m mainly US patients in the TriNetX repository and ~60m UK patients in Clinical Practice Research Datalink (CPRD). These will be scanned for individuals aged 16-54 years with epilepsy and on valproate who either continued, switched to lamotrigine or levetiracetam, or discontinued valproate between 2014-2024, creating four groups. Randomisation to these groups will be emulated by baseline confounder adjustment using g-methods. Mortality and morbidity outcomes will be assessed and compared between groups over 1-10 years, employing time-to-first-event and recurrent events analyses. A causal prediction model will be developed from these data to aid in predicting the safest alternative antiseizure medications. Together, these findings will optimise informed decision-making about valproate withdrawal and alternative treatment selection, providing immediate and vital information for patients, clinicians and regulators.
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Anticonvulsivantes , Epilepsia , Ácido Valproico , Humanos , Ácido Valproico/efectos adversos , Ácido Valproico/uso terapéutico , Femenino , Masculino , Adulto , Adolescente , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Epilepsia/tratamiento farmacológico , Estudios Retrospectivos , Levetiracetam/uso terapéutico , Levetiracetam/efectos adversos , Lamotrigina/efectos adversos , Lamotrigina/uso terapéuticoRESUMEN
INTRODUCTION: Status Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as "new-onset status epilepticus" (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term "established NOSE" (eNOSE) is generally employed in this context. This study aims to describe the main clinical characteristics of a large sample of patients suffering from eNOSE, compare the ASM efficacy, and explore the risk factors associated with ASM treatment unresponsiveness and eNOSE-associated mortality. METHODS: Adult patients diagnosed with eNOSE were retrospectively selected between January 2016 and December 2022. We reviewed demographics, clinical data, diagnostic work-up, and treatment. We considered the last ASM introduced before the eNOSE termination as effective. RESULTS: 123 patients were included (age: 67.9 ± 17.3). eNOSE acute etiology was mostly reported. In the overall cohort, phenytoin showed the highest response rate (p = 0.01). In the pairwise comparisons, valproate was superior to levetiracetam (p = 0.02) but not to lacosamide (p = 0.50). Phenytoin had a significantly higher resolution rate than levetiracetam (p = 0.001) but not lacosamide (p = 0.14). Thirty patients were refractory to ASM treatment. No predictors of refractoriness were identified. Thirty-nine patients died. Age and GCS were identified as eNOSE-related mortality risk factors. CONCLUSION: eNOSE frequently has an acute etiology with several associated syndromes. Phenytoin is more effective in managing eNOSE, even though lacosamide, valproate, and levetiracetam can represent further therapeutic options. Age and GCS are the main risk factors for eNOSE-associated mortality.
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Anticonvulsivantes , Estado Epiléptico , Humanos , Estado Epiléptico/mortalidad , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/diagnóstico , Estado Epiléptico/terapia , Masculino , Femenino , Anticonvulsivantes/uso terapéutico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Anciano de 80 o más Años , Adulto , Resultado del Tratamiento , Levetiracetam/uso terapéutico , Factores de Riesgo , Fenitoína/uso terapéutico , Fenitoína/efectos adversos , Ácido Valproico/uso terapéuticoRESUMEN
PURPOSE: This retrospective study aimed to analyze anti-seizure medication (ASM) prescription trends in Japan, particularly among older adults and women of childbearing age, to inform future treatment strategies and optimize ASM selection criteria. METHODS: Data were extracted from the National Database Open Data Japan for fiscal years (FY) 2018-2021, covering prescriptions across sex and 5-year age groups. We conducted data imputation for prescriptions under 1,000 units to maintain anonymity, calculated the estimated number of patients using standard adult maintenance doses, and adjusted for pediatric dosing using Augsberger's formula. RESULTS: Our analysis revealed a 7.6% increase in ASM usage, with a notable shift from older to newer ASMs, such as levetiracetam (LEV) and lamotrigine (LTG). LEV and LTG prescriptions increased by 26.7% and 15.0% from FY 2018 to FY 2021, respectively, whereas older ASMs such as phenytoin, declined. Sex-specific analysis showed a higher LTG prescription rate among women, especially in adolescent and young adult cohorts, where the female-to-male prescription ratio increased from 1.65 to 1.85. Valproate (VPA) and LEV accounted for 57.0% of ASM prescriptions in older adults. The number of inpatient LTG prescriptions was notably lower than that of outpatient LTG prescriptions across age groups. Pediatric use of generics was lower than that in other age groups. CONCLUSION: This study revealed that newer ASMs are being used increasingly, with a significant proportion of VPA continuously prescribed among women of childbearing age. In older adults, VPA and LEV accounted for more than half of the ASM prescriptions. These findings are crucial for developing future treatment strategies and improving the ASM selection criteria.
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Anticonvulsivantes , Bases de Datos Factuales , Humanos , Anticonvulsivantes/uso terapéutico , Femenino , Japón , Masculino , Estudios Retrospectivos , Adulto , Adolescente , Adulto Joven , Anciano , Persona de Mediana Edad , Niño , Bases de Datos Factuales/tendencias , Preescolar , Prescripciones de Medicamentos/estadística & datos numéricos , Lactante , Epilepsia/tratamiento farmacológico , Levetiracetam/uso terapéutico , Lamotrigina/uso terapéutico , Anciano de 80 o más Años , Convulsiones/tratamiento farmacológico , Recién Nacido , Ácido Valproico/uso terapéutico , Factores de EdadRESUMEN
Background and Objectives: This study was performed for the purpose of assessing whether antiepileptic levetiracetam treatment produces a change in brain volumes in children with epilepsy. To that end, we compared the volumes of the basal ganglia (caudate nucleus, putamen, globus, hip-pocampus, and thalamus) at magnetic resonance imaging (MRI) before and after treatment (months 18-24) in pediatric epilepsy patients using levetiracetam. Materials and Methods: This retrospective study involved a volumetric comparison of patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic between 01.08.2019 and 01.11.2023 and diagnosed with epilepsy, and who underwent cranial MRI before and 18-24 months after treatment at the radiology department. The demographic and clinical characteristics (age, sex, family history of epilepsy, type of epilepsy, and EEG features (normal, abnormal, epileptiform)) of the patients included in the study were recorded. Results: The comparison of basal ganglia volumes at cranial MRI before and at months 18-24 of treatment revealed significant differences in the left caudate nucleus, right putamen, left putamen, left globus pallidus, right thalamus, left thalamus, and right hippocampal regions. Conclusions: In conclusion, differing findings are encountered at cranial imaging in patients with epilepsy, depending on the seizure frequency, activity, and the type of antiepileptic drugs used. This study compared basal ganglia volumes on cranial MRIs taken before and 18-24 months after treatment in pediatric epilepsy patients using levetiracetam. A significant increase was observed in the volumes of basal ganglia (caudate nucleus, putamen, globus pallidus, hippocampus, and thalamus) on the MRIs of pediatric epilepsy patients using levetiracetam.
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Anticonvulsivantes , Epilepsia , Levetiracetam , Imagen por Resonancia Magnética , Humanos , Levetiracetam/uso terapéutico , Femenino , Masculino , Niño , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Anticonvulsivantes/uso terapéutico , Adolescente , Epilepsia/tratamiento farmacológico , Preescolar , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacosRESUMEN
Introducción. El levetiracetam (LEV) es un antiepiléptico aprobado por el Instituto de Salud Pública de Chile como terapia concomitante en crisis epilépticas en niños mayores de cuatro años. Sin embargo, es ampliamente indicado desde el periodo neonatal, lo que hace necesario evaluar su utilización fuera de ficha técnica. Objetivo. Determinar el perfil de prescripción-indicación de LEV en el tratamiento de las crisis epilépticas en menores de cuatro años en un hospital de alta complejidad del sur de Chile. Población y método. Estudio observacional, descriptivo y retrospectivo. Se revisaron las historias clínicas de quienes iniciaron tratamiento con LEV entre 2014 y 2019, y se recopilaron datos sobre variables sociodemográficas, farmacológicas y clínicas. El análisis se basó en la descripción del perfil de los pacientes, prescripción, seguimiento y seguridad. Resultados. Se incluyeron 68 pacientes: 40 (58,8 %) de sexo masculino, 49 (72,1 %) con edad gestacional ≥ 37 semanas. La etiología principal de la epilepsia fue de tipo estructural (35,3 %); el LEV se utilizó principalmente en niños diagnosticados con malformación del sistema nervioso central (17,6 %) y predominó la monoterapia (55,9 %). En el 50 % se usó LEV para crisis focales. Cinco niños (7,3 %) presentaron trastornos de tipo psiquiátrico clasificados como probables reacciones adversas al medicamento. Conclusión. El LEV se utilizó en niños con diferentes diagnósticos con baja frecuencia de eventos adversos. El perfil de utilización varió en los diferentes grupos etarios. Es necesario identificar en futuros estudios la efectividad especialmente en el recién nacido y en epilepsias refractarias.
Introduction. Levetiracetam (LEV) is an antiepileptic drug approved by the Chilean Institute of Public Health as concomitant therapy for epileptic seizures in children older than 4 years of age. However, it is widely prescribed from the neonatal period, which makes it necessary to evaluate its off-label use. Objective. To determine the prescription-indication profile of LEV in the treatment of epileptic seizures in children younger than 4 years in a tertiary care hospital in southern Chile. Population and method. Observational, descriptive, and retrospective study. The medical records of patients who started treatment with LEV between 2014 and 2019 were reviewed, and data on sociodemographic, pharmacological, and clinical variables were collected. The analysis was based on the description of the profile of patients, prescriptions, follow-up, and safety. Results. A total of 68 patients were included: 40 (58.8%) were males, 49 (72.1%) were born at a gestational age ≥ 37 weeks. The main etiology of epilepsy was structural (35.3%); LEV was mostly used in children diagnosed with central nervous system malformation (17.6%), and monotherapy was the prevailing dosage (55.9%). LEV was used for focal seizures in 50% of cases. Five children (7.3%) had psychiatric disorders, classified as probable adverse drug reactions. Conclusion. LEV was used in children with various diagnoses, with a low rate of adverse events. The profile of drug use varied in the different age groups. Future studies are needed to identify effectiveness, especially in newborn infants and patients with refractory epilepsy.
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Humanos , Masculino , Femenino , Recién Nacido , Lactante , Epilepsia/tratamiento farmacológico , Levetiracetam/efectos adversos , Levetiracetam/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Chile , Estudios Retrospectivos , Uso Fuera de lo Indicado/estadística & datos numéricos , Centros de Atención TerciariaRESUMEN
PURPOSE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls. METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province. FINDINGS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group. IMPLICATIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.
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Anticoagulantes , Anticonvulsivantes , Humanos , Estudios Retrospectivos , Femenino , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Masculino , Estudios de Casos y Controles , Anciano , Persona de Mediana Edad , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Italia , Interacciones Farmacológicas , Ácido Valproico/administración & dosificación , Ácido Valproico/uso terapéutico , Ácido Valproico/efectos adversos , Levetiracetam/administración & dosificación , Levetiracetam/uso terapéutico , Levetiracetam/efectos adversos , Quimioterapia Combinada , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Anciano de 80 o más Años , Convulsiones/tratamiento farmacológico , AdultoRESUMEN
We describe a 44-year-old man with a complaint of atonic seizures of the left upper limb, followed by generalized seizures. Brain MRI showed isolated juxtacortical white matter T2 hyperintensity with gadolinium (Gd) enhancement of the adjacent cortical gray matter and subcortical white matter in the right frontal convexity. Treatment with levetiracetam was effective for seizure suppression, and he had no other neurological abnormalities. Human leukocyte antigen typing revealed B54 and Cw1, which indicated the possibility of neuro-Sweet disease. However, a general examination, which included vital signs and eye and skin findings, was normal. A cerebrospinal fluid test showed a mild elevation in protein levels without pleocytosis and a normal range of interleukin-6. Electroencephalography showed intermittent slow waves without epileptic discharge in the bilateral temporal lobes. We detected subtle flow voids in the pia mater of the left frontal lobe, which suggested cerebrovascular disease, and specifically, the possibility of dural arteriovenous fistulas. Computed tomography angiography showed abnormally dilated perimedullary veins in the left frontal lobe. Cerebral angiography confirmed the existence of four dural arteriovenous fistulas, which included two retrograde leptomeningeal venous drainages in the right frontal cortical veins supplied by the anterior branch of the right middle meningeal artery. The other dural arteriovenous fistulas were retrograde leptomeningeal venous drainages in the left frontal cortical veins supplied by the anterior and posterior convexity branches of the left middle meningeal artery. The patient underwent successful endovascular embolization of all dural arteriovenous fistulas with Onyx injection. A follow-up MRI showed gradual improvement of the T2 hyperintensity and Gd enhancement. He remained seizure-free for 2 years following endovascular embolization.
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Malformaciones Vasculares del Sistema Nervioso Central , Angiografía Cerebral , Gadolinio , Levetiracetam , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Masculino , Adulto , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Gadolinio/administración & dosificación , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Levetiracetam/administración & dosificación , Convulsiones/etiología , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/patología , Piracetam/administración & dosificación , Piracetam/análogos & derivados , Medios de Contraste/administración & dosificación , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: The effects of levetiracetam (LEV) on bone mineral density (BMD) and bone metabolism are currently inconclusive, and this study was designed to answer this question. METHODS: Citations from PubMed, Embase, Cochrane Library, and Web of Science databases (up to February 4, 2024) were reviewed. The effects of LEV on BMD as well as bone metabolism indicators were measured by calculating the standardized mean difference (SMD) with a 95% confidence interval (CI). This study was registered with PROSPERO (CRD42024509560). RESULTS: A total of 612 individuals from 13 studies were included in the present analysis. Of the items related to bone metabolism, LEV was found to be associated significantly with decreased serum calcium with an SMD of -0.47 (95 % CI, -0.77- -0.16; p = 0.04). However, changes in other markers (including serum phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and parathyroid hormone) were not statistically significantly correlated with the use of LEV (p > 0.05). Also, when compared to the control groups, the changes in BMD of the observation groups were not significant (p > 0.05). CONCLUSIONS: The use of LEV may significantly reduce serum calcium in patients with epilepsy, and regular monitoring of bone metabolism-related indicators is recommended.
Asunto(s)
Anticonvulsivantes , Densidad Ósea , Epilepsia , Levetiracetam , Levetiracetam/uso terapéutico , Levetiracetam/farmacología , Humanos , Densidad Ósea/efectos de los fármacos , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/farmacología , Huesos/efectos de los fármacos , Huesos/metabolismo , Calcio/sangre , Calcio/metabolismoRESUMEN
AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.
Asunto(s)
Anticonvulsivantes , Epilepsia , Levetiracetam , Saliva , Humanos , Levetiracetam/farmacocinética , Levetiracetam/sangre , Femenino , Saliva/química , Saliva/metabolismo , Embarazo , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/sangre , Anticonvulsivantes/análisis , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/sangre , Adulto Joven , Monitoreo de Drogas/métodos , Piracetam/análogos & derivados , Piracetam/análisis , Piracetam/farmacocinética , Piracetam/sangre , Estudios Prospectivos , Estudios de Cohortes , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVE: To compare the effects of levetiracetamï¼LEVï¼, lamotrigine(LTG), oxcarbazepine(OXC), topiramate(TPM) and valproate (VPA) on postictal state (PIS). METHODS: A total of 187 epilepsy patients undergoing monotherapy were enrolled in a long-term follow-up study at the Affiliated Hospital of Yangzhou College. This included 30 patients on levetiracetam, 41 on valproate, 30 on oxcarbazepine, 28 on topiramate, and 31 on lamotrigine. A control group of 28 newly diagnosed or previously untreated epilepsy patients was also included. The Liverpool Seizure Severity Scale 2.0 (LSSS2.0) and the Seizure Severity Questionnaire (SSQ) were utilized to evaluate the patients' condition, with comparison based on the results of the postictal status items. EEG during PIS termination was assessed using the Grand Total EEG score (GTE) as an objective tool to measure the impact of Antiseizure medications (ASMs) on the post-seizure state. RESULTS: The LSSS2.0 score indicated a statistically significant difference in post-seizure status score among the 5 groups (p < 0.05). The difference between the 5 groups and the control group was statistically significant (p < 0.05). Results of the SSQ demonstrated that all 5 drugs significantly reduced the post-seizure status score compared to the control group (p < 0.05). The GTE score revealed that, in the later stage of the seizure, the GTE score of the levetiracetam group, valproate group, oxcarbazepine group, and lamotrigine group significantly decreased compared to the control group (P < 0.05). There was no significant decrease in the GTE score in the topiramate group (P < 0.05). CONCLUSION: Levetiracetam, lamotrigine, oxcarbazepine, topiramate, and valproate demonstrate favorable efficacy in ameliorating the severity of post-seizure condition. Further investigations are warranted to assess the potential of other widely employed anti-seizure medications in enhancing post-seizure status.
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Anticonvulsivantes , Electroencefalografía , Epilepsia , Humanos , Anticonvulsivantes/uso terapéutico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Adulto Joven , Epilepsia/tratamiento farmacológico , Adolescente , Resultado del Tratamiento , Levetiracetam/uso terapéutico , Ácido Valproico/uso terapéutico , Lamotrigina/uso terapéutico , Oxcarbazepina/uso terapéutico , Oxcarbazepina/farmacología , Índice de Severidad de la EnfermedadAsunto(s)
Anticonvulsivantes , Unidades de Cuidados Intensivos , Levetiracetam , Humanos , Levetiracetam/administración & dosificación , Levetiracetam/uso terapéutico , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapéutico , Piracetam/análogos & derivados , Piracetam/administración & dosificación , Piracetam/uso terapéuticoRESUMEN
INTRODUCTION: People with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV. METHODS: Pooled casenote data for patients prescribed LEV (2000-2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed. RESULTS: 173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV's efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID. CONCLUSION: PwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM.
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Anticonvulsivantes , Epilepsia , Discapacidad Intelectual , Levetiracetam , Humanos , Levetiracetam/efectos adversos , Levetiracetam/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Discapacidad Intelectual/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estudios de Casos y Controles , Epilepsia/tratamiento farmacológico , Adulto Joven , Anciano , Resultado del Tratamiento , AdolescenteRESUMEN
PURPOSE: Many patients with glioblastoma suffer from tumor-related seizures. However, there is limited data on the characteristics of tumor-related epilepsy achieving seizure freedom. The aim of this study was to characterize the course of epilepsy in patients with glioblastoma and the factors that influence it. METHODS: We retrospectively analyzed the medical records of glioblastoma patients treated at the University Hospital Erlangen between 01/2006 and 01/2020. RESULTS: In the final cohort of patients with glioblastoma (n = 520), 292 patients (56.2 %) suffered from tumor-related epilepsy (persons with epilepsy, PWE). Levetiracetam was the most commonly used first-line antiseizure medication (n = 245, 83.9 % of PWE). The onset of epilepsy was preoperative in 154/292 patients (52.7 %). 136 PWE (46.6 %) experienced only one single seizure while 27/292 PWE (9.2 %) developed drug-resistant epilepsy. Status epilepticus occurred in 48/292 patients (16.4 %). Early postoperative onset (within 30 days of surgery) of epilepsy and total gross resection (compared with debulking) were independently associated with a lower risk of further seizures. We did not detect dose-dependent pro- or antiseizure effects of radiochemotherapy. CONCLUSION: Tumor-related epilepsy occurred in more than 50% of our cohort, but drug-resistant epilepsy developed in less than 10% of cases. Epilepsy usually started before tumor surgery.
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Anticonvulsivantes , Neoplasias Encefálicas , Epilepsia , Glioblastoma , Humanos , Glioblastoma/complicaciones , Glioblastoma/terapia , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Anticonvulsivantes/uso terapéutico , Epilepsia/complicaciones , Epilepsia/epidemiología , Epilepsia/etiología , Anciano , Adulto , Levetiracetam/uso terapéutico , Epilepsia Refractaria/etiología , Epilepsia Refractaria/epidemiología , Epilepsia Refractaria/terapia , Convulsiones/etiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Few studies evaluate physicians' choice of antiseizure medication (ASM) to treat patients with newly diagnosed epilepsy. The objective of this study was to analyze the choice of ASM and its use by age, sex, psychiatric comorbidities, and concurrent treatment with other drugs (antidepressant medications and contraceptives) in patients who initiated epilepsy treatment using monotherapy. METHODS: Included in this study were persons (any age) with an incident hospital diagnosis of epilepsy during 2010-2022 in the Swedish Patient Register (SPR), preceding a first dispensing of any ASM (as reported in the Swedish Prescribed Drug Register, SPDR) for the period 2010-2022. Incident patients were identified using retrospective information during 2000-2009 in the SPR. Primary outcome was first dispensed ASM by age, sex, comorbidity, and comedication with antidepressants or contraceptives (SPDR). Secondary outcomes were time to ASM switch or termination assessed by survival analyses. RESULTS: Of 67,984 patients included (mean age 46; 46% female), 66,441 initiated ASM treatment using monotherapy. Relative risk (RR) for initiating treatment using monotherapy did not differ between age groups, sex, or patients with concurrent treatment with antidepressants, contraceptives, or psychiatric illness (RR and 95% CI did include 1.0). The share initiating treatment using levetiracetam increased from 10% in 2010 to 55% in 2022; valproic acid: 10%-5%. The likelihood of initiating treatment using 1 of the 5 most frequent ASMs differed between all compared groups (0.3 < RR < 1; 95% CI < 1; 1 < RR < 15; 1 <95% CI). Seven percent of female patients of childbearing age initiated treatment with valproic acid, levetiracetam was the most frequent initial ASM in patients with psychiatric comorbidity (40.2%), and lamotrigine the most prescribed initial ASM to women on contraceptives (50.4%). Highest likelihoods of treatment termination were found among children (1.72 < RR < 3.07; 1 <95% CI) and among patients with psychiatric comorbidity (initiated on carbamazepine, RR 1.38; 1 <95% CI or lamotrigine, RR 1.31; 1 <95% CI). Thirty-one percent to 47% of patients switched from an initial monotherapy to a new monotherapy within 5 years. Twenty percent to 42% terminated ASM treatment within 5 years. DISCUSSION: Levetiracetam and lamotrigine were the most frequently dispensed initial ASMs, also among patients with comorbidities or comedications complicating the use of these ASMs, highlighting the need for improved education of prescribers concerning ASM selection in relation to individual patient characteristics. Use of ASMs in hospital is not captured in the SPDR.
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Anticonvulsivantes , Epilepsia , Humanos , Femenino , Masculino , Anticonvulsivantes/uso terapéutico , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Persona de Mediana Edad , Suecia/epidemiología , Adulto Joven , Adolescente , Estudios Retrospectivos , Anciano , Niño , Sistema de Registros , Preescolar , Antidepresivos/uso terapéutico , Levetiracetam/uso terapéutico , Lactante , Sustitución de Medicamentos/tendencias , Ácido Valproico/uso terapéuticoRESUMEN
Levetiracetam (LEV) is being used by women with reproductive-age epilepsy at a significantly higher rate. The purpose of the study was to assess how levetiracetam treatment during pregnancy affected the offspring's weight and cerebellum. Forty pregnant rats were divided into two groups (I, II). Two smaller groups (A, B) were created from each group. The rats in group I were gavaged with approximately 1.5 mL/day of distilled water either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). The rats in group II were gavaged with about 1.5 mL/day of distilled water (containing 36 mg levetiracetam) either continuously during pregnancy (for subgroup IA) or continuously during pregnancy and 14 days postpartum (for subgroup IB). After the work was completed, the body weight of the pups in each group was recorded, and their cerebella were analyzed histologically and morphometrically. Following levetiracetam treatment, the offspring showed decreased body weight and their cerebella displayed delayed development and pathological alterations. These alterations manifested as, differences in the thicknesses of the layers of cerebellar cortex as compared to the control groups; additionally, their cells displayed cytoplasmic vacuolation, nuclear alterations, fragmented rough endoplasmic reticulum and lost mitochondrial cristae. Giving levetiracetam to pregnant and lactating female rats had a negative impact on the body weight and cerebella of the offspring. Levetiracetam should be given with caution during pregnancy and lactation.