RESUMEN
Temporal lobe epilepsy (TLE) is considered to be the most common form of epilepsy, and it has been seen that most patients are refractory to antiepileptic drugs. A strong association of this ailment has been established with psychiatric comorbidities, primarily mood and anxiety disorders. The side of epileptogenic may contribute to depressive and anxiety symptoms; thus, in this study, we performed a systematic review to evaluate the prevalence of depression in TLE in surgical patients. The literature search was performed using PubMed/Medline, Web of Science, and PsycNet to gather data from inception until January 2019. The search strategy was related to TLE, depressive disorder, and anxiety. After reading full texts, 14 articles meeting the inclusion criteria were screened. The main method utilized for psychiatric diagnosis was Diagnostic and Statistical Manual of Mental Disorders/Structured Clinical Interview for DSM. However, most studies failed to perform the neuropsychological evaluation. For those with lateralization of epilepsy, focus mostly occurred in the left hemisphere. For individual depressive diagnosis, 9 studies were evaluated, and 5 for anxiety. Therefore, from the data analyzed in both situations, no diagnosis was representative in preoperative and postoperative cases. In order to estimate the efficacy of surgery in the psychiatry episodes and its relation to seizure control, the risk of depression and anxiety symptoms in epileptic patients need to be determined before surgical procedures. Rigorous preoperative and postoperative evaluation is essential for psychiatry conditions in patients with refractory epilepsy candidates for surgery.
Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Trastornos de Ansiedad , Depresión , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Epilepsia del Lóbulo Temporal/cirugía , HumanosRESUMEN
Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration.
Asunto(s)
Epilepsia , MicroARNs , Amígdala del Cerebelo , Animales , Muerte Súbita , Epilepsia/complicaciones , ARN , Ratas , Convulsiones , Remodelación VentricularRESUMEN
The imbalance between antioxidant system and reactive oxygen species (ROS) generation is related to epileptogenesis, neuronal death, and seizure frequency. Treatment with vitamin E has been associated with neuroprotection and control of seizures. In most experimental studies, vitamin E treatment has short duration. Therefore, the aim of this study was to verify the role of long-term treatment with vitamin E in rats submitted to the pilocarpine model of epilepsy. Rats were divided into two main groups: control (Ctr) and pilocarpine (Pilo). Each one was subdivided according to treatment: vehicle (Ctr V and Pilo V) or vitamin E at dosages of 6â¯IU/kg/day (Ctr E6 and Pilo E6) or 60â¯IU/kg/day (Ctr E60 and Pilo E60). Treatment lasted 120â¯days from status epilepticus (SE). There were no statistical differences concerning treatment in the Ctr group for all variables, so the data were grouped. Carbonyl content in the hippocampus of Pilo V and Pilo E6 was higher compared with that of the Ctr group (8⯱â¯1.5, 7.1⯱â¯1, and 3.1⯱â¯0.3â¯nmol carbonyl/mg protein, respectively for Pilo V, Pilo E6, and Ctr; pâ¯<â¯0.05). Carbonyl content was restored to control values in Pilo E60 rats (4.2⯱â¯1.1 and 3.1⯱â¯0.3â¯nmol carbonyl/mg protein, respectively for Pilo E60 and Ctr; pâ¯>â¯0.05). The volume of the hippocampal formation (6.5⯱â¯0.3, 6.6⯱â¯0.4, 6.3⯱â¯0.3, and 7.4⯱â¯0.2, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and subfields CA1 (1.6⯱â¯0.1, 1.4⯱â¯0.2, 1.5⯱â¯0.1, and 2⯱â¯0.05, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and CA3 (1.7⯱â¯0.1, 1.5⯱â¯0.2, 1.4⯱â¯0.1, and 2⯱â¯0.1, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) was reduced in the Pilo group regardless of treatment. Parvalbumin immunostaining was increased in the hilus of the Pilo E60 group compared with that in the Ctr group (26⯱â¯2 and 39.6⯱â¯8.3 neurons, respectively for Ctr and Pilo E60). No difference was found in seizure frequency and Neo-Timm staining. Therefore, long-term treatment with 60â¯IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency.
Asunto(s)
Antioxidantes/farmacología , Epilepsia/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Pilocarpina/metabolismo , Convulsiones/tratamiento farmacológico , Vitamina E/farmacología , Análisis de Varianza , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Masculino , Parvalbúminas/metabolismo , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. METHODS: We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. RESULTS: The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6⯱â¯33â¯days. The mean (SD) age at death was 12.9⯱â¯14.1â¯months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). DISCUSSION: The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe disease, but well-reported data are lacking to clarify EIEE-related causes of death.
Asunto(s)
Espasmos Infantiles/mortalidad , Edad de Inicio , Causas de Muerte , Electroencefalografía/efectos adversos , Humanos , Lactante , Mortalidad Prematura , SíndromeRESUMEN
Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.
Asunto(s)
Muerte Súbita/etiología , Países Desarrollados , Epilepsia/complicaciones , Mortalidad Prematura , Factores de Edad , Bases de Datos Bibliográficas/estadística & datos numéricos , Epilepsia/epidemiología , Humanos , Factores de Riesgo , Factores SexualesAsunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Proteínas Tirosina Quinasas Receptoras , Receptores ColinérgicosAsunto(s)
Medicina , Música , Enfermedad de Parkinson , Percepción Auditiva , Marcha , Humanos , Enfermedad de Parkinson/terapiaRESUMEN
Previously, we demonstrated that male Wistar rats submitted to neonatal status epilepticus showed abnormal social behavior characterized by deficit in social discrimination and enhanced emotionality. Taking into account that early insult can produce different biological manifestations in a gender-dependent manner, we aimed to investigate the social behavior and anxiety-like behavior in female Wistar rats following early life seizures. Neonate female Wistar rats at 9 days postnatal were subject to pilocarpine-induced status epilepticus and the control received saline. Behavioral tests started from 60 days postnatal and were carried out only during the diestrus phase of the reproductive cycle. In sociability test experimental animals exhibited reduced motivation for social encounter and deficit in social discrimination. In open field and the elevated plus maze, experimental animals showed enhanced emotionality with no changes in basal locomotor activity. The results showed that female rats submitted to neonatal status epipepticus showed impaired social behavior, characterized by reduced motivation to novelty and deficit in social discrimination in addition to enhanced emotionality.
Asunto(s)
Ansiedad/etiología , Conducta Exploratoria/fisiología , Motivación/fisiología , Convulsiones/complicaciones , Trastorno de la Conducta Social/etiología , Discriminación Social/psicología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Femenino , Aprendizaje por Laberinto , Ratas , Ratas WistarRESUMEN
During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1ß, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures.
Asunto(s)
Biomarcadores/sangre , Epilepsia/sangre , Epilepsia/prevención & control , Ácidos Grasos Omega-3/uso terapéutico , Inflamación/sangre , Animales , Conducta Animal , Proteína C-Reactiva/metabolismo , Convulsivantes , Citocinas/sangre , Epilepsia/inducido químicamente , Masculino , Pilocarpina , Ratas , Ratas Wistar , Estado Epiléptico/sangre , Estado Epiléptico/inducido químicamenteRESUMEN
Aging is often accompanied by cognitive decline, memory impairment and an increased susceptibility to neurodegenerative disorders. Most of these age-related alterations have been associated with deleterious processes such as changes in the expression of inflammatory cytokines. Indeed, higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines are found in the aged brain. This perturbation in pro- and anti-inflammatory balance can represent one of the mechanisms that contribute to age-associated neuronal dysfunction and brain vulnerability. We conducted an experimental study to investigate whether an aerobic exercise program could promote changes in inflammatory response in the brains of aged rats. To do so, we evaluated the levels of tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1ß), interleukin 6 (IL6) and interleukin 10 (IL10) in the hippocampal formation of 18 month old rats that underwent treadmill training over 10 consecutive days. Quantitative immunoassay analyses showed that the physical exercise increased anti-inflammatory cytokine levels IL10 in the hippocampal formation of aged rats, when compared to the control group. The hippocampal levels of pro-inflammatory cytokines IL1ß, IL6 and TNFα were not statistically different between the groups. However, a significant reduction in IL1ß/IL10, IL6/IL10 and TNFα/IL10 ratio was observed in the exercised group in relation to the control group. These findings indicate a favorable effect of physical exercise in the balance between hippocampal pro- and anti-inflammatory during aging, as well as reinforce the potential therapeutic of exercise in reducing the risk of neuroinflammation-linked disorders.
Asunto(s)
Envejecimiento/fisiología , Hipocampo/fisiología , Inflamación/fisiopatología , Condicionamiento Físico Animal/fisiología , Animales , Técnica del Anticuerpo Fluorescente , Inmunoensayo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Plasticidad Neuronal/fisiología , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The important role of cation-chloride co-transporters in epilepsy is being supported by an increasing number of investigations. However, enormous complexity is involved since the action of these co-transporters has effects on the ionic homeostasis influencing directly the neuronal excitability and the tissue propensity to sustain seizure. To unravel the complex mechanisms involving the co-transporters action during seizure, this paper shows simulations of non-synaptic epileptiform activity and the effect of the blockage of the two different types of cation-chloride co-transporters present in the brain: Na, K and 2Cl co-transporter (NKCC) and K and Cl co-transporter (KCC). The simulations were performed with an electrochemical model representing the non-synaptic structure of the granule cell layer of the dentate gyrus (DG) of the rat hippocampus. The simulations suggest: (i) the potassium clearance is based on the systemic interplay between the Na/K pump and the NKCC co-transporters; (ii) the simultaneous blockage of the NKCC of the neurons and KCC of glial cells acts efficiently suppressing the epileptiform activities; and (iii) the simulations show that depending on the combined blockage of the co-transporters, the epileptiform activities may be suppressed or enhanced.
Asunto(s)
Simulación por Computador , Epilepsia/tratamiento farmacológico , Simportadores de Cloruro de Sodio-Potasio/efectos de los fármacos , Simportadores/antagonistas & inhibidores , Animales , Electroencefalografía , Epilepsia/fisiopatología , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Ratas , Cotransportadores de K ClRESUMEN
Complementary therapies for preventing or treating epilepsy have been extensively used. This review focuses on the positive effects of physical exercise programs observed in clinical studies and experimental models of epilepsy and their significance as a complementary therapy for epilepsy. Information about the antiepileptogenic and neuroprotective effects of exercise is highlighted. Considering that exercise can exert beneficial actions such as reduction of seizure susceptibility, reduction of anxiety and depression, and consequently, improvement of quality of life of individuals with epilepsy, exercise can be a potential candidate as non-pharmacological treatment of epilepsy.
Asunto(s)
Terapias Complementarias/métodos , Epilepsia/rehabilitación , Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Animales , Epilepsia/fisiopatología , HumanosRESUMEN
The lateral-posterior thalamic nuclei (LP) have been shown to play an important role in controlling epileptic activity. In addition, thalamic atrophy and neuronal loss have been observed in epilepsy. The objective of this study was to investigate whether lateral-posterior neuronal activation may be observed shortly after a single generalized seizure in rats submitted to the pilocarpine model of epilepsy. The results showed an increased lateral-posterior activation as soon as the seizure occurred, suggesting that neuronal loss in the thalamus is not only the consequence of chronic epilepsy.