Introduction: Valproic acid (VPA) is a drug mainly used to treat epilepsy. Hyperammonaemic encephalopathy due to VPA is a rare but serious complication. The mechanism by which VPA influences the increase in ammonia consists in blocking the urea cycle, thereby inhibiting N-acetylglutamate synthase and diminishing acetyl coenzyme A. Generally, the treatment employed has been to withdraw VPA and to administer arginine, carnitine, antibiotics, glucose and protein restriction. Previous experience with carglumic acid is limited to reports of isolated cases of paediatric patients.
Case reports: We report the cases of two adult patients with encephalopathy due to VPA who were treated with carglumic acid, in addition to the conventional measures. Following treatment with the drug, ammonia levels can be seen to return to normal values. In one of the two cases, owing to the existence of another cause of encephalopathy, no clinical improvement was observed.
Conclusions: From the biochemical point of view, treating encephalopathy due to VPA with carglumic acid is a logical step, as it reverses the blockage of the urea cycle conditioned by VPA. The mechanism proposed as being the one by which brain toxicity and, therefore, encephalopathy are produced is the passage of ammonia in the form of glutamine to the inside of the cell, which then returns to ammonia and glutamate in the mitochondria and leads to oxidative stress. Carglumic acid must be considered an important part of the treatment in adult patients with hyperammonaemic encephalopathy due to VPA, although a randomised clinical trial needs to be conducted with the drug in order to test its efficacy.
Title: Tratamiento de la encefalopatia por acido valproico con acido carbaglumico: descripcion de dos casos y revision de la bibliografia.
Introduccion. El acido valproico (VPA) es un farmaco principalmente usado en la epilepsia. La encefalopatia hiperamoniemica por VPA es una complicacion grave e infrecuente. El mecanismo por el que el VPA influye en la elevacion del amonio es bloqueando el ciclo de la urea, inhibiendo la N-acetilglutamato sintasa y disminuyendo la acetil coenzima A. De forma general, el tratamiento que se ha empleado ha sido la suspension del VPA y la administracion de arginina, carnitina, antibioticos, glucosa y restriccion proteica. La experiencia con acido carbaglumico se limita a comunicaciones de casos aislados de pacientes pediatricos. Casos clinicos. Descripcion de dos casos de pacientes adultos con encefalopatia por VPA tratados, ademas de las medidas convencionales, con acido carbaglumico. Tras el tratamiento con el farmaco se aprecia una normalizacion de los niveles de amonio. En uno de los casos, al existir otra causa de encefalopatia, no se aprecio mejora clinica. Conclusiones. Desde el punto de vista bioquimico es logico tratar la encefalopatia por VPA con acido carbaglumico, ya que revierte el bloqueo del ciclo de la urea condicionado por el VPA. El mecanismo propuesto por el que se produce la toxicidad cerebral y, por tanto, la encefalopatia, es el paso de amonio en forma de glutamina al interior celular, que retorna a amonio y glutamato en la mitocondria y genera estres oxidativo. El acido carbaglumico ha de considerarse como parte importante del tratamiento en pacientes adultos con encefalopatia hiperamoniemica por VPA, aunque es necesario realizar un ensayo clinico aleatorizado con el farmaco para comprobar su eficacia.