[Treatment of encephalopathy by means of valproic acid with carglumic acid. Reply]. / Tratamiento de la encefalopatia inducida por acido valproico con acido carbaglumico. Replica.

TITLE: Tratamiento de la encefalopatia inducida por acido valproico con acido carbaglumico. Replica.

[Cognitive impairment as a predictor of functional decline after hospitalization: DECOFIRH Study]. / Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.

AIM: Cognitive impairment is underdiagnosed in the elderly. We aimed to study the rate of positive responses to an informant-based questionnaires and functional disability after hospital discharge. PATIENTS AND METHODS: Observational prospective case series of patients aged 70-85 years-old admitted for hospitalization in an Internal Medicine ward. All medical records were reviewed and those patients with no previous diagnosis of dementia or related neurological conditions, no previous recent hospitalization or not having a caregiver were evaluated after signing an informed consent. A medical interview including the Alzheimer's Disease 8 (AD8), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Barthel Index was completed. Barthel Index was obtained three months after discharge. RESULTS: During a 3-month period a total of 809 admissions were screened and 79 (9.7%) fulfilled the study criteria. Patient's mean age was 80 years-old. Common comorbidities were arterial hypertension (83.5%), major surgery (54.4%) and heart disorders (50.6%). The most frequent cause of admission was infectious disease (37.9%). Test positivity for cognitive impairment was 30.3% for IQCODE and 34.1% for AD8. At admission 37.9% of the patients were functionally independent. At three months this percentage dropped to 24%. CONCLUSIONS: In this small sample size, almost a third of older patients, without major comorbidities or neurological disorders, admitted to a general hospital showed an informant-based suggestion of cognitive impairment previously undiagnosed. Functional impairment affects almost a quarter of these patients three months after admission.

TITLE: Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.Objetivo. El deterioro cognitivo esta infradiagnosticado. El estudio DECOFIRH pretende detectar la tasa de deterioro cognitivo no conocido y su impacto en la situacion funcional de estos pacientes tras un ingreso hospitalario mediante cuestionarios realizados a un informador. Pacientes y metodos. Estudio observacional prospectivo realizado sobre una serie de casos, de pacientes comprendidos entre 70 y 85 años, que ingresan en el Servicio de Medicina Interna de un hospital terciario. Se excluyo a los pacientes con diagnostico de demencia o enfermedades neurologicas graves, asi como a los que habian sido hospitalizados recientemente. Los tests empleados en la deteccion de deterioro cognitivo fueron Alzheimer's Disease 8 (AD8) e Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Asimismo, se evaluo la situacion funcional mediante el indice de Barthel en el momento del ingreso y tres meses despues. Resultados. Durante los tres meses de seguimiento ingresaron 809 pacientes y cumplieron los criterios de inclusion 79 (9,7%) de ellos. Su edad media era de 80 años. Mediante el IQCODE se detecto una tasa de deterioro cognitivo del 30,3%, y con el AD8, del 34,1%. En el ingreso, el 37,9% de los pacientes era funcionalmente independiente. A los tres meses, este porcentaje cayo al 24%. Conclusiones. En nuestra muestra, casi un tercio de los ancianos sin comorbilidades sistemicas o neurologicas graves dio positivo para la deteccion de deterioro cognitivo segun nuestros tests basados en el informador, sin ser este conocido previamente. El deterioro funcional afecta casi a una cuarta parte de estos pacientes a los tres meses del ingreso.

[Treatment of encephalopathy by means of valproic acid with carglumic acid: two case reports and a review of the literature]. / Tratamiento de la encefalopatia por acido valproico con acido carbaglumico: descripcion de dos casos y revision de la bibliografia.

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.