Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe epilepsy.

The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection, neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of the Prnp was associated with decreased brain volume in healthy volunteers and schizophrenic patients. We investigate the association between the cerebellum volume and the presence of variant allele Valine at codon 129 of the Prnp gene in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS patients. The cerebellum volume corrected by the intracranial volume of patients with the normal Prnp genotypes was compared with that of patients presenting the variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16 showed Met129Val, and 5 had Val129Val. There were no association among clinical, demographic, electrophysiological, antiepileptic drugs used, and the presence of the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was not associated with the analyzed cerebellum volume. Prnp variant alleles at codon 129 are not associated with cerebellum volume in patients with refractory MTLE-HS.

Cognitive and surgical outcome in mesial temporal lobe epilepsy associated with hippocampal sclerosis plus neurocysticercosis: a cohort study.

BACKGROUND: Where neurocysticercosis (NCC) is endemic, chronic calcified neurocysticercosis (cNCC) can be observed in patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). Considering that both disorders cause recurrent seizures or cognitive impairment, we evaluated if temporal lobectomy is cognitively safe and effective for seizure control in MTLE-HS plus cNCC. METHODS: Retrospective cohort study of neuropsychological profile and surgical outcome of 324 MTLE-HS patients submitted to temporal lobectomy, comparing the results according to the presence or absence of cNCC. FINDINGS: cNCC occurred in 126 (38.9%) of our MTLE-HS patients, a frequency higher than expected, more frequently in women than in men (O.R. = 1.66; 95% C.I. = 1.05-2.61; p = 0.03). Left-side (but not right side) surgery caused impairment in selected neuropsychological tests, but this impairment was not accentuated by the presence of cNCC. Ninety-four (74.6%) patients with MTLE-HS plus cNCC and 153 patients (77.3%) with MTLE-HS alone were Engel class I after surgery (O.R. = 1.16; 95% C.I. = 0.69-1.95; p = 0.58). However, the chances of Engel class IA were significantly lower in MTLE-HS plus cNCC than in patients with MTLE-HS alone (31.7% versus 48.5%; O.R. = 2.02; 95% C.I. = 1.27-3.23; p = 0.003). Patients with MTLE-HS plus cNCC showed higher rates of Engel class ID (15.1% versus 6.6%; O.R. = 2.50; 95% C.I. = 1.20-5.32; p = 0.012). INTERPRETATION: cNCC can be highly prevalent among MTLE-HS patients living in areas where neurocysticercosis is endemic, suggesting a cause-effect relationship between the two diseases. cNCC does not add further risk for cognitive decline after surgery in MTLE-HS patients. The rates of Engel class I outcome were very similar for the two groups; however, MTLE-HS plus cNCC patients achieved Engel IA status less frequently, and Engel ID status more frequently. Temporal lobectomy can be safely performed in most patients with MTLE-HS plus cNCC without affecting cognitive outcome. Long-term surgical seizure control in MTLE-HS plus cNCC is still satisfactory, as long as selected patients remain under medication.

Sudden unexpected death in epilepsy: from the lab to the clinic setting.

Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.

Vagus nerve stimulator in patients with epilepsy: indications and recommendations for use.

Epilepsy comprises a set of neurologic and systemic disorders characterized by recurrent spontaneous seizures, and is the most frequent chronic neurologic disorder. In patients with medically refractory epilepsy, therapeutic options are limited to ablative brain surgery, trials of experimental antiepileptic drugs, or palliative surgery. Vagal nerve stimulation is an available palliative procedure of which the mechanism of action is not understood, but with established efficacy for medically refractory epilepsy and low incidence of side-effects. In this paper we discuss the recommendations for VNS use as suggested by the Brazilian League of Epilepsy and the Scientific Department of Epilepsy of the Brazilian Academy of Neurology Committee of Neuromodulation.

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.

Do pets reduce the likelihood of sudden unexplained death in epilepsy?

PURPOSE: To assess the relationship between the presence of pets in homes of epilepsy patients and the occurrence of sudden unexpected death in epilepsy (SUDEP). METHODS: Parents or relatives of SUDEP patients collected over a ten-year period (2000-2009) in a large epilepsy unit were asked if the patient lived together with any domestic pet at the time of death or not. Patients who did not experience SUDEP served as controls. RESULTS AND CONCLUSIONS: Eleven out of the 1092 included patients (1%) experienced SUDEP, all with refractory symptomatic epilepsy, but none of them had pets in their homes at the time of death. In contrast, the frequency of pet-ownership in the control group (n=1081) was 61%. According to previous studies there are some indications that human health is directly related to companionship with animals in a way that domestic animals prevent illness and facilitate recovery of patients. Companion animals can buffer reactivity against acute stress, diminish stress perception and improve physical health. These factors may reduce cardiac arrhythmias and seizure frequency, factors related to SUDEP. Companion animals may have a positive effect on well-being, thus improving epilepsy outcome.

Impact of pediatric epilepsy surgery on intellectual efficiency.

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. Seizure improvement group achieved significant Performance Scale improvement (p = 0.01) and no seizure improvement group showed 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.

Epileptologists probe vagus nerve stimulation in children with refractory epilepsy: a promise against sudden unexpected death in epilepsy.

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.

Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy.

PURPOSE: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. METHODS: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. RESULTS: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R.=2.9; 95% C.I.=1.1-7.7; p=0.033); normal MRI (H.R.=4.8; 95% C.I.=1.4-16.6; p=0.012), and MRI with lesion involving eloquent cortex (H.R.=3.8; 95% C.I.=1.2-12.0; p=0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long-term surgical outcome in up to 80% of patients. CONCLUSION: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series.

Mortality in children with severe epilepsy: 10 years of follow-up.

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), sepsis (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.

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?

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.

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.

When your child with epilepsy dies suddenly: febrile seizures are part of the process?

Febrile seizures (FS) affect almost 2-5% 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.

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!

The epilepsies are one of the most common serious brain disorders and 20 to 30% 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.

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.