Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Neurotoxicidad subaguda por metotrexato en pacientes con enfermedad oncohematológica. Reporte de tres casos / Subacute methotrexate neurotoxicity in patients with oncohematological disease. A report of 3 cases

El metotrexato es un fármaco análogo del ácido fólico ampliamente utilizado en el tratamiento de enfermedades autoinmunes, leucemias y linfomas. Su uso puede ocasionar la aparición de múltiples efectos adversos entre los que se encuentran aquellos relacionados con la presencia de toxicidad neurológica, que puede presentarse de forma aguda, subaguda o crónica. La neurotoxicidad subaguda es aquella que ocurre típicamente entre los 2 y los 14 días posteriores a la administración y puede manifestarse con una amplia gama de síntomas neurológicos. En la mayoría de los casos, no recurre con futuras exposiciones al medicamento. Presentamos tres casos de neurotoxicidad subaguda por metotrexato con manifestaciones clínicas diferentes en pacientes oncohematológicos que se internaron entre los años 2018 y 2020. Dos de ellos presentaron recurrencia frente a la nueva administración del fármaco y todos evidenciaron lesiones en resonancia magnética nuclear.

Methotrexate is a folic acid analogue widely used in the treatment of autoimmune diseases, leukemias, and lymphomas. Methotrexate use may cause multiple adverse effects, including those related to the presence of neurological toxicity, which may be acute, subacute, or chronic. Subacute neurotoxicity typically occurs between 2 and 14 days after administration and may present as a wide range of neurological symptoms. In most cases, it does not recur with future exposures to the drug. Here we describe 3 cases of subacute methotrexate neurotoxicity with different clinical manifestations in patients with oncohematological disease who were hospitalized between 2018 and 2020. Two of them showed recurrence with a new drug administration. Lesions were observed in the magnetic resonance imaging tests of all of them.

Imaging features of 10 patients with toxic encephalopathy caused by diquat / 中华劳动卫生职业病杂志

Objective: To explore the CT and MRI imaging findings of diquat toxic encephalopathy. Methods: CT and MRI imaging features of 10 patients with diquat poisoning encephalopathy who had been clinically diagnosed were retrospectively reviewed. Results: CT was performed in all 10 patients, and MRI was performed in 8 patients. In 10 patients, 7 had positive signs on CT, and 8 patients with MRI examination had abnormal changes in the images. The main CT findings were symmetrical hypodensity in bilateral cerebellar hemisphere, brainstem, thalamus and basal ganglia, and swelling of brain tissue. The main MRI findings were symmetrical lesions and brain edema in the deep nuclei of cerebellar hemisphere, brainstem, thalamus and basal ganglia, low signal on T1WI, high signal on T2WI and T2-FLAIR, and cytotoxic edema on diffusion weighted imaging (DWI) . On review after treatment, both CT and MRI showed resorption of the lesion, which narrowed in size. Conclusion: The imaging findings of diquat poisoning encephalopathy are characteristic and the location of the lesion is characteristic, and CT and MRI have a certain diagnostic value in diquat poisoning encephalopathy, which is important for clinical treatment.

Tremorgenic syndrome caused by Ipomoea pes caprae in cattle / Síndrome tremorgênica causada pela ingestão de Ipomoea pes caprae em bovinos

Poisonous plants are a significant cause of death among adult cattle in Brazil. Plants that affect the central nervous system are widely spread throughout the Brazilian territory and comprise over 30 toxic species, including the genus Ipomoea, commonly associated with a lysosomal storage disease and a tremorgenic syndrome in livestock. We describe natural and experimental Ipomoea pes caprae poisoning in cattle from a herd in the Northside of Rio de Janeiro, Brazil. Affected cattle presented episodes of severe ataxia, abnormal posture followed by falling, muscular tremor, contraction, and spasticity, more prominent in the limbs, intensified by movement and forthcoming, and recumbence. Grossly, a substantial amount of leaves and petioles were found in the rumen. Histopathological examination showed degenerative neuronal changes, mostly in cerebellar Purkinje cells, which were confirmed with Bielschowsky silver. The characteristic clinical changes and mild histological lesion strongly suggested a tremorgenic syndrome. Lectin- immunohistochemistry evaluation reinforced this hypothesis; all lectins tested failed to react with affect neurons and Purkinje cells, which ruled out an underlying lysosomal storage disease. One calf given I. pes caprae leaves experimentally developed clinical signs similar to natural cases. On the 28th day of the experiment, the plant administration was suspended, and the calf recovered within four days. I. pes caprae's spontaneous tremorgenic syndrome in cattle is conditioned to exclusive feeding for several months. We were able to experimentally reproduce toxic clinical signs 12 days following the ingestion.(AU)

A intoxicação por plantas tóxicas está entre as três causas de morte mais importantes em bovinos adultos no Brasil. O grupo das plantas que causam alterações neurológicas, muito bem representada no país, encerra mais de trinta espécies tóxicas, entre as quais do gênero Ipomoea, amplamente distribuídas no território brasileiro. As plantas tóxicas desse gênero podem causar doenças do armazenamento ou síndrome tremorgênica. Descrevem-se a intoxicação natural e reprodução experimental por Ipomoea pes caprae em bovinos, verificada no norte do Estado do Rio de Janeiro. Foram observados episódios de intensa ataxia locomotora, postura anormal seguida de queda, incapacidade de levantar-se, tremores, contrações, espasticidades musculares nos membros, intensificados após estimulação ou a simples aproximação e decúbito. Nos bovinos afetados há mais de 6 meses, os sinais clínicos tornavam-se permanentes. À necropsia havia apenas significativa quantidade de folhas e pecíolos da planta no rúmen. O estudo histopatológico evidenciou lesões neuronais degenerativas principalmente nos neurônios de Purkinje. A impregnação argêntica pela técnica de Bielschowsky ratificou esses achados microscópicos. As lesões histológicas sutis associadas ao quadro clínico indicam que trata-se de intoxicação tremorgênica. O fato de não haver nenhum armazenamento intracitoplasmático, confirmado pelo resultado do estudo lectino-histoquímico (não houve afinidade das lectinas Con-A, WGA e sWGA e de outras lectinas empregadas aos neurônios de Purkinje e outros neurônios afetados), é suficiente para descartar a possibilidade de tratar-se de doença do armazenamento. No bezerro intoxicado experimentalmente verificaram-se sinais clínicos semelhantes, entretanto, com a interrupção do fornecimento da planta no 28º dia, os sinais clínicos desapareceram após quatro dias. I. pes caprae causa síndrome tremorgênica espontânea em bovinos, quando ingerida como alimentação exclusiva durante períodos prolongados (muitos meses). Experimentalmente, os primeiros sinais clínicos da intoxicação foram reproduzidos após 12 dias de ingestão da planta.(AU)

Anestesia general en infantes: consideraciones neurobiológicas y neuropsicológicas / General anesthesia in infants: neurobiological and neuropsychological concerns

Resumen La anestesia general es una herramienta imprescindible para el proceso quirúrgico, ya que disminuye el dolor, reduce la ansiedad y genera inconsciencia. Sin ella, las cirugías serían dolorosas, riesgosas y emocionalmente traumáticas. La reciente emisión de una alerta sobre el uso de fármacos anestésicos en niños menores de 3 años por parte de la Food and Drug Administration (FDA) de los Estados Unidos generó controversia en torno a sus posibles efectos negativos. En este artículo se abordan los principales hitos del desarrollo neurobiológico del niño y se revisan las posibles consecuencias neuropsicológicas del uso de anestesia general en esta población. La mayoría de los reportes que abordan este tema son de tipo retrospectivo y arrojan resultados controversiales por sus inherentes dificultades metodológicas. Sin embargo, el estudio prospectivo sobre seguridad del uso de anestesia general en niños de la Clínica Mayo (MASK, Mayo Anesthesia Safety in Kids), junto con otros estudios a gran escala, han confirmado algunos datos obtenidos en los estudios experimentales que dieron sustento a la alerta emitida por la FDA. Así, las evidencias hasta ahora publicadas sugieren que el uso de anestesia general es seguro para el desarrollo cognitivo general del niño, aunque evidencian también alteraciones focalizadas en procesos cognitivos específicos que deben ser consideradas por el médico y la familia ante un procedimiento quirúrgico-anestésico.

Abstract General anesthetics are crucial drugs for surgical interventions, which are indicated to induce analgesia, diminish pain, and reduce anxiety in order to facilitate invasive procedures. In pediatric patients, benefits of general anesthetics also include abolishment of motility. Besides their probed benefits on surgery, the recent warning of the Food and Drug Administration (FDA) on the use of general anesthetics in children yielded a controversy on their potential neurotoxic effects. In this review, the main facts of the cerebral development are studied, and the available evidence concerning the use of general anesthesia on the neuropsychological development of children is analyzed. Most of the studies found were uncontrolled retrospective cohorts for which conclusions are difficult to obtain. However, a few group of controlled studies, including the Mayo Anesthesia Safety in Kids study (MASK), have partially supported the FDA warning. Cumulated evidence appears to support the safety use of general anesthetics, but no conclusive data supporting that it may induce massive effects on the cognitive development of exposed children has been reported. Important evidence suggests that specific cognitive functions may result altered under long-term expositions. Such data must be considered for those involved in anesthetic procedures.

Evaluation of the neurotoxic effects of intrathecal administration of (S)-(+)-Ketoprofen on rat spinal cords: randomized controlled experimental study / Avaliação dos efeitos neurotóxicos da administração intratecal do (S)-(+)-cetoprofeno em medula espinhal de rato: estudo experimental randômico e controlado

Abstract Background and objectives Intrathecal administration of non-steroidal anti-inflammatory drugs is more efficacious for post-operative pain management. Cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs like (S)-(+)-Ketoprofen, may be effective at lower intrathecal doses than parenteral ones. Preclinical safety regarding possible neurotoxicity associated with the intrathecal (S)-(+)-Ketoprofen was not evaluated. Here we analysed the neurotoxicity of intrathecally administered (S)-(+)-Ketoprofen in rats. Methods A randomized placebo-controlled experimental study was conducted. Sprague-Dawley rats (250-300 g) aged 12-16 weeks were randomly divided into 2 treatments [100 and 800 µg (S)-(+)-Ketoprofen] and control (sterile water) groups. Intrathecal catheters were placed via the atlantoaxial space in anesthetized rats. Pinch-toe tests, motor function evaluations and histopathological examinations of the spinal cord and nerve roots were performed at days 3, 7 and 21. Spinal cord sections were evaluated by light microscopy for the dorsal axonal funiculus vacuolation, axonal myelin loss, neuronal chromatolysis, neuritis, meningeal inflammation, adhesions, and fibrosis. Results Rats in all the groups exhibited normal pinch-toe testing response (score = 0) and normal gait at each observed time (motor function evaluation score = 1). Neurotoxicity was higher with treatments on days 3 and 7 than that on day 21 (2, 3, 0, p = 0.044; 2, 5, 0, p = 0.029, respectively). On day 7, the total scores reflecting neuronal damage were higher in the 800 µg group than those in the 100 µg and Control Groups (5, 3, 0, p = 0.048, respectively). Conclusion Intrathecal (S)-(+)-Ketoprofen caused dose-dependent neurohistopathological changes in rats on days 3 and 7 after injection, suggesting that (S)-(+)-Ketoprofen should not be intrathecally administered.

Resumo Justificativa e objetivos A administração intratecal de anti-inflamatórios não esteroides é mais eficaz no tratamento da dor pós-operatória. Anti-inflamatórios não esteroides, como o (S)-(+)-cetoprofeno, pode ser eficaz em doses intratecais inferiores às parenterais. A segurança pré-clínica relativa à possível neurotoxicidade associada ao (S)-(+)-cetoprofeno intratecal não foi avaliada. Neste estudo avaliamos a neurotoxicidade do (S)-(+)-cetoprofeno administrado por via intratecal em ratos. Métodos Conduzimos um estudo experimental randomizado e controlado por placebo em ratos Sprague-Dawley (250-300 g) com idades entre 12 e 16 semanas. Eles foram randomicamente divididos em dois grupos de tratamento [100 e 800 µg de (S)-(+)-cetoprofeno] e um de controle (água estéril). Cateteres intratecais foram colocados através do espaço atlantoaxial nos ratos anestesiados. Testes de pinça, avaliações da função motora e exames histopatológicos da medula espinhal e das raízes nervosas foram realizados nos dias 3, 7 e 21 do estudo. Os cortes da medula espinhal foram avaliados por microscopia de luz para vacuolização do funículo axonal dorsal, perda de mielina axonal, cromatólise neuronal, neurite, inflamação, aderências e fibrose das meninges. Resultados Em todos os grupos, os ratos exibiram resposta normal ao teste de pinça (pontuação = 0) e marcha normal em cada tempo observado (escore de avaliação da função motora = 1). A neurotoxicidade foi maior com os tratamentos nos dias 3 e 7 do que no dia 21 (2, 3, 0, p = 0,044; 2, 5, 0, p = 0,029, respectivamente). No dia 7, os escores totais refletindo o dano neuronal foram maiores no grupo com 800 µg que nos grupos com 100 µg e controle (5, 3, 0, p = 0,048, respectivamente). Conclusão A administração intratecal de (S)-(+)-cetoprofeno causou alterações neuro-histopatológicas dose-dependentes em ratos nos dias 3 e 7 após a aplicação e sugerindo que o (S)-(+)-cetoprofeno não deve ser administrado por via intratecal.

Colistin induced neurotoxity: a case report and review of literature / Neurotoxicidade induzida pela colistina: relato de caso e revisão de literatura

OBJECTIVE: To describe a case of neurotoxity associated to Colistin. CASE DESCRIPTION: A 29-year-old black male under treatment for urinary tract infection with identification of Klebsiella pneumoniae in urine culture resistant to all carbapenem antibiotics, presented visual turbidity, paresthesia on the face and upper left limb, slowed and discordant speech in the fourth day of Colistin use. Symptoms improved after reduction of the dose of colistin with adjustment for renal function, with complete reversion after discontinuation of the drug. CONCLUSIONS: Colistin-mediated neurotoxicity must be suspected in patients with altered mental status of unknown etiology and therapy promptly interrupted.

OBJETIVO: Descrever um caso de neurotoxidade associada à Colistina. DESCRIÇÃO DO CASO (desnecessário repetição): Um homem negro de 29 anos sob tratamento para infecção do trato urinário com identificação de Klebsiella pneumoniae (escrever corretamente) em cultura de urina resistente a carbapenêmicos, apresentou turvação visual, parestesia em face e membro superior esquerdo, discurso lento e discordante na quarto dia de uso da Colistina. Os sintomas melhoraram após a redução da dose de colistina com ajuste para a função renal, com reversão completa após a descontinuação do fármaco. CONCLUSÕES: A neurotoxicidade mediada por colistina deve ser suspeitada em pacientes com estado mental alterado de etiologia desconhecida e a terapia prontamente interrompida.

Por que a ingestão de carambola é proibida para pacientes com doença renal crônica? / Why eating star fruit is prohibited for patients with chronic kidney disease?

Resumo Novos estudos têm mostrado o mecanismo pelo qual a carambola (Averrhoa carambola) torna-se tóxica para indivíduos com doença renal crônica (DRC). O objetivo deste trabalho foi revisar a literatura atual sobre o tema. Trata-se de artigo de revisão, com publicações de 2000 a 2014 disponíveis em bases de dados científicas. Há relatos de que a neurotoxicidade ocorre devido à presença de oxalato na carambola; porém, achados recentes mostram que o efeito neurotóxico se dá pela toxina caramboxina, que parece inibir o sistema GABAérgico, que é o principal sistema inibitório do sistema nervoso central (SNC), envolvendo alterações como soluços e confusão mental, até quadros mais sérios como convulsões e morte. É importante a ação multiprofissional para alertar os pacientes com DRC quanto à proibição do consumo da carambola.

Abstract New studies have shown the mechanism by which the star fruit (Averrhoa carambola) becomes toxic to individuals with chronic kidney disease (CKD). The aim of this study was to review the current literature on the topic. This is a review article, with publications from 2000 to 2014 available in scientific database. There are reports that neurotoxicity is due to the presence of oxalate in star fruit, but recent findings show that the neurotoxic effect of the toxin is by caramboxin, which appears to inhibit the GABAergic system which is the major inhibitory system in the central nervous system (CNS), involving changes as sobs and confusion, to more serious conditions such as seizures and death. It is important to multidisciplinary action to alert patients with CKD as the prohibition of the star fruit consumption.

Efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo animal / Neurotoxic effect of aqueous extract of boldo (Peumus boldus) in an animal model

Objetivos : Evaluar el efecto neurotóxico del extracto acuoso de boldo (Peumus boldus) en un modelo experimental. Materiales y métodos. Se diseñó un experimento, que incluyó 20 ratas macho Holtzman de 250 ± 15 gr, distribuidas aleatoriamente en cuatro grupos: el control negativo recibió solución salina (SS) por vía oral (VO), el control positivo que recibió 6-hidroxidopamina por vía intracraneal (VIC) y SS por VO, el grupo experimental 1 recibió extracto acuoso de boldo (EAB) por VO y el grupo experimental 2 recibió 6-hidroxidopamina por VIC y EAB por VO, en todos los casos durante 21 días. Se realizó una evaluación neurológica, la cual tuvo tres componentes: a) clínico, evaluado con el test de rotarod, b) bioquímico, mediante la determinación de niveles séricos de ácido úrico, y c) histopatológico, por inmunohistoquímica para neuronas dopaminérgicas de sustancia negra. Se empleó la prueba de Kruskal Wallis y el test de Dunn para evaluar las diferencias entre los grupos. Resultados. Se encontró disminución significativa en el tiempo de latencia del test de rotarod entre los grupos control negativo y control positivo (p<0,01), control negativo y experimental 1 (p=0,09), control negativo y experimental 2 (p<0,01), control positivo y experimental 1 (p=0,04), y experimental 1 y 2 (p=0,09). En la determinación de ácido úrico no hubo diferencia significativa intergrupal. En el conteo neuronal hubo depleción de neuronas dopaminérgicas totales, pero sin diferencia intergrupal. Conclusiones. Se evidencio un efecto neurotóxico del extracto acuoso de boldo en ratas macho de la cepa Holtzman a nivel clínico.

Objectives. To assess the neurotoxic effect of the aqueous extract of boldo (Peumus boldus) in an experimental model. Materials and methods. 20 male Holtzman rats of 250 ± 15 g were randomized into four groups: the negative control received saline solution (SS) orally (PO), the positive control received 6-hydroxydopamine intracranially (IC) and SS by PO. Experimental group 1 received aqueous extract of boldo (AEB) by PO, and experimental group 2 received 6-hydroxydopamine intracranially and AEB by PO. The experiment lasted 21 days. A neurological assessment was performed which had three components: a) clinical, evaluated with the rotarod test, b) biochemical, by measuring serum levels of uric acid, and c) histopathology, by immunohistochemistry for substantia nigra dopaminergic neurons. The Kruskal Wallis test and the Dunn test were used to assess differences between groups. Results. A significant decrease was found in the latency time of the rotarod test between the negative and positive control group (p<0.01), negative control and experimental 1 (p=0.09), negative control and experimental 2 (p<0.01), positive control and experimental 1 (p=0.04), and experimental 1 and 2 (p=0.09). There was no significant intergroup difference in the identification of uric acid. There was a depletion of the total dopaminergic neurons in the neuronal count, without intergroup difference. Conclusions. A neurotoxic effect of aqueous extract of boldo was recognized at a clinical level in Holtzman male rats.

Heptachlor induced nigral dopaminergic neuronal loss and Parkinsonism-like movement deficits in mice

Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo.

Efeitos neurotóxicos de sulfato de magnésio intratecal / Neurotoxic effects of intrathecal magnesium sulphate / Efectos neurotóxicos de sulfuro de magnesio intratecal

JUSTIFICATIVA E OBJETIVOS: Avaliar os potenciais efeitos neurotóxicos em nível ultraestrutural desulfato de magnésio administrado por via intratecal em dose única ou múltipla. MÉTODOS: Estudo realizado com 24 ratos Sprague-Dawley, peso médio entre 250 e 300 g. Apósjejum de 4 horas, os ratos receberam 10 mg.kg-1 de cloreto de xilazina por via intraperitoneale, em seguida, foram divididos aleatoriamente em três grupos. Grupo I (n = 8) recebeu 0,9% desoro fisiológico normal, Grupo II (n = 8) recebeu uma injeção de 0,02 mL de sulfato de magnésioa 15% por via intratecal e Grupo III (n = 8) recebeu 0,02 mL de sulfato de magnésio a 15% umavez por dia durante sete dias. As injeções foram aplicadas dentro de 0,40x50 milímetros daárea lombar. Após sete dias, os animais foram sacrificados sob anestesia com uma injeção deformaldeído a 10% na aorta e os tecidos foram fixados. A medula espinal foi, então, examinadae histopatologicamente avaliada sob microscópio eletrônico. O teste de Kruskal-Wallis foi usadopara avaliação estatística. Um valor de p < 0,05 foi considerado estatisticamente significativo. RESULTADOS: Neurodegeneração significativa foi detectada nos ratos que receberam uma únicainjeção ou injeções repetidas de sulfato de magnésio, em comparação com o grupo controle. O escore na avaliação histopatológica desse grupo também foi alto. CONCLUSÃO: Com base no exame de microscopia eletrônica, descobrimos que a administraçãointratecal de sulfato de magnésio induziu neurodegeneração.

BACKGROUND AND OBJECTIVES: To assess the potential neurotoxic effects at the ultrastructural level of magnesium sulfate administered intrathecally as a single or multi-dose. METHODS: Our study was conducted with 24 Sprague-Dawley rats that weighed 250-300 g. After a 4-hour fast, the rats were given 10 mg.kg-1 xylazine chloride intraperitoneal and then randomly allocated into three groups. Group I (n = 8) received 0.9% normal saline, Group II (n = 8) was given one intrathecal injection of 0.02 mL of 15% magnesium sulphate, and Group III (n = 8) was given 0.02 mL of 15% magnesium sulphate once a day for seven days. The injections were given within 0.40x50 mm from the lumbar area. After seven days, the animals were sacrificed under anesthesia with an aortic injection of 10% formaldehyde and their tissues were fixed. The medulla spinalis was then examined and histopathologically evaluated under an electron microscope. The Kruskal-Wallis test was used for statistical evaluation. A value of p < .05 was considered to be statistically significant. RESULTS: Significant neurodegeneration was detected in rats given single or repeated magnesium sulphate injections compared to the control group. The histopathological evaluation score of this group was also high. CONCLUSIONS: Based on electron microscopic examination, we found that intrathecal magnesium sulphate administration induced neurodegeneration.

JUSTIFICATIVA Y OBJETIVOS: Evaluar los potenciales efectos neurotóxicos en nivel ultraestructural de sulfuro de magnesio administrado por vía intratecal en dosis única o múltiple. MÉTODOS: Estudio realizado con 24 ratones Spraque-Dawley, con un peso promedio entre los 250 y los 300 g. Después del ayuno de 4 horas, los ratones recibieron 10 mg.kg-1 de cloruro de xilazina por vía intraperitoneal y enseguida fueron divididos aleatoriamente en tres grupos. El grupo I (n = 8) recibió 0,9% de suero fisiológico normal, Grupo II (n = 8) recibió una inyección de 0,02 mL de sulfuro de magnesio al 15% por vía intratecal y Grupo III (n = 8) recibió 0,02 mL de sulfuro de magnesio al 15% una vez por día durante siete días. Las inyecciones fueron aplicadas dentro de 0,40x50 milímetros del área lumbar. Después de siete días, los animales fueron sacrificados con anestesia con una inyección de formaldehido al 10% en la aorta y los tejidos fueron pegados. La médula espinal se examinó y fue histopatológicamente evaluada bajo microscopio electrónico. El test de Kruskal-Wallis fue usado para la evaluación estadística. Un valor de p < 0,05 fue considerado estadísticamente significativo. RESULTADOS: La neurodegeneración significativa fue detectada en los ratones que recibieron una sola inyección o inyecciones repetidas de sulfuro de magnesio, en comparación con el grupo control. El puntaje en la evaluación histopatológica de ese grupo también fue alto. CONCLUSIONES: Basándonos en el examen de microscopía electrónica, descubrimos que la administración intratecal de sulfuro de magnesio indujo a la neurodegeneración.

Niveles de plomo en sangre en niños venezolanos publicaciones en artículos científicos (1993-2006) / Blood lead levels in venezuelan children reported in scientific articles

El objetivo de esta investigación fue realizar una revisión de los níveles de plomo en sangre en niños venezolanos reportados en los artículos científicos publicados entre los años 1993-2996. El estudio fue del tipo documental y las bases de datos consultadas fueron PubMed/MEDLINE, EBDCO, ProQuest, Scielo, REVENCYT, FUNDACID BC UC, utilizando las palabras clave: niños, níveles de plomo en sangre, revisión, Venezuela. En total fueron recopilados 13 artículos, el 85% de estos fueron del tipo descriptivo. La mayor proporción (39%) de estudios revisados fueron clasificados como ambientales. La media de las medias de los níveles de plomo en sangre reportadas en los estudios fue de 12,61 ± 3,95% µg/dL, IC95%[10,23; 14,99 µg/dL]. En el 84,6% de las investigaciones realizadas se observaron medias de plomo en sangre en niños mayores a su límite permisible (10 µg/dL) Esta investigación podría servir de evidencia sobre los niveles de plomo observados en niños venezolanos, contribuyendo con el análisis y discusión de futuras investigaciones.

The objetive of this research was to conduct a review of blood lead levels in venezuelan children reported in the scientific articles published between the years 1993-2006. A documentary study was carried out, databases consulted were PubMed/MEDLINE, EBSCO, ProQuest, Scielo, REVENCYT; FUNDACID BC UC, using key word: children, levels of blood lead, review, Venezuela. Were collected in total 13 articles, 85% of these were descriptive. The largest proportion (39%) of studies reviewed were classified as environmental. The average of the average levels of blood lead reported in the studies was 12.61 ± 3.95 µg/dL, IC95% [10.23; 14.99 µg/dL]. In the 84.6% of investigations carried out in children whit blood lead were it was observed an average of blood lead higher to the allowable limit (10 µg/dL). This research could provide evidence on the blood lead levels observed in venezuelan children, helping with the analysis and discussion of future research.

Using systematic reviews and meta-analyses to support regulatory decision making for neurotoxicants: lessons learned from a case study of PCBs / Utilizando revisões sistemáticas e meta-análise de apoio às decisões regulatórias para neurotóxicos: lições de um estudo de caso dos PCBs

We examined prospective cohort studies evaluating the relation between prenatal and neonatal exposure to polychlorinated biphenyls (PCBs) and neurodevelopment in children to assess the feasibility of conducting a meta-analysis to support decision making. We described studies in terms of exposure and end point categorization, statistical analysis, and reporting of results. We used this evaluation to assess the feasibility of grouping studies into reasonably uniform categories. The most consistently used tests included Brazelton's Neonatal Behavioral Assessment Scale, the neurologic optimality score in the neonatal period, the Bayley Scales of Infant Development at 5-8months of age, and the McCarthy Scales of Children's Abilities in 5-year-olds. Despite administering the same tests at similar ages, the studies were too dissimilar to allow a meaningful quantitative examination of outcomes across cohorts. These analyses indicate that our ability to conduct weight-of-evidence assessments of the epidemiologic literature on neurotoxicants may be limited, even in the presence of multiple studies, if the available study methods, data analysis, and reporting lack comparability.

Foram examinados estudos de grupo que avaliaram a relação entre a exposição pré-natal e neonatal aos bifenilos policlorados (PCB) e o desenvolvimento neuropsicomotor em crianças a fim de avaliar a viabilidade da realização de uma meta-análise para suporte à tomada de decisão. Nós descrevemos os estudos em termos de exposição, categorizações, análise estatística e elaboração de relatórios de resultados. Nós utilizamos esta avaliação para verificar a viabilidade de agrupar os estudos em categorias razoavelmente uniformes. Os testes mais utilizados foram Brazelton Neonatal Behavioral Assessment Scale, a pontuação de otimalidade neurológica no período neonatal, as Escalas Bayley de Desenvolvimento Infantil de 5 a 8 meses de idade, e as Escalas McCarthy de habilidades das crianças em 5 anos de idade. Apesar de administrar os mesmos testes com idades semelhantes, os estudos foram muito diferentes para permitir uma análise quantitativa significativa dos resultados entre grupos. Estas análises indicam que a nossa capacidade de realizar avaliações da literatura epidemiológica sobre neurotóxicos pode ser limitada - mesmo na presença de vários estudos - se não existe nenhuma forma de comparação com os métodos de estudo disponíveis e análise dos dados.

Abordagem inicial no atendimento ambulatorial em distúrbios neurotoxicológicos: parte III - solventes orgânicos / Initial approach to outpatient treatment of neurotoxicological disorders: Part III – organic solvents

Introdução: Milhões de pessoas são expostas diariamente aos solventes. Inúmeros solventes podem causar intoxicação aguda. Menos clara é a associação da exposição crônica e em baixas doses poder produzir alteração neurológica. Diversas atividades ocupacionais estão envolvidas com a sua exposição. Condição bastante diferente é o seu uso inadvertido com intuito alucinógeno. Método: Trata-se de revisão atualizada da literatura a partir de pesquisa na base de dados MEDLINE e LILACS. Também utilizou-se livros e documentos publicados em formato eletrônico.Discussão: Distúrbios neuromusculares, distúrbios do movimento, alterações cognitivo-comportamentais e neurofisiológicas têm sido relacionados a inúmeros agentes tóxicos nos últimos anos. A proposta deste artigo é revisar os principais distúrbios neurológicos associados à exposição crônica por solventes orgânicos. A fim de facilitar a abordagem inicial no atendimento ambulatorial aos distúrbios neurotoxicológicos foram confeccionadas tabelas descrevendo os principais agentes tóxicos, as fontes de exposição envolvidas e suas principais manifestações neurológicas. Conclusão: Tolueno, bissulfeto de carbono e n-Hexano são alguns solventes envolvidos nos distúrbios neurotoxicológicos, Contudo, fica evidente nesta revisão que são necessários novos estudos a fim de determinar a real associação destes e outros solventes nos distúrbios crônicos do sistema nervoso central e periférico.

Introduction: Millions of peoples are exposed to solvents every day. Most solvents cause acute intoxication. Less evident is the association of chronic exposure and in low doses in producing neurological disorders. Innumerable occupational activities are involved in the exposure to solvents. Their inadvertent use with hallucinogenous intention is an entirely different condition. Method: The method consists of an updated review of the literature based on research in the MEDLINE and LILACS databases, as well as books and documents published online. Discussion: Neuromuscular disorders, movement disorders, cognitive-behavioral and neurophysiological changes have been attributed to innumerable toxic agents in recent years. This article proposes to review the main neurological disorders associated with chronic exposure to organic solvents. To facilitate the initial approach to treatment of neurotoxicological disorders of outpatient, tables were devised to describe the main toxic agents, the sources of exposure involved and their main neurological manifestations. Conclusions: Toluene, carbon bisulfate and n-hexane are some of the solvents involved in neurotoxicological disorders. However, this review reveals the need for new studies to determine the real association of these and other solvents in chronic disorders of the central and peripheral nervous systems.

Abordagem inicial no atendimento ambulatorial em distúrbiosneurotoxicológicos. Parte II - agrotóxicos / Initial approach to outpatient treatment of neurotoxicological disorders. Part II – pesticides

Introdução: A venda de agrotóxicos no Brasil representa 86% do mercado consumidor da América Latina, com um faturamento anual que chega a US$ 7 bilhões. O desconhecimento e a falta de percepção dos riscos inerentes a utilização dessas substâncias é constatada com frequência aumentando as chances de intoxicação por tais agentes. Métodos: Trata-se de revisão atualizada da literatura a partir de pesquisa na base de dados MEDLINE e LILACS. Também utilizaram-se livros e documentos publicados em formato eletrônico. Resultados e discussão: Distúrbios neuromusculares, distúrbios do movimento, alterações cognitivo-comportamentais e neurofisiológicas têm sido relacionados a inúmeros agentes tóxicos nos últimos anos. A proposta deste artigo é revisar os principais distúrbios neurológicos associados à exposição crônica por agrotóxicos. A fim de facilitar a abordagem inicial no atendimento ambulatorial aos distúrbios neurotoxicológicos foram confeccionadas tabelas descrevendo os principais agentes tóxicos, as fontes de exposição envolvidas e suas principais manifestações neurológicas. Conclusão: Inseticidas, herbicidas, fungicidas e fumigantes são alguns agrotóxicos envolvidos nos distúrbios neurotoxicológicos. Contudo, fica evidente nesta revisão que são necessários novos estudos a fim de determinar a real associação destes e outros agrotóxicos nos distúrbios crônicos do sistema nervoso central e periférico.

Introduction: The sale of pesticides in Brazil represents 86% of the Latin American consumer market, with annual revenues reachingup to US$ 7 billion. Lack of knowledge and unawareness of the risks inherent to the use of these substances is frequently found, increasingthe possibility of intoxication by these agents. Methods: The method consists of an updated review of the literature based on research in theMEDLINE and LILACS databases, as well as books and documents published online. Results and discussion: Neuromusculardisorders, movement disorders, cognitive-behavioral and neurophysiologic alterations have been attributed to innumerable toxic agents in recentyears. This article proposes to review the main neurological disorders associated with chronic exposure to pesticides. To make easy the initialapproach to outpatient treatment of neurotoxicological disorders, tables were devised to describe the main toxic agents, the sources of exposureinvolved and their main neurological manifestations. Conclusion: Insecticides, herbicides, fungicides and fumigants are some of the pesticides involved in neurotoxicological disorders. However, this review reveals the need for new studies to determine the real association of these and other pesticides in chronic disorders of the central and peripheral nervous systems.

Neurotoxic Manifestations of an Overdose Intrathecal Injection of Gadopentetate Dimeglumine

The intravenous administration of gadopentetate dimeglumine (GD) is relatively safe and rarely causes systemic toxicity in the course of routine imaging studies. However, the general safety of intrathecal GD has not been established. We report a very rare case of an overdose intrathecal GD injection presenting with neurotoxic manifestations, including a decreased level of consciousness, global aphasia, rigidity, and visual disturbance.

Contrast agent neurotoxicity mimicking subarachnoid haemorrhage

We are presenting an unusual complication of the intravascular angiographic contrast agent in a 58-year-old male patient with the diagnosis of subarachnoid haemorrhage [SAH]. After cerebral angiography, his clinical condition deteriorates. Computed tomography scan of the brain showed the picture of SAH due to the contrast agent of extravasation. Appropriate treatment, with avoidance of additional contrast agent administration was resolved in complete neuroradiological recovery within 2 days

Morphine: axon regeneration, neuroprotection, neurotoxicity, tolerance, and neuropathic pain

Opioids have been used medicinally for millennia for their potent effects on nociception. However, the past 20 years have led to important insights into the influences and mechanisms of opioid actions, which are more extensive than merely analgesia, including human synthesis of opioids, critical roles of opioids during development and following nerve injury, and actions of different opiate alkaloids and their receptors. Due to the vast literature on opioids, the scope of this review has been limited to opioid actions in maintaining neuron viability during development, promoting neurological function following nerve injuries, in inflammation, disease and against ischemia; alleviating neuropathic pain; raising and lowering cellular immunity; and mechanisms modifying morphine tolerance.

Aracnoides trabecular, piamadre espinal humana y anestesia subaracnoidea / Trabecular arachnoid membrane, human spinal piamater and subarachnoid anesthesia

En los textos de anestesiología se aportan pocos detalles sobre la aracnoides trabecular y la piamadre espinal humana, a pesar de ser estructuras íntimamente relacionadas con los anestésicos locales administrados en una anestesia subaracnoidea. Complicaciones tales como el síndrome de cauda equina y el síndrome de irritación radicular transitorio posterior a la realización de bloqueos subaracnoideos, sumado a la alta permeabilidad que ha sido asociada con la piamadre, nos ha motivado a investigar sobre la ultraestructura de estas meninges. Método. Las muestras estudiadas se tomaron de cadáveres recientes y fueron examinadas por microscopía electrónica de transmisión y de barrido. Resultados. El trabeculado aracnoideo rodeaba a las raíces nerviosas, a la médula y a los vasos que se encontraban dentro del espacio subaracnoideo, limitando zonas. La piamadre estaba formada por un plano celular y por un compartimiento subpial. En el plano celular existían perforaciones naturales, especialmente en la región del cono medular y en las raíces nerviosas. Conclusiones. La inyección accidental de anestésicos locales dentro de las fundas que formaban el trabeculado aracnoideo podría justificar una dilución inadecuada de estas soluciones y el origen de síndromes neurotóxicos transitorios o permanentes. La alta permeabilidad de la piamadre podría deberse, en parte, a la existencia de perforaciones naturales, las cuales facilitarían un pasaje rápido de las sustancias introducidas en el líquido cefalorraquídeo hacia las raíces nerviosas y la médula espinal. En este caso, la membrana basal ubicada por debajo de las fibras colágenas del compartimiento subpial sería la única estructura limitante previa al tejido glio-neuronal de la médula.

Few details are to be found in anesthesiology texts concerning the trabecular arachnoid membrane and the human spinal pia mater in spite of being structures that are intimately related to local anesthetics administered in subarachnoid anesthesia. We were driven to investigate the ultrastructure of these meninges by complications such as the cauda equina syndrome and the transitory radicular irritation syndrome following subarachnoid blocks, added to the high permeability associated to the pia mater. Method. The samples analyzed were taken from recently deceased cadavers and were examined under transmission and scanning electron microscopy. Results. The arachnoid trabeculation surrounded the nerve roots, the spinal cord and the vessels within the subarachnoid space, limiting areas. The pia mater was formed by a cellular plane and by a sub-pial compartment. There were natural perforations in the cellular plane, particularly in the medullar cone region and the nerve roots. Conclusions. Accidental injection of local anesthetics into the sheaths formed by arachnoid trabeculation could be the cause of inadequate dilution of these solutions and the source of transitory or permanent neurotoxic syndromes. The high permeability of the pia mater could be partly due to the existence of natural perforations, which enable the quick passage of the substances introduced in the cerebrospinal fluid into the nerve roots and spinal cord. ln this case, the basal membrane located underneath the collagen fibers of the subpial compartment would be the only limiting structure before the glioneural tissue of the spinal cord.

Os textos de anestesiologia fornecem poucos detalhes sobre a aracnóide trabecular e a pia-máter espinhal humana, apesar delas serem estruturas intimamente relacionadas com os anestésicos locais administrados em uma anestesia subaracnóidea. Complicações tais como a síndrome de cauda eqüina e a síndrome de irritação radicular transitória posterior a bloqueios subaracnóideosas quais se soma a alta permeabilidade, que tem sido associada à pia-máter -levou-nos a pesquisar a ultraestrutura dessas meninges. Método. As amostras estudadas foram coletadas de cadáveres recentes e examinadas por microscopia eletrónica de transmissão e de varredura. Resultados. A trabeculação aracnóidea rodea va as raízes nervosas, a medula e os vasos no interior do espaço subaracnóide, limitando zonas. A pia-máter estava formada por um plano celular e um espaço subpial. No plano celular existiam perfurações naturais, especialmente na regiáo do cone medular e nas raízes nervosas. Conclusóes. A injeção acidental de anestésicos locais no interior das coberturas que formavam a trabeculação aracnoidea poderia justificar uma diluição inadequada das soluções e a origem de síndromes neurotóxicas transitórias ou permanentes. A causa da alta permeabilidade da pia-máter seria, em parte, a existencia de perfurações naturais que facilitariam a rápida passagem das substancias introduzidas no líquido cefalorraquiano para as raizes nervosas e a medula espinhal. Neste caso, a membrana basal localizada abaixo das fibras colágenas do espaço subpial seria a única estrutura limitante anterior ao tecido glio-neuronal da medula.