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

Aspectos metabólicos e funcionais do zinco na síndrome de Down / Metabolic and functional aspects of zinc in Down syndrome

Este estudo relata os aspectos funcionais do zinco, bem como a participação desse mineral nas alterações metabólicas presentes em indivíduos portadores de Síndrome de Down. A maioria dos trabalhos realizados observou que o estado nutricional relativo ao zinco nesses pacientes está inadequado, com alterações no sistema antioxidante, imunológico e no metabolismo dos hormônios da tireóide. Estudos in vitro apontam que o zinco participa como cofator da enzima deiodinase tipo II na conversão periférica de Tiroxina em Triiodotironina, e que essa reação está diminuída em indivíduos portadores de Síndrome de Down, o que contribui para a manifestação de distúrbios, como o hipotireoidismo subclínico. As alterações na compartimentalização do zinco no organismo desses indivíduos também favorecem a expressão excessiva da enzima cobre/zinco (Cu/Zn) superóxido dismutase, com aumento do estresse oxidativo, e ainda alterações no sistema imune. Na Síndrome de Down, tem sido demonstrada melhora no metabolismo dos hormônios tireoidianos e na função imune, após a suplementação com zinco. Portanto, o papel metabólico do zinco na Síndrome de Down deve ser mais pesquisado, tendo em vista que esse mineral pode contribuir no controle das alterações metabólicas comumente presentes em indivíduos portadores dessa síndrome.

This study reports the functional aspects of zinc as well as its participation in the metabolic changes present in individuals with Down syndrome. Most of the studies performed observed that the nutritional status related to zinc in these patients is inadequate, with changes in the antioxidant and immunological systems and in the metabolism of thyroid hormones. In vitro studies show that zinc participates as a cofactor of the enzyme deiodinase type II in the peripheral conversion of thyroxin into triiodothyronine, and that this reaction is decreased in individuals with Down syndrome, contributing to the manifestation of disorders such as subclinical hypothyroidism. Changes in zinc compartmentation in the body of these individuals also favor an excessive expression of the copper/zinc enzyme (Cu/Zn) superoxide dismutase, with increased oxidative stress, and also changes in the immune system. In Down syndrome, zinc supplementation has been shown to improve thyroid hormone metabolism and immune function. Therefore, the metabolic role of zinc in Down syndrome should be further researched, knowing that this mineral can.