Reducing VNS stimulation parameters: Is it safe?

Introduction Vagal nerve stimulation (VNS) is an adjuvant therapy used in the treatment of patients with refractory epilepsy who are not candidates for resective surgery or who have limited results after surgical procedures. Currently, there is enough evidence to support its use in patients with various types of epilepsy. Therefore, the present study was conducted to explore the possibility of optimizing therapy by reducing the consumption of the system's battery. Methods The prospective and double-blind analysis consisted in the evaluation of 6 patients submitted to VNS implantation for 3 months, followed by adjustment of the stimulation settings and continuity of follow-up for another month. The standard protocol was replaced by another with a frequency value of 20 Hz instead of 30 Hz to increase battery life. The safety of this procedure was evaluated through the assessment of two main variables: seizures and side effects. Results The stimulation at 20 Hz showed 68% reduction in the incidence of seizures (p»0.054) as well as low incidence of side effects. Conclusion The present study suggests that the reduction of the stimulation frequency from 30 to 20 Hz is a safe procedure, and it does not compromise the effectiveness of therapy.

The antiepileptic activity of Safranal in kindling model of epilepsy in male rats

Abstract Recent studies suggested that safranal exerts anticonvulsant properties. The present study aimed to investigate the effect of safranal on epileptic activities in the amygdala electrical kindling model in male rats. Animals were implanted with a recording electrode on the skull and a tripolar in the amygdala. After 10 days of recovery, the afterdischarge (AD) threshold of each animal was determined and stimulated once daily the AD threshold for full kindling development. Then, parameters including afterdischarge duration (ADD), stage 4 latency (S4L), stage 5 duration (S5D), and stimulation threshold were determined before and after injection of safranal (0.05, 0.1, 0.2 ml/ kg; i.p). While the dose of 0.05 ml/kg had no significant effect, the dose of 0.1 ml/kg increased the AD threshold as well as S4L and decreased the S5D (P<0.05). Injection of 0.2 ml/kg of the safranal significantly decreased the ADD and S5D (P<0.05) and 83.3% of animals had no stage 4 and stage 5 of kindling (P<0.001). Based on the obtained data safranal has anticonvulsant effects dosedependently. It seems that a dose of 0.2 ml/kg is the minimum effective dose. Further investigation is warranted to conduct the clinical implications for the treatment of epileptic disorders

Anesthetic management of a patient with 15q tetrasomy for dental treatment / Manejo anestésico de paciente com tetrassomia 15q para tratamento odontológico

Abstract Background and objectives 15q tetrasomy is a chromosomal abnormality that is a part of the heterogeneous group of extra structurally abnormal chromosomes. This syndrome is characterized by epilepsy, central hypotonia, developmental delay and intellectual disability, and autistic behavior. This is the first report of the anesthetic management of a patient with this syndrome. Case report We administered general anesthesia for dental treatment in a patient with 15q tetrasomy. Conclusions Appropriate planning for the prevention of complications such as seizures and hypotonia, and for delayed emergence from anesthesia, is required. Specifically, choosing short-acting drugs that do not induce seizures, together with suitable monitoring, resulted in successful anesthetic management of the patient with 15q tetrasomy.

Resumo Justificativa e objetivos Tetrassomia 15q é uma anomalia cromossômica que faz parte do grupo heterogêneo de cromossomos extras, estruturalmente anormais. Essa síndrome é caracterizada por epilepsia, hipotonia central, atraso no desenvolvimento e deficiência intelectual e comportamento autista. Este é o primeiro relato do manejo anestésico de um paciente com essa síndrome. Relato de caso Administramos anestesia geral para tratamento odontológico em um paciente com tetrassomia 15q. Conclusões Um planejamento adequado para prevenir complicações como convulsões e hipotonia e para emergência tardia da anestesia é necessário. O manejo anestésico bem-sucedido do paciente com tetrassomia 15q foi o resultado específico da escolha de fármacos de curta duração que não induzem convulsões e monitoração adequada.

Epilepsia asociada al accidente cerebrovascular / Post-stroke epilepsy

El accidente cerebrovascular (ACV) es la causa más común de convulsiones y epilepsia observada en estudios poblacionales de adultos. Las convulsiones ocurren dentro de las 24 horas posteriores al ACV en un alto porcentaje de pacientes. La patogénesis de estas convulsiones de inicio temprano puede estar relacionada con cambios iónicos locales y liberación de altos niveles de neurotransmisores excito-tóxicos en el área lesionada. Una lesión permanente con cambios en la excitabilidad neuronal parece ser responsable de convulsiones de inicio tardío después del ACV. Los factores de riesgo más comúnmente identificados con el comienzo agudo o tardío de las convulsiones post ACV son la gravedad y la localización cortical. La mayoría de las convulsiones post ACV son focales al inicio pero pueden generalizarse secundariamente, el estatus epiléptico es poco frecuente. La eficacia de las drogas antiepilépticas para estas convulsiones no ha sido rigurosamente evaluada en estudios controlados, aunque la mayoría de las convulsiones pueden ser controladas con un solo agente. Dada la frecuencia relativamente baja de convulsiones recurrentes después del ACV y la ausencia de predictores absolutos de epilepsia post ACV, la decisión de cuándo tratar a los pacientes con una convulsión después de un ACV es difícil.

Stroke is the most common cause of seizures and epilepsy in population stuies of adults. Seizures occur within 24 hours of the stroke in a high percent of patients. The pathogenesis of these early-onset seizures may be related to local ion shifts and release of high levels of excitotoxic neurotransmitters in the area of ischemic injury. The risk of late-onset seizures may increase over time, an underlying permanent lesion that leads to persistent chnges in neuronal excitability appears to be responsible for late-onset seizures after stroke. The most consistently identified risk factors for acute and late post-stroke seizures are stroke severity and cortical location. Most seizures following stroke are focal at onset, but secondary generalization is common, particularly in patients with late-onset seizures. Status epilepticus is relatively uncommon. The efficacy of antiepileptic drugs for these post-stroke seizures has not been rigorously assessed in controlled trials, although most seizures can be controlled with a single agent. Given the relatively low frequency of recurrent seizures after stroke, and an absence of absolute predictors of poststroke epilepsy, the decision of when to treat patients for a post-stroke seizure is difficult.

Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith / Apesar do desapontamento com a morte súbita cardíaca nas epilepsias, os epileptologistas mantêm a fé

ABSTRACT Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with intractable epilepsy. Probably, optimization of seizure control will prevent some of these deaths. Briefly, we integrated in this paper some data about the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP.

RESUMO A morte súbita nas epilepsias (SUDEP) é a causa mais comum de morte em indivíduos com epilepsia refratária. Provavelmente, o controle das crises epilépticas irá evitar algumas dessas mortes. Resumidamente, nós descrevemos nesse artigo alguns dados sobre a epidemiologia, fatores de risco, etiologia e medidas preventivas na SUDEP.

Anterior temporal lobectomy versus selective amygdalohippocampectomy in patients with mesial temporal lobe epilepsy / Lobectomia temporal anterior versus amigdalohipocampectomia seletiva para epilepsia de lobo temporal mesial

ABSTRACT Objective To contribute our experience with surgical treatment of patients with mesial temporal lobe epilepsy (mTLE) undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SelAH). Method This is a retrospective observational study. The sample included patients with medically refractory mTLE due to unilateral mesial temporal sclerosis who underwent either ATL or SelAH, at Hospital de Clinicas – UFPR, from 2005 to 2012. We report seizure outcomes, using Engel classification, cognitive outcomes, using measurements of verbal and visuospatial memories, as well as operative complications. Result Sixty-seven patients (33 ATL, 34 SelAH) were studied; median follow-up was 64 months. There was no statistically significant difference in seizure or neuropsychological outcomes, although verbal memory was more negatively affected in ATL operations on patients’ dominant hemispheres. Higher number of major complications was observed in the ATL group (p = 0.004). Conclusion Seizure and neuropsychological outcomes did not differ. ATL appeared to be associated with higher risk of complications.

RESUMO Objetivo Contribuir com nossa experiência para o tratamento cirúrgico de pacientes com epilepsia do lobo temporal mesial submetidos a lobectomia temporal anterior (LTA) ou amigdalohipocampectomia seletiva (AHS). Método Estudo retrospectivo observacional. Foram incluídos pacientes com epilepsia refratária devido a esclerose mesial temporal unilateral, submetidos a LTA ou AHS no Hospital de Clínicas – UFPR, entre 2005-2012. Foram comparados os resultados cognitivos (análises de memórias verbal e visuoespacial), controle de crises (Engel) e complicações cirúrgicas. Resultados Sessenta e sete pacientes (33 LTA, 34 AHS) foram estudados; o período de acompanhamento médio foi de 64 meses. Não houve diferença no controle das crises ou resultado neuropsicológico, mas a memória verbal foi mais negativamente afetada nos pacientes submetidos à LTA no hemisfério dominante. Maior número de complicações graves ocorreu no grupo de LTA (p = 0.004). Conclusão Controle de crises e resultados neuropsicológicos não diferiram. LTA pareceu estar associada a um maior risco cirúrgico.

Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom / A ressecção total de gliomas temporais de baixo grau é um importante fator no controle das crises convulsivas

Objective To present a surgical series of patients with low grade temporal gliomas causing intractable epilepsy, focusing on long-term seizure outcome.Method A retrospective study was conducted with patients with temporal low-grade gliomas (LGG).Results Sixty five patients with were operated in our institution. Males were more affected than females and the mean age at surgery was 32.3 ± 8.4 (9-68 years). The mean age at seizure onset was 25.7 ± 9.2 (11-66 years). Seizure outcome was classified according with Engel classification. After one year of follow up, forty two patients (64.6%) were Engel I; seventeen (26.2%) Engel II; four (6.2%) Engel III and two (3.1%) Engel IV. Statistically significant difference in seizure outcome was obtained when comparing the extension of resection. Engel I was observed in 39 patients (69.6%) with total resection and in only 3 (33.3%) patients with partial resection.Conclusion Gross-total resection of temporal LGGs is a critically important factor in achieving seizure-freedom.

Objetivo Apresentar uma série cirúrgica de pacientes com gliomas temporais de baixo grau, causando epilepsia de difícil controle.Método Estudo retrospectivo de pacientes com diagnóstico de glioma temporal de baixo grau temporais.Resultados 65 pacientes com foram operados em nossa instituição. A média de idade de início das crises foi de 25,7 ± 9,2 (11-66 anos). Após um ano de acompanhamento, quarenta e dois pacientes (64,6%) estavam Engel I; dezessete (26,2%) Engel II; quatro (6,2%) Engel III e dois (3,1%) Engel IV. Houve diferença estatisticamente significativa no resultado do controle das crises quando se compara a extensão da ressecção. Engel I foi observada em 39 pacientes (69,6%) com a ressecção total e em apenas 3 (33,3%) pacientes com ressecção parcial.Conclusão A ressecção total de glioma temporal de baixo grau temporais é um fator extremamente importante no controle das crises.

Isolation of compound and CNS depressant activities of Mikania scandens Willd with special emphasis to brain biogenic amines in mice.

Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.

Update in the management of severe traumatic brain injury

Traumatic brain injury is the main cause of death and disability in the young population, which presumes a large number of years of potential life lost and a great economic impact. Vital and functional outcomes after suffering a traumatic brain injury depend both on the severity of the initial biomechanical impact (primary injury) and on the presence and the severity of systemic or intracranial insults that magnify and/or produce new brain injuries, the so-called secondary injuries. Currently, no treatment in effective in improving functional recovery, except for usual medical care. Therefore, the main purpose of the care provided to a patient with severe cranial trauma is based on preventing and treating secondary brain injuries by maintaining an adequate cerebral perfusion and oxygenation. Increased intracranial pressure is associated with mortality and with unfavorable functional outcomes is patients with severe traumatic brain injury. The main clinical practice guidelines recommend using a number of staggered therapeutic measures. However, although these measures seem to be efficient in reducing intracranial pressure, this effect is not often translated into clinical improvement. This review describes the essential principles of the management of patients with severe traumatic brain injury in intensive care units.

Complications of post-operative seizure prophylaxis in patients submitted to cranial irradiation

The clinical status of patients with malignant intracranial tumors, such as high-grade gliomas, is often aggravated by seizure activity. Phenytoin is typically employed as prophylactic anticonvulsant in this setting. In such patients, severe systemic drug reactions such as erythema multiforme (EM) may occur. However, in a subgroup of patients with brain radiation therapy, EM-like lesions appear to develop in an increased ratio. The acronym ‘EMPACT’ (E: erythema; M: multiform; associated with P: phenytoin; A: and; C: cranial, radiation; T: therapy) has been suggested to best describes this syndrome. In this article, the authors present a case report of a patient treated with phenytoin for seizure prophylaxis, during the post-operative period following resection of a malignant glioma, and who presented a severe cutaneous rash, evolving with serious consequences due to abrupt change of seizure medications. Because of these predictable complications we abandoned our routine institutional protocol which employed phenytoin for seizure prophylaxis for patients in the post-operative period following malignant tumor resection and which expect to be irradiated in the near future. Once both carbamazepine and barbiturates show cross-sensitivity with phenytoin and may interfere with serum levels of chemotherapy drugs, we now advocate, as other worldwide renown neuro-oncological centers, the use of valproate gabapentin, or alternatively, as recent literature guidelines suggests levetiracetam (keppra), for seizure prophylaxis in this select subset of patients.

El estado clínico de los pacientes con tumores malignos intracraneales, como los gliomas de alto grado, es a menudo agravado por la actividad convulsiva. La fenitoína es normalmente empleadaa como anticonvulsivante profiláctico en esto contexto. En estos pacientes, graves reacciones sistémicas, como eritema multiforme (EM) puedem ocurrir. Sin embargo, en un subgrupo de pacientes con terapia de radiación en el cerebro, lesiones de EM, parece que se desarrollan en una proporción mayor. ‘EMPACT’ La sigla (E: eritema, M: multiforme; asociados con P: fenitoína; A: y C: la radiación craneal, T: La terapia) Se ha sugerido que mejor describe este síndrome. En esto artículo, los autores presentan un caso clínico de un paciente tratado con fenitoína para la profilaxia de convulsiones, durante el período post-operatorio después de la resección de un glioma maligno, y que presenta una erupción cutánea grave, que evoluciona con consecuencias graves debido al cambio brusco de medicamentos anticonvulsivos. Debido a estas complicaciones predecibles, que abandonamos nuestro protocolo institucional de rutina que la fenitoína empleadas para la profilaxia de convulsiones en los pacientes en el período post-operatorio después de la resección del tumor maligno y que esperan ser irradiado en un futuro próximo. Una vez que ambos carbamazepina y los barbitúricos mostran sensibilidad cruzada con fenitoína y puede interferir con los niveles séricos de drogas de la quimioterapia, ahora defendemos, como otros centros de renombre mundial neuro-oncológico, el uso de gabapentina valproato, o bien, como orientación la literatura reciente sugiere levetiracetam (keppra), para la profilaxia de las convulsiones en este subgrupo seleccionado de pacientes.

The role of magnesium sulfate in prevention of seizures induced by pentylenetetrazole in rats / O papel do sulfato de magnésio na prevenção de crises induzidas por pentilenotetrazol em ratos

Magnesium sulfate (MgSO4) has been used to prevent seizures in eclampsia. This study examined the central effects of MgSO4 on different types of pentylenetetrazole (PTZ)-induced seizures. Male Wistar rats were submitted to intracerebroventricular (ICV) administration of MgSO4 at different doses followed by intraperitoneal administration of PTZ. The latency to the onset of the first seizure induced by PTZ was significantly increased by ICV administration of MgSO4 at a dose of 100 µg compared to the control treatment. In addition, the total period during which animals presented with seizures was significantly reduced at this dose of MgSO4. Furthermore, the latency to the onset of the first partial complex seizure was significantly increased by the lowest dose of MgSO4. However, a high dose of MgSO4 had no effect or even potentiated the effect of PTZ. These results suggest that, depending on the dose, MgSO4 may be important in prevention of epileptic seizures.

Sulfato de magnésio (MgSO4) é utilizado para prevenir crises epilépticas na eclampsia. Este estudo examina os efeitos do MgSO4 em diferentes tipos de crise induzidas por pentilenotetrazol (PTZ). Ratos Wistar foram submetidos à administração intracerebroventricular (ICV) de diferentes doses de MgSO4 seguida de administração intraperitoneal de PTZ. A latência para o início da primeira crise induzida por PTZ foi aumentada pela administração ICV de MgSO4 na dose de 100 µg quando comparada ao tratamento controle. Além disso, o período durante o qual os animais apresentaram crises foi reduzido com a mesma dose de MgSO4. A latência para o início da primeira crise parcial complexa também foi aumentada com a dose menor de MgSO4 (32 µg). No entanto, a maior dose (320 µg) de MgSO4 não foi efetiva ou até potencializou os efeitos do PTZ. Esses resultados sugerem que, dependendo da dose, o MgSO4 pode ser útil na prevenção de crises epilépticas.

Inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on seizures and brain damage induced by pilocarpine in rats / Ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol) nas convulsões e dano cerebral em ratos induzidos pela pilocarpina

Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/kg, i.p.) and α-tocopherol (200 or 400 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model) in rats. Ascorbic acid or α-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and α-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and α-tocopherol in treatments for neurodegenerative diseases.

A epilepsia de lobo temporal é a mais comum forma de epilepsia em humanos. O estresse oxidativo é um dos mecanismos de morte celular induzida pelas crises convulsivas. Os compostos antioxidantes apresentam efeitos neuroprotetores devido à sua capacidade de inibir a produção de radicais livres. Os objetivos do presente trabalho foram estudar de forma comparativa a ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol) sobre as alterações comportamentais e histopatológicas no hipocampo de ratos após convulsões induzidas pela pilocarpina. A fim de determinar os efeitos neuroprotetores destas drogas, o presente trabalho estudou os efeitos do ácido ascórbico (250 ou 500 mg/kg, i.p.) e do α-tocoferol (200 ou 400 mg/kg, i.p.) sobre o comportamento e as lesões cerebrais observados após convulsões induzidas pela pilocarpina (400 mg/kg, i.p., P400), em ratos. As injeções de ácido ascórbico ou α-tocoferol antes da administração de pilocarpina reduzem o número de animais que convulsionam. Estes achados sugerem que os radicais livres podem induzir o desenvolvimento de lesão cerebral durante as crises epilépticas. No modelo P400, o ácido ascórbico e o α-tocoferol, diminuem significativamente os danos cerebrais. Os compostos antioxidantes podem exercer efeitos neuroprotetores, e esses resultados podem estar associados à inibição da produção de radicais livres. Estes resultados sugerem um promissor potencial terapêutico tanto para o ácido ascórbico quanto para o α-tocoferol no tratamento de doenças neurodegenerativas.

Does sudden unexpected death in children with epilepsy occur more frequently in those with high seizure frequency? / Morte súbita em crianças com epilepsia ocorre naquelas que apresentam maior frequência de crises?

People with epilepsy are more likely to die prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). Several studies have reported a moderate or high seizure frequency among SUDEP cases and SUDEP is considered rare in patients in remission. METHOD: We reviewed the occurrence of SUDEP in our epilepsy unit over an 8-year period to identify a potential association between seizure frequency and SUDEP occurrence in children with epilepsy. RESULTS: From 835 patients evaluated, 12 had suffered SUDEP and nearly all of the SUDEP cases in our children are related to chronic uncontrolled epilepsy (daily - 50.0 percent, two to four/week - 41.7 percent, monthly - 8.3 percent). CONCLUSION: SUDEP is not a rare event in children and increased mortality was recorded in those individuals who had not responded to pharmacologic treatment. Improved seizure control seems to be one of the most important measures to prevent SUDEP.

Pessoas com epilepsia têm maior chance de morrer prematuramente e a principal causa de morte relacionada à epilepsia é a morte súbita em epilepsia (SUDEP). Vários estudos têm relatado uma freqüência de crises moderada ou elevada em pacientes com SUDEP e SUDEP é considerada rara em pacientes em remissão. MÉTODO: Revisamos a ocorrência de SUDEP em nossa unidade de epilepsia por um período de oito anos com o objetivo de identificar uma possível associação entre freqüência de crises e a ocorrência de SUDEP em crianças com epilepsia. RESULTADOS: De 835 pacientes avaliados, 12 evoluíram com SUDEP e a maioria das crianças apresentava epilepsia crônica não controlada (50 por cento com crises diárias; 41,7 por cento com duas a quatro crises/semana; 8,3 por cento com crises mensais). CONCLUSÃO: SUDEP não é um evento raro em crianças e maior mortalidade foi observada em indivíduos que não responderam ao tratamento medicamentoso. Melhor controle de crises parece ser uma das principais medidas na prevenção de SUDEP.

Physical exercise in rats with epilepsy is protective against seizures: evidence of animal studies / Exercício físico em ratos com epilepsia como fator protetor contra crises epilépticas: evidencias de estudos em animais

People with epilepsy have been discouraged from participating in physical activity due to the fear that it will exacerbate seizures. Clinical and animal studies indicate a reduction of seizure frequency as well as decrease susceptibility to subsequently evoked seizures after an exercise program. Analyses from experimental studies of animals with epilepsy submitted to physical training programs were performed. In all studies the physical training was able to reduce the number of spontaneous seizures in rats with epilepsy. Seizure occurrence during exercise was relatively absent in the majority of studies. No death was found in animals with epilepsy during 1680 h of exercise. Based on these results it is plausible encouraging persons with epilepsy to non-pharmacological treatments and preventative measures such as physical exercise.

Pessoas com epilepsia têm sido desencorajadas da prática de atividade física por receio do exercício físico exacerbar as crises epilépticas. Estudos clínicos e em animais mostram uma redução da frequência de crises, assim como diminuição da susceptibilidade a crises subseqüentes após programa de exercício físico. Neste estudo realizamos uma análise de estudos experimentais de animais com epilepsia submetidos a programas de exercício físico. Em todos os estudos, o treinamento físico foi capaz de reduzir o número de crises espontâneas em ratos com epilepsia. A ocorrência de crises durante o exercício físico foi relativamente ausente na maioria dos estudos. Nenhuma morte foi encontrada em animais com epilepsia durante 1680 h de exercício físico. Baseados nestes resultados parece aceitável encorajar as pessoas com epilepsia a tratamentos não farmacológicos e medidas preventivas como o exercício físico.

experimental design for finding of minimum dosage of carbamazepine and valproate in preventing of seizure attacks

Previous studies have shown that physicians use high doses of Carbamazepine [CBZ] and Valproate [VPA] to control of epileptic attacks, while these drugs incur of many side effects include of gastrointestinal, hematologic, psychiatric, cardiac and other side effects. The aim of this study was to determine the minimum therapeutic dose with and an acceptable blood level of these drugs. This semi-experimental study was done in 56 epileptic patients in during of one year. At the first demographic data including of age, sex, weight and the period of drug taking was recorded. Then the drug CBZ and VPA were prescribed to adults [more than 12 years old] 9-11 mg/kg and 12-14 mg/kg respectively, and in children [less than 12 years old] 12-14 and 12-15 mg/kg respectively. Serum levels of CBZ and VPA were measured monthly by gas chromatography method that is separation technique, is mostly employed in chemical analysis. The results indicated that serum levels of CBZ and VPA in adult were 7.4 and 74.7 and serum levels of drugs in children were 8.2 and 66.8 respectively. Also patients have not epilepsy attack in during the period of assessment. These findings showed that with a much lower dosage of the drugs, which is suggested in texts can lead to an appropriate blood level of CBZ and VPA for controlling the epileptic seizures

Association of lamotrigine and valproate in refractory epilepsies of children and adolescents / Associação de lamotrigina e valproato de sódio no tratamento de epilepsia refratária em crianças e adolescentes

OBJECTIVE: To evaluate the efficacy or eventual side-effects of the association of lamotrigine and sodium valproate in the control of refractory epilepsies. METHOD: A retrospective analysis of 37 children with a mean age of 12 years taking exclusivelly lamotrigine and sodium valproate. Efficacy of seizure control was considered satisfactory if there was a reduction in seizures >50 percent or total control. RESULTS: The association of lamotrigine and sodium valproate was considered satisfactory in 65 percent of the studied children, independent of seizure type. Total seizure control was obtained in 33 percent and 35 percent had an unsatisfactory response or remained unchanged. Primary generalized tonic clonic seizures were the most common type with 84 percent of day-time seizures having a good response to treatment. Side-effects were seen in 11 percent of patients and the most common was tremor. CONCLUSION: Total or satisfactory control of seizures was seen in the majority of patients and side-effects were uncommon.

OBJETIVO: Avaliar a eficácia ou eventuais efeitos colaterais da associação de lamotrigina e valproato de sódio no controle de epilepsia refrataria. MÉTODO: Análise retrospectiva de 37 crianças e adolescentes com idade média de 12 anos tratadas exclusivamente com lamotrigina e valproato de sódio. A eficácia do controle de crises foi considerada satisfatória se o controle das crises foi >50 por cento ou total. RESULTADOS: A associação de lamotrigina e valproato de sódio foi considerada satisfatória em 65 por cento, independente do tipo de crise. O controle total de crises foi obtido em 33 por cento e em 35 por cento a resposta foi insatisfatória ou permaneceu inalterada. Crise generalizada primaria tônico clonica foi o mais comum, com 84 por cento das crises ocorrendo durante o dia, com boa resposta ao tratamento. Efeitos colaterais foram vistos em 11 por cento dos pacientes, sendo tremor o mais freqüente. CONCLUSÃO: Controle total ou satisfatório das crises ocorreu na maioria dos pacientes, sendo pouco freqüente os efeitos colaterais.

Enteral nutrition and phenytoin administration in head trauma patients

Seizure is common after head trauma and neurosurgery. Phenytoin is the most common anti-convulsant drug used in epileptic patients and for prevention of seizure in patients with head trauma and stroke. This drug has unique pharmacokinetic and pharmacodynamic characteristics. Phenytoin administration along with enteral nutrition in ICU patients may be accompanied by decreased phenytoin absorption and inadequate therapeutic concentration. The present study was performed to assess the effect of enteral nutrition on the pharmacokinetic therapeutic parameters of phenytoin given to our patients. In a clinical trial, the study group was divided into two groups of 15 patients each. After obtaining steady-state phenytion serum concentration, two blood samples were obtained from each patient on 2 consecutive days and then analyzed. The mean was assessed on the basis of serum albumin level of the patient. Clearance and maximum metabolic capacity were also calculated. Serum phenytoin level was below the therapeutic range [10- 20 mg/l] in 70% of patients in group 1 and was higher than the therapeutic range in 70% of patients in group 2 who received oral phenytoin [by dissolving in water] 2h after enteral nutrition. Mean phenytion concentration was 6.3 +/- 4mg/l and 24.7 +/- 9.4mg/l in group 1 and group 2, respectively. We found oral phenytoin administration with enteral nutrition [gavage solutions] to result in a significant decrease in absorption and blood concentration of phenytoin. We recommend administration of phenytoin with water only. In addition, monitoring of phenytoin serum concentration is necessary for assessment of therapeutic concentration and prevention of side effects

The clinical spectrum of malformations of cortical development

BACKGROUND: Malformations of cortical development (MCD) usually manifest in childhood with epilepsy, developmental delay and focal neurological abnormalities. OBJECTIVE: To evaluate the presentation and severity of epilepsy in the different types of MCD. METHOD: We evaluated the first 100 consecutive patients with a neuroimaging diagnosis of MCD. They were identified among all the high resolution magnetic resonance imaging exams performed at our service between 1997 and 2001. The causes of referral were diverse, according to the routine of the neurology outpatient clinic. After magnetic resonance imaging diagnosis of the subtype of MCD a detailed clinical assessment was performed. RESULTS: There were 55 females and 45 males, with ages ranging from five months to 71 years old (mean=15.2 years). Seventy-seven patients presented with epilepsy. Sixty-one had partial epileptic syndromes, 13 secondary generalized syndromes, and in three, the type of epileptic syndrome could not be established. Epilepsy was less frequent in patients with the MCD subtypes of polymicrogyria and schizencephaly (p<0.001). Patients with schizencephaly and polymicrogyria had their seizures more easily controlled by antiepileptic drugs (p<0.001). CONCLUSION: That the frequency of epilepsy is lower and seizures are more easily controlled in the setting of polymicrogyria and schizencephaly. Patients with MCD frequently present with secondary generalized epilepsy early in childhood.

INTRODUÇÃO: As malformações do desenvolvimento cortical (MDC) geralmente se manifestam na infância, na forma de crises epilépticas, retardo do desenvolvimento neuropsicomotor ou anormalidades focais. OBJETIVO: Avaliar a apresentação clínica e a gravidade da epilepsia nos diferentes tipos de MDC. MÉTODO: Cem pacientes com diagnóstico de MDC estabelecido por neuroimagem foram avaliados. Os pacientes foram identificados através de exames de ressonância magnética de alta resolução realizados entre 1997 e 2001. As causas para investigação por imagem foram diversas, conforme as indicações de rotina dos ambulatórios de neurologia. Após a determinação do subtipo de MDC, uma avaliação clínica detalhada foi realizada. RESULTADOS: Entre os 100 pacientes, 55 eram do sexo feminino e 45 do masculino, com idade variando entre 5 meses e 71 anos (média=15,2 anos). Setenta e sete pacientes apresentaram epilepsia. Sessenta e um tinham síndrome epiléptica parcial, 13 síndrome epiléptica secundariamente generalizada e em três, o tipo de crise não pode ser definido. Epilepsia foi menos freqüente em pacientes com polimicrogiria e esquizencefalia (p<0.001). As crises epilépticas foram controladas mais facilmente por drogas antiepilépticas em pacientes com polimicrogiria e esquizencefalia (p<0.001). CONCLUSÃO: A freqüência de epilepsia é menor e as crises são mais facilmente controladas em pacientes com polimicrogiria e esquizencefalia. Pacientes com MDC freqüentemente apresentam síndrome epiléptica secundariamente generalizada.

Epilepsia refratária: a experiência do Núcleo Avançado de Tratamento das Epilepsias do Hospital Felício Rocho (NATE) no período de março de 2003 a dezembro de 2006 / Refractory epilepsy: the experience of the NATE

INTRODUÇÃO: A epilepsia é um problema de saúde pública. Afeta mais de cinqüenta milhões de pessoas em todo mundo e mais de vinte milhões deles continuam apresentando crises que não controlam satisfatoriamente com o uso de medicamentos. As epilepsias refratárias correspondem a cerca de 20 por cento dos pacientes epilépticos e boa parte desses apresentam crises parciais complexas passíveis de tratamento cirúrgico. A indicação cirúrgica criteriosa tem se mostrado eficiente para o controle das crises. OBJETIVO: Apresentar dados epidemiológicos e cirúrgicos dos pacientes submetidos ao tratamento cirúrgico no NATE. METODOLOGIA: Estudo retrospectivo com análise de prontuários e classificação do controle de crises de 46 pacientes considerando a Escala de Engel. RESULTADOS: Predomina o sexo masculino, solteiros, sem história familiar para epilepsia. Pacientes procedentes do Estado de Minas Gerais e outros estados da união. Início das crises na infância para 58,8 por cento dos pacientes sendo o tipo de crise mais freqüente a crise parcial complexa. O déficit de memória foi a queixa cognitiva mais comum. CONCLUSÃO: O controle de crise foi compatível com Engel Ia (sem crise) para 67 por cento dos pacientes. O tratamento cirúrgico revelou-se eficiente para o controle das crises dos pacientes portadores de epilepsia refratária ao tratamento medicamentoso.

INTRODUCTION: Epilepsy is a health public problem. Afflicts more than 50 million people worldwide, and more than 20 million of those affected do not have satisfactory seizures control with medicine. The refractory epilepsy represents 20 percent of all epileptic patients and most of them present partial seizures which can be treated by surgical treatment. The careful surgical recommendation can be efficient to seizure control. PURPOSE: The aim of this study was to present epidemiological and surgical data about patients submitted to surgical treatment in NATE - Advanced Center of Epilepsy Treatment. METHOD: We used a retrospective assessment method and control seizure classification from Engel Scale for 46 epileptic patients submitted to surgical treatment. RESULTS: Our results showed predominant male patients, single, without family history for epilepsy. The patients were from cities of Minas Gerais State and from another States in Brazil. The first seizure occurred in the childhood for 58,8 percent of patients and the more frequent seizure type was complex partial seizure. The predominant cognitive complaint was about memory. CONCLUSION: The surgical treatment for seizure control was good for 67 percent of patients that display Engel Ia classification (without seizures) and has a high likelihood for success in medically intractable temporal lobe epilepsy.

Peri-ictal complexity loss as determined by approximate entropy analysis in the electrocorticogram obtained from chronic subdural recordings in patients with refractory temporal lobe epilepsy

RATIONALE: The development of closed-loop devices suitable for use in the treatment of epileptic patients would very likely rely on the adequate development of paradigms able to forecast the occurrence of seizures. In this paper, we studied the usefulness of approximate enthropy, of a non-linear paradigm, in this patient population. METHODS: We applied approximate entropy (ApEn) analysis to study the variability in the complexity of the peri-ictal electrocorticogram (ECoG) of patients with refractory epileptic seizures of the temporal lobe origin. Three patients were implanted with chronic subdural grids. The ApEn algorithm measured the complexity of interictal, peri-ictal and ictal phases. We selected one representative channel disclosing interictal activity for each patient and two channels per patient with ictal recordings. RESULTS: In all patients, we found one channel where the interictal activity registered in the ECoG was associated with high complexity and where ApEn was higher than 0.59. But in the other two channels, for each patient that presented interictal/ictal transitions, clinical manifestations of epileptic seizures occurred around 3.5 seconds after the entropy drop, when entropy was below 0.5. In contrast, when entropy was higher than 0.5, clinical manifestation occurred 9.5 seconds after the entropy drop. The 3.5 seconds shorter delay possibly indicates focal activity in the channel analyzed. CONCLUSIONS: Our results suggest that ApEn may be a useful instrument for early detection of epileptic activity. Its application may be indicated for prevention and diagnosis of epileptic seizures.

RACIONAL: O desenvolvimento de aparatos retroalimentáveis para o tratamento de pacientes epilépticos dependerá em grande parte do desenvolvimento adequado de paradigmas que possam antever as crises. Neste trabalho, estudamos a utilidade da entropia aproximada (ApEn), um paradigma não-linear, em pacientes portadores de epilepsia. MÉTODOS: Aplicamos a análise de entropia aproximada (ApEn) no estudo de variabilidade da complexidade do eletrocorticograma (ECoG) de pacientes com epilepsia refratária com origem no lobo temporal. Três pacientes foram implantados com matrizes de eletrodos subdurais. O algoritmo ApEn mediu a complexidade das fases interictal, peri-ictal e ictal. Selecionamos um canal representativo de cada paciente manifestando atividade interictal e dois canais de cada paciente com registro ictal. RESULTADOS: Em cada paciente, encontramos um canal cuja atividade interictal registrada no ECoG foi associada a alta complexidade com ApEn maior que 0.59. Nos outros dois canais, para cada paciente que apresentou transição interictal/ictal, as manifestações clínicas das crises epilépticas ocorreram cerca de 3.5 segundos depois após a queda da entropia abaixo de 0.5. Em comparação, quando a entropia foi maior que 0.5, as manifestações clínicas ocorreram 9,5 segundos após a queda da entropia. A curta latência (3.5 segundos) indicou possivelmente o local de início da atividade focal. CONCLUSÕES: Nossos resultados sugerem que ApEn pode ser um instrumento útil na detecção precoce da atividade epiléptica. Sua aplicação pode estar indicada na prevenção ou diagnóstico das crises epilépticas.