Síndrome DRESS inducido por ácido valproico en una niña que respondió a la ciclosporina con análisis de HLA / Valproic acid-induced DRESS in a child responding to cyclosporine with HLA analysis

El síndrome de erupción medicamentosa con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms, DRESS), también conocido como síndrome de hipersensibilidad inducida por medicamentos, es una reacción rara potencialmente mortal que causa una erupción grave y que puede provocar insuficiencia multiorgánica. Como con otras erupciones medicamentosas graves, los linfocitos T específicos para un medicamento tienen una función crucial en el síndrome DRESS. El modelo de hapteno/pro-hapteno, el modelo de interacción farmacológica y el modelo alterado de repertorio de péptidos son tres modelos diferentes desarrollados para describir la relación/interacción entre un medicamento o sus metabolitos y el sistema inmunitario. Analizamos nuestra experiencia con el tratamiento con ciclosporina en un caso de síndrome DRESS resistente a esteroides causado por ácido valproico en una niña y sus resultados clínicos, de laboratorio y de antígeno leucocitario humano (HLA).

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is a potentially life-threatening rare reaction that causes a severe rash and can lead to multiorgan failure. As in other severe drug eruptions, drug-specific T lymphocytes play a crucial role in DRESS. The hapten/pro-hapten model, pharmacological interaction model, and altered peptide repertoire model are three different models developed to describe the relationship/interaction between a medication or its metabolites and the immune system. We discuss our experience with cyclosporine treatment in a steroid-resistant DRESS syndrome caused by valproic acid in a girl, as well as her clinical, laboratory, and human leukocyte antigens (HLA) study results

Mechanism of valproic acid-induced dendritic spine and synaptic impairment in the prefrontal cortex for causing core autistic symptoms in mice / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of valproic acid (VPA) -induced impairment of the dendritic spines and synapses in the prefrontal cortex (PFC) for causing core symptoms of autism spectrum disorder (ASD) in mice.@*METHODS@#Female C57 mice were subjected to injections of saline or VPA on gestational days 10 and 12, and the male offspring mice in the two groups were used as the normal control group and ASD model group (n=10), respectively. Another 20 male mice with fetal exposure to VPA were randomized into two groups for stereotactic injection of DMSO or Wortmannin into the PFC (n=10). Open field test, juvenile play test and 3-chamber test were used to evaluate autistic behaviors of the mice. The density of dendrite spines in the PFC was observed with Golgi staining. Western blotting and immunofluorescence staining were used to detect the expressions of p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and the synaptic proteins PSD95, p-Syn, and Syn in the PFC of the mice.@*RESULTS@#Compared with the normal control mice, the mice with fetal exposure to VPA exhibited obvious autism-like behaviors with significantly decreased density of total, mushroom and stubby dendritic spines (P < 0.05) and increased filopodia dendritic spines (P < 0.05) in the PFC. The VPA-exposed mice also showed significantly increased expressions of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR (P < 0.01) and lowered expressions of PSD95 and p-Syn/Syn in the PFC (P < 0.05 or 0.001). Wortmannin injection into the PFC obviously improved the ASD-like phenotype and dendritic spine development, down-regulated PI3K/Akt/mTOR signaling pathway and up-regulated the synaptic proteins in VPA-exposed mice.@*CONCLUSION@#In male mice with fetal exposure to VPA, excessive activation of PI3K/Akt/mTOR signaling pathway and decreased expressions of the synaptic proteins PSD95 and p-Syn cause dendritic spine damage and synaptic development disturbance in the PFC, which eventually leads to ASD-like phenotype.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients / Efeitos do levetiracetam e lamotrigina, em mono e politerapia, na densidade mineral óssea de pacientes epilépticos

ABSTRACT The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Methods Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. Results In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Conclusion Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

RESUMO O objetivo deste estudo foi determinar o efeito da lamotrigina (LTG) e levetiracetam (LEV) como mono e politerapia em marcadores bioquímicos de remodelação óssea e densidade mineral óssea em pacientes adultos egípcios com epilepsia. Métodos Quarenta e oito pacientes foram divididos em quatro grupos: dois grupos receberam monoterapia de LTG ou LEV e os outros dois grupos receberam politerapia (valproato [VPA] + LTG ou VPA + LEV). Trinta participantes saudáveis controle foram incluídos no estudo. Os participantes preencheram um questionário nutricional e de atividade física. Marcadores bioquímicos do metabolismo ósseo e mineral e densidade mineral óssea da coluna lombar foram medidos no início e aos seis meses. Resultados No grupo de monoterapia LEV, os marcadores de formação óssea mostraram uma diminuição significativa nos níveis séricos de fosfatase alcalina e osteocalcina sérica, enquanto o marcador de reabsorção óssea mostrou um aumento significativo nos níveis de desoxipiridinolina urinária. Após seis meses de tratamento, a densidade mineral óssea mostrou uma diminuição significativa em todos os grupos tratados, enquanto entre os grupos de monoterapia, esta diminuição significativa foi mais prevalente no grupo de monoterapia LEV em comparação com o grupo de monoterapia LTG. Além disso, houve correlação negativa significativa entre os níveis de desoxipiridinolina urinária e densidade mineral óssea no grupo de monoterapia LEV. Conclusão Utilizando antiepilépticos de nova geração, as monoterapias LEV e a politerapia mostraram efeitos prejudiciais no osso, mas a LTG não.

Momordica cochinchinensis (L. ) spreng: aril extract prevents adverse reproductive parameters of male rats Induced with valproic acid / El extracto del arilo Momordica cochinchinensis (L. ) Spreng previene los parámetros reproductivos adversos inducidos con ácido valproico en ratas macho

This study aimed to investigate protective effect of Momordica cochinchinensis (MC) aril extract on adverse reproductive parameters of male rat induced with valproic acid (VPA) commonly used in treatment for antiepileptic diseases. Male Wistar rats were divided into 6 groups (control, VPA, 200 mg/kg BW of PE only, and 50, 100, 200 mg/kg BW MC+VPA, respectively). Animals were pretreated with aqueous MC extract for 23 days before co-administered with VPA induction for 10 days. At the end of experiment, all male reproductive parameters and testicular histology were examined. The results showed all doses of PE significantly protect the decrease the weights of epididymis and seminal vesicle but not of body and testicular weights. MC extract also increased sperm concentration and seminiferous tubular diameters in MC+VPA co-administrative groups. Moreover, testicular histology of MC+VPA groups showed significant declining of testicular histopathologies as compared to VPA group. It was concluded that M. Cochinchinensis aril extract can prevent adverse male reproductive parameters and testicular damage induced with VPA.

El objetivo fue investigar el efecto protector del extracto de arilo de Momordica cochinchinensis (MC) sobre los parámetros reproductivos adversos de la rata macho inducida con ácido valproico (AV) que se utiliza comúnmente en el tratamiento de enfermedades epilépticas. Las ratas se dividieron en 6 grupos (control, AV, 200 mg/kg por peso corporal de PE solamente, y 50, 100, 200 mg/kg por peso corporal MC+AV, respectivamente). Los animales fueron tratados previamente con extracto acuoso MC durante 23 días, antes de la administración de AV durante 10 días. Al término del experimento, se examinaron todos los parámetros reproductivos masculinos y la histología testicular. Los resultados indicaron que todas las dosis de PE protegen de manera significativa la disminución de los pesos de epidídimo y vesículas seminales, pero no de peso corporal y testicular. El extracto de MC también aumentó la concentración de espermatozoides y los diámetros de los túbulos seminíferos en los grupos de administración con MC+AV. Por otra parte, la histología testicular de los grupos MC+AV mostró una disminución significativa de histopatologías testiculares en comparación con el grupo AV. En conclusión, el extracto de arilo M. cochinchinensis puede prevenir la aparición de parámetros reproductivos masculinos negativos y los daños testiculares inducidos con AV.

Intoxicación severa por ácido valproico / Severe poisoning by valproic acid

El ácido valproico es utilizado en el manejo de las crisis de ausencias simples y complejas, mioclonías y convulsiones tónico-clónicas generalizadas. Es efectivo en las crisis parciales, como profilaxis de segunda línea para la migraña y en el trastorno bipolar. Debido a su amplio uso han aumentado los casos de intoxicación en los últimos años. Los objetivos de este trabajo son describir las manifestaciones clínicas y evolución de una intoxicación severa por ácido valproico, secundaria a ingesta intencional; destacar la importancia del metabolismo de la droga para el manejo clínico de la intoxicación, la necesidad de un laboratorio capaz de proporcionar una rápida cuantificación de la misma y analizar las opciones terapéuticas actuales.

Valproic acid is used in crisis management both simple and complex absence, myoclonus and tonic-clonic seizures. It is effective in partial seizures, as second line prophylaxis for migraine and bipolar disorder. Its widespread use has increased cases of poisoning in recent years. The aim of this review is to describe the clinical manifestations and evolution of a severe valproic acid intoxication secondary to intentional consumption as well as emphasize the importance of drug metabolism for clinical management of poisoning, the need for a laboratory provide rapid quantification of this drug and discuss current treatment options.

Preliminary evaluation of children treated with metronomic chemotherapy and valproic acid in a low-income country: Metro-Mali-02.

BACKGROUND: Metronomics is defined by the combination of metronomic chemotherapy and drug repositioning. Since off‑patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, metronomics appears to be an invaluable alternative to bring affordable targeted therapies in low‑income countries. OBJECTIVE: The aim of this study was to report on the preliminary efficacy and safety of a metronomic vincristine/cyclophosphamide/methotrexate/ valproic acid regimen given to children with refractory cancer of various tumor types or with a very advanced disease. MATERIALS AND METHODS: This prospective, single‑center study evaluated the use of a metronomics protocol, consisting of a first cycle of weekly vincristine 1.5 mg/m2 (days: 1, 8, 15 and 22), daily cyclophosphamide 25 mg/m2 (days: 1‑21), twice weekly methotrexate 15 mg/m² (days: 21‑42) and daily valproic acid (30 mg/kg/d) followed by a 1‑week break. For the following cycles, vincristine was administrated only at week 1 and 5 of the cycle. This treatment was proposed to children with refractory disease and patients who were not eligible for the protocols available in the hospital. Adverse events were determined through laboratory analyses and investigator observations. RESULTS: From January 2010 to January 2011, 7 children (mean age: 5.4 ± 3 years old) were treated. Most frequent diagnosis was retinoblastoma. Two partial responses were observed in patients with neuroblastoma and retinoblastoma. These two patients are alive with stable disease at last follow‑up (6 and 26 months, respectively) after stopping treatment. CONCLUSION: Metronomics allows treating patients with advanced or refractory or relapsing disease and the introduction of targeted treatments in low‑income countries. The potential of metronomics in children and young adults living in middle‑ and low‑income countries warrants further larger studies.

Fatal toxic epidermal necrolysis induced by sodium valproate

A 26 years old manual labourer from Azad Jammu Kashmir presented with four days history of an extensive exfoliation of skin involving the entire body. Histology of the lesion showed epidermal necrolysis. The patient was a recently diagnosed case of epilepsy and had been started on therapy with sodium valproate three weeks ago. Following admission in our center, intensive care and wound care were instituted according to standard protocols. Despite all therapeutic measures the patient kept on deteriorating and developed multi-organ failure with pneumonia. He died on 7[th] day of hospitalization

Vitamina D en niños con enfermedades neurológicas en la edad pediátrica / The role of vitamin D in neurological diseases in children

La vitamina D (VD) y sus acciones en el ser humano son objeto de una activa investigación en años recientes, ligada a la descripción de nuevos roles metabólicos, además de su conocida participación en el metabolismo del calcio y del hueso. En niños, algunas enfermedades neurológicas crónicas, como la parálisis cerebral, presentan un riesgo aumentado de deficiencia de VD, explicándose por una ingesta deficiente de ella, una menor exposición solar, requerimiento asociado al proceso de crecimiento, enfermedades intercurrentes y al uso frecuente de drogas antiepilépticas. En esta revisión se analizan los factores asociados a la deficiencia de VD y se plantea la necesidad de evaluar sistemáticamente el estado nutricional de esta vitamina en pacientes con enfermedades neurológicas de riesgo, sus posibles efectos metabólicos, implicancias clínicas y la necesidad de usar alimentos fortificados o suplementación con VD.

Vitamin D (VD) has been object of an active research in the last years, especially in relation with the findings of its new roles, besides its well known participation in calcium and bone metabolism. In children, some chronic neurologic diseases, like cerebral palsy, show an increased risk of VD deficiency, which could be explained by low intake, reduced sun exposure, requirements associated to growth process, intercurrent diseases and frequent use of antiepileptic drugs. In this review, factors associated to VD deficiency are analyzed, pointing to the need of a systematic assessment of the VD nutritional status in patients with neurological diseases associated to this deficiency, its possible metabolic effects, clinical implications and the need of fortified foods or VD supplementation.

Bipolaridad: monitoreo terapéutico de drogas antiepilépticas / Bipolarity: Therapeutic monitoring of antiepileptic drugs

Objetivo: Revisión bibliográfica del monitoreo de los fármacos utilizados en el tratamiento de la bipolaridad y las recomendaciones que de allí se derivan para su aplicación en el ámbito de la asistencia clínica de pacientes con patología bipolar. Método: Búsqueda en medline y medscape desde 1998 hasta mayo 2011 de los siguientes términos: monitoreo, valproato, lamotrigina, carbamacepina, gabapentina, topiramato, antiepilépticos, trastornos bipolares, interacciones farmacológicas y eventos adversos. Fueron consultadas las guías de tratamiento (CANMAT: Canadian Network for Mood and Anxiety Treatments, update 2009), aprobaciones de la FDA (Food and Drug Administation, EEUU) y recomendaciones de la Asociación Americana de Psiquiatría (APA). Resultados: Los fármacos para los cuales se halló evidencia documentada en bipolaridad, hasta el momento son: valproato, lamotrigina y carbamacepina; no habiendo evidencia que avale el uso de gabapentina o topiramato. Los principales eventos adversos de los antiepilépticos son los del sistema nervioso; requieren evaluación clínica, ya que carecen de un laboratorio específico. Constituye una excepción la hiperamoniemia producida por valproato que puede medirse en el laboratorio y ser causa de encefalopatía o asociarse, con más frecuencia, a trastornos cognitivos. El monitoreo de valproato está recomendado, así como el de amonio. El monitoreo de lamotrigina podría ser útil. La titulación debe ser lenta, para disminuir riesgo de rash potencialmente fatal. Considerar el inicio del tratamiento con monodroga. Se recomienda el monitoreo de carbamacepina y en caso de polifarmacia: el monitoreo del epóxido de carbamacepina. En los tres fármacos considerar interacciones y la posibilidad de toxicidad aún dentro del rango terapéutico

Objective: Literature review of monitoring of AEDs used in the treatment of bipolarity and the recommendations arising from there for use in the field of clinical care of patients with bipolar disease. Method: Search Medscape and medline from 1998 to May 2011 of the following terms: monitoring, valproate, lamotrigine, carbamazepine, gabapentin, topiramate, antiepileptics, bipolar disorders, drug interactions and adverse events. having consulted in addition to treatment guidelines Canadian Network for Mood and Anxiety Treatments, update 2009 (CANMAT), approvals of the Food and Drug Administration, USA (FDA) and recommendations of the American Psychiatric Association (APA). Results: Drugs with documented evidence for use in bipolar disorder are: valproate, lamotrigine and carbamazepine, there being no evidence to support the use of gabapentin or topiramate. It is important to consider that the main adverse effects of antiepileptic drugs (AEDs) develop in the Nervous System. These symptoms require clinical evaluation, since they lack a specific laboratory, except hyperammonemia: a parameter measurable in the laboratory, produced by valproate that is associated with encephalopathy and cognitive disorders. Valproate monitoring is recommended, as well as ammonium. Monitoring of lamotrigine may be useful. The titration should be slow always, to avoid risk of potentially fatal rash. Consider, where possible, the beginning of treatment with single drug. Carbamazepine monitoring is recommended and in case of polypharmacey: the monitoring of carbamazepine epoxide becomes useful. In all cases should be evaluated possible interactions and their mechanisms to have in mind the possibility of toxicity symptoms even with plasma dosages within the therapeutic range

Trastornos neurocognitivos en la hiperamonemia inducida por ácido valproico / Neurocognitive disorders of Valpoic Acid-Induced Hyperammonemia

El objetivo de este trabajo se orienta a dar cuenta de los trastornos neurocognitivos debidos al uso del ácido valproico, por su capacidad de inducir hiperamonemias, las que en muy pocos casos pueden implicar cuadros clínicos severos, y en otros, los más comunes, ocasionar síntomas cognitivos leves pero que pueden revestir importancia en la vida cotidiana de un paciente. Resulta necesario diferenciarlos de aquellos síntomas cognitivos que son una consecuencia de la enfermedad bipolar en sí misma, cuando dicho fármaco se lo usa como estabilizador del ánimo

The aim of this paper is oriented to account for neurocognitive disorders due to use of valproic acid, their ability to induce hyperammonemias, which in rare cases can lead to severe clinical symptoms, and in others, the most common, cause mild cognitive symptoms but of potential importance in the daily life of a patient. It is necessary to differentiate them from those cognitive symptoms wich are a consequence of bipolar disorder itself, when the drug is used as a mood stabilizer

Evaluación de la función tiroídea en pacientes pediátricos durante el uso de fármacos antiepilépticos / Assessment of thyroid in pediatric patients during the use of antiepileptic drugs

El objetivo principal de este trabajo es evaluar las alteraciones en la función tiroídea de pacientes pediátricos con epilepsia en tratamiento con fármacos antiepilépticos (FAEs). Un segundo objetivo es evaluar la severidad y manifestaciones clínicas de estas alteraciones y los FAEs asociados a ellas. Se revisó las historias clínicas de pacientes de 0-18 años, en control por epilepsia, pertenecientes a la unidad de Neuropsiquiatría Infantil del Hospital Dr. Lautaro Navarro Avaria de Punta Arenas, durante el periodo comprendido entre julio del 2008 y junio del 2009. Criterios de inclusión: estar en tratamiento con FAEs y tener registro de evaluación de función tiroídea en su ficha clínica. De los 59 pacientes que cumplieron con los criterios de inclusión, 21 tenían niveles de hormona tiro-estimulante (TSH) elevados, seis de ellos presentaron manifestaciones clínicas de hipotiroidismo. La mayoría presentó hipotiroidismo subclínico y recibía tratamiento con ácido valproico (VPA) como monoterapia. Es por esto y considerando que el desarrollo cerebral de los niños es altamente sensible a los niveles de tiroxina, parece fundamental el monitoreo de la función tiroídea en niños y adolescentes en tratamiento con FAES.

Our aim was to evaluate severity and clinical manifestations of thyroid function abnormalities in pediatric epileptic patients in therapy with antiepileptic drugs (AED). Medical histories of patients attending to the Pediatric Neuropsychiatric Unit of Dr. Lautaro Navarro Avaria Hospital, Punta Arenas were reviewed. Fifty nine epileptic patients aged between 0-18 years, on AED therapy between July 2008 and June 2009, with evaluation of thyroid function were included. Thyroid-stimulating hormone (TSH) serum levels were high in 21 of the 59 patients, six of them showed clinical signs of hypothyroidism. Most of them exhibited TSH values in the subclinical hypothyroidism range and were on valproic acid (VPA) monotherapy. Considering that children’s brain development is highly sensitive to thyroxine levels, we emphasize the relevance of monitoring thyroid function in children and adolescents receiving antiepileptic treatment.

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Encefalopatía inducida por ácido valproico: serie de siete casos / Valproic acid-induced encephalopathy: series of seven cases

Introducción: La encefalopatía inducida por ácido valproico (AV) es una complicación infrecuente caracterizada por disminución del nivel de conciencia, déficits neurológicos focales, enlentecimiento cognitivo, vómitos, somnolencia y letargia, con o sin hiperamonemia. El electroencefalograma (EEG) muestra enlentecimiento difuso. Los hallazgos EEG, las manifestaciones clínicas y la hiperamonemia tienden a normalizarse con la suspensión del AV. Pacientes y Métodos: Se presenta una serie de 7 pacientes que desarrollaron encefalopatía por AV, en el Servicio de Neurología del Hospital del Salvador, entre 2003 y 2010. Se detallan dos casos clínicos ilustrativos. Resultados: La serie está compuesta por 5 mujeres y 2 hombres. Cinco pacientes desarrollaron hiperamonemia (amonemia sobre 50 ug/dl). El promedio de edad fue de 55 años (37 a 82 años). Las dosis de AV fueron de 375 a 2.000 mg (promedio = 903). La latencia entre el inicio o ajuste significativo del AVfue de 3 días hasta 16 años y un mes. Todos los pacientes presentaban daño orgánico cerebral. La politerapia con fenobarbital, fenitoína y carbamazepina fue significativa. El patrón de EEG más frecuente fue el enlentecimiento difuso. Una paciente de 82 años desarrolló actividad pseudoperiódica sugerente de un status epilepticus no convulsivo. En todos los pacientes hubo normalización clínica, de laboratorio y del EEG con la suspensión del AV. Conclusiones: La encefalopatía inducida por ácido valproico es una reacción adversa reversible pero potencialmente fatal que requiere un alto índice de sospecha. El daño orgánico cerebral y la politerapia parecen ser importantes factores de riesgo para su producción.

Introduction: Valproic acid (VA) induced encephalopathy is an unusual complication characterized by decreasing level of consciousness, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy, with or without hyperammonemia. Electroencephalography (EEG) is characterized by continuous generalized slowing. The EEG findings, as well as clinical manifestations and hyperammonemia, tend to normalize after VA withdrawal. Patients and Methods: We present a series of seven patients who developed VA-induced encephalopathy at the Neurology Department of Hospital Salvador between 2003 and 2010. We report two illustrative cases in extenso. Results: Our series is composed by five women and two men. Five patients developed hyperammonemia (ammonemia above 50 ug/dl). 55years was the average of patients (range: 37 to 82 years). VA dose was between 375 and 2.000 mg (average 903 mg). Latency between start or important change in VA dose was 3 days to 16 years and a month. All patients had brain damage. Polytherapy with phenobarbital, phenytoin and carbamazepine was significant. The most frequent EEG pattern was diffuse slowing. A 82-year-old female developed a seudo-periodic activity suggesting a non-convulsive status epilepticus. The clinical manifestations, EEG findings and laboratory normalized after VA withdrawal. Conclusions: Acid valproic-induced encephalopathy is a reversible but potentially fatal adverse reaction that requires a high index of suspicion. Brain damage and polytherapy seem to be important risk factors.

Lesão hepática grave induzida por fármacos anticonvulsivantes: relato de casos / Serious liver injury induced by anticonvulsants drugs: case reports

JUSTIFICATIVA E OBJETIVOS: Inúmeros medicamentos empregados rotineiramente na prática médica podem apresentar como efeito adverso significativo a agressão hepática, manifestando-se, por vezes, com lesões graves irreversíveis, sendo possível causa de óbito em determinadas situações. O objetivo deste estudo foi relatar dois casos de pacientes que apresentaram hepatotoxicidade por fármacos anticonvulsivantes, suas consequências e possível prevenção. RELATO DOS CASOS: Caso 1: Paciente do sexo feminino, 12 anos, com história de epilepsia, em uso de carbamazepina (CBZ), haloperidol, clorpromazina e clobazan. Ao exame clínico apresentava-se sonolenta e confusa, com exames laboratoriais contendo dosagem de CBZ elevada e enzimas hepáticas alteradas. Apresentou piora progressiva com surgimento de icterícia, elevação de enzimas hepáticas e diminuição do nível de consciência. A paciente evoluiu com broncopneumonia, hemorragia pulmonar, insuficiência respiratória e óbito. Caso 2: Paciente do sexo masculino, 4 anos, em uso contínuo de depakene, foi encaminhado com quadro de sonolência, icterícia, diminuição do nível de consciência, náuseas e dor abdominal. Houve agravamento do quadro hemodinâmico, com abalos mioclônicos, choque hipovolêmico e óbito. Durante a internação apresentou elevação de enzimas hepáticas e, assim como no primeiro caso, as sorologias virais eram negativas e a tomografia de crânio não apresentava anormalidades. CONCLUSÃO: Nos últimos anos, lesões hepáticas induzidas por diferentes agentes têm sido cada vez mais observadas. E, progressivamente, a importância dada a esse fenômeno tem aumentado de maneira significativa. Sendo o fígado o principal órgão metabolizador corporal, é esperado um comprometimento proporcionalmente extenso à medida que um número crescente de substâncias farmacológicas é utilizado. Diante do exposto, destaca-se a importância do uso racional de interações medicamentosas, na tentativa de prevenir lesões possivelmente evitáveis.

BACKGROUND AND OBJECTIVES: Countless medicines employees routinely in medical practice can present as significant adverse effect the hepatic aggression, manifesting, sometimes, with serious irreversible injuries, being a possible cause of death in determined situations. The objective of this study was reported two cases of patients who presented hepatotoxicity by anticonvulsants, its consequences and possible prevention. CASE REPORTS: Case 1: Female patient, 12 years, with a history of epilepsy, in use of carbamazepine (CBZ), haloperidol, chlorpromazine and clobazam. On clinical examination the patient was drowsy and confused, with laboratory containing elevation of CBZ dosage and liver enzymes changed. There was progressive worsening, with appearance of jaundice, elevation of liver enzymes and decreased level of consciousness. The patient evolved with bronchopneumonia, pulmonary hemorrhage, respiratory failure and death.Case 2: Male patient, 4 years, in continuous use of depakene, was directed with drowsiness, jaundice, decreased level of consciousness, nausea and abdominal pain. There was aggravation of hemodynamic status, with myoclonic tremors, hypovolemic shock and death. During hospitalization in our department, presented liver enzymes elevated and, as in the first case, viral serology was negative and tomography of skull showed no abnormalities. CONCLUSION: In recent years, liver injury induced by different agents has been increasingly observed. And gradually, the importance given to this phenomenon has increased significantly. Being the liver the main metabolizing organ body is expected a proportionally extensive involvement as a growing number of pharmacological substances is used. Given the above, highlights the importance of rational use of drug interactions in an attempt to prevent possibly avoidable injuries.

Modification in body weight associated with antiepileptic drugs / Alteração de peso corpóreo associado às drogas antiepilépticas

Antiepileptic drugs (AED) may cause body weight changes. OBJECTIVE: To evaluate the dietary habits and body weight associated with AED in epileptic patients. METHOD: Sixty-six patients were subjected to two interviews, and had their weight and body mass index calculated and compared at both times, interval between six to eight months. RESULTS: It was observed that 59.1 percent showed weight gain. The patients who had no weight gain had a greater proportion of individuals who engaged in some form of physical activity. However, of the 45 patients who maintained their initial dietary and medication pattern, 75.6 percent recorded a weight gain. Weight gain was seen in 66.7 percent of patients on carbamazepine (n=18), 60 percent on valproate (n=5), 50 percent on carbamazepine+clobazam treatment (n=14), and 58.3 percent of patients on other(s) polytherapy (n=12). CONCLUSION: The patient should be alerted to possible weight gain, and should be advised about dieting and participating in regular physical activity.

Drogas antiepilépticas (DAE) podem causar alteração do peso corpóreo. OBJETIVO: Avaliar o hábito alimentar e do peso corpóreo associado às DAE em pacientes epilépticos. MÉTODO: Sessenta e seis pacientes foram submetidos a duas entrevistas, e tiveram peso e índice de massa corpórea (IMC) calculados e comparados nos dois momentos, com intervalo de 6 a 8 meses. RESULTADOS: Apresentaram aumento de peso 59,1 por cento dos pacientes. Porém, os pacientes que não tiveram ganho de peso apresentaram maior proporção de indivíduos desenvolvendo alguma atividade física. Enquanto que dentre os 45 que mantiveram o padrão alimentar e medicação inicial 75,6 por cento registraram ganho de peso. Observou-se ganho de peso em 66,7 por cento dos pacientes com carbamazepina (n=18); 60 por cento com valproato (n=5); 50 por cento com carbamazepina e clobazam (n=14); 58,3 por cento dos pacientes com politerapia (n=12). CONCLUSÃO: Deve-se alertar o paciente sobre o ganho de peso, orientar quanto à dieta alimentar e, principalmente, incentivar atividade física regular.

Síndrome de hipersensibilidad a anticonvulsivantes (síndrome de DRESS): comunicación de 4 casos / Anticonvulsant hypersensitivity syndrome (DRESS syndrome): report of 4 cases

El síndrome de hipersensibilidad a anticonvulsivante es una reacción frecuente y potencialmente fatal, que se caracteriza por fiebre, erupción cutánea y compromiso de órganos internos. Difenilhidantína, fenobarbital y carbamazepina son los anticonvulsivantes aromáticos que más frecuentemente lo producen. Comunicamos 4 pacientes adultos, 2 masculinos y 2 femeninos de entre 20 y 42 años que presentaron hallazgos clínicos, bioquímicos e histológicos compatibles con un síndrome de hipersensibilidad a drogas secundario a anticonvulsivantes que se inició luego de 4 a 8 semanas del inicio del fármaco. Las drogas causantes fueron difenilhidantoína, carbamazepina y la asociación de ácido valproico y lamotrigina.