Impacto de la cirugía de la epilepsia infantil en el rendimiento intelectual / Impact of pediatric epilepsy surgery on intellectual efficiency

Introducción. La cirugía de la epilepsia podría ser una opción terapéutica muy prometedora para el control de las crisis en pacientes con crisis refractarias que no responden a la medicación. Otro factor importante a favor de la opción quirúrgica son los resultados cognitivos. Objetivo. Investigar la correlación entre los resultados tanto de las crisis como cognitivos tras la cirugía para tratar la epilepsiaen una población pediátrica.Pacientes y métodos. Se evaluó de manera retrospectiva a un total de 59 pacientes pediátricos antes y al menos seis meses después de la cirugía mediante la tercera edición de la escala de inteligencia para niños de Wechsler (escala global, escala verbal y escala manipulativa). Se dividió a los pacientes en dos grupos en función de la presencia o ausencia de la mejoría del control de las crisis tras la cirugía. Los datos que se recogían de cada niño incluían: tipo de epilepsia, etiología, edad de comienzo de la epilepsia, duración de la epilepsia y frecuencia de las crisis.Resultados. Al comparar los datos mediante un análisis multivariado de la varianza se observaron diferencias significativas en las escalas global, verbal y manipulativa preoperatorias (p = 0,01) con unos resultados mejores en el grupo con reducción de las crisis que en el grupo sin reducción de las crisis. El grupo con mejoría de las crisis consiguió una mejoría significativa en la escala manipulativa (p = 0,01) y el grupo sin mejoría de las crisis obtuvo un empeoramiento significativoen la escala verbal (p = 0,01).Conclusiones. Nuestros resultados sugieren que el éxito de la cirugía para el tratamiento de la epilepsia en la infancia cuando se logra un control de las crisis podría conllevar también una mejoría en la escala manipulativa, mientras que lapersistencia de las crisis podría empeorar la escala verbal (AU)

Introduction. Epilepsy surgery may be a promising alternative therapy for seizure control in patients with refractory seizures, resistant to medication. Cognitive outcome is another important factor in favor of the surgical decision. Aim. To investigate the correlation between seizure outcome and cognitive outcome after epilepsy surgery in a pediatric population. Patients and methods. A total of 59 pediatric patients were retrospectively assessed with the WISC-III (Full Scale, Verbal Scale and Performance Scale) before and, at least, 6 months after surgery. Patients were divided into two groups according whether or not improvement of seizure control after surgery. Data collected for each child included: epileptic syndrome, etiology, age at epilepsy onset, duration of epilepsy and seizure frequency. Results. Comparison using a MANOVA test revealed significant differences across pre-operative Full Scale, Verbal Scale and Performance Scale (p = 0.01) with seizure reduction group performing better than no seizure reduction group. Seizureimprovement group achieved significant Performance Scale improvement (p = 0.01) and no seizure improvement groupshowed significant Verbal Scale worsened after surgery (p = 0.01).Conclusions. Our results suggest that the success of the epilepsy surgery in childhood when the seizure control is achieved may also provide an improvement in the Performance Scale whereas the seizure maintenance may worsen the Verbal Scale (AU)

When your child with epilepsy die suddenly: febrile seizures are part of the process? / Quando seu filho com epilepsia morre subitamente: crises febris fazem parte do processo?

Febrile seizures (FS) affect almost 2-5 percent of children and factors related to an increase susceptibility of children to FS may involve an imbalance of inflammatory cytokines and genetic factors. FS had low morbidity, but may be associated with the occurrence of late chronic epilepsy. Here we describe factors related to FS and its possible correlation with SUDEP.

Crises febris (CF) afetam aproximadamente 2-5 por cento das crianças e os fatores envolvidos com essa maior susceptibilidade das crianças às CF podem estar relacionados com uma ação inadequada de citocinas inflamatórias, além de fatores genéticos. As CF têm baixa morbidade, mas podem estar associadas à ocorrência de epilepsia crônica. Nós discutiremos os fatores relacionados com CF, considerando-se sua possível associação com SUDEP.

Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks.

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

Fish consumption, contaminants and sudden unexpected death in epilepsy: many more benefits than risks / Consumo de peixe, contaminantes e morte súbita em epilepsia: mais benefícios do que riscos

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.

Pessoas com epilepsia têm um risco aumentado de morrer de forma prematura e a causa mais comum de morte relacionada à epilepsia encontra-se na categoria de morte súbita inesperada em epilepsia (SUDEP). SUDEP é um problema significativo para pacientes com epilepsia crônica não controlada. O principal objetivo nas pesquisas em SUDEP é o desenvolvimento de métodos capazes de levar à sua prevenção e ações outras que não medicamentosas e cirúrgicas que podem ser úteis. Os aspectos nutricionais, como por exemplo, a deficiência do ácido graxo ômega-3 pode ter um papel interessante neste cenário. Alguns estudos animais e clínicos têm sugerido que os ácidos graxos ômega-3 podem ser úteis na prevenção e no tratamento da epilepsia e, consequentemente, na SUDEP. Os únicos alimentos que contêm grandes proporções de ômega-3 são os frutos do mar (peixes e mariscos). No entanto, alguns peixes podem estar contaminados com metilmercúrio, o que pode levar a um efeito contrário ao benefício trazido pelos ácidos graxos ômega-3. Aqui, resumimos o conhecimento do papel do consumo de peixe nas pesquisas em epilepsia.

Quantitative study of the response to genetic selection of the Wistar audiogenic rat strain (WAR).

To study the relationship between genetics and epilepsy, Wistar rats susceptible to audiogenic seizure were selected from the main breeding stock of the Ribeirão Preto School of Medicine at the University of São Paulo, Brazil, and inbred. The criteria for selection were the highest seizure severity index (SI) and shortest latencies of the first running fit (LI). Because behavioral response to sound stimulation (120 dB) at 70 to 78 days of age was very stable, SI and LI were evaluated within this age range. Analysis of 9450 observations in 1575 animals from the 3rd to 17th generations demonstrated significant effects of generation, parity, and litter on SI and of generation and litter on LI. The SI and LI averages were, respectively, 37.13 and 22.82 s in the 3rd generation and 83.06 and 7.84 in the 17th generation. Heritabilities of both characters were estimated, by maximum likelihood, as 0.37 +/- 0.066 and 0.44 +/- 0.059, respectively. Because a significant regression related individual breeding values for both SI and LI to generation number, we concluded that genetic selection has a positive impact on the traits analyzed. Therefore, the Wistar audiogenic rat (WAR) strain appears, as per the 17th to 20th generations of genetic selection to be an audiogenic rat strain suitable for epilepsy studies.

Time evolution of acoustic 'information' processing in the mesencephalon of Wistar rats.

A traditional analysis of intra-encephalic auditory evoked potentials does not highlight the dynamical evolution of the auditory 'information' processing in neither time nor space. This work presents a method for tracing such signal evolution throughout the primary auditory pathway in the mesencephalon of adult anesthetized Wistar rats, using a unilateral 3 kHz tone burst stimulus. The results of the acoustic evoked potentials mapping are presented as conventional 20 ms recordings and re-analyzed in intervals of 1 ms-time windows. The parameter used, as an 'activity' correlate, was the maximum/minimum voltage difference obtained from each time window. The methodology used clearly indicates sequential signal propagation from the dorsal and ventral nuclei of the lateral lemniscus up to the inferior colliculus.

[Compulsory notification of cysticercosis in Ribeiräo Preto-SP, Brazil]. / Notificação compulsória da cisticercose em Ribeirão Preto-SP.

Cysticercosis is a severe public health problem in several regions of Asia, Africa and Latin America. Epidemiologic studies based on the frequency of cases observed in specialized neurology, neurosurgery and computed tomography services, at autopsy and in seroepidemiologic studies do not permit the determination of the true prevalence of the disease in the population. The objective of the present study was to investigate the prevalence of cysticercosis by compulsory notification. The coefficient of prevalence was 54 cases/100,000 inhabitants in the municipality of Ribeirão Preto. The results also indicated that cysticercosis is not under control in our region since 21% of cases presented the active form of the disease. Compulsory notification proved to be a valuable resource for the epidemiologic study of cysticercosis, also permitting the mapping of more affected areas for a better direction of prevention strategies.

Diuresis and natriuresis in non-seizing and in kindled rats from a genetically audiogenic susceptible strain.

Audiogenic seizures are evoked by acoustic stimulation in susceptible (S) but not in resistant (R) rats. Repeated audiogenic seizures recruit limbic areas, a model called audiogenic kindling. In order to evaluate excretory patterns (urinary volume, Na+ and K+ excretion), S and R animals were non-stimulated, submitted to one (acute) or 10 (kindled) stimulations or to two aqueous overloads (5% b.w.). Non-stimulated S animals displayed a significant increase (p < 0.05) in Na+ excretion at 60, 80, 100 and 120 min. Acutely stimulated S animals showed greater natriuresis than non-stimulated animals at 40, 60, 80 and 100 min. Kindled S animals displayed the greatest natriuresis (p < 0.005) at 40, 60, 80, 100 and 120 min and the highest diuretic response (p < 0.05) at 40, 60 and 80 min. Abnormalities of the endogenous hydroelectrolytic profile of non-stimulated S animals and their overt expression in kindled rats may be related to alterations in neuroendocrine systems regulating hydroelectrolytic balance, in addition to the long-lasting effects of kindled seizures.

NMDA-dependent audiogenic seizures are differentially regulated by inferior colliculus subnuclei.

Wistar rats were classified as susceptible (S) and resistant (R) to audiogenic seizures (AS) by evaluation of their response to high intensity sound stimulation (110.3 dB). R rats usually do not respond with any convulsive behavior to sound stimulation, whereas S animals develop a complex wild running sequence plus tonic-clonic seizure patterns after sound stimulation. Thus, R rats were injected with phosphate buffer (PB; 0.2 microliter) or N-methyl-D-aspartate (NMDA) in three different doses (2.0 micrograms, 2.5 micrograms and 3.0 micrograms/0.2 microliter) into central ventral or cortical dorsal inferior colliculus (IC) nuclei. Dose-response curves were evaluated by means of an ethological method in which behavioral sequences typical of S and R animals were quantitated. Animals displayed more severe spontaneous audiogenic-like seizures with the dose of 2.5 micrograms/0.2 microliter NMDA, which were potentiated by the acoustic stimulus. Significant differences were apparent between central and cortical nuclei and more severe seizures were observed in IC cortical microinjected animals. These audiogenic seizures were blocked with microinjections of 2-amino-7-phosphono-heptanoate (AP7) applied just before 2.5 micrograms NMDA microinjections into central or cortical nuclei. In S rats, AP7 totally blocked AS when microinjected into the central IC and partially, but significantly, blocked AS when applied into the cortical IC nucleus. In the last case, wild running was still present in 100% of the animals after AP7 treatment. These data may suggest an NMDA-dependent differential participation of IC subnuclei in the development of AS.

Midbrain substrates of audiogenic seizures in rats.

Audiogenic seizures (AS) are a rodent model of generalized tonic-clonic seizures, induced in susceptible (S) animals by high intensity (110 dB) acoustic stimulation. Resistant (R) animals do not respond to the sound with any seizure-related behavior, but they display facial automatisms and grooming clusters. Genetic selection and neuroethology are the basic tools used in our laboratory to perform behavioral analysis of AS S and R animals. Based upon selective lesion and microinjection (GABA, clobazam, NMDA) studies of substantia nigra (SN), inferior colliculus (IC), superior colliculus (SC), and on specific knife cuts at midcollicular levels, we have suggested differential roles for these substrates in the origin and spreading of AS. The IC central nucleus is suggested to be the most critical area involved in the afferent pathway whose activation is necessary for AS origin. IC cortical nuclei seem to be the most important structures involved in the transduction of sensory to motor activity. SC, SN and other reticular subnuclei are suggested to be modulators or components of the efferent pathway. Although the midbrain is considered to be the only network necessary for acute AS origin, both emotion-linked acoustic memories and plastic changes linked to audiogenic kindling involve midbrain-forebrain connections. This paper reviews the behavioral manifestations of acute and chronic AS, our contribution to the knowledge of some AS neurobiological midbrain substrates and the suggested implications of midbrain-forebrain interactions typical of AS kindling.

Thoracic lymph node metastasis and carcinomatous lymphangitis after inoculation of Walker 256 tumor through the trachea.

1. Experimental models of carcinomatous lymphangitis have not been described. This is an important clinical entity which usually results in the patients' death, although its natural history is still controversial. This study was undertaken to investigate whether the pattern of lung involvement after Walker 256 tumor inoculation through the trachea is a good model of carcinomatous lymphangitis. 2. Fifty male Wistar rats were inoculated through the trachea with 2.5 x 10(6) Walker 256 tumor cells and killed in groups of 5 animals each at 6 h and on days 1, 3, 7, 14, 21, 28, 35, 45, and 60 of the experiment. The lungs and thoracic lymph nodes were examined by light microscopy. 3. There were no tumors in the 25 animals killed before the 21st day of the experiment. The remaining 25 rats were sacrificed after 3 weeks of the experiment; 52% of them displayed thoracic lymph node metastases, and 40% developed a mild carcinomatous lymphangitis. The lung involvement did not correlate with respiratory distress, tumor dissemination or additional histological abnormalities. 4. We conclude that invasion of the lung is possible after intratracheal tumor cell inoculation, and that spreading follows a lymphatic pattern. This finding establishes this approach as a viable experimental model of carcinomatous lymphangitis. New approaches to increase the intensity and frequency of lung involvement, as well as the development of respiratory distress should be pursued in order to improve the efficiency of this model.

Thoracic lymph node metastasis and carcinomatous lymphangitis after inoculation of Walker 256 tumor through the trachea

1. Experimental models of carcinomatous lymphangitis have not been described. This is an important clinical entity which usually results in the patients' death, although its natural history is still controversial. This study was undertaken to investigate whether the pattern of lung involvement after Walker 256 tumor inoculation through the trachea is a good model of carcinomatous lymphangitis. 2. Fifty male Wistar rats were inoculated through the trachea with 2.5 x 10(6) Walker 256 tumor cells and killed in groups of 5 animals each at 6 h and on days 1, 3, 7, 14, 21, 28, 35, 45, and 60 of the experiment. The lungs and thoracic lymph nodes were examined by light microscopy. 3. There were no tumors in the 25 animals killed before the 21st day of the experiment. The remaining 25 rats were sacrificed after 3 weeks of the experiment; 52 per cent of them displayed thoracic lymph node metastases, and 40 per cent developed a mild carcinomatous lymphangitis. The lung involvement did not correlate with respiratory distress, tumor dissemination or additional histological abnormalities. 4. We conclude that invasion of the lung is possible after intratracheal tumor cell inoculation, and that spreading follows a lymphatic pattern. This finding establishes this approach as a viable experimental model of carcinomatous lymphangitis. New approaches to increase the intensity and frequency of lung involvement, as well as the development of respiratory distress should be pursued in order to improve the efficiency of this model

Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. II. Effects of nigral clobazam microinjections.

Male Wistar rats were classified as susceptible (S) and resistant (R) to audiogenic seizures (AS) by evaluation of their response to high-intensity sound stimulation (110.3 dB). R rats injected with bicuculline into the inferior colliculus (IC) preferentially displayed audiogenic-like seizures with gyri, jumping and atonic falling, without important tonic-clonic components but with postictal contralateral asymmetry and hyperreactivity. These audiogenic-like seizures were blocked by clobazam microinjection into the substantia nigra (SN) and partially modified by SN vehicle injection. Injection of vehicle or clobazam into the SN of susceptible rats (S) did not modify the occurrence of AS. This may suggest the participation of GABAergic regulation in the development of audiogenic-like seizures in R rats and a defect in GABAergic neurotransmission in S rats.

Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. I. Effects of midcollicular knife cuts.

Audiogenic seizures (AS) are a model of generalized tonic-clonic seizures. The inferior colliculus (IC) and the GABAergic neurotransmission seems to be the most critical site and neurotransmitter system, respectively, of the auditory midbrain involved in AS origin and development. Thus, audiogenic-like seizures are evoked by GABAA antagonists such as bicuculline (BIC). Wistar audiogenic AS resistant (R) rats were sham-transected through the midcollicular line and microinjected with IC bicuculline (BIC; 80 ng/0.2 microliters) (n = 8); transected through the midcollicular line and microinjected with IC saline 0.9% (n = 8); transected through the cortex above the midcollicular line and microinjected with IC BIC (n = 3); transected through the midcollicular line up to 6.0 mm depth and microinjected with IC BIC (80 ng/0.2 microliters or 120 ng/0.3 microliters (n = 8). Wistar AS susceptible (S) rats were submitted to cortical transections (n = 8) and midcollicular transections (n = 7). Animals were studied by means of an ethological method before and after microinjections and/or transections in order to evaluate possible pathways in the AS-like evoked seizures. Bicuculline-evoked seizures were very similar to those evoked by acoustic stimulation, but lacked the tonic-clonic component. No modification in animal behavior was observed in the presence of sound, once the AS-like behavior was initiated. A small percentage of the animals, however, presented procursive behavior which was increased by sound. The IC BIC-evoked patterns were almost totally blocked by midcollicular but not cortical transections. Furthermore, midcollicular but not cortical transections blocked the tonic-clonic component of AS in genetically S animals without modifying the wild running component. These data suggest that the inferior colliculus-superior colliculus connection may be involved in the sensorimotor transduction necessary for AS-like behaviors.

New insights into behavioral evaluation of audiogenic seizures. A comparison of two ethological methods.

Wistar male rats were tested for susceptibility to audiogenic seizures (AS) and classified into sensitive (S) and resistant (R) groups by means of a severity index (SI). Susceptible animals were those which displayed wild running behavior (gyri, jumping and atonic falling) followed by generalized tonic-clonic seizures and consequently had an SI = 0.85 (maximum; n = 10). Resistant animals were considered those with no convulsive response to the acoustic stimulation having an SI = 0 (n = 10). Behavioral sequences of susceptible and resistant animals were recorded and analyzed using two ethological methods which basically considered behavior item frequency and statistical interactions of sequential patterns. Both methods include the concept of cluster analysis but do not include a simultaneous analysis of behavior frequency and time spent in each behavior. Thus, a third method is proposed to graphically display both frequency and temporal patterns in a more complex cluster analysis. The methods discussed here allow comparisons of behavioral sequences in a given experimental situation such as susceptible against resistant animals, acute and chronic seizures, comparison of pre- and postdrug effects, etc. Consequently, they may be the micro-behavioral substrate for correlation with contemporary molecular analysis of epileptic seizures.

Epilepsia experimental: da análise comportamental à biologia molecular / Experimental epilepsy: behavioral analysis to molecular biology

A epilepsia é uma patologia neurológica que afeta milhöes de pessoas em todo o mundo, sendo que 25 por cento destes, continuam apresetnado convulsöes, apesar do tratamento medicamentoso. Nas últimas décadas tem ocorrido um desenvolvimento importante nas pesquisas na área da fisiopatologia das epilepsias, mas seus mecanismos moleculares ainda säo desconhecidos. Ainda é difícil correlacionar aspectos clínicos das epilepsias com mecanismos neurais, porque o progresso nas técnicas de biologia molecular näo foram seguidos por uma evoluçäo concomitante da análise comportamental. Este trabalho tem como objetivo revisar a avaliaçäo comportamental nas pesquisas sobre epilepsia e sua correlaçäo com a biologia molecular