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The presence of dysmorphic neurons with strong cytoplasmatic accumulation of heavy non-phosphorylated neurofilament is crucial for the diagnostics of focal cortical dysplasia type II (FCDII). While ILAE's classification describes neocortical dysplasias, some groups have reported patients with mesial t abnormal neurons in the hippocampus of mesial temporal lobe epilepsy. Here we report a patient with such abnormal neurons in the hippocampus and compared it with previous reports of hippocampal dysplasia. Finally, we discuss the need for diagnostic criteria of hippocampal dysplasia.
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Epilepsia del Lóbulo Temporal , Hipocampo , Adulto , Humanos , Epilepsia , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Imagen por Resonancia Magnética , Malformaciones del Desarrollo Cortical/diagnóstico , Malformaciones del Desarrollo Cortical/patología , Malformaciones del Desarrollo Cortical de Grupo I/diagnóstico , Malformaciones del Desarrollo Cortical de Grupo I/patologíaRESUMEN
INTRODUCTION: Sodium valproate (VPA) is the most effective antiseizure medication (ASM) in genetic generalized epilepsies (GGEs). However, the frequent adverse effects and the high risk inflicted on the exposed offspring make it imperative to search for the lowest daily VPA dose able to control seizures for most patients. In the current published series, the VPA value of <1000 mg was the most adopted. OBJECTIVE: This study aims to provide a cutoff VPA value below which a given daily dose can be considered a low dose in patients with GGEs. METHODS: This retrospective, observational cohort study included patients with clinical and electroencephalographic diagnoses of GGEs based on the ILAE criteria. Patients were followed up for at least two years using VPA in mono- or polytherapy. Clinical data, VPA dose, and associated ASMs were analyzed. Adverse effects were also evaluated. We related seizure control to VPA doses through uni- and multivariate statistical analyses. RESULTS: From 225 patients, 169 (75%) had good seizure control, with most (60%) receiving monotherapy. The cutoff daily VPA dose capable of distinguishing these patients from those without seizure control was up to 1000 mg (p = 0.006) in univariate analyses and up to 700 mg in multivariate analyses. For patients in polytherapy, the cutoff was up to 1750 mg and 1800 mg in uni- and multivariate analyses, respectively. CONCLUSIONS: The lowest daily VPA dose in monotherapy able to control seizures for most GGE patients was up to 700 mg, a value that can be used as a low dose criterion in studies assessing the therapeutic VPA ranges. Patients using higher VPA doses or in polytherapy present a lower probability of seizure control.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Epilepsia Generalizada , Humanos , Ácido Valproico/efectos adversos , Anticonvulsivantes/efectos adversos , Estudios Retrospectivos , Epilepsia Generalizada/tratamiento farmacológico , Epilepsia Generalizada/genética , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológicoRESUMEN
The Sotos syndrome is an autosomal dominant disorder characterized by haploinsufficiency of NSD1 gene, with some individuals affected by epilepsy and, rarely, drug-resistant seizures. A 47-years-old female patient with Sotos syndrome was diagnosed with focal-onset seizures in left temporal lobe, left-side hippocampal atrophy, and neuropsychological testing with decreased performance in several cognitive domains. Patient was treated with left-side temporal lobe resection and developed complete awake seizure control in 3-years of follow-up, with marked improvement in quality-of-life. In selected, clinically concordant patients, resective surgeries may play a significant role in improving patient's quality of life and seizure control.
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This educational review article aims to provide information on the central nervous system (CNS) infectious and parasitic diseases that frequently cause seizures and acquired epilepsy in the developing world. We explain the difficulties in defining acute symptomatic seizures, which are common in patients with meningitis, viral encephalitis, malaria, and neurocysticercosis, most of which are associated with increased mortality and morbidity, including subsequent epilepsy. Geographic location determines the common causes of infectious and parasitic diseases in a particular region. Management issues encompass prompt treatment of acute symptomatic seizures and the underlying CNS infection, correction of associated predisposing factors, and decisions regarding the appropriate choice and duration of antiseizure therapy. Although healthcare provider education, to recognize and diagnose seizures and epilepsy related to these diseases, is a feasible objective to save lives, prevention of CNS infections and infestations is the only definitive way forward to reduce the burden of epilepsy in developing countries.
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Enfermedades Transmisibles , Encefalitis Viral , Epilepsia , Neurocisticercosis , Enfermedades Transmisibles/complicaciones , Encefalitis Viral/complicaciones , Epilepsia/complicaciones , Epilepsia/etiología , Humanos , Neurocisticercosis/complicaciones , Neurocisticercosis/epidemiología , Convulsiones/complicaciones , Convulsiones/etiologíaRESUMEN
Depression is the most frequent psychiatric comorbidity seen in mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS). Moreover, the HS is the most frequent pathological hallmark in MTLE-HS. Although there is a well-documented hippocampal volumetric reduction in imaging studies of patients with major depressive disorder, in epilepsy with comorbid depression, the true role of the hippocampus is not entirely understood. This study aimed to verify if patients with unilateral MTLE-HS and the co-occurrence of depression have differences in neuronal density of the hippocampal sectors CA1-CA4. For this purpose, we used a histopathological approach. This was a pioneering study with patients having both clinical disorders. However, we found no difference in hippocampal neuronal density when depression co-occurs in patients with epilepsy. In this series, CA1 had the lowest counting in both groups, and HS ILAE Type 1 was the most prevalent. More studies using histological assessments are needed to clarify the physiopathology of depression in MTLE-HS.
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BACKGROUND: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. OBJECTIVE: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. METHODS: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. RESULTS: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. CONCLUSION: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.
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Epilepsia Refractaria , Epilepsias Parciales , Adulto , Anticonvulsivantes/uso terapéutico , Niño , Método Doble Ciego , Quimioterapia Combinada , Humanos , Levetiracetam/uso terapéutico , Calidad de Vida , Resultado del TratamientoRESUMEN
Introduction: Many neuropsychiatric and neurodegenerative disorders produce Theory of Mind impairment. We aimed to implement a Brazilian Portuguese version of the Faux Pas Recognition Test (FPRT) and evaluate its psychometric properties.Methods: We first completed an English-Brazilian Portuguese translation and adaptation to obtain an FPRT Brazilian Portuguese version. We performed a multicentric study with 153 healthy participants (68.6% women), mean age of 38.8 years (SD = 14.6) and 12.9 years of schooling (SD = 4.5). Linear regression analysis was performed to evaluate the association of social class, age, schooling, and FPRT scores. The psychometric analyses comprised item analysis, exploratory factor analysis, reliability, and validity analysis.Results: Normative data in a Brazilian population is presented. A positive correlation of scores with years of schooling, social class, and an inverse relation with age was found. The exploratory factorial analysis found a two-component structure, one component, consisting of questions 1 through 6 (Eigenvalue 5.325) and another component, consisting of questions 7 and 8 (Eigenvalue 1.09). Cronbach's alpha of the 20 stories was .72. All control stories had a poor discriminative index.Conclusion: The FPRT Brazilian Portuguese version demonstrated good internal consistency and, psychometric properties and is adequate for use even in lower educational contexts in Brazil.
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Traducciones , Adulto , Brasil , Femenino , Humanos , Masculino , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.
RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.
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Humanos , Niño , Adulto , Epilepsias Parciales , Epilepsia Refractaria , Calidad de Vida , Método Doble Ciego , Resultado del Tratamiento , Quimioterapia Combinada , Levetiracetam/uso terapéutico , Anticonvulsivantes/uso terapéuticoRESUMEN
This study aimed to analyse the effect of neuropsychological activation methods on interictal epileptiform discharges, compared to standard activation methods, for both focal and generalized epilepsies. This was a multicentre, prospective study including 429 consecutive EEG recordings of individuals with confirmed or suspected diagnosis of epilepsy. Neuropsychological activation included reading aloud in foreign and native language, praxis and a letter cancelation task (each with a duration of three minutes). After counting interictal discharges in three-minute time windows, activation and inhibition were assessed for each procedure, accounting for spontaneous fluctuations (95% CI) and compared to the baseline condition with eyes closed. Differences between generalized and focal epilepsies were explored. Interictal epileptiform discharges were present in 59.4% of the recordings. Activation was seen during hyperventilation in 31%, in at least one neuropsychological activation method in 15.4%), during intermittent photic simulation in 13.1% and in the resting condition with eyes open in 9.9%. The most frequent single cognitive task eliciting activation was praxis (10.3%). Lasting activation responses were found in 18-25%. Significant inhibition was found in 88/98 patients with baseline interictal epileptiform discharges, and was not task-specific. Adding a brief neuropsychological activation protocol to the standard EEG slightly increased its sensitivity in patients with either focal or generalized epilepsy. However, in unselected epilepsy patients, this effect seems only exceptionally to result in ultimate diagnostic gain, compared to standard procedures. From a diagnostic perspective, cognitive tasks should be reserved for patients with a suspicion of cognitive reflex epilepsy/seizures and probably require longer exposure times. Further research is needed to explore potential therapeutic applications of the observed inhibition of interictal epileptiform discharges by cognitive tasks in some patients.
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Epilepsias Parciales/diagnóstico , Epilepsias Parciales/fisiopatología , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatología , Pruebas Neuropsicológicas , Desempeño Psicomotor/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Atención/fisiología , Niño , Protocolos Clínicos , Electroencefalografía , Femenino , Neuroimagen Funcional , Humanos , Hiperventilación/fisiopatología , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Estudios Prospectivos , Lectura , Adulto JovenRESUMEN
Towards the end of the 19th century, two writers who are considered the uppermost representatives of their respective national literatures, Dostoyevsky of Russia and Machado de Assis of Brazil had epilepsy, probably both temporal lobe epilepsy, but their attitudes were opposite. Dostoyevsky was as open about his diagnosis as Machado was secretive, but both included seizure experiences in their works. Two of Dostoyevsky's many epileptic characters, Prince Myshkin in The Idiot and Kirillov in Devils, report the same ecstatic aura as Dostoyevsky did privately. That Kirillov only has isolated auras probably reflects the early phase of Dostoyevsky's epilepsy. A hitherto overlooked feature, these reports with numerous reformulations and metaphors are linguistically characteristic for self-reports of epileptic auras, related to the indescribability of the experiences. In Idiot, two seizure prodromes with great artistic skill are integrated into the fictional context. Machado in his writings never talked overtly about seizures and epilepsy, but experiences of complex partial seizures can be identified in two of his novels, Brás Cubas and Quincas Borba. One depicts a complex visual illusion, the other seems precipitated by a coincidence of several ambivalent decisions with a specific memory. Quincas Borba (1891) has several features that can be understood as an homage to Dostoyevsky's Idiot (1869). Both writers share the notion that seizures can be triggered by strong emotions, and both stand out by their mastership of seamlessly integrating seizure experiences into the fictional and psychological cosmos of their novels. This article is part of the Special Issue "NEWroscience 2018".
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Epilepsia del Lóbulo Temporal , Epilepsia , Personajes , Brasil , Humanos , ConvulsionesRESUMEN
PURPOSE: To evaluate impulsiveness in adult patients with JME and its relationship with personality traits and executive functioning. METHODS: Patients completed psychiatric evaluation (DSM IV), Barratt Impulsiveness Scale (BIS-11), Neo Revised Personality Inventory (NEO PI-R) and executive functioning evaluation comprising Controlled Oral Word Association (COWA), Digit Span, Trail Making Tests (TMT), Stroop Test (ST) and Wisconsin Card Sorting Test (WSCT). Healthy controls (63 % female, mean age 35.7 yrs. (±8.37)) were examined to allow calculation of z-scores. RESULTS: 50 patients (70 % female; mean age 32.5 yrs. (±9.2)) presented higher scores of Total (z=-0.37; pâ¯=â¯0.005) and Motor Impulsiveness (z=-0.79; pâ¯<â¯0.001) on BIS-11. Motor Impulsiveness was associated with higher rates of mild psychiatric disorders (depression and anxiety) (pâ¯=â¯0.035) and worse myoclonic seizure control (pâ¯=â¯0.007). NEO PI-R showed differences on Neuroticism (z=-0.60; pâ¯<â¯0.001), Openness (zâ¯=â¯0.38; pâ¯=â¯0.043), Agreeableness (z=-0.38; pâ¯=â¯0.033) and Conscientiousness (z=-0.53; pâ¯=â¯0.003). There were positive correlations between BIS-11 and Neuroticism with Total, Motor and Non-Planning Impulsiveness, on the other hand, Conscientiousness was negatively correlated with these as well as with Attentive Impulsiveness. Patients performance was worse than that of controls on COWA (z=-0.43; pâ¯=â¯0.009) and WCST's Total Number of Completed Categories (z=-2.08; pâ¯=â¯0.005), Trials Taken to Complete First Category (z=-1.56; pâ¯=â¯0.013), Percentage of Total Errors (z=-1.56; pâ¯<â¯0.001), Perseverative Errors (z=-0.73; pâ¯=â¯0.002), Non-Perseverative Errors (z=-1.05; pâ¯=â¯0.003) and Conceptual Level Responses (z=-1.52; pâ¯<â¯0.001). Non-Planning Impulsiveness correlated with Performance (ST and TMT). CONCLUSION: Patients with JME present with impulsive behavior, personality features and executive dysfunction which are linked and may lead to lack of commitment in treatment and affect other aspects of life.
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Función Ejecutiva , Epilepsia Mioclónica Juvenil , Personalidad , Adulto , Femenino , Humanos , Masculino , Epilepsia Mioclónica Juvenil/psicología , Pruebas Neuropsicológicas , Inventario de PersonalidadRESUMEN
Neurocysticercosis is a neglected and usually poverty-related disease of high public importance. The mechanisms by which the calcified lesions cause epilepsy are not known, but have been attributed to residual perilesional gliosis or an inflammatory process. This case shows that an inflammatory response to a calcified granuloma may be associated with the development of epilepsy. The increase in glutamate and kinin B1 (pro-epileptogenic) receptors added by reduced expression of kinin B2 (anti-epileptogenic) receptors may explain the chronic epileptogenesis associated with the lesion, corroborating the hypothesis of inflammatory mechanisms involved in the pathophysiology of epilepsy in these patients.
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Epilepsia Refractaria , Neurocisticercosis , Biomarcadores , Niño , Epilepsia Refractaria/diagnóstico , Epilepsia Refractaria/etiología , Epilepsia Refractaria/inmunología , Electroencefalografía , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Neurocisticercosis/complicaciones , Neurocisticercosis/diagnóstico , Neurocisticercosis/inmunología , Neurocisticercosis/patologíaRESUMEN
PURPOSE: Self-limited epilepsy with centrotemporal spikes, formerly called benign epilepsy with centrotemporal spikes, or rolandic epilepsy, is an age-related and well-defined epileptic syndrome. Since seizures associated with rolandic spikes are infrequent and usually occur during sleep, and repetitive or prolonged EEG recording for diagnostic purposes is not necessary for diagnosis, reports of ictal video-electroencephalographic seizures in this syndrome are rare. We aimed to show ictal video-EEG of typical rolandic seizures. METHODS: We report the ictal video-EEG recordings of two children with rolandic epilepsy who presented typical rolandic seizures during routine recording. RESULTS: Case 1: A 9-year-old boy, with normal development, had his first seizure at 8 years old, characterized by paresthesia in his left face, blocking of speech, and drooling. Carbamazepine was started with seizure control. Case 2: A 10-year-old boy, with normal development, started with focal seizures during sleep, characterized by eye and perioral deviation, and speech arrest at age of 7. He started using oxcarbazepine. Both patients underwent routine electroencephalography for electroclinical diagnosis and presented a seizure. CONCLUSION: Although self-limited epilepsy with centrotemporal spikes is a very common epileptic syndrome, seizure visualization is very difficult, and these videos may bring didactical information for recognition of this usual presentation of benign childhood focal epilepsy.
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Electroencefalografía , Epilepsia Rolándica , Carbamazepina/uso terapéutico , Niño , Documentación , Epilepsia Rolándica/complicaciones , Epilepsia Rolándica/diagnóstico , Epilepsia Rolándica/tratamiento farmacológico , Humanos , Masculino , Convulsiones/complicaciones , Convulsiones/diagnósticoRESUMEN
Semiology is the backbone of any correct categorization of seizures, as epileptic or not, focal or bilateral, and is fundamental to elucidating how they are anatomically generated in the brain. An anatomical hypothesis derived from seizure history is the precondition for optimally designed ancillary studies. Without understanding seizure semiology, no rational therapy is possible. This article describes the semiological approach using patient history based on full use of patients' self-reports as well as descriptions by witnesses. Auras represent the subjective aspects of seizures and provide important semiological clues as observable signs, sometimes including rather precise direct anatomical information. Methods of extracting, facilitating and analysing self-reports including linguistic conversation analysis are presented in detail. It is highlighted that prodromes, seizure triggers and reflex epileptic mechanisms can provide crucial information for diagnostics and therapy. Special issues considering seizure semiology in children are discussed in a separate section. Other sections are dedicated to the two most important issues of differential diagnosis: how to distinguish (1) focal from "generalized" epilepsies, particularly when focal seizure phenomena appear in a bilateral epilepsy; and (2) epileptic from a series of non-epileptic events.
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Epilepsia/diagnóstico , Epilepsia/fisiopatología , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Adulto , Niño , HumanosRESUMEN
Seizure recurrence (SR) after epilepsy surgery in patients with medically resistant temporal lobe epilepsy and mesial temporal sclerosis (TLE-MTS) can compromise medical treatment and quality of life (QOL). However, there is a scarcity of interventions specifically addressing this issue in the literature. We aimed to evaluate the impact of a four-week psychotherapeutic intervention on the levels of resilience, behavioral symptoms, and QOL of patients with drug-resistant TLE-MTS who underwent corticoamygdalohippocampectomy (CAH) and who presented with late SR. Fifty patients who had been diagnosed with TLE-TMS, undergone CAH, and presented with late SR were included. The study instruments included a clinical and sociodemographic questionnaire and the Brazilian versions of the Connor-Davidson Resilience Scale (CD-RISC-10), the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Interictal Dysphoric Disorder Inventory (IDDI), and the Quality of Life in Epilepsy Inventory (QOLIE-31). Significant reductions in the IDDI (pâ¯<â¯0.001) and NDDI-E (pâ¯<â¯0.001) scores, improvements in the CD-RISC-10 (pâ¯<â¯0.001) and QOLIE-31 (pâ¯<â¯0.001) scores, and positive correlations between resilience levels and QOL (pâ¯<â¯0.01), as well as a negative correlation between depressive symptoms and resilience (pâ¯<â¯0.01) and QOL (pâ¯<â¯0.01), were observed after the psychotherapeutic intervention. Improvements in the resilience levels and QOL, with concomitant reductions in depressive symptoms, were observed in patients with TLE-MTS and late SR after a brief psychotherapeutic intervention. Since there is a lack of studies that measured the impact of interventions in this patient subpopulation, these results may support the development of treatment strategies for this specific group.
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Epilepsia Refractaria/terapia , Epilepsia del Lóbulo Temporal/terapia , Psicoterapia/métodos , Resiliencia Psicológica , Adulto , Análisis de Varianza , Brasil , Depresión/psicología , Trastorno Depresivo/complicaciones , Epilepsia Refractaria/psicología , Epilepsia del Lóbulo Temporal/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Convulsiones/terapia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Temporal lobe epilepsy (TLE) is a chronic disease, characterized by severe and refractory seizures, triggered in the hippocampus and/or amygdala, disrupting the blood-brain barrier. This disruption can sustain, or aggravate, the epileptic condition. The aim of this study was to evaluate the activation of the kallikrein-kinin system in patients with TLE, as it relates to the maintenance of blood-brain barrier. Human hippocampal sclerotic tissues removed after surgery for seizure control, plasma, and serum were used in the following assays: immunostaining for white blood cells in the TLE hippocampus, C-reactive protein in serum, quantification of plasma kallikrein (PKal) and cathepsin B (CatB) activity in serum and plasma, quantification of C1-inhibitor, analysis of high-molecular-weight kininogen (H-kininogen) fragments, and activation of plasma prekallikrein for comparison with healthy controls. Infiltration of white blood cells in the sclerotic hippocampus and a significant increase in the neutrophil/lymphocyte ratio in the blood of TLE patients were observed. High levels of C-reactive protein (TLE = 1.4 ± 0.3 µg/mL), PKal (TLE = 5.4 ± 0.4 U/mL), and CatB (TLE = 4.9 ± 0.4 U/mL) were also evident in the serum of TLE patients comparing to controls. A strong linear correlation was observed between active CatB and PKal in the serum of TLE patients (r = 0.88). High levels of cleaved H-kininogen and free PKal, and low levels of C1-inhibitor (TLE = 188 ± 12 µg/mL) were observed in the serum of TLE patients. Our data demonstrated that the plasma kallikrein-kinin system is activated in patients with TLE. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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Catepsina B/sangre , Epilepsia del Lóbulo Temporal/metabolismo , Inflamación/metabolismo , Sistema Calicreína-Quinina/fisiología , Calicreínas/sangre , Adulto , Femenino , Hipocampo/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Mesial temporal lobe epilepsy (MTLE) is usually associated with drug-resistant seizures and cognitive deficits. Efforts have been made to improve the understanding of the pathophysiology of MTLE for new therapies. In this study, we used proteomics to determine the differential expression of proteins in the hippocampus of patients with MTLE compared to control samples. By using the two-dimensional electrophoresis method (2-DE), the proteins were separated into spots and analyzed by LC-MS/MS. Spots that had different densitometric values for patients and controls were selected for the study. The following proteins were found to be up-regulated in patients: isoform 1 of serum albumin (ALB), proton ATPase catalytic subunit A (ATP6V1A), heat shock protein 70 (HSP70), dihydropyrimidinase-related protein 2 (DPYSL2), isoform 1 of myelin basic protein (MBP), and dihydrolipoamide S-acethyltransferase (DLAT). The protein isoform 3 of the spectrin alpha chain (SPTAN1) was down-regulated while glutathione S-transferase P (GSTP1) and protein DJ-1 (PARK7) were found only in the hippocampus of patients with MTLE. Interactome analysis of the nine proteins of interest revealed interactions with 20 other proteins, most of them involved with metabolic processes (37%), presenting catalytic activity (37%) and working as hydrolyses (25%), among others. Our results provide evidence supporting a direct link between synaptic plasticity, metabolic disturbance, oxidative stress with mitochondrial damage, the disruption of the bloodâ»brain barrier and changes in CNS structural proteins with cell death and epileptogenesis in MTLE. Besides this, the presence of markers of cell survival indicated a compensatory mechanism. The over-expression of GSTP1 in MTLE could be related to drug-resistance.
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PURPOSE: Eye closure sensitivity (ECS) has been described as a reflex trait in juvenile myoclonic epilepsy (JME). However, there is no consensus regarding its significance on prognosis. The aim of this study is to clarify the long-term impact of ECS documented by a clinical interview and a video-EEG neuropsychological protocol (VNPP) in a series of 133 JME patients. METHODS: Data from 22 JME patients with ECS confirmed by a VNPP (Group 1) were compared with those of 20 JME patients without any reflex traits (Group 2). They were followed for a mean of 8.21 years (SD=±5.044). The frequency of seizures was assessed using a diary. Except for photosensitivity (PS), any other reflex traits occurrence, drugs/alcohol abuse intake, noncompliance, and Jeavons syndrome, were considered exclusion criteria. RESULTS: Group 1 had a lower age at epilepsy onset (p = 0.028), higher incidence of febrile seizures (13.6%), and familial history of epilepsy (p = 0.023). Only 18.2% had self-perception of eyelid myoclonia (EM) (kappa coefficient = 0.193), which persisted in 77.3% of patients. Limb myoclonia, tonic-clonic seizures (TCS) and/or myoclonic-tonic-clonic seizures (MTCS), as well as absences were more frequent (p = 0.015; p = 0.013; p = 0.011, respectively) in Group 1. PS did not influenced frequency of EM (p = 1.0), absences (p = 0.648), or TCS/MTCS (p = 0.934). Psychiatric comorbidities were not different between groups. CONCLUSIONS: ECS is related to a worse outcome regarding control of all seizure types, persistence of EM, and higher frequency of limb myoclonia, as well as the total number of TCS and/or MTCS.
Asunto(s)
Párpados/fisiopatología , Epilepsia Mioclónica Juvenil/diagnóstico , Epilepsia Mioclónica Juvenil/fisiopatología , Reflejo/fisiología , Adulto , Factores de Edad , Anticonvulsivantes/uso terapéutico , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Epilepsia Mioclónica Juvenil/tratamiento farmacológico , Pronóstico , Estadísticas no Paramétricas , Adulto JovenRESUMEN
PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.