Encefalopatía epiléptica de inicio precoz en un paciente con mutación en SCN8A / Early onset epileptic encephalopathy in a patient with mutation in SCN8A

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Placebos, neuropathic pain and gender / Los placebos, el dolor neuropàtico y de género

INTRODUCTION: the placebos' analgesic effect seems to depend on different factors such as socio-cultural, psychological and genetic aspects. The effects of gender on placebos' analgesic response have rarely been documented in clinical studies, even though there have been some reports in experimental studies. OBJETIVE: study the analgesic effect of anticonvulsant and antidepressive drugs in adults suffering from painful diabetic neuropathy and its relationship with gender MATERIAL AND METHODS: a search and systematic selection was made of all clinical trials for analgesic treatment of diabetic neuropathy with anticonvulsant and antidepressive drugs published between January 2000 and February 2011. Randomized, placebo-compared clinical trials were included which had studied the analgesic effect of anticonvulsant and antidepressive drugs in adults suffering from painful diabetic neuropathy, evaluated in such a way that improvement in pain could be objectively classified. The following information was obtained from each article: criteria for diagnosing diabetic neuropathy, medicaments received and improvement of pain in the group being treated and in the placebo group according to patient gender. RESULTS: 12 studies fulfilling the inclusion criteria were found which analyzed latest generation anticonvulsant and antidepressive agents used in managing pain in diabetic neuropathy. Only one study included gender-discriminated results regarding controlling pain in the placebo group. CONCLUSION: the foregoing easily justifies the need for and importance of studying the relationship between gender and placebo response. This association has not been suitably reported to date, except by very few studies.

INTRODUCCIÓN: el efecto analgésico del placebo parece depender de diversos factores tales como los aspectos socio-culturales, psicológicos y genéticos. Los efectos del género en la respuesta analgésica del placebo rara vez se documenta en los estudios clínicos, a pesar de que ha habido algunos informes en los estudios experimentales. OBJETIVO: estudiar el efecto de los antiepilépticos y fármacos antidepresivos en la neuropatía diabética en relación con el género MATERIAL Y MÉTODOS: se realizó una búsqueda y selección sistemática de todos los ensayos clínicos para el tratamiento analgésico de la neuropatía diabética con antiepilépticos y fármacos antidepresivos publicados entre enero de 2000 y febrero de 2011. Se incluyeron todos los estudios clínicos aleatorizados, comparados con placebo que estudiaran el efecto analgésico de los antiepilépticos y fármacos antidepresivos en adultos con neuropatía diabética dolorosa, que evaluaran la mejoría en el dolor de manera objetiva. En cada artículo se obtuvo la siguiente información: criterios para el diagnóstico de la neuropatía diabética, medicamentos recibidos y mejoría del dolor en el grupo en tratamiento y en el grupo placebo, según el sexo del paciente. RESULTADOS: 12 estudios cumplían los criterios de inclusión. Sólo un estudio incluyó discriminación de género, los resultados en relación con el control del dolor en el grupo placebo. CONCLUSIONES: los hallazgos de esta investigación justifica la necesidad y la importancia de estudiar la relación entre el género y la respuesta al placebo. Esta asociación no ha sido debidamente reportada hasta la fecha, excepto por muy pocos estudios.

New Generation Antidepressants in Painful Diabetic Neuropathy / Antidepresivos de nueva generation en neuropatia diabetica dolorosa / Antidepressivos de nova geração na neuropatia diabetica dolorosa

The incidence of diabetic neuropathy increases with the duration of diabetes and the degree of hyperglycaemia. Pain is one of the most common and incapacitating symptoms of diabetic neuropathy and its pharmacological control is complex. The effectiveness of antidepressive agents has been described in different types of neuropathic pain, but their effectiveness, when used as analgesics in painful diabetic neuropathy, still remains controversial. Objective: To review the possible role of new-generation antidepressive agents in the treatment of pain in diabetic peripheral neuropathy. This work has thus consisted of a meta-analysis for determining which antidepressive agent had the best analgesic potential in managing pain in patients suffering from painful diabetic neuropathy. Methods: This search covered the Cochrane, MEDLINE, EMBASE and LILACS databases, between January 2000 and August 2007. The following information was obtained from each article: criteria for diagnosing diabetic neuropathy, patients' age average, antidepressant drug received and dose, sample size, duration of the disease and treatment follow-up, outcome measurement, evaluation of pain and rescue medication. Results: A combined RR: 1.67 (95% CI 1.38 - 2.02) was obtained; this result indicated that the antidepressive agent duloxetine, was effective for controlling pain in diabetic neuropathy. The corresponding NNT for Duloxetine was established, according to our interests; NNT = 6 (95% CI 5- 8) for achieving greater than 50% analgesia in patients suffering from painful diabetic neuropathy. Discussion: Antidepressive agents are frequently employed in the specific case of diabetic neuropathy; their analgesic benefit has been demonstrated.

La incidencia de neuropatía diabética aumenta con la duración de la diabetes y el grado de hiperglicemia. El dolor es uno de los síntomas más comunes e incapacitantes de la neuropatía diabética y su control farmacológico es complejo. La efectividad de los antidepresivos ha sido descrita en diferentes tipos de dolor neuropático, pero su verdadera efectividad, al ser usados como analgésicos en el dolor en la neuropatía diabética, aún es controvertida. Objetivo: Realizar una revisión sistemática y meta-análisis para determinar el nivel de evidencia en relación con la potencia analgésica de estos nuevos antidepresivos para el manejo del dolor en el paciente con neuropatía diabética dolorosa. Métodos: La búsqueda cubrió las bases de datos Cochrane, MEDLINE, EMBASE y LILACS entre enero de 2000 y agosto de 2007. De cada artículo se obtuvo la siguiente información: criterios para diagnóstico de neuropatía diabética, edad promedio de los pacientes, antidepresivo recibido y dosis, tamaño de la muestra, duración de la enfermedad, seguimiento del tratamiento, medidas de desenlace, evaluación del dolor y medicación de rescate. Resultados: Se obtuvo un RR combinado de 1,67 (IC 95% 1,38 - 2,02). El NNT correspondiente para la Duloxetina fue de 6 (95% CI 5- 8), para obtener una analgesia superior a 50% en pacientes con dolor por neuropatía diabética. Discusión: Se ha demostrado que los antidepresivos son empleados con frecuencia y efectivos como analgésicos para el dolor por neuropatía diabética.

A incidência de neuropatia diabética aumenta com a duração da diabetes e o grau de hiperglicemia. A dor é um dos sintomas mais comuns e incapacitantes da neuropatia diabética e seu controle farmacológico é complexo. A efetividade dos antidepressivos tem sido descrita em diferentes tipos de dor neuropática, mas sua verdadeira efetividade, quando utilizados como analgésicos na dor na neuropatia diabética, ainda é controvertida. Objetivo: realizar uma revisão sistemática e meta-análise para determinar o nível de evidencia em relação com a potência analgésica destes novos antidepressivos para o manejo da dor no paciente com neuropatia diabética dolorosa. Métodos: A procura cobriu as bases de dados Cochrane, MEDLINE, EMBASE e LILACS entre janeiro de 2000 e agosto de 2007. De cada artigo se obteve a seguinte informação: critérios para diagnóstico de neuropatia diabética, idade em media dos pacientes, antidepressivo recebido e dose, tamanho da amostra, duração da enfermidade, seguimento do tratamento, medidas de desenlace, avaliação da dor e medicação de resgate. Resultados: obteve-se um RR combinado de 1,67 (IC 95% 1,38 - 2,02). O NNT correspondente para a Duloxetina foi de 6 (95% CI 5- 8), para obter uma analgesia superior a 50% em pacientes com dor por neuropatia diabética. Discussão: tem se demonstrado que os antidepressivos são empregados com freqüência e efetivos como analgésicos para a dor por neuropatia diabética.

Antiepileptic drugs in treatment of pain caused by diabetic neuropathy.

Pain is frequent in diabetic neuropathy and is very hard to manage. Antiepileptic drugs have been used in treating pain for several decades. Their effectiveness has been described in different types of neuropathic pain, but when used as analgesics in painful diabetic neuropathy it still remains controversial. To clarify this effectiveness, a meta-analysis was performed to determine which antiepileptic drug had the best analgesic potential for managing pain in patients suffering from painful diabetic neuropathy. The search covered the Cochrane, MEDLINE, EMBASE, and LILACS databases, between January 1966 and September 2005. The following information was obtained from each article: criteria for diagnosing diabetic neuropathy, patients' age average, antiepileptic drug received and dose, sample size, duration of the disease and treatment follow-up, outcome measurement, evaluation of pain, and rescue medication. A combined 2.33 relative risk (95% confidence interval [CI] 1.88-2.88) was obtained; this result indicated that the antiepileptic drugs studied were effective for controlling pain in diabetic neuropathy. The corresponding necessary number to treat (NNT) values were established for evaluating which antiepileptic drug was most effective as an analgesic, according to our interests; pregabalin was shown to be the antiepileptic drug having the lowest NNT (NNT=3.24 and 95% CI 2.12-6.81) for achieving greater than 50% analgesia in patients suffering from painful diabetic neuropathy. Antiepileptic drugs are frequently used in the specific case of diabetic neuropathy; the combined result of this meta-analysis has demonstrated their analgesic benefit.

Manganese and epilepsy: a systematic review of the literature.

Manganese is an essential trace element for the development and function of the central nervous system. Alterations in manganese concentrations, whether excessive or deficient, can be accompanied by convulsions. This article represents a systematic review of available quantitative evidence that might clarify this issue. We searched The Cochrane Library, Medline and LILACS databases from January 1966 through June 2006 and reviewed all resulting English and Spanish language publications, as well as those possibly relevant in other languages based on their abstracts. The final selection included for this review comprises all investigations in humans and animals that compared manganese levels in any tissue of a group with spontaneous or induced convulsions (with or without antiepileptic treatment) and a convulsion-free control group. The literature search identified thirteen publications since then relevant to the issue, four of which failed to meet our criteria for inclusion. Of the remaining nine, six were in humans and three in rodents. At present, there is no satisfactory explanation for the relationship between low manganese levels and the presence of convulsions. There is a documented correlation between low blood manganese levels and the presence of convulsions in both humans and animals. The lack of evidence indicating whether this is a cause or an effect of the convulsions clearly justifies more detailed follow-up investigations in humans.