Optimization of vigabatrin dosage in children with epileptic spasms: A population pharmacokinetic approach.

AIMS: Vigabatrin is an antiepileptic drug used to treat some forms of severe epilepsy in children. The main adverse effect is ocular toxicity, which is related to the cumulative dose. The aim of the study is to identify an acceptable exposure range, both through the development of a population pharmacokinetic model of vigabatrin in children enabling us to calculate patient exposure and through the study of therapeutic response. METHODS: We performed a retrospective study including children with epilepsy followed at Necker-Enfants Malades hospital who had a vigabatrin assay between January 2019 and January 2022. The population pharmacokinetic study was performed on Monolix2021 using a nonlinear mixed-effects modelling approach. Children treated for epileptic spasms were classified into responder and nonresponder groups according to whether the spasms resolved, in order to identify an effective plasma exposure range. RESULTS: We included 79 patients and analysed 159 samples. The median age was 4.2 years (range 0.3-18). A 2-compartment model with allometry and creatinine clearance on clearance best fit our data. Exposure analysis was performed on 61 patients with epileptic spasms. Of the 22 patients who responded (36%), 95% had an AUC0-24 between 264 and 549 mg.h.L-1. CONCLUSIONS: The population pharmacokinetic model allowed us to identify bodyweight and creatinine clearance as the 2 main factors explaining the observed interindividual variability of vigabatrin. An acceptable exposure range was defined in this study. A target concentration intervention approach using this pharmacokinetic model could be used to avoid overexposure in responder patients.

Concise approach to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids. Synthesis of vigabatrin.

γ-Aminobutyric acid (GABA) and GABA derivatives have attracted increased attention over the years in the fields of medicinal chemistry and chemical biology due to their interesting biological properties and synthetic relevance. Here, we report a short synthetic route to γ-(het)aryl- and γ-alkenyl-γ-aminobutyric acids, including the antiepileptic drug vigabatrin, from readily available donor-acceptor cyclopropanes and ammonia or methylamine. This protocol includes a facile synthesis of 2-oxopyrrolidine-3-carboxamides and their acid hydrolysis to γ-aryl- or γ-alkenyl-substituted GABAs, which can serve as perspective building blocks for the synthesis of various GABA-based N-heterocycles and bioactive compounds.

Epileptic spasms relapse is associated with response latency but not conventional attributes of post-treatment EEG.

OBJECTIVE: Relapse of epileptic spasms after initial treatment of infantile epileptic spasms syndrome (IESS) is common. However, past studies of small cohorts have inconsistently linked relapse risk to etiology, treatment modality, and EEG features upon response. Using a large single-center IESS cohort, we set out to quantify the risk of epileptic spasms relapse and identify specific risk factors. METHODS: We identified all children with epileptic spasms at our center using a clinical EEG database. Using the electronic medical record, we confirmed IESS syndrome classification and ascertained treatment, response, time to relapse, etiology, EEG features, and other demographic factors. Relapse-free survival analysis was carried out using Cox proportional hazards regression. RESULTS: Among 599 children with IESS, 197 specifically responded to hormonal therapy and/or vigabatrin (as opposed to surgery or other second-line treatments). In this study, 41 (21%) subjects exhibited relapse of epileptic spasms within 12 months of response. Longer duration of IESS prior to response (>3 months) was strongly associated with shorter latency to relapse (hazard ratio = 3.11; 95% CI 1.59-6.10; p = 0.001). Relapse was not associated with etiology, developmental status, or any post-treatment EEG feature. SIGNIFICANCE: This study suggests that long duration of IESS before response is the single largest clinical predictor of relapse risk, and therefore underscores the importance of prompt and successful initial treatment. Further study is needed to evaluate candidate biomarkers of epileptic spasms relapse and identify treatments to mitigate this risk. PLAIN LANGUAGE SUMMARY: Relapse of infantile spasms is common after initially successful treatment. With study of a large group of children with infantile spasms, we determined that relapse is linked to long duration of infantile spasms. In contrast, relapse was not associated with the cause of infantile spasms, developmental measures, or EEG features at the time of initial response. Further study is needed to identify tools to predict impending relapse of infantile spasms.

Developmental epileptic encephalopathy caused by homozygosity of a c.172+1G>C variant in the WWOX gene.

BACKGROUND: Variations in the WWOX gene have been identified as the leading cause of several central nervous system disorders. However, most previous reports have focused on the description of clinical phenotype, neglecting functional verification. Herein, we presented a case of a patient with developmental epileptic encephalopathy (DEE) caused by WWOX gene variation. CASE PRESENTATION: Our patient was a 13-month-old girl with abnormal facial features, including facial hypotonia, arched eyebrows, a broad nose, and a depressed nasal bridge. She also had sparse and yellow hair, a low anterior hairline, and a short neck. Before the age of 8 months, she was suffering from mild seizures. Her developmental delay gradually worsened, and she suffered infantile spasms. After treatment with vigabatrin, seizures subsided. WWOX gene homozygous variation c.172+1G>C was identified using whole exome sequencing. Further minigene assay confirmed that the variation site affected splicing, causing protein truncation and affecting its function. CONCLUSION: Clinical phenotype and minigene results suggest that WWOX gene homozygous variation c.172+1G>C can cause severe DEE. We also concluded that vigabatrin can effectively treat seizures.

Electroretinogram as a Screening Tool to Assess Vigabatrin-Induced Retinal Toxicity in Children With Infantile Spasms.

PURPOSE: To assess the utility of electroretinogram (ERG) as a screening tool for vigabatrin-induced retinal toxicity in children with infantile spasms. METHODS: This was an observational cohort study including children with infantile spasms receiving treatment with vigabatrin. A 30-Hz flicker potential ERG, using the RETeval system (LKC Technologies), was done at baseline before starting vigabatrin at 6 months and 1 year. The amplitudes were recorded. RESULTS: Eleven children were included in the study. The most common etiologic factor for infantile spasms was tuberous sclerosis (36.4%) followed by West syndrome (27.3%). The mean age of the children was 7.14 ± 2.9 months, with a range of 3 to 16 months. The mean difference in amplitude was 3.21 ± 2.45 and 5.72 ± 4.18 µV at 6 and 12 months follow-up, respectively (P < .001). Eight of the 11 children (72.7%) showed vigabatrin-induced retinal toxicity, and all 8 children were receiving vigabatrin for more than 6 months. CONCLUSIONS: ERG can be used for vigabatrin-induced retinal toxicity monitoring in children with infantile spasms. Vigabatrin-induced retinal toxicity is related to the duration of treatment rather than cumulative dosage. [J Pediatr Ophthalmol Strabismus. 2024;61(4):273-278.].

Epidemiology and outcome of infantile spasms in Denmark in 1996-2019.

PURPOSE: To investigate the treatment of infantile epileptic spasm syndrome (IESS) in Denmark. METHODS: National retrospective cohort study of all patients born 1996-2019 who had a diagnosis of IESS in the National Patient Registry. Medical records were reviewed to evaluate the diagnosis. Patients were included if semiology was compatible with IESS, or if unclear semiology if there was an abnormal EEG or EEG with hypsarrhythmia. RESULTS: Number of cases with a register based IESS diagnosis was 538. Medical records were unavailable in 48 and 164 did not fulfil the inclusion criteria. Thereby the cohort consisted of 326 children. Mean age at onset of IESS was 5.9 months and mean lead time to treatment was 26.6 days (SD= 63.5). Consistent with the Danish treatment guidelines most patients received vigabatrin as first treatment. In the cohort 44.7 % of patients solely received vigabatrin, whereas combined vigabatrin and corticosteroid was given to 28.3 % (either hydrocortisone or prednisolone). Other anti-seizure medication was given to 28.4 % within 90 days of IESS onset. Aetiology was prenatal (40.3 %), perinatal (10.5 %), postnatal (3.7 %), with unknown timing (10.2 %) or with unknown aetiology (33.5 %). The cohort was followed to a mean age of 8.2 years. At latest follow-up severe neurodevelopmental outcome was seen in 44.2 % and 76.4 % still had epilepsy. The incidence of IESS was 22 per 100.000 live births. CONCLUSION: In Denmark treatment algorithm is based on start of treatment with vigabatrin. A total of 44.7 % became seizure free by vigabatrin. Neurodevelopmental outcome was severe. A national incidence could be established.

Societal costs of illness for infantile epileptic spasms syndrome and evolutionary cost prediction in the era of WHO's IGAP.

BACKGROUND: To achieve the goal of improving the quality of life for persons with epilepsy within the framework of the WHO's Intersectoral Global Action Plan (IGAP), our study aimed to assess the societal financial burden linked to infantile epileptic spasms syndrome (IESS), ensuring that children afflicted with IESS receive high-quality healthcare without enduring substantial financial constraints. METHODS: Between August 2022 and March 2023, 92 children with IESS (male: female: 2:1), recently diagnosed or previously followed-up, were recruited. We gathered costs for drugs, tests, and medical services, along with legal guardians' monthly income. Total expenditure was determined by multiplying unit costs by the yearly service usage commencing from the onset. Time series analysis was utilised to forecast the financial burden from 2022 to 2032. RESULTS: Clinicians' first choice of treatment was ACTH (n = 60, 65·2%), prednisolone (n = 25, 27·2%), and vigabatrin (n = 7, 7·6%) and the median cost of treatment during the initial year was INR 39,010 [USD 479·2]. The median direct medical, direct non-medical, and indirect cost were INR 31,650 [USD 388·4], INR 6581 [USD 80·8], and INR 10,100 [USD 124·07], respectively. Families lost a median of 12 days of work annually. Drug costs and loss of wages were the key factors in the financial burden. The projected and adjusted figures exhibited an incremental growth rate of 2·6% tri-annually. INTERPRETATION: This pioneering study in developing countries, the first of its kind, evaluates the societal cost, financial hardship, and trajectory of incremental cost in IESS. The primary drivers of the financial burden were pharmacological treatment and family work adjustments. The government shoulders 62% of the financial burden, and projected a triannual growth of 2·6% from 2022 to 2032. Our results rationalize policymakers' focus on incorporating IESS into social security programs, particularly in developing countries.

Differential toxic and antiepileptic features of Vigabatrin raceme and its enantiomers.

BACKGROUND: The study aimed to investigate the potential pharmacological and toxicological differences between Vigabatrin (VGB) and its enantiomers S-VGB and R-VGB. The researchers focused on the toxic effects and antiepileptic activity of these compounds in a rat model. METHODS: The epileptic rat model was established by intraperitoneal injection of kainic acid, and the antiepileptic activity of VGB, S-VGB, and VGB was observed, focusing on the improvements in seizure latency, seizure frequency and sensory, motor, learning and memory deficits in epileptic rats, as well as the hippocampal expression of key molecular associated with synaptic plasticity and the Wnt/ß-catenin/GSK 3ß signaling pathway. The acute toxic test was carried out and the LD50 was calculated, and tretinal damages in epileptic rats were also evaluated. RESULT: The results showed that S-VGB exhibited stronger antiepileptic and neuroprotective effects with lower toxicity compared to VGB raceme. These findings suggest that S-VGB and VGB may modulate neuronal damage, glial cell activation, and synaptic plasticity related to epilepsy through the Wnt/ß-catenin/GSK 3ß signaling pathway. The study provides valuable insights into the potential differential effects of VGB enantiomers, highlighting the potential of S-VGB as an antiepileptic drug with reduced side effects. CONCLUSION: S-VGB has the highest antiepileptic effect and lowest toxicity compared to VGB and R-VGB.

Early Subclinical Status Epilepticus May Contribute to Developmental Delays in Infants With Tuberous Sclerosis Complex.

We present a case of a newborn with a prenatally discovered cardiac rhabdomyoma leading to early genetic diagnosis of tuberous sclerosis complex (TSC). This early diagnosis prompted a presymptomatic electroencephalography (EEG) that revealed subclinical seizures meeting the definition for status epilepticus on day 1 of life. Antiseizure medications (ASMs), including vigabatrin, were started. The EPISTOP and PREVeNT trials demonstrated that early life initiation of vigabatrin may reduce the degree of refractory epilepsy and epileptic spasms (ES) in this population (TSC). Although neonatal seizures are a known entity in TSC, continuous neonatal EEG monitoring is not standard at birth. This case supports early consideration for neonatal EEG monitoring to identify and treat neonatal seizures, reduce risk for infantile spasms, and potentially improve neurodevelopmental outcomes.

A newborn with convulsions 12 days after birth was misdiagnosed as neonatal intracranial hemorrhage: Case report.

INTRODUCTION: Cases with early diagnosis of neonatal tuberous sclerosis syndrome (TSC) are relatively seldom seen, and misdiagnosis of intracranial hemorrhage is even more rare. We retrospectively analyzed the clinical data of a case of neonatal tuberous sclerosis with atypical early symptoms and misdiagnosed as more common intracranial hemorrhage of the newborn. PATIENT CONCERNS: The child was female and had no obvious cause of convulsion 12 days after birth. The local hospital was initially diagnosed as "neonatal intracranial hemorrhage, congenital heart disease," and still had convulsions after 5 days of treatment, so it was transferred to neonatal intensive care unit of our hospital. DIAGNOSIS: After admission, cardiac color ultrasound, magnetic resonance imaging, and electroencephalogram were performed, and TSC was diagnosed in combination with clinical symptoms. However, no known pathogenic mutations such as TSC1 and TSC2 were detected by peripheral blood whole exon sequencing. INTERVENTION: After a clear diagnosis, sirolimus, and vigabatrin were given. But there were still convulsions. Topiramate, valproic acid, and oxcarbazepine were successively added to the outpatient department for antiepileptic treatment, and vigabatrin gradually decreased. OUTCOME: Up to now, although the seizures have decreased, they have not been completely controlled. CONCLUSIONS: The TSC of neonatal tuberous sclerosis is different from that of older children. It is usually characterized by respiratory distress and arrhythmia, and may be accompanied by convulsions, but the activity between attacks is normal. However, neonatal intracranial hemorrhage can be caused by premature delivery, birth injury, hypoxia, etc. Its characteristics are acute onset, severe illness, and rapid progression. Consequently, the diagnosis of these 2 diseases should not only be based on medical imaging, but also be combined with their clinical characteristics. When the imaging features are inconsistent with the clinical diagnosis, a comprehensive evaluation should be made again. The timing and pattern of onset of neonatal convulsions can help in differential diagnosis. If there is cardiac rhabdomyoma, subependymal or cortical nodule, skin low melanoma, etc, the possibility of neonatal TSC should be considered, and the diagnosis should be made according to its diagnostic criteria to avoid or reduce misdiagnosis.

Encefalopatia toxica secundaria a vigabatrina: Reporte de caso / Toxic encephalopathy secondary to vigabatrin: Case report

El síndrome de West es una encefalopatía epiléptica caracterizada por espasmos en flexión, hipsarritmia en el electroencefalograma y retraso en el neurodesarrollo. Reportamos el caso de una paciente de 11 meses con diagnóstico de Síndrome de West y encefalopatía tóxica secundaria al uso de vigabatrina

West syndrome is an epileptic encephalopathy characterized by flexing spasms, hypsarritmia in the electroencephalogram and delayed neurodevelopment. We report an 11-month-old patient with a diagnosis of West syndrome and toxic encephalopathy secondary to the use of vigabatrin

Vigabatrina comparado con hormona adrenocorticotrópica para el tratamiento de espasmos infantiles y Síndrome de West / Vigabatrin compared with adrenocorticotropic hormone for the treatment of infantile spasms and West Syndrome

OBJETIVO: Determinar los riesgos y beneficios del uso de vigabatrina comparada con hormona adrenocorticotrópica (ACTH) para el tratamiento de espasmos infantiles. MÉTODO: Se realizó una búsqueda en Epistemonikos. Se extrajeron datos desde las revisiones identificadas. Se realizó un metaanálisis a partir de estudios primarios y se utilizó el método GRADE para la presentación de resultados. RESULTADOS: Se identificaron nueve revisiones sistemáticas. Se observó que el uso de vigabatrina en comparación con ACTH disminuye la resolución de espasmos (RR 0,8, IC 95% 0,65 - 0,98) y podría disminuir la resolución de hipsarritmia (RR 0,71, IC 95% 0,48 - 1,05). No fue posible determinar si el uso de vigabatrina disminuye el riesgo de desarrollar efectos adversos (RR 0,75, IC 95% 0,23 - 2,45) por certeza de evidencia muy baja. CONCLUSIONES: La evidencia parece inclinarse a favor del uso de ACTH. Sin embargo debe considerarse la necesidad de nuevas investigaciones para esclarecer su seguridad.

OBJECTIVE: To determine the risks and benefits of the use of vigabatrin compared to ACTH for the treatment of infantile spasms. METHOD: A search in Epistemonikos was performed. Data were extracted from the identified reviews. A meta-analysis was performed from primary studies and the GRADE method was used to present the results. RESULTS: Nine systematic reviews were identified. Vigabatrin use compared to ACTH was found to decrease resolution of spasms (RR 0.8, 95% CI 0.65 - 0.98) and might decrease resolution of hypsarrhythmia (RR 0.71, 95% CI 0 .48 - 1.05). It was not possible to determine whether the use of vigabatrin reduces the risk of developing adverse effects (RR 0.75, 95% CI 0.23 - 2.45) due to very low certainty of evidence. CONCLUSIONS: The evidence seems to lean in favor of the use of ACTH. However, the need for new research should be considered to clarify its safety.

Efectos Adversos del Tratamiento con Vigabatrina en Síndrome de West: reporte de 2 casos / Adverse Effects of Vigabatrin Use for West Syndrome treatment: a report of 2 Clinical Cases

El síndrome de West (SW) es un síndrome epiléptico de la infancia temprana. Dentro de los fármacos de primera línea utilizados para su tratamiento se encuentran la hormona adrenocorticotropa (ACTH) y Vigabatrina. Estudios sugieren igual efectividad en el uso a largo plazo de ambos para controlar el SW. En Chile, el uso de Vigabatrina ha aumentado dada su mayor disponibilidad, facilidad de uso y menor costo. Se describen 2 casos clínicos presentando complicaciones agudas infrecuentes secundarias a su uso. Ambos pacientes con antecedentes de SW y trisomía 21. Primer caso: Lactante de 11 meses que inicia tratamiento con 100 mg/kg/día de Vigabatrina a los 7 meses, aumentando a 150 mg/kg/día por mala respuesta. Evolucionó con un síndrome extrapiramidal, con alteraciones radiológicas características. Segundo caso: Lactante de 7 meses, que tras iniciar tratamiento con vigabatrina (100 mg/kg/día) desarrolla rash facial sugerente de hipersensibilidad a fármacos antiepilépticos (FAEs), sin compromiso mucoso ni alteraciones sistémicas. Ambas regresan a su basal luego de suspensión o disminución de dosis del medicamento. Destaca la importancia de la monitorización de efectos adversos en el uso de FAEs y atender la aparición de reacciones poco conocidas. Las alteraciones imagenológicas por Vigabatrina son conocidas, no así el síndrome extrapiramidal asociado (primer caso). Por otra parte, las reacciones cutáneas están ampliamente descritas para múltiples FAEs, pero no para Vigabatrina (segundo caso). Dado el uso frecuente de Vigabatrina para tratar SW y otras epilepsias, es fundamental conocer y manejar reacciones adversas poco conocidas como las aquí presentadas. Palabras claves: Síndrome de West, Síndrome de Down, espasmos infantiles, vigabatrina, reacciones adversas, toxicidad, alergia, rash.

West Syndrome is an epileptic syndrome which typically presents in early childhood. In regard to treatment, the first line includes adrenocorticotropic hormone (ACTH) and Vigabatrin. Studies suggest similar response in the long term to both treatments. In Chile, Vigabatrin is being used more frequently as it is more available, of easier administration and lower cost. We present in the following report 2 clinical cases that presented acute infrequent complications secondary to its use in patients with both Down and West Syndrome. First case: 11-month-old infant who was initially treated with 100mg/kg/day of Vigabatrin at 7 months of age and increased to 150mg/kg/day due to lack of response. She evolved with an extrapyramidal syndrome with radiological manifestations. The second case: 7-month old toddler who initiated treatment with 100mg/kg/day of Vigabatrin and developed a facial rash, suggestive of hypersensitivity to antiepileptic drugs, with no mucosal or systemic involvement. Both patients returned to their previous condition shortly after Vigabatrin was decreased or discontinued. We emphasize the importance of the early monitorization of adverse effects in the use of antiepileptic drugs and awareness of less common reactions. Radiological findings associated with the use of Vigabatrin are well known, but not the clinical evolution with symptomatic extrapyramidal symptoms, as in the first case. Allergic reactions to the use of antiepileptic drugs have also been reported to several drugs, but not to Vigabatrin (second case). As Vigabatrin is being used more frequently to treat WS and other epilepsies it is important to know and manage uncommon adverse reactions as the ones presented in this report. Keywords: West Syndrome, Down Syndrome, infantile spasms, vigabatrin, adverse reactions, toxicity, allergy, rash

Síndrome transicional: del síndrome de West al síndrome de Lennox-Gastaut / Transional syndrome: from West to Lennox-Gastaut syndromes

El síndrome de West o espasmos infantiles, es una encefalopatía epiléptica clasificada como epilepsias y síndromes generalizados. Hay múltiples informes de la evolución de síndrome de West a síndrome de Lennox-Gastaut de un 25 hasta 60%, sin reconocerse una causa específica. Se ha comunicado que pueden ser solo una entidad epiléptica dependiente de la edad y que estaría en relación con el grado de inmadurez cerebral. En esta revisión retrospectiva de 130 casos de espasmos infantiles, solo 14 (10.7%) evolucionaron a Lennox-Gastaut. El haber recibido en todos los casos vigabatrina como tratamiento nos hace suponer que la baja incidencia podría estar relacionada con el uso de este fármaco. Dado que la vigabatrina tiene una acción gabaérgica y aumenta los niveles de ACTH podría explicar esta relación, pero esto deberá confirmarse con el mejor conocimiento de los mecanismos íntimos de estas graves encefalopatías.

West syndrome or infantile spasms is an epileptic encephalopathy, classified as generalized epilepsies and syndromes. There are multiple reports of the evolution from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is determined. It has been reported that they may be only an epileptic entity age dependent that it would be in relation to the degree of brain immaturity. In this retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us suppose that the low incidence could be related to the use of this drug. Given that vigabatrin has a gabaergic action and increased levels of ACTH, may explain this relationship but this must be confirmed with the best knowledge of the intimate mechanisms of these serious epileptic encephalopathies.

Vigabatrín en el tratamiento de epilepsia causada por trastornos del desarrollo cortical / Vigabatrin in the treatment of epilepsy caused by cortical developmental disorders

Introducción. Se presenta una serie de pacientes que recibieron vigabatrín como tratamiento farmacológico para manejo de epilepsia causada por trastornos del desarrollo cortical. Objetivos. Evaluar la efectividad en cuanto a control de crisis en estos pacientes, teniendo en cuenta los hallazgos previos de la semejanza histológica y funcional de los trastornos del desarrollo cortical con las lesiones de la esclerosis tuberosa. Material y métodos. Se revisaron las historias de los pacientes con diagnóstico de trastorno del desarrollo cortical que recibieron este tratamiento como pacientes de la Liga Central Contra la Epilepsia, en el periodo comprendido entre los años 2005 a 2008. Se registraron datos sobre tipo de trastorno del desarrollo cortical, clasificación de la epilepsia, control de crisis antes y después del tratamiento con vigabatrín y presencia de efectos adversos. Resultados. Se revisaron 14 historias, el 57,11 % varones, con edades comprendidas entre 4 y 28 años. La forma de epilepsia más común fue la focal de diferente localización, y el tipo de malformación cortical más común fue la displasia cortical focal. El 50% de los pacientes mostró control superior al 90% respecto a las crisis registradas antes del inicio de tratamiento con Vigabatrin. Sólo un paciente mostró clínicamente disminución del campo visual y mejoró con la suspensión del tratamiento. Conclusión. En nuestra experiencia en pacientes pediátricos y adultos Vigabatrín es un tratamiento efectivo y seguro para el manejo de pacientes con epilepsia secundaria a trastornos del desarrollo cortical. Debe vigilarse estrechamente la posible aparición de los efectos adversos.

Introduction. We present a case series diagnosed with cortical developments disorders on vigabatrin treatment. Objetive. The study aims to evaluate the effectiveness in terms of crisis control these patients, according to histological findings and functional disorders caused by tuberous sclerosis.. Materials and methods. We reviewed records of patients diagnosed with cortical developmental disorder treated with Vigabatrin, in the period between 2005 to 2008 at the Liga central contra la epilepsia Bogotá, Colombia. Data about type of disturbance of cortical development, classification of epilepsy, treatment before and after treatment with vigabatrin and presence of adverse effects. Results. We reviewed 14 records, being 57.11% males, aged between 4 and 28 years. The most common form of epilepsy was the focal of a different location and type of cortical malformation was the most common focal cortical dysplasia. The response obtained in terms of seizure control in 50% of the patients was over 90% with respect to seizure frequency prior to the start of vigabatrin. Only one patient showed clinically decreased visual field and improved with the cessation of treatment. Conclusion. Vigabatrin is an effective and safe treatment for the management of patients with epilepsy secondary to cortical development disorders. Should closely monitor the possible occurrence of adverse effects.

Efectividad del vigabatrín en niños: estado del arte: [revisión] / Effectiveness of vigabatrin in children: state of the art: [review]

Síndrome de West y epilepsia focal. En el primer caso la evidencia es comparable con la descrita para esteroides, sin embargo la incidencia de efectos colaterales es menor. Es de elección, con adecuado nivel de evidencia, en el manejo de epilepsia causada por esclerosis tuberosa. Se puede recomendar en el manejo de epilepsia focal, vigilando la aparición de crisis paradójicas.

We present a review regard the effectiveness of vigabatrine in the treatment of childhood epilepsy, emphasizing on West syndrome and focal epilepsy. In the first case, evidence is comparable with corticosteroids but with lesser side effects. In epilepsy caused by tuberous sclerosis Vigabatrine is the drug of choice. Vigabatrine can be recommended in the treatment of focal epilepsy monitoring the occurrence of paradoxical crisis.

Uso clínico de vigabatrin en epilepsia: [revisión] / Clinical use of vigabatrin in epilepsy: [review]

El Vigabatrin (VGB) es un medicamento anticonvulsivante cuyo uso en epilepsia se conoce desde hace tres décadas, está indicado en el control de crisis parciales complejas en epilepsias focales refractarias y en espasmos infantiles, especialmente los asociados a Esclerosis tuberosa, pero la descripción de efectos secundarios con la parición de defectos de los campos visuales (DCV) comenzó a limitar su uso en particular en Estados Unidos y otros países; sin embargo, en Europa, especialmente en el Reino Unido y Francia y en Asia principalmente en Japón, asi como en Latinoamérica, se continuó con su formulación, con buenos resultados en cuanto a control de crisis y manejo farmacocinético y se continuó acumulando experiencia en la aparición de efectos adversos especialmente el DCV. En Agosto de 2009, la Food and Drug Administration (FDA) aprueba su uso en Estados Unidos, como terapia adjunta para el tratamiento de crisis parciales complejas en adultos y en espasmos infantiles. La FDA implementa y recomienda métodos y estrategias de evaluación y control por los posibles efectos secundarios. En este artículo se revisan generalidades sobre las propiedades farmacológicas y farmacocinéticas, modo de acción, indicaciones en epilepsia y la relevancia de la limitación de su uso por los efectos colaterales en particular en los trastornos de la visión.

Vigabatrin is an antiepileptic drug, used in epilepsy since three decades ago, is indicated in the treatment of refractory complex partial seizures and infantile spasms, specially associated to tuberous sclerosis, but the Visual Fields Defects (VFD), has limited its use in some countries. Nevertheless in others such as United Kingdom, France, in Asia like Japan and Latinamerica, its use has continue, and now VGB was approved in the USA in August 2009 by the Food and Drug administration (FDA) as adjunctive therapy for the treatment of refractory complex partial seizures in adults and for the infantile spasm. The FDA implemented a Risk Evaluation and Mitigation Strategy to control for the possibility of adverse drug events. In this paper we review generalities, pharmacokinetic and pharmacologic properties and its role like antiepileptic drug, indications according to type of seizures and use limitations due to visual field defects.