ABSTRACT
SUMMARY: Studies have shown the adverse effects of epileptic seizures on reproductive health. The aim of the present study was to investigate morphological changes, apoptosis and GABA localization in the testis tissue of genetic absence epilepsy rats. Testis tissues of GAERS and Wistar rats were processed for paraffin embedding and electron microscopy. Sections were stained with hematoxylin and eosin, Masson's trichrome and periodic acid-Schiff reaction. GABA immunohistochemistry was applied for determining the alterations in GABA levels. GABA immunoreactivity was observed in the seminiferous tubules and interstitial areas of both GAERS and Wistar rats. GABA immunoreactivity was found to be decreased in GAERS compared to Wistar group. Electron microscopic observations showed that GABA was present in manchette microtubules, sperm tail and neck at different phases of spermiogenesis. Qualitative observations revealed that testis tissues of GAERS showed reduced sperm in the seminiferous tubules compared to the Wistar controls. In conclusion, we demonstrated GABAergic system in the seminiferous tubules of control and GAERS rats, in parallel with the previous studies; and there were alterations in this system in GAERS. We suggest that these alterations in absence epilepsy may also affect the gonadal system, resulting in decreased sperm production.
RESUMEN: Los estudios han demostrado los efectos adversos de las convulsiones epilépticas sobre la salud reproductiva. El objetivo del presente estudio fue investigar los cambios morfológicos, la apoptosis y la localización de GABA en el tejido testicular de ratas con epilepsia de ausencia genética. Se procesaron tejidos testiculares de ratas GAERS y Wistar para inclusión en parafina y microscopía electrónica. Las secciones se tiñeron con hematoxilina y eosina, tricrómico de Masson y reacción de ácido peryódico de Schiff. Se aplicó inmunohistoquímica de GABA para determinar las alteraciones en los niveles de GABA. Se observó inmunorreactividad de GABA en los túbulos seminíferos y las áreas intersticiales de las ratas GAERS y Wistar. Se encontró que la inmunorreactividad de GABA estaba disminuida en GAERS en comparación con el grupo Wistar. Las observaciones microscópicas electrónicas mostraron que GABA estaba presente en los microtúbulos, la cola y el cuello del espermatozoide en diferentes fases de la espermiogénesis. Las observaciones cualitativas revelaron que los tejidos testiculares de GAERS mostraron una reducción de los espermatozoides en los túbulos seminíferos en comparación con los controles Wistar. En conclusión, demostramos el sistema GABAérgico en los túbulos seminíferos de ratas control y GAERS, en paralelo con estudios previos; y además se observaron alteraciones en este sistema en GAERS. Sugerimos que estas alteraciones en epilepisa de ausencia genética también pueden afectar el sistema gonadal, resultando en una disminución de la producción de semen.
Subject(s)
Animals , Pregnancy , Rats , Testis/metabolism , Epilepsy, Absence , gamma-Aminobutyric Acid/metabolism , Testis/ultrastructure , Immunohistochemistry , Microscopy, Electron , Rats, WistarABSTRACT
Absence seizures (AS) are generalized non-convulsive seizures characterized by a brief loss of consciousness and spike-and-wave discharges (SWD) in an electroencephalogram (EEG). A number of animal models have been developed to explain the mechanisms of AS, and thalamo-cortical networks are considered to be involved. However, the cortical foci have not been well described in mouse models of AS. This study aims to use a high density EEG in pathophysiologically different AS models to compare the spatiotemporal patterns of SWDs. We used two AS models: a pharmacologically induced model (gamma-hydroxybutyric acid, GHB model) and a transgenic model (phospholipase beta4 knock-out, PLCβ4 model). The occurrences of SWDs were confirmed by thalamic recordings. The topographical analysis of SWDs showed that the onset and propagation patterns were markedly distinguishable between the two models. In the PLCβ4 model, the foci were located within the somatosensory cortex followed by propagation to the frontal cortex, whereas in the GHB model, a majority of SWDs was initiated in the prefrontal cortex followed by propagation to the posterior cortex. In addition, in the GHB model, foci were also observed in other cortical areas. This observation indicates that different cortical networks are involved in the generation of SWDs across the two models.
Subject(s)
Animals , Mice , Electroencephalography , Epilepsy, Absence , Frontal Lobe , Models, Animal , Prefrontal Cortex , Seizures , Somatosensory Cortex , UnconsciousnessABSTRACT
GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.
Subject(s)
Child , Female , Humans , Infant, Newborn , Apnea , Ataxia , Cerebrospinal Fluid , Clothing , Cognition , Dyskinesias , Dystonia , Early Diagnosis , Epilepsy , Epilepsy, Absence , Glucose , Diet, Ketogenic , Microcephaly , Movement Disorders , Phenotype , Quality of Life , Retrospective Studies , SeizuresABSTRACT
Aplastic anemia may develop secondary to environmental exposure to entities such as chemicals, medical drugs, and infectious agents. Fatal complications from antiepileptic medications may occur despite careful and appropriate use. We report the case of a 9-year-old girl with a presenting diagnosis of aplastic anemia following treatment with ethosuximide for absence seizures. Aplastic anemia can now be cured with stem cell transplantation or immunosuppressive therapy. In this case, however, because of the impossibility of bone marrow transplantation and the specific needs of the patient's parents, three courses of methylprednisolone pulse therapy were administered. Following the therapy, there was improvement in pancytopenia and complete remission in the bone marrow. No adverse side effects of therapy were observed. The authors suggest that methylprednisolone pulse therapy may be a treatment for acquired aplastic anemia.
Subject(s)
Child , Female , Humans , Anemia, Aplastic , Anticonvulsants , Bone Marrow , Bone Marrow Transplantation , Diagnosis , Environmental Exposure , Epilepsy, Absence , Ethosuximide , Methylprednisolone , Pancytopenia , Parents , Stem Cell TransplantationABSTRACT
OBJECTIVE@#To investigate the clinical significance of high-frequency oscillations (HFOs) on scalp electroencephalography (EEG) in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS).@*METHODS@#Twenty-one CSWS patients treated for epilepsy from January 2006 to December 2016 in Pediatric Department of Peking University First Hospital were enrolled into the study. Selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs were compared between (a). HFO-positive group and HFO-negative group before methylprednisolone treatment and (b). excellent seizure outcome group and not-excellent seizure outcome group after methylprednisolone treatment. Interictal HFOs and spikes in pre- and post-methylprednisolone scalp EEG were measured and analyzed.@*RESULTS@#Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs tended to have more frequent epileptic negative myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%) were associated with spikes. The highest amplitudes of HFOs were significantly positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by methylprednisolone treatment were statistically significant for both HFOs (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and 39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and HFOs changes was respectively 100% decrease and 47% decrease in the excellent seizure outcome group, and they were 79% decrease and 18% increase in the not-excellent seizure outcome group.@*CONCLUSION@#Prevalence of HFOs might reflect some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone treatment than spikes and had a good correlation with the prognosis of seizures, and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.
Subject(s)
Child , Humans , Anticonvulsants/therapeutic use , Electroencephalography/methods , Epilepsy/physiopathology , Epilepsy, Absence , Methylprednisolone , Scalp , Seizures , SleepABSTRACT
Magnetic resonance imaging (MRI) is recommended for patients with epileptic seizures to rule out an underlying focal lesion. However, abnormalities in idiopathic generalized epilepsy, including childhood absence epilepsy, cannot usually be identified using brain imaging modalities such as MRI. Peri-ictal MRI abnormalities have been most commonly reported secondary to status epilepticus and are rarely observed in patients with focal seizures and generalized tonic-clonic seizures. Transient peri-ictal MRI abnormalities in absence epilepsy are extremely rare. A five-year-old girl presented with a three-day history of absence seizures that persisted despite continued treatment with sodium valproate. Electroencephalography showed bursts of generalized 3-Hz spike-and-wave discharges, during and after hyperventilation. Abnormal cortex thickening in the left perisylvian region was detected on T2-weighted brain MRI, and cortical dysplasia or a tumor was suspected. The patient started treatment with lamotrigine and was seizure-free after one month. The abnormal MRI lesion was completely resolved at the two-month follow-up. We report on a patient with childhood absence epilepsy and reversible brain MRI abnormalities in the perisylvian region. To our knowledge, this is the first report of transient MRI abnormalities after absence seizures. Transient peri-ictal MRI abnormalities should be considered for differential diagnosis in patients with absence seizures and a focal abnormality on brain MRI.
Subject(s)
Female , Humans , Brain , Diagnosis, Differential , Electroencephalography , Epilepsy , Epilepsy, Absence , Epilepsy, Generalized , Follow-Up Studies , Hyperventilation , Magnetic Resonance Imaging , Malformations of Cortical Development , Neuroimaging , Seizures , Status Epilepticus , Valproic AcidABSTRACT
Introducción: El diagnóstico temprano de los Episodios Paroxísticos No Epilépticos (EPNE) y la clara diferenciación con crisis epilépticas es esencial para su manejo y evitar tratamientos innecesarios. Conocer la frecuencia y características clínicas permite mejorar las estrategias diagnósticas, disminuyendo la cantidad de estudios complementarios solicitados y los días de internación, mejorando la calidad de atención. Materiales y Métodos: estudio descriptivo y retrospectivo de revisión de historias clínicas de pacientes de un mes a 16 años de edad internados por convulsión en el Hospital Británico durante el periodo de junio 2013 a junio 2015. Resultados: Se obtuvo una muestra de 71 pacientes: 25.4% tuvieron como diagnóstico EPNE, 74.6% tuvieron otros diagnósticos. Se compararon ambos grupos. La edad de presentación de los EPNE fue en la mayoría de los casos antes de los 2 años de edad con hipotonía como presentación clínica más frecuente. En el resto de la población analizada, la edad de presentación fue a los 3.5 años y prevalecieron los movimientos tónicos clónicos generalizado. Los EEG realizados fueron normales en el 100% de los EPNE mientras que en los trastornos convulsivos resultó patológico en el 56.5% Conclusiones: Se observaron diferencias significativas entre los pacientes con EPNE en comparación con el resto de la población analizada. Los EPNE presentan crisis de menos de 1 minuto de duración, suelen no tener episodio post-ictal, presentan una mayor incidencia de hipotonía y el EEG es normal. Los pacientes con EPNE no requirieron medidas de cuidados intensivos lo que habla de la benignidad de estos eventos.
Introduction: Paroxysmal nonepileptic disorders can cause diagnostic confusion,and it is important to differentiate them from epileptic disorders, so that a correct management and treatment can be established. In order to settle a correct diagnostic strategy it is essential to know the incidence and the clinical presentation of this pathology. With an accurate diagnosis, the number of complementary studies and the length of the hospital stay will diminish. Methodology: A retrospective descriptive study of clinical histories from pediatric patients, aged 1 month to 16 years, admitted at the British Hospital of Buenos Aires with seizure diagnosis during the lapse of time between June 2013 and June 2015, was undertaken. Results: A total of 71 patients were analyzed. 25.4% had non-epileptic paroxysmal events, 74.5% had other diagnosis. Both groups were compared. Patients with non-epileptic paroxysmal events presented symptoms before the 2 years of age, hypotonia was the most common clinical presentation and these patients had a normal electroencephalogram (EEG). The other group presented symptoms at 3.5 years of age, tonic-clonic movement was the most frequent symptom and 56, 5% had abnormal EEG. Conclusion: Significant differences were found between patients with nonepileptic paroxysmal events and the rest of the patients analyzed. Patients with non- epileptic paroxysmal disorder present events of less than one minute of duration with no postictal state, hypotinia is the most frequent symptom seen and the EEG results normal. Patients with nonepileptic paroxysmal disorder did not require admission to intensive care unit; this reflects the benign condition of the pathology
Subject(s)
Humans , Infant , Child, Preschool , Child , Adolescent , Seizures/diagnosis , Epidemiology, Descriptive , Retrospective Studies , Epilepsy, Absence/diagnosis , Early Diagnosis , Diagnostic ErrorsABSTRACT
OBJECTIVE: The anti-epileptogenic drug levetiracetam has anticonvulsant and anti-epileptogenesis effects. Synergy between cell death and inflammation can lead to increased levels of apoptosis inhibitory factors and brain-derived neurotrophic factor, aberrant neurogenesis and extended axon sprouting. Once hyperexcitation of the neural network occurs, spontaneous seizures or epileptogenesis develops. This study investigated whether the anti-epileptogenic effect of levetiracetam is due to its alternate apoptotic activity. METHODS: Adult male Noda epileptic rats were treated with levetiracetam or vehicle control for two weeks. mRNA quantification of Bax, Bcl-2 and GAPDH expression were performed from prefrontal cortex and hippocampus tissue samples. RESULTS: The levetiracetam-treated group showed a significant increase of Bax/Bcl-2 mRNA expression ratio in the prefrontal cortex than the control group, but no change in the Bax/Bcl-2 mRNA expression ratio in hippocampus. CONCLUSION: Idiopathic generalized epilepsy including childhood absence epilepsy develop at childhood and recover spontaneously during adolescence. The aberrant neural excitable network is pruned by a neural-maturing action. This study suggests the mechanism of acquired anti-epileptogenesis by levetiracetam treatment may be similar to spontaneous recovery of idiopathic generalized epilepsy during adolescence.
Subject(s)
Adolescent , Adult , Animals , Humans , Male , Rats , Apoptosis , Axons , Brain-Derived Neurotrophic Factor , Cell Death , Epilepsy, Absence , Epilepsy, Generalized , Hippocampus , Inflammation , Neurogenesis , Prefrontal Cortex , RNA, Messenger , SeizuresABSTRACT
BACKGROUND AND PURPOSE: Childhood absence epilepsy (CAE) is one of the most common types of pediatric epilepsy. It is generally treated with ethosuximide (ESM), valproic acid (VPA), or lamotrigine (LTG), but the efficacy and adverse effects of these drugs remain controversial. This study compared initial therapy treatment outcomes, including VPA-LTG combination, and assessed clinical factors that may predict treatment response and prognosis. METHODS: Sixty-seven patients with typical CAE were retrospectively enrolled at the Korea University Medical Center. We reviewed patients' clinical characteristics, including age of seizure onset, seizure-free interval, duration of seizure-free period, freedom from treatment failure, breakthrough seizures frequency, and electroencephalogram (EEG) findings. RESULTS: The age at seizure onset was 7.9±2.7 years (mean±SD), and follow-up duration was 4.4±3.7 years. Initially, 22 children were treated with ESM (32.8%), 23 with VPA (34.3%), 14 with LTG (20.9%), and 8 with VPA-LTG combination (11.9%). After 48 months of therapy, the rate of freedom from treatment failure was significantly higher for the VPA-LTG combination therapy than in the three monotherapy groups (p=0.012). The treatment dose administrated in the VPA-LTG combination group was less than that in the VPA and LTG monotherapy groups. The shorter interval to loss of 3-Hz spike-and-wave complexes and the presence of occipital intermittent rhythmic delta activity on EEG were significant factors predicting good treatment response. CONCLUSIONS: This study showed that low-dose VPA-LTG combination therapy has a good efficacy and fewer side effects than other treatments, and it should thus be considered as a firstline therapy in absence epilepsy.
Subject(s)
Child , Humans , Academic Medical Centers , Electroencephalography , Epilepsy , Epilepsy, Absence , Ethosuximide , Follow-Up Studies , Freedom , Korea , Prognosis , Retrospective Studies , Seizures , Treatment Failure , Valproic AcidABSTRACT
Introdução: Uma importante aplicação da técnica de Ressonância Magnética funcional é em pesquisa clínica, acerca das funções cognitivas de pacientes, como por exemplo atenção, memória, linguagem, dentre outras. Pacientes com Epilepsia Idiopática da Infância podem apresentar déficits cognitivos e não possuem alterações estruturais detectáveis o que facilita a aplicação de técnicas computacionais de registro e normalização em estudos de neuroimagem o que possibilita a geração de imagens de um grupo de indivíduos e suas diversas possibilidades de inferências estatísticas. Este estudo teve como objetivo descrever as funções cognitivas em pacientes com Epilespia Rolândica (ER) e Epilepsia de Ausência (EA) através da RMf. Métodos: 57 indíviduos, 23 pacientes com ER ((média= 10,7 anos), 20 pacientes com EA (média= 9,9 anos) e 14 controles saudáveis (média=10 anos) foram submetidos ao vídeo-EEg, testes neuropsicológicos para avaliação das funções cognitivas (QI, funções executivas, dentre outras) e um paradigma de atenção Stoptask Gonogo e um paradigma Resting State (RS). Os dados foram analisados e foram gerados mapas limirializados de ativação da função BOLD. Resultados: As principais áreas ativas em pacientes e controles no paradigma Stoptask foram: hemisférios cerebelares bilateral, córtex orbito frontal bilateral, giros fusiformes, ínsula bilateral, córtex dorso latero pré-frontal, giro do Cíngulo anterior direito e esquerdo, bordas dos sulcos intraparietais, giros frontais superiores, eye-field.(p < 0,01). No paradigma RS as áreas encontradas foram: Córtex medial prefrontal, giro angular, giro supramarginal, giro do cíngulo posterior, giro frontal superior, sulco intraparietal, área motora suplementar, córtex prefrontal lateral (p < 0,05). OS mapas comparativos de grupos mostraram diferenças em ativaçao entre pacientes e controles. Discussão: Nossos mapas de ativação da resposta BOLD são semelhantes aos encontrados por outros autores na...
Introduction: An important application of functional MRI is in clinical research about the cognitive functions of patients, such as attention, memory, language, among others. Patients with Idiopathic Epilepsy of Childhood may show cognitive deficits and have no detectable structural changes which facilitates the application of computational techniques and standardization of registration in neuroimaging studies, which enables to obtain a group map of individuals and their various possibilities for statistical inferences. This study aimed to describe the cognitive functions in patients with Rolandic Epilepsy (RE) and absence epilepsy (AE) by fMRI. Methods: 57 individuals, 23 patients with RE (mean = 10.7 years), 20 patients with AE (mean = 9.9 years) and 14 healthy controls (mean = 10 years) underwent video-EEG, neuropsychological tests for assessment of cognitive function (IQ, executive functions, amongothers) theu also perform an attention paradigm Stoptask Gonogo and the Resting State (RS). Data were analyzed and maps were generated for BOLD activation function. Results: The main areas active in patients and controls in the paradigm Stoptask were bilateral cerebellar hemispheres, bilateral frontal orbital cortex, fusiform gyrus, bilateral insula, dorsal lateral prefrontal cortex, anterior cingulate gyrus right and left edges of the intraparietal sulcus, superior frontal gyrus, eye -field. (p < 0.01). In the RS paradigm areas observed were: medial prefrontal cortex, angular gyrus, supramarginal gyrus, posterior cingulate gyrus, superior frontal gyrus, intraparietal sulcus, supplementary motor area, lateral prefrontal cortex (p < 0.05). there were no statistically significant differences between group means (p < 0,01)Discussion: Our activation maps of BOLD response are similar to those found by other authors in the literature both in Stoptask paradigm as in the RS. The diferences between groups may be due cognitive deficts in patients group. Conclusions:...
Subject(s)
Humans , Male , Female , Child , Adolescent , Epilepsy, Absence , Epilepsy, Rolandic , Executive Function , Magnetic Resonance Imaging , Neuropsychological TestsABSTRACT
PURPOSE: Ethosuximide (ESX) is currently not available due to various reasons in Korea. The aim of this study is to compare the efficacy of valproate (VPA) and lamotrigine (LTG) when ESX monotherapy was replaced by VPA or LTG. METHODS: A retrospective study was done for a total of 34 patients treated with ESX in 5 different hospitals affiliated with Catholic University of Korea from January, 2010 to December, 2012. They all were initially treated with ESX, but later switched to VPA or LTG. The subjects were selected based on clinical symptoms and electroencephalography findings. RESULTS: Among 34 patients, VPA was prescribed to 17 patients (50.0%) and LTG to 17 patients (50.0%). Twenty patients (58.8%) achieved the seizure freedom after 3 months of the treatments, 13 patients (76.5%) by VPA and 7 (41.2%) by LTG respectively. Four patients (23.5%) with VPA and 10 (58.8%) with LTG were replaced by other anticonvulsants due to ineffectiveness and/or side effects of medication. When we compare the efficacy of seizure reduction between VPA and LTG after 3 month period of the treatment, the efficacy of VPA was better than that of LTG (P=0.04). CONCLUSION: The results of this study suggest that the VPA is a better alternative anticonvulsant than LTG for the patients with absence epilepsy who are unable to continue ESX.
Subject(s)
Child , Humans , Anticonvulsants , Electroencephalography , Epilepsy , Epilepsy, Absence , Ethosuximide , Freedom , Korea , Retrospective Studies , Seizures , Valproic AcidABSTRACT
A Síndrome de Lennox-Gastaut (SLG) é uma encefalopatia epiléptica grave da infância caracterizada por múltiplos tipos de crises intratáveis, anormalidades cognitivas e comportamentais e alterações eletroencefalográficas características. Na grande maioria dos casos as crises se tornam refratárias mesmo com politerapia, sendo indicado tratamentos alternativos. O uso de calosotomia é descrito para ajudar no controle das crises, entretanto novas terapias como o estimulador de nervo vago (ENV) começaram a ser utilizadas. Neste caso, relatamos um paciente com SLG, que apesar das drogas antiepilépticas apresentava crises diárias, que foi submetido a ENV, com redução das crises. Discutimos o tratamento não farmacológico da SLG, comparando a calosotomia com ENV...
The Lennox-Gastaut Syndrome (LGS) is a severe childhood epileptic encephalopathy characterized by multiple types of intractable seizures, cognitive and behavioral abnormalities and specific electroencephalographic features. Most patients are refractory even with polytherapy, so alternative treatment is indicated. Callosotomy is indicated in these cases, however vagus nerve stimulator (VNS) is a less invasive option. This is a case report of a patient with LGS, which despite antiepileptic drugs had daily seizures, who underwent VNS, with reduction of seizures. We discuss the nonpharmacological treatment of LGS, comparing the callosotomy with VNS...
Subject(s)
Humans , Male , Infant , Child, Preschool , Child , Adult , Epilepsy, Absence/diagnosis , Epilepsy, Absence/drug therapy , Epilepsy/surgery , Epilepsy/complications , Vagus Nerve Stimulation/methods , Anticonvulsants/administration & dosage , Anticonvulsants/therapeutic use , Treatment OutcomeABSTRACT
Wistar audiogenic rat (WAR) é um modelo genético de epilepsia de crises audiogênicas desencadeadas após alta intensidade de estimulação sonora. Outro modelo genético recentemente identificado é o da epilepsia generalizada com crises de ausência (GEAS). O objetivo do presente estudo foi caracterizar o perfil de expressão gênica destas duas cepas através de uma análise em larga escala. Para os estudos de expressão foi utilizada inicialmente a tecnologia de microarranjos seguida da validação dos resultados por técnica quantitativa de PCR em tempo real. Os resultados foram analisados em ambiente R, utilizando os pacotes AFFY e RankProd do bioconductor, utilizando o algoritmo MAS 5 os array foram normalizados e calculou-se a intensidade do sinal e a detecção (presença ou ausência de expressão). Após a detecção, os transcritos que estavam ausentes foram removidos. Para a análise estatística foi utilizado o teste RankProd, que é biologicamente projetado para testar e detectar genes diferencialmente expressos em experimentos de microarranjos. Foi utilizado um valor de p ? 0,01 e pfp ? 0,05, a fim de considerar os transcritos diferencialmente expressos. No geral, nossos resultados mostram uma assinatura molecular similar nos dois modelos de ratos genéticos analisados. Houve uma sobreposição na lista de genes diferencialmente expressos encontrados em ambos os modelos, quando comparado com controles. Além disso, descobrimos que duas importantes vias moleculares para epileptogênese: neurotransmissão GABAérgica e potencialização de longo prazo pós-sináptica NMDA-dependente, foram encontrados em ambos os modelos, quando combinamos os dados dos animais WAR e GEAS. No entanto, algumas diferenças nas vias de sinalização expressas nos dois modelos também foram identificadas. Portando os resultados mostram claramente a natureza heterogênea e complexa dos mecanismos moleculares envolvidos na epileptogênese.
Wistar audiogenic rat (WAR) is a genetic epilepsy model susceptible to audiogenic seizures, after high-intensity sound stimulation. Another genetic model we have recently identified is the generalized epilepsy with absence seizures (GEAS) rat. The aim of the present study was to characterize and compare the genetic profile of these two strains using gene expression analysis. Experiments were performed initially using microarray technology followed by quantitative real-time PCR. Results were analyzed in R environment using the Affy and RankProd packages from Bioconductor, using the algorithm MAS 5 we normalized the arrays and calculated the signal intensity and the detection (presence or absence of expression), after the detection, transcripts which were absent in all samples were removed. For statistical analysis we used the Rank Product test, which is biologically motivated and designed to test and detect differentially expressed genes in replicated microarray experiments. This is a simple non-parametric statistical method based on ranks of fold changes. We used a p-value ? 0.01 and a pfp ? 0.05 in order to consider a given transcript to be differentially expressed Overall, the results show a different molecular signature in the two genetic rat models analyzed, since different enriched gene ontology categories were found. However, there was some overlap in the list of genes differentially expressed found in both models when comparing to controls. In addition, we found that two important molecular pathways for epileptogenesis: GABAergic neurotransmission and: Neurophysiological process NMDA-dependent postsynaptic long-term potentiation in CA1 hippocampal neurons, were found to be present in both models when combining data from WAR and GEAS animals.
Subject(s)
Animals , Rats , Epilepsy , Gene Expression , Models, Genetic , Epilepsy, Absence , Epilepsy, Reflex , Genes , Microarray AnalysisABSTRACT
Jeavons syndrome is one of the underrecognized epileptic syndromes, characterized by eyelid myoclonia with or without absence seizures, eye closure-induced seizures, electroencephalography (EEG) paroxysms, and photosensitivity. This syndrome is considered to be among idiopathic generalized epilepsies, but the underlying pathophysiology is unknown. Recent studies using functional MRI and EEG have suggested an important role of both thalamus and occipital cortex in the fundamental pathophysiology underlying Jeavons syndrome. We described here a patient with typical Jeavons syndrome, in whom SPCET studies performed ictally and interictally revealed ictal hyperperfusion mainly confined to the both occipital and parietal cortices and ictal hypoperfusion in the diffuse frontal and temporal cortices. Our SPECT findings of ictal hyperperfusion in occipital and parietal cortices and ictal hypoperfusion in widespread cortices are, to certain degree, in line with previous EEG and fMRI studies, suggesting that the interactions between occipital and other cortical areas might be implicated in generalized spike-waves generation and a photosensitivity in Jeavons syndrome.
Subject(s)
Humans , Electroencephalography , Epilepsy, Absence , Epilepsy, Generalized , Eye , Eyelids , Magnetic Resonance Imaging , Seizures , Thalamus , Tomography, Emission-Computed, Single-PhotonABSTRACT
Jeavons syndrome is one of the underrecognized epileptic syndromes, characterized by eyelid myoclonia with or without absence seizures, eye closure-induced seizures, electroencephalography (EEG) paroxysms, and photosensitivity. This syndrome is considered to be among idiopathic generalized epilepsies, but the underlying pathophysiology is unknown. Recent studies using functional MRI and EEG have suggested an important role of both thalamus and occipital cortex in the fundamental pathophysiology underlying Jeavons syndrome. We described here a patient with typical Jeavons syndrome, in whom SPCET studies performed ictally and interictally revealed ictal hyperperfusion mainly confined to the both occipital and parietal cortices and ictal hypoperfusion in the diffuse frontal and temporal cortices. Our SPECT findings of ictal hyperperfusion in occipital and parietal cortices and ictal hypoperfusion in widespread cortices are, to certain degree, in line with previous EEG and fMRI studies, suggesting that the interactions between occipital and other cortical areas might be implicated in generalized spike-waves generation and a photosensitivity in Jeavons syndrome.
Subject(s)
Humans , Electroencephalography , Epilepsy, Absence , Epilepsy, Generalized , Eye , Eyelids , Magnetic Resonance Imaging , Seizures , Thalamus , Tomography, Emission-Computed, Single-PhotonABSTRACT
BACKGROUND AND PURPOSE: Since the gamma-aminobutyric acid type-A receptor subunit gamma2 gene (GABRG2) mutation was discovered in an Australian family with childhood absence epilepsy (CAE) and febrile convulsions, a few screening studies for the GABRG2 mutation have been conducted in sporadic individuals with CAE from other ethnic groups. The aim of this study was to determine whether or not the previously reported genetic mutations and single-nucleotide polymorphisms (SNPs) of GABRG2 can be reproduced in sporadic Korean individuals with CAE, compared to healthy Korean individuals. METHODS: Thirty-five children with CAE in Chonnam National University Hospital and healthy controls (n=207) were enrolled, and the medical records of patients with CAE were reviewed. CAE was diagnosed according to the Classification and Terminology of the International League Against Epilepsy. All nine exons of GABRG2 were directly sequenced. In addition, the two SNPs found in our CAE patients were analyzed: C315T in exon 3 (E3) and C588T in exon 5 (E5). The frequencies of the two SNPs in the CAE patients were compared with data from healthy controls (for E3 and E5) and from previously reported Korean population data (only for E3). RESULTS: No mutation of GABRG2 was found in our CAE patients. In addition, the allele and genotype frequencies of the two polymorphisms did not differ significantly between CAE patients, healthy controls, and the Korean general population (p>0.05). CONCLUSIONS: Our study of sporadic Korean individuals with CAE found no evidence that GABRG2 contributes to the genetic basis of CAE.
Subject(s)
Child , Humans , Alleles , Epilepsy , Epilepsy, Absence , Ethnicity , Exons , gamma-Aminobutyric Acid , Genotype , Mass Screening , Medical Records , Polymorphism, Single Nucleotide , Seizures, FebrileABSTRACT
As características, as causas, os cursos e os tratamentos dos vários tipos de convulsões serão aqui apresentados. Os tipos mais comuns de desordens convulsivas são: 1. grande mal, às vezes chamada tônico-clônica generalizada; 2. ausência ou pequeno mal; 3. psicomotora ou complexa parcial; 4. mioclônica ou espasmo convulsivo; e 5. febril, em crianças pequenas. Os tipos de convulsões mais raras são: status epilepticus; atônica; parcial; jacksoniana; e espasmo infantil.
The characteristics, causes, treatment and courses of various types of convulsive disorders are presented here. The most common types of convulsive disorders are: 1. great evil, sometimes called generalized tonic-clonic; 2. absence or petit mal; 3. psychomotor or complex partial; 4. myoclonic or convulsive spasm; and 5. febrile, illness in young children. The types of convulsions are rare: status epilepticus; atonic; partial; jacksonian; and infantile spasms.
Subject(s)
Humans , Male , Female , Anticonvulsants/therapeutic use , Seizures/surgery , Seizures/diagnosis , Seizures/etiology , Seizures/drug therapy , Diet, Ketogenic , Epilepsy, Absence , Epilepsy, Complex Partial , Epilepsy, Temporal Lobe , Epilepsy, Tonic-Clonic , Epilepsies, Myoclonic , Epilepsies, Partial , Seizures, Febrile , Spasms, Infantile , Status EpilepticusABSTRACT
To find the occurrence of adult onset idiopathic generalized epilepsy [AOIGE] in patients attending the neurology outpatient department of a tertiary care centre. A prospective observational study was conducted in the Neurology outpatient department of Civil Hospital, Karachi between January 2004 and December 2008. All patients with new onset generalized epilepsy at age >25 years and with no evidence of an epileptogenic focus on history, clinical examination, electrophysiology, radiology or laboratory investigations were included. A structured pro forma evaluating detailed history, neurological and other systemic examination, electrophysiological, radiological and laboratory investigations were used to rule out focal epilepsy. Results were analyzed using SPSS 15. A total of 426 patients were enrolled. On evaluation, majority [85.6%] were diagnosed as cases of symptomatic epilepsy with various etiologies like stroke, intracranial mass lesion, post infectious or post traumatic states and other rarer causes. In the remaining 61 patients [14.3%] there was no evidence of an epileptogenic focus on seizure history, clinical examination or investigations and were labeled as cases of AOIGE. Most patients [60.6%] were males and mean age of onset of seizures was 35.7 years. Three seizure types; generalized tonic clonic, myoclonic and absences were identified. It was concluded that although adult onset idiopathic generalized epilepsy is not a common occurrence, but it does exist. However, adult onset epilepsies must be thoroughly investigated to rule out symptomatic epilepsy which is commoner than idiopathic epilepsy in this age group
Subject(s)
Humans , Male , Female , Adult , Prospective Studies , Seizures , Epilepsies, Myoclonic , Epilepsy, AbsenceABSTRACT
PURPOSE: Typical absence seizures are characterized by the daily presentation of frequent staring and typical 3Hz spike and wave discharges in otherwise healthy children. Typical absence seizures can present in childhood absence epilepsy and related syndromes. Lamotrigine (LTG) has been anecdotally used as a monotherapy for this seizure type; however, the efficacy and tolerability has remained unknown. The aim of this study was to evaluate the efficacy, tolerability, and long-term outcome of LTG in patients with newly diagnosed typical absence seizures. METHODS: Medical records of 36 patients having newly diagnosed typical absence seizures were analyzed. Patients were included based on the history of typical absence seizures and 3 Hz spike and wave discharges in interictal EEG. LTG was administered at a starting dose of 10 mg/day and increased by 10 mg/week until seizure freedom or reaching a dose of 10 mg/kg/day. RESULTS: Thirty-one patients had childhood absence epilepsy (CAE) and five had juvenile absence epilepsy (JAE). Thirty patients (83.3%) experienced more than 50% reduction of seizure frequency after 4 weeks of initial titration. Twenty-three patients (63.9%) achieved seizure freedom for 4 weeks after a mean duration of 8.3 weeks of treatment, and the cumulative numbers of patients with seizure freedom were 6 (16.7%), 18 (50.0%), and 23 (63.9%) within 4, 8, and 12 weeks, respectively. After 12 months of treatment, 12 patients (33.3%) showed normalized EEG findings, and their symptoms also disappeared. Four patients had uncontrolled seizures despite of dose increment and consequently needed additional treatment with valproic acid or ethosuximide. Most adverse effects, including skin rash (n=4), headache (n=1), and dizziness (n=1), were transient and tolerable. CONCLUSION: Lamotrigine, as a first-line monotherapy in newly diagnosed patients with typical absence seizures, could be safely used with good efficacy in seizure control.