Can physical exercise have a protective effect in an animal model of sleep-related movement disorder?

The purpose of the present study was to determine whether physical exercise (PE) has a protective effect in an experimental animal model of sleep-related movement disorder (A11 dopaminergic nuclei lesions with 6-OHDA). Rats were divided into four groups (Control PE-CTRL/PE, SHAM/PE, A11 lesion/NPE, A11 lesion/PE). Two experiments were performed: (1) the rats underwent PE before (2 weeks) and after (4 weeks) the A11 lesion; and (2) the rats underwent PE only after (4 weeks) the A11 lesion. Electrode insertion surgery was performed and sleep analyses were conducted over a period of 24h (baseline and after PE) and analyzed in 6 blocks of 4h. The results demonstrated that the A11 lesion produced an increased percentage of wakefulness in the final block of the dark period (3-7am) and a significant enhancement of the number of limb movements (LM) throughout the day. Four weeks of PE was important for reducing the number of LMs in the A11 lesion group in the rats that performed PE before and after the A11 lesion. However, in the analysis of the protective effect of PE on LM, the results showed that the number of LMs was lower at baseline in the group that had performed 2 weeks of PE prior to the A11 lesion than in the group that had not previously performed PE. In conclusion, these findings consistently demonstrate that non-pharmacological manipulations had a beneficial effect on the symptoms of sleep-related movement disorder.

Environmental air pollution is an aggravating event for sudden unexpected death in epilepsy / Exposicao ambiental a poluicao do ar e um evento agravante para a ocorrencia de morte subita nas epilepsias

It is extremely difficult to estimate the occurrence of sudden unexpected death in epilepsy (SUDEP). On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with refractory epilepsy may prevent fatal events in these individuals. In this context, we should not ignore that urban air pollution is a leading problem for environmental health and is able to cause serious cardiovascular dysfunctions that culminate in sudden death. In this regard, we aimed to determine whether environmental exposure to air pollution is an aggravating event for SUDEP.

É extremamente difícil estimar a ocorrência de morte súbita em epilepsia (SUDEP). Por outro lado, detectar e avaliar cuidadosamente novos factores de risco que podem contribuir para o aparecimento de alterações cardiovasculares em pessoas com epilepsia refratária poderá ser capaz de impedir a ocorrência de eventos fatais nestes indivíduos. Neste contexto, não devemos negligenciar hoje que a poluição do ar nas grandes cidades é um problema para a saúde ambiental, podendo causar graves disfunções cardiovasculares, que culminam em morte súbita. Neste sentido, propusemos nesse trabalho que a exposição ambiental a poluição do ar é um evento agravante para a ocorrência de SUDEP.

Epileptologists probe vagus nerve stimulation in children with refractory epilepsy: a promise against sudden unexpected death in epilepsy / Epileptologistas indicam a estimulação do nervo vago em crianças com epilepsia refratária: uma promessa contra a morte súbita em epilepsia

It is clear that sudden unexpected death in epilepsy (SUDEP) is mainly a problem for people with refractory epilepsy, but our understanding of the best way to its prevention is still incomplete. Although the pharmacological treatments available for epilepsies have expanded, some antiepileptic drugs are still limited in clinical efficacy. In the present paper, we described an experience with vagus nerve stimulation (VNS) treatment by opening space and providing the opportunity to implement effective preventative maps to reduce the incidence of SUDEP in children and adolescents with refractory epilepsy.

Está claro que a morte súbita e inesperada em epilepsias (SUDEP) é principalmente um problema para as pessoas com epilepsia refratária, mas o entendimento para estabelecer medidas preventivas ainda está incompleto. Embora os tratamentos farmacológicos disponíveis para epilepsias tenham sido expandidos, algumas drogas antiepilépticas ainda são limitadas em termos de eficácia clínica. No presente trabalho, foi descrita uma experiência com a estimulação do nervo vago (VNS), abrindo espaço e fornecendo a oportunidade de implementar eficazes mapas preventivoss para reduzir a incidência da SUDEP em crianças e adolescentes com epilepsia refratária.

Serum levels of magnesium in sudden cardiac deaths among people with schizophrenia: hit or miss? / Níveis séricos de magnésio em morte súbita entre pessoas com esquizofrenia: erro ou acerto?

Schizophrenia is a devastating mental disorder, affecting cognitive, emotional, and behavioral conditions, ability to work, social functioning, family stability and self-esteem of the patient. People with schizophrenia show a two to three-fold increased risk to die prematurely than those without schizophrenia. Understanding the mechanisms behind sudden cardiac death in individuals with schizophrenia is a key to prevention. Although different mechanisms may be related, there are clear indications that cardiac abnormalities play a potential role. Some antipsychotics may be associated with cardiovascular adverse events, e.g., QT interval prolongation, metabolic dysfunction, blood pressure and heart rate alterations. Magnesium (Mg) abnormalities may lead to various morphological and functional dysfunctions of the heart and low levels of serum Mg are considered to be at high risk for sudden cardiac death. As low serum Mg is associated with detrimental effects on the heart and that antipsychotic-treated schizophrenia patients frequently affect the heart rate, possibly, these factors together must change the normal functioning of the heart and consequently being able to culminate in a catastrophic event.

A esquizofrenia é uma doença mental que afeta as condições cognitivas, emocionais e comportamentais, a capacidade de trabalho, a estabilidade familiar e social e a auto-estima do paciente. Pessoas com esquizofrenia apresentam um risco de duas a três vezes maior de morrer prematuramente em relação às pessoas sem esquizofrenia. A compreensão dos mecanismos envolvidos na morte súbita em indivíduos com esquizofrenia é de suma importância para sua prevenção. Apesar de diferentes mecanismos associados à doença, evidências mostram que as anormalidades cardíacas desempenham papel importante neste contexto. Alguns antipsicóticos podem estar associados com eventos cardiovasculares adversos, como o prolongamento do intervalo QT, disfunção metabólica e alterações na pressão arterial e no ritmo cardíaco. Anormalidades do magnésio (Mg) podem levar a várias alterações morfológicas e funcionais do coração assim como a um alto risco para a morte súbita. Como baixos níveis séricos de Mg estão associados a efeitos nocivos ao coração e indivíduos com esquizofrenia tratados com antipsicóticos frequentemente apresentam alteração do ritmo cardíaco, possivelmente, estes fatores em conjunto podem alterar o funcionamento normal do coração e, consequentemente, culminar em um evento catastrófico.

Mortality in children with severe epilepsy: 10 years of follow-up / Mortalidade em crianças com epilepsia severa: 10 anos de seguimento

Epilepsy is the main neurological condition in children and adolescents. Unfortunately patients with medical refractory epilepsy are more susceptible for clinical complications and death. We report a prospectively evaluated cohort of children followed for approximately 10 years. Fifty-three of 1012 patients died. Forty-two patients died due to epilepsy or its clinical complications and the main causes of death were pneumonia (in 16 cases), sepses (in 9 patients), status epilepticus (in 8 patients). In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP). Mental retardation was significantly more frequent in patients who did not die from SUDEP. SUDEP may be a significant condition associated with mortality in children and adolescents with epilepsy.

Epilepsia é uma das condições neurológicas mais comuns em crianças e adolescentes. Infelizmente, pacientes com epilepsias refratárias ao tratamento medicamentoso estão mais susceptíveis a complicações clínicas e óbito. Neste trabalho reportamos, em uma análise prospectiva, um cohort de crianças acompanhadas por aproximadamente dez anos. Cinquenta e três de 1012 pacientes foram a óbito. Quarenta e dois pacientes morreram em decorrência da epilepsia ou de suas complicações clínicas; as principais causas foram pneumonia (16 casos), sepse (9 casos) e estado de mal epiléptico (8 casos). Em 11 pacientes a causa da morte foi SUDEP. A presença de retardo mental foi significantemente associada a mortalidade em crianças e adolescentes com epilepsia.

Sudden death in a child with epilepsy: potential cerebellar mechanisms? / Morte súbita em uma criança com epilepsia: potenciais mecanismos cerebelares?

Epilepsy is the most common neurological disorder in humans. People with epilepsy are more likely to die prematurely than those without epilepsy, with the most common epilepsy-related category of death being sudden unexpected death in epilepsy (SUDEP). The central mechanisms underlying the fatal process remain unclear, but cardiac and respiratory mechanisms appear to be involved. Recently, cerebellar, thalamic, basal ganglia and limbic brain structures have been shown to be implicated in respiratory and cardiac rate regulation. We discuss here the potential mechanisms underlying the fatal process, with a description of cerebellar actions likely failing in that SUDEP process.

Epilepsia é uma das doenças neurológicas mais comuns em seres humanos. Pessoas com epilepsia têm maior chance de morrer prematuramente do que pessoas sem epilepsia, sendo a principal causa de óbito a morte súbita em epilepsia (SUDEP). Os mecanismos centrais envolvidos neste processo fatal não são claros, mas mecanismos cardíacos e respiratórios parecem estar envolvidos. Recentemente, regiões cerebrais como o cerebelo, núcleos talâmicos, gânglios basais e estruturas límbicas foram relacionadas com a variação das frequências cardíaca e respiratória. Aqui, discutiremos potenciais mecanismos envolvidos na SUDEP, com uma descrição do possível papel do cerebelo na sua ocorrência.

Sudden unexpected death in an adolescent with epilepsy: all roads lead to the heart?

The incidence of sudden unexpected death in epilepsy (SUDEP) has been estimated from 0.5-1.4/1,000 person-years in people with treated epilepsy, and 9/1,000 person-years in candidates for epilepsy surgery. Potential risk factors for SUDEP include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure type and winter temperatures. The arrythmogenic side-effect of antiepileptic drugs and seizures may increase the risk of SUDEP. In this report, we describe a patient with prolonged post-ictal tachycardia in EEG video recordings with a typical case of SUDEP: a 16-year-old boy with medically intractable complex partial seizures. Magnetic resonance imaging revealed left mesial temporal sclerosis. During non-invasive video-EEG monitoring, the patient presented a post-ictal heart rate increased for five hours. Two months after video-EEG, he died from SUDEP during a tonic-clonic secondary generalized seizure. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many studies. Evaluation of this patient with EEG-video monitoring, including measurement of heart rate, contributed to an identification of ictal tachycardia that may have played a role in the SUDEP. Premature mortality seems to be increased in patients with epilepsy, and cardiac abnormalities may be a possible cause of SUDEP.

The utility of omega-3 fatty acids in epilepsy: more than just a farmed tilapia! / A utilidade do ácido graxo ômega-3 na epilepsia: mais do que uma criação de tilápias!

The epilepsies are one of the most common serious brain disorders and 20 to 30 percent of people developing epilepsy continue to have seizures and are refractory to treatment with the currently available therapies. Approximately one in a 1000 patients with chronic epilepsy will die suddenly, unexpectedly, and without explanation, even with post-mortem examination and this phenomenon is called sudden unexplained death in epilepsy (SUDEP). Understanding the mechanisms underlying SUDEP may lead to the identification of previously unrecognized risk factors that are more amenable to correction. We discuss here the possible implications of omega-3 fatty acids consumption on SUDEP prevention.

As epilepsias encontram-se entre as mais sérias doenças neurológicas; 20 a 30 por cento dos pacientes com epilepsia continuam apresentando crises e são refratários as terapias disponíveis atualmente. Aproximadamente um em cada 1000 pacientes com epilepsia crônica irá morrer de forma súbita, não esperada e sem explicação, mesmo com o exame pós-morte. Este fenômeno é denominado morte súbita e inesperada em epilepsia (SUDEP). Compreender os mecanismos envolvidos nos casos de SUDEP pode levar à identificação de fatores ainda não reconhecidos e passíveis de serem corrigidos. Discutiremos a seguir as possíveis implicações do consumo do ácido graxo ômega-3 na prevenção dos casos de SUDEP.

Serum magnesium: a clinical biomarker for sudden unexpected death in epilepsy? / Magnésio sérico: um biomarcador cerebral para morte súbita em epilepsia?

INTRODUCTION: Epilepsy is one of the most common chronic neurological disorder in the world and has a higher mortality rate than would be expected in a healthy population. One of the most related category of death is sudden unexpected death in epilepsy (SUDEP). Many risk factors have been related to SUDEP, but the mechanisms involved in its genesis is still unknown. OBJECTIVE: Here we describe one case of a patient with low serum magnesium levels that suffered of SUDEP. CONCLUSION: we discuss a possible cause-effect relation, suggesting that magnesium may be, in some cases, a biomarker of SUDEP.

INTRODUÇÃO: Epilepsia é uma das doenças neurológicas crônicas mais comuns, com uma elevada taxa de mortalidade quando comparada com a população saudável. Uma das principais causas de morte é a morte súbita em epilepsia (SUDEP). Muitos fatores de risco têm sido correlacionados com SUDEP, mas os mecanismos envolvidos na sua gênese são ainda desconhecidos. OBJETIVOS: será descrito um caso de um paciente com nível sérico de magnésio baixo que sofreu SUDEP. CONCLUSÕES: discutiremos uma possível relação de causa-efeito, sugerindo que o magnésio pode ser, em alguns casos, um biomarcador de SUDEP.

Inflammation and adipose tissue: effects of progressive load training in rats.

INTRODUCTION: Cytokines (IL-6, IL-10 and TNF-α) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol. METHODS: Male Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-α and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver. RESULTS: OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups. CONCLUSION: In conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue.

What are the similarities between stress, sudden cardiac death in Gallus gallus and sudden unexpected death in people with epilepsy / Similaridades entre stress, morte súbita cardíaca na espécie Gallus gallus e morte súbita em epilepsia

Individuals with epilepsy are at higher risk of sudden unexpected death in epilepsy (SUDEP), responsible for 7.5 percent to 17 percent of all deaths in epilepsy. Many factors are current associated with SUDEP and possible effect of stress and cardiac arrhythmia are still not clear. Sudden death syndrome (SDS) in chickens is a disease characterized by an acute death of well-nourished and seeming healthy Gallus gallus after abrupt and brief flapping of their wings, similar to an epileptic seizure, with an incidence estimated as 0.5 to 5 percent in broiler chickens. A variety of nutritional and environmental factors have been included: but the exactly etiology of SDS is unknown. Studies had suggested that the hearts of broiler chickens are considerably more susceptible to arrhythmias and stress may induce ventricular arrhythmia and thus, sudden cardiac death. In this way, SDS in Gallus gallus could be an interesting model to study SUDEP.

Indivíduos com epilepsia têm maior risco de sofrer morte súbita e inexplicada em epilepsia (SUDEP), responsável por 7,5 por cento a 17 por cento de todas as mortes em epilepsia. Diversos fatores têm sido associados com SUDEP e um possível efeito do stress e das arritmias cardíacas ainda não é claro. A síndrome da morte súbita (SDS) em galinhas é uma situação caracterizada por uma morte aguda em Gallus gallus bem nutridos e aparentemente saudáveis após um evento curto e abrupto de bater de asas, semelhante a uma crise epiléptica, com incidência de 0,5 a 5 por cento em granjas. Uma ampla variedade de fatores nutricionais e ambientais tem sido considerada, mas a causa exata da SDS é desconhecida. Estudos têm sugerido que o coração das galinhas criadas em granjas é mais sensível a arritmias cardíacas e que o stress poderia levar a arritmias cardíacas e, portanto, a morte súbita cardíaca. Assim, SDS em Gallus gallus pode ser considerado um interessante modelo de SUDEP.

Carbamazepine does not alter the intrinsic cardiac function in rats with epilepsy / Carbamazepina não altera o funcionamento cardíaco intrínseco em ratos com epilepsia

Among the causes for sudden unexpected death (SUDEP) in epilepsy, the effects of antiepileptic drugs on the heart have been poorly explored. Based on this, the aim of our study was to evaluate the heart rate (in vivo and isolated ex vivo) and ventricular pressure (isolated ex vivo) of rats with and without epilepsy treated with carbamazepine. Four groups of adult, male Wistar rats (200-250 g) were studied: [A] control rats (n=8), received neither pilocarpine nor carbamazepine [B] carbamazepine-treated rats (n=8), received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks; [C] rats with epilepsy that received just saline solution (n=8); [D] rats with epilepsy that received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks (n=8). Our results showed significant increase in heart rate in animals with epilepsy (with and without the use of carbamazepine) when compared to the control groups in vivo. In contrast, we did not find differences during isolated ex vivo experiments comparing animals with and without epilepsy and despite the use of carbamazepine. Our results suggest that, in isolation, carbamazepine may not be a potential risk factor for sudden unexpected death in epilepsy.

Entre as causas de morte súbita em epilepsia (SUDEPE), os efeitos das drogas antiepilépticas no coração têm sido pobremente explorados. Desta forma, o objetivo deste estudo foi avaliar a frequência cardíaca (in vivo e de forma isolada ex vivo) e a pressão ventricular (de forma isolada ex vivo) de ratos com e sem epilepsia tratados com carbamazepina. Quatro grupos de ratos Wistar machos adultos (peso 200 a 250 g) foram estudados: [A] ratos controle (n=8), não receberam pilocarpina ou carbamazepina; [B] ratos tratados com carbamazepina (n=8), receberam dose diária de carbamazepina de 120 mg/kg intraperitoneal, durante duas semanas (n=8); [C] ratos com epilepsia que receberam solução salina; [D] ratos com epilepsia que receberam dose diária de carbamazepina de 120 mg/kg intraperitoneal durante duas semanas. Nossos resultados evidenciaram uma diferença estatisticamente significativa na média da freqüência cardíaca in vivo entre os animais com epilepsia (com e sem o uso de carbamazepina) quando comparados aos grupos controles in vivo. Em contraste, não observamos diferenças estatísticas nos experimentos ex vivo quando comparados os animais com ou sem epilepsia, a despeito do uso da carbamazepina. Nossos resultados sugerem que, de forma isolada, a carbamazepina pode não ser um fator de risco potencial para a ocorrência de morte súbita em epilepsia.

Thalamic nuclear abnormalities as a contributory factor in sudden cardiac deaths among patients with schizophrenia

Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a "cerebral" focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP) that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance.

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.