RESUMO
Abnormal high frequency oscillations (HFOs) in EEG recordings are thought to be reflections of mechanisms responsible for focal seizure generation in the temporal lobe and neocortex. HFOs have also been recorded in patients and animal models of infantile spasms. If HFOs are important contributors to infantile spasms then anticonvulsant drugs that suppress these seizures should decrease the occurrence of HFOs. In experiments reported here, we used long-term video/EEG recordings with digital sampling rates capable of capturing HFOs. We tested the effectiveness of vigabatrin (VGB) in the TTX animal model of infantile spasms. VGB was found to be quite effective in suppressing spasms. In 3 of 5 animals, spasms ceased after a daily two week treatment. In the other 2 rats, spasm frequency dramatically decreased but gradually increased following treatment cessation. In all animals, hypsarrhythmia was abolished by the last treatment day. As VGB suppressed the frequency of spasms, there was a decrease in the intensity of the behavioral spasms and the duration of the ictal EEG event. Analysis showed that there was a burst of high frequency activity at ictal onset, followed by a later burst of HFOs. VGB was found to selectively suppress the late HFOs of ictal complexes. VGB also suppressed abnormal HFOs recorded during the interictal periods. Thus VGB was found to be effective in suppressing both the generation of spasms and hypsarrhythmia in the TTX model. Vigabatrin also appears to preferentially suppress the generation of abnormal HFOs, thus implicating neocortical HFOs in the infantile spasms disease state.
Assuntos
Anticonvulsivantes/uso terapêutico , Neocórtex/efeitos dos fármacos , Espasmos Infantis/tratamento farmacológico , Vigabatrina/uso terapêutico , Animais , Anticonvulsivantes/farmacologia , Mapeamento Encefálico , Modelos Animais de Doenças , Eletroencefalografia , Humanos , Lactente , Masculino , Neocórtex/fisiopatologia , Ratos , Espasmos Infantis/fisiopatologia , Vigabatrina/farmacologiaRESUMO
OBJECTIVE: To evaluate therapeutic efficacy upon augmenting the initial communication to patients regarding the diagnosis of psychogenic nonepileptic seizures (PNES) with a novel, brief group psychoeducation administered by the same team that provided the video-electroencephalography (VEEG) confirmed diagnosis and within 4 weeks of the diagnosis. METHODS: Prior to discharge from the epilepsy monitoring unit (EMU), a standardized communication strategy was utilized to explain the diagnosis of PNES to all patients prior to enrollment. Enrolled patients were then randomized to either participation in three successive and monthly group psychoeducational sessions (intervention group), or routine seizure clinic follow-up visits (control group). Both groups completed questionnaires at time of enrollment, and then at approximately 3 months (follow-up 1) and 6 months (follow-up 2) after discharge, assessing for: (1) primary outcomes that include a measure of psychosocial functioning, as well as interval difference in seizure frequency/intensity; and (2) secondary outcomes that include interval seizure-related emergency room visits or hospitalizations, development of new and medically unexplained symptoms, and results of an internal measure of knowledge and perception outcomes. RESULTS: The majority (73%) of patients from the intervention group commenced on therapy sessions within 4 weeks after learning of the diagnosis. Although we did not observe significant group difference in seizure frequency/intensity, patients from the intervention group showed significant improvement on the Work and Social Adjustment Scale (WSAS) scores at both follow-up 1 (p = 0.013) and follow-up 2 (p = 0.038) after discharge from the EMU. In addition, we observed a trend toward lesser likelihood for seizure-related emergency room visits or hospitalizations for the intervention group (p = 0.184), as well as meaningful insights from an internal measure of intervention outcomes. SIGNIFICANCE: These findings suggest that our cost/resource effective, brief group psychoeducational program, when administered early and by the same team who confirmed and communicated the diagnosis of PNES, may contribute to significant functional improvement among participating patients.
Assuntos
Educação de Pacientes como Assunto/métodos , Transtornos Psicofisiológicos/terapia , Psicoterapia Breve/métodos , Convulsões/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicofisiológicos/psicologia , Convulsões/psicologia , Resultado do TratamentoRESUMO
Infantile spasms are a unique disorder of infancy and early childhood. The average age at onset of infantile spasms is 6 months and the average incidence of the disorder is approximately 0.31 per 1000 live births. Approximately one-quarter of patients will spontaneously stop having spasms within 1 year of onset. There are three main types of epileptic spasms: flexor, extensor, and mixed flexor-extensor. Spasms frequently occur in clusters and commonly occur upon arousal from sleep. The motor spasms are frequently confused with other normal and abnormal infant behaviors. Typically, the interictal EEG reveals hypsarrhythmia or one of its variants. A variety of ictal EEG patterns may be seen, the most common of which is a generalized slow-wave transient followed by an attenuation of the background activity in all regions. The primary treatment objective is to improve the EEG and stop the spasms as soon as possible and to avoid prolonged treatment durations with any form of therapy. Currently, there is no conclusive evidence that medical or surgical treatment of infantile spasms significantly alters long-term outcome. Although the pathophysiological mechanism underlying infantile spasms is unknown, several animal models of infantile spasms have been developed in recent years.
Assuntos
Espasmos Infantis , Animais , Modelos Animais de Doenças , Humanos , Lactente , Recém-Nascido , Espasmos Infantis/diagnóstico , Espasmos Infantis/epidemiologia , Espasmos Infantis/terapiaRESUMO
It remains uncertain whether particular ictal manifestations of psychogenic nonepileptic events (PNEE) can reflect distinctive psychological processes or prognostic outcomes. We hypothesize that the integrity of ictal sensorium may affect the clinical outcome of PNEE following disclosure of diagnosis. We prospectively studied 47 veterans who were diagnosed with video-EEG-confirmed PNEE, presented with the diagnosis utilizing a standardized communication strategy, and followed for their clinical progress. When compared to patients with intact ictal sensorium, significantly smaller proportion of patients with impaired ictal sensorium endorsed improvement of either PNEE frequency or intensity across both the initial 1- to 3-month (p=0.005) and ensuing 6- to 9-month (p=0.01) follow-ups. However, improvement among patients with impaired ictal sensorium was more significantly associated with their level of understanding for the PNEE diagnosis across both the initial (rho=0.41, p=0.017) and ensuing (rho=0.43, p=0.015) follow-ups. Our study presents preliminary evidence underscoring the potential clinical significance of ictal sensorial integrity when evaluating patients with PNEE.
Assuntos
Estado de Consciência , Transtornos Psicofisiológicos/diagnóstico , Transtornos Psicofisiológicos/psicologia , Convulsões/diagnóstico , Transtornos de Sensação/etiologia , Adulto , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Transtornos Psicofisiológicos/complicações , Convulsões/complicações , Convulsões/psicologia , Transtornos de Sensação/psicologia , Estatísticas não Paramétricas , Gravação em VídeoRESUMO
While infantile spasms is the most common catastrophic epilepsy of infancy and early-childhood, very little is known about the basic mechanisms responsible for this devastating disorder. In experiments reported here, spasms were induced in rats by the chronic infusion of TTX into the neocortex beginning on postnatal days 10-12. Studies of focal epilepsy suggest that high frequency EEG oscillations (HFOs) occur interictally at sites that are most likely responsible for seizure generation. Thus, our goal was to determine if HFOs occurred and where they occurred in cortex in the TTX model. We also undertook multiunit recordings to begin to analyze the basic mechanisms responsible for HFOs. Our results show that HFOs occur most frequently during hypsarrhythmia and NREM sleep and are most prominent contralateral to the TTX infusion site in the homotopic cortex and anterior to this region in frontal cortex. While HFOs were largest and most frequent in these contralateral regions, they were also commonly recorded synchronously across multiple and widely-spaced recordings sites. The amplitude and spatial distribution of interictal HFOs were found to be very similar to the high frequency bursts seen at seizure onset. However, the latter differed from the interictal events in that the high frequency activity was more intense at seizure onset. Microwire recordings showed that neuronal unit firing increased abruptly with the generation of HFOs. A similar increase in neuronal firing occurred at the onset of the ictal events. Taken together, results suggest that neocortical networks are abnormally excitable, particularly contralateral to TTX infusion, and that these abnormalities are not restricted to small areas of cortex. Multiunit firing coincident with HFOs is fully consistent with a neocortical hyperexcitability hypothesis particularly since they both occur at seizure onset.
Assuntos
Modelos Animais de Doenças , Eletroencefalografia , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Fatores Etários , Animais , Animais Recém-Nascidos , Eletroencefalografia/métodos , Neocórtex/efeitos dos fármacos , Ratos , Espasmo/induzido quimicamente , Espasmo/fisiopatologia , Tetrodotoxina/toxicidadeRESUMO
PURPOSE: To evaluate whether certain preinduction clinical characteristics may influence the success rate of induction. METHODS: We prospectively enrolled and attempted inductions on 51 patients who were suspected to have psychogenic nonepileptic events based on clinical grounds. In addition to careful examination of the reported ictal semiology, we administered a battery of four psychological instruments to our enrolled patients. KEY FINDINGS: We found that among 42 cases of successful induction, 92.9% (n=39) of these cases were successfully induced on the first attempt (i.e., without prior induction exposure). We observed that induction showed significantly higher rate of success in cases that demonstrate: (1) hypermotor ictal semiology (p=0.029); (2) more prevalent self-reporting of uncommon cognitive and affective symptoms (p=0.035); or (3) higher tendency to rely on coping strategies of "instrumental support" (p=0.013) and "active coping" (p=0.027), when compared to noninducible cases. SIGNIFICANCE: Singular administration of placebo induction on preselected patients with these clinical characteristics may reduce costs by shortening video electroencephalography-(EEG) monitoring sessions and improve the diagnostic yield of video-EEG even for patients with very infrequent events.
Assuntos
Transtornos Psicofisiológicos/fisiopatologia , Transtornos Psicofisiológicos/psicologia , Convulsões/fisiopatologia , Convulsões/psicologia , Adulto , Idoso , Eletroencefalografia/métodos , Feminino , Genética Comportamental/métodos , Humanos , Hiperventilação/complicações , Hiperventilação/fisiopatologia , Hiperventilação/psicologia , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/efeitos adversos , Estudos Prospectivos , Testes Psicológicos , Transtornos Psicofisiológicos/etiologia , Fatores de Risco , Convulsões/etiologiaRESUMO
PURPOSE: To describe high frequency (HF) electrographic activity accompanying ictal discharges in the tetrodotoxin (TTX) model of infantile spasms. Previous studies of HF oscillations in humans and animals suggest that they arise at sites of seizure onset. We compared HF oscillations at several cortical sites to determine regional differences. METHODS: TTX was infused for 4 weeks into the neocortex of rats beginning on postnatal days 11 or 12. Electroencephalography (EEG) electrodes were implanted 2 weeks later and video-EEG recordings were analyzed between postnatal days 31 and 47. EEG recordings were digitally sampled at 2,048 Hz. HF EEG activity (20-900 Hz) was quantified using compressed spectral arrays and band-pass filtering. KEY FINDINGS: Multiple seizures were analyzed in 10 rats. Ictal onset was associated with multiple bands of rhythmic HF activity that could extend to 700 Hz. The earliest and most intense discharging typically occurred contralaterally to where TTX was infused. HF activity continued to occur throughout the seizure (even during the electrodecrement that is recorded with more traditional filter settings), although there was a gradual decrease of the intensity of the highest frequency components as the amplitude of lower frequency oscillations increased. Higher frequencies sometimes reappeared in association with spike/sharp-waves at seizure termination. SIGNIFICANCE: The findings show that HF EEG activity accompanies ictal events in the TTX model. Results also suggest that the seizures in this model do not originate from the TTX infusion site. Instead HF discharges are usually most intense and occur earliest contralaterally, suggesting that these homologous regions may be involved in seizure generation.
Assuntos
Modelos Animais de Doenças , Eletroencefalografia/métodos , Neocórtex/fisiopatologia , Espasmos Infantis/fisiopatologia , Animais , Animais Recém-Nascidos , Eletroencefalografia/efeitos dos fármacos , Humanos , Recém-Nascido , Neocórtex/efeitos dos fármacos , Ratos , Espasmos Infantis/induzido quimicamente , Espasmos Infantis/diagnóstico , Tetrodotoxina/toxicidadeRESUMO
BACKGROUND: Postoperative electroencephalographic (EEG) seizures are reported to occur in 14% to 20% of neonates after cardiac surgery with cardiopulmonary bypass (CPB). EEG seizures are associated with prolonged deep hypothermic circulatory arrest and with adverse long-term neurodevelopmental outcomes. We performed video/EEG monitoring before and for 72 hours after neonatal cardiac surgery, using a high-flow CPB protocol and cerebral oxygenation monitoring, to ascertain incidence, severity, and factors associated with EEG seizures. METHODS: The CPB protocol included 150 mL/kg/min flows, pH stat management, hematocrit >30%, and high-flow antegrade cerebral perfusion. Regional cerebral oxygen saturation (rSo(2)) was monitored, with a treatment protocol for rSo(2) <50%. EEG was assessed for seizures. RESULTS: Sixty-eight patients (36 single ventricle [SV] and 32 2-ventricle [2V]) were monitored for a total of 4824 hours. The total midazolam dose was 2.4 mg/kg (1.5-7.3 mg/kg) (median, 25th-75th percentile) for the SV group and 1.3 mg/kg (1.0-2.7 mg/kg) for the 2V group (P = 0.009). One SV patient experienced 2 brief EEG seizures postoperatively (1.5% incidence; 95% confidence interval: 0.3%-7.9%). The SV patients experienced a significant incidence of cerebral desaturation (rSo(2) <45% for >240 minutes total) perioperatively (18 of 36 SV vs 0 of 32 2V patients, P < 0.001). This difference did not affect electrographic seizure occurrence or other EEG characteristics. CONCLUSIONS: EEG seizures are infrequent in neonates undergoing surgery with high-flow CPB. Cerebral desaturation did not affect EEG seizure occurrence; however, benzodiazepines may play a role in suppressing postoperative seizures caused by cerebral hypoxemia in this patient population. Using this anesthetic and surgical protocol, EEG seizures are a poor surrogate marker for acute neurological injury in this population.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Eletroencefalografia , Complicações Pós-Operatórias/epidemiologia , Convulsões/epidemiologia , Convulsões/etiologia , Anestesia , Anestésicos/uso terapêutico , Química Encefálica/fisiologia , Circulação Cerebrovascular/fisiologia , Feminino , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Humanos , Hipnóticos e Sedativos/uso terapêutico , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Dor Pós-Operatória/tratamento farmacológico , Perfusão , Cuidados Pós-Operatórios , Gravação em VídeoRESUMO
This paper describes the design and test results of a three-stage automated system for neonatal EEG seizure detection. Stage I of the system is the initial detection stage and identifies overlapping 5-second segments of suspected seizure activity in each EEG channel. In stage II, the detected segments from stage I are spatiotemporally clustered to produce multichannel candidate seizures. In stage III, the candidate seizures are processed further using measures of quality and context-based rules to eliminate false candidates. False candidates because of artifacts and commonly occurring EEG background patterns such as bifrontal delta activity are also rejected. Seizures at least 10 seconds in duration are considered for reporting results. The testing data consisted of recordings of 28 seizure subjects (34 hours of data) and 48 nonseizure subjects (87 hours of data) obtained in the neonatal intensive care unit. The data were not edited to remove artifacts and were identical in every way to data normally processed visually. The system was able to detect seizures of widely varying morphology with an average detection sensitivity of almost 80% and a subject sensitivity of 96%, in comparison with a team of clinical neurophysiologists who had scored the same recordings. The average false detection rate obtained in nonseizure subjects was 0.74 per hour.
Assuntos
Eletroencefalografia/métodos , Epilepsia/diagnóstico , Processamento de Sinais Assistido por Computador , Algoritmos , Artefatos , Epilepsia/complicações , Humanos , Recém-Nascido , Sensibilidade e EspecificidadeRESUMO
Infantile spasms syndrome (ISS) is a catastrophic pediatric epilepsy with motor spasms, persistent seizures, mental retardation, and in some cases, autism. One of its monogenic causes is an insertion mutation [c.304ins (GCG)(7)] on the X chromosome, expanding the first polyalanine tract of the interneuron-specific transcription factor Aristaless-related homeobox (ARX) from 16 to 23 alanine codons. Null mutation of the Arx gene impairs GABA and cholinergic interneuronal migration but results in a neonatal lethal phenotype. We developed the first viable genetic mouse model of ISS that spontaneously recapitulates salient phenotypic features of the human triplet repeat expansion mutation. Arx((GCG)10+7) ("Arx plus 7") pups display abnormal spasm-like myoclonus and other key EEG features, including multifocal spikes, electrodecremental episodes, and spontaneous seizures persisting into maturity. The neurobehavioral profile of Arx mutants was remarkable for lowered anxiety, impaired associative learning, and abnormal social interaction. Laminar decreases of Arx+ cortical interneurons and a selective reduction of calbindin-, but not parvalbumin- or calretinin-expressing interneurons in neocortical layers and hippocampus indicate that specific classes of synaptic inhibition are missing from the adult forebrain, providing a basis for the seizures and cognitive disorder. A significant reduction of calbindin-, NPY (neuropeptide Y)-expressing, and cholinergic interneurons in the mutant striatum suggest that dysinhibition within this network may contribute to the dyskinetic motor spasms. This mouse model narrows the range of critical pathogenic elements within brain inhibitory networks essential to recreate this complex neurodevelopmental syndrome.
Assuntos
Transtornos Cognitivos/genética , Modelos Animais de Doenças , Proteínas de Homeodomínio/genética , Transtornos Mentais/genética , Convulsões/genética , Fatores de Transcrição/genética , Repetições de Trinucleotídeos/genética , Fatores Etários , Animais , Transtornos Cognitivos/mortalidade , Transtornos Cognitivos/fisiopatologia , Feminino , Técnicas de Introdução de Genes , Proteínas de Homeodomínio/fisiologia , Interneurônios/metabolismo , Interneurônios/patologia , Masculino , Transtornos Mentais/mortalidade , Transtornos Mentais/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo , Convulsões/fisiopatologia , Síndrome , Fatores de Transcrição/fisiologiaRESUMO
PURPOSE: Kv4.2 subunits contribute to the pore-forming region of channels that express a transient, A-type K(+) current (A-current) in hippocampal CA1 pyramidal cell dendrites. Here, the A-current plays an important role in signal processing and synaptic integration. Kv4.2 knockout mice show a near elimination of the A-current in area CA1 dendrites, producing increased excitability in this region. In these studies, we evaluated young adult Kv4.2 knockout mice for spontaneous seizures and the response to convulsant stimulation in the whole animal in vivo and in hippocampal slices in vitro. METHODS: Electroencephalogram electrode-implanted Kv4.2 knockout and wild-type mice were observed for spontaneous behavioral and electrographic seizures. The latency to seizure and status epilepticus onset in Kv4.2 knockout and wild-type mice was assessed following intraperitoneal injection of kainate. Extracellular field potential recordings were performed in hippocampal slices from Kv4.2 knockout and wild-type mice following the bath application of bicuculline. RESULTS: No spontaneous behavioral or electrographic seizures were observed in Kv4.2 knockout mice. Following kainate, Kv4.2 knockout mice demonstrated a decreased seizure and status epilepticus latency as well as increased mortality compared to wild-type littermates. The background strain modified the seizure susceptibility phenotype in Kv4.2 knockout mice. In response to bicuculline, slices from Kv4.2 knockout mice exhibited an increase in epileptiform bursting in area CA1 as compared to wild-type littermates. DISCUSSION: These studies show that loss of Kv4.2 channels is associated with enhanced susceptibility to convulsant stimulation, supporting the concept that Kv4.2 deficiency may contribute to aberrant network excitability and regulate seizure threshold.
Assuntos
Convulsivantes/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Canais de Potássio Shal/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Western Blotting , Canalopatias/fisiopatologia , Dendritos/efeitos dos fármacos , Dendritos/fisiologia , Estimulação Elétrica , Eletroencefalografia/estatística & dados numéricos , Hipocampo/fisiologia , Camundongos , Camundongos Knockout , Fenótipo , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Convulsões/induzido quimicamente , Convulsões/etiologia , Convulsões/fisiopatologia , Canais de Potássio Shal/efeitos dos fármacos , Canais de Potássio Shal/genética , Estado Epiléptico/fisiopatologiaRESUMO
PURPOSE: Depression is a highly prevalent, relatively underdiagnosed and undertreated comorbid condition in epilepsy. The purpose of this study was to determine the effect of using a validated self-reporting depression scale on the ability to detect depression in people with epilepsy receiving care in a busy clinical setting. METHODS: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. We performed a retrospective chart review of 192 consecutive patients who had completed the NDDI-E while receiving care at a seizure clinic in the largest public hospital in Houston, Texas. For comparison, charts of 192 consecutive patients receiving care immediately prior to the implementation of the NDDI-E in the same clinic were assessed. RESULTS: Fifty-five (28.6%) of patients screened positive for depression with the NDDI-E. They subsequently received a semi-structured psychiatric interview based on the DSM-IV model and 89% (n=49) were confirmed to have major depression. Use of the NDDI-E thus resulted in the detection of active depression in 25.5% (n=49) of the patients, whereas only 2.6% (n=5) of patients in the group not systematically screened were found to have active depression (p<0.0001). Thirty-two of the 49 (65%) patients with depression detected by screening were not previously diagnosed or treated. Multivariate analysis revealed that a history of depression, seizure frequency, and topiramate use were independent predictors of depression. Lamotrigine use was protective against depression. DISCUSSION: Use of the NDDI-E significantly improved the ability to detect depression in epilepsy patients in a busy clinical practice.
Assuntos
Epilepsia/complicações , Epilepsia/epidemiologia , Adulto , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Intervalos de Confiança , Depressão/complicações , Depressão/diagnóstico , Depressão/epidemiologia , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Razão de Chances , Autoimagem , Inquéritos e QuestionáriosRESUMO
Extracelluar signal-regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down-regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 were evident at a synaptosomal level during SE. Western blotting was performed on rat hippocampal whole cell, membrane, synaptosomal, and surface biotinylated extracts following systemic kainate using an antibody generated against the Kv4.2 ERK sites and for Kv4.2, ERK, and phospho-ERK. ERK activation was associated with an increase in Kv4.2 phosphorylation during behavioral SE. During SE, ERK activation and Kv4.2 phosphorylation were evident at the whole cell and synaptosomal levels. In addition, while whole-cell preparations revealed no alterations in total Kv4.2 levels, a decrease in synaptosomal and surface expression of Kv4.2 was evident after prolonged SE. These results demonstrate ERK pathway coupling to Kv4.2 phosphorylation. The finding of decreased Kv4.2 levels in hippocampal synaptosomes and surface membranes suggest additional mechanisms for decreasing the dendritic A-current, which could lead to altered intrinsic membrane excitability during SE.
Assuntos
Canais de Potássio Shal/metabolismo , Estado Epiléptico/metabolismo , Animais , Eletroencefalografia/métodos , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Canais de Potássio Shal/antagonistas & inibidores , Canais de Potássio Shal/biossíntese , Estado Epiléptico/fisiopatologia , Transmissão Sináptica/fisiologia , Sinaptossomos/metabolismo , Sinaptossomos/fisiologia , Regulação para Cima/fisiologiaRESUMO
PURPOSE: Infantile spasms is one of the most severe epileptic syndromes of infancy and early childhood. Progress toward understanding the pathophysiology of this disorder and the development of effective therapies has been hindered by the lack of a relevant animal model. We report here the creation of such a model. METHODS: The sodium channel blocker, tetrodotoxin (TTX), was chronically infused into the developing neocortex or hippocampus of infant rats by way of an osmotic minipump starting on postnatal day 10-12. RESULTS: After a minimum of 10 days of infusion, approximately one-third of these rats began to display very brief (1-2 s) spasms, which consisted of symmetric or asymmetric flexion or extension of the trunk and sometimes involvement of one or both forelimbs. The typical ictal EEG pattern associated with the behavioral spasms consisted of an initial generalized, high amplitude, slow wave followed by an electrodecrement with superimposed fast activity. The interictal EEG revealed multifocal spikes and sharp waves, and in most animals that had spasms a hypsarrhythmic pattern was seen, at least intermittently, during NREM sleep. Like in humans, the spasms in the rat often occurred in clusters especially during sleep-wake transitions. Comparison of the ictal and interictal EEGs recorded in this model and those from humans with infantile spasms revealed that the patterns and the frequency components of both the ictal events and hypsarrhythmia were very similar. DISCUSSION: The TTX model of infantile spasms should be of value in furthering an understanding of the pathophysiology of this seizure disorder.
Assuntos
Eletroencefalografia/estatística & dados numéricos , Hipocampo/fisiopatologia , Neocórtex/fisiopatologia , Bloqueadores dos Canais de Sódio , Espasmos Infantis/induzido quimicamente , Tetrodotoxina , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Eletrodos Implantados , Hipocampo/efeitos dos fármacos , Humanos , Lactente , Bombas de Infusão Implantáveis , Masculino , Neocórtex/efeitos dos fármacos , Ratos , Ratos Wistar , Bloqueadores dos Canais de Sódio/administração & dosagem , Bloqueadores dos Canais de Sódio/farmacologia , Espasmos Infantis/fisiopatologia , Tetrodotoxina/administração & dosagem , Tetrodotoxina/farmacologia , Gravação de VideoteipeRESUMO
The temporal latency between an encephalopathic event and the onset of infantile spasms cannot be determined in the majority of symptomatic cases (e.g. genetic conditions, cerebral malformations). However, we can measure this interval when a previously normal infant sustains brain injury followed by infantile spasms. This information has implications for understanding the underlying pathophysiologic basis for infantile spasms and, also, is germane to allegations that a close temporal relationship between vaccination and the onset of this seizure disorder establishes causation. We identified 19 published cases with sufficient information. The interval between brain injury and the onset of infantile spasms ranged from 6 weeks to 11 months (mean = 5.1 months). A similar temporal latency occurs in children with perinatal cerebral infarction and infantile spasms. We conclude that infantile spasms do not occur acutely following an encephalopathic event. This interval of weeks to months is consistent with prior studies indicating temporal latency between brain injury and the onset of other types of epilepsy, as well as with the previously proposed developmental desynchronization hypothesis. The findings refute claims that a close temporal association between an immunization and the onset of infantile spasms establishes causation.
Assuntos
Encefalopatias/complicações , Encefalopatias/fisiopatologia , Espasmos Infantis/etiologia , Espasmos Infantis/fisiopatologia , Fatores Etários , Idade de Início , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesão Encefálica Crônica/complicações , Lesão Encefálica Crônica/fisiopatologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/fisiopatologia , Pré-Escolar , Encefalite/complicações , Encefalite/fisiopatologia , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/fisiopatologia , Lactente , Recém-Nascido , Meningite/complicações , Meningite/fisiopatologia , Fatores de TempoRESUMO
Video-EEG monitoring is a standard tool to evaluate possible seizures. However, there are limited data available for the elderly population, and no data are available for the elderly veteran population. The records of 71 veterans ages 60 and older who underwent video-EEG monitoring at the Michael E. DeBakey Veterans Affairs Medical Center from 1999 to 2006 were reviewed. The average age was 68 years, and 94% were male. Typical events occurred in 34 of 71 patients (48%). Twelve patients (35%) had epileptic seizures; most were temporal lobe seizures (75%). The remaining 22 patients (65%) had a nonepileptic event. Of these, 10 (45%) had psychogenic nonepileptic seizures and 12 (55%) had other physiologic nonepileptic events. AEDs were previously prescribed in 14 of the 22 nonepileptic patients (64%). In our study, most events were nonepileptic, partly reflecting the unique nature of the VA population. There was a slightly higher number of physiologic nonepileptic events; however, psychogenic seizures are also frequently seen. Most of the patients with nonepileptic events were previously treated with AEDs. Most of the epileptic events captured were temporal lobe seizures. Video-EEG monitoring in the elderly is useful in the characterization of paroxysmal events.
Assuntos
Envelhecimento , Eletroencefalografia , Monitorização Fisiológica/métodos , Convulsões/diagnóstico , Veteranos , Gravação em Vídeo , Idoso , Anticonvulsivantes/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , TexasRESUMO
Pachygyria, joint contractures and facial abnormalities have been reported in the literature very rarely. These features constitute a new lethal syndrome. We describe a male infant who represents an additional case of the same lethal syndrome first described in 1989. The patient also presented an early-onset epileptic encephalopathy with a suppression-burst EEG pattern.
Assuntos
Anormalidades Múltiplas/fisiopatologia , Encéfalo/fisiopatologia , Contratura/congênito , Epilepsia/fisiopatologia , Face/anormalidades , Articulações/anormalidades , Anormalidades Múltiplas/patologia , Encéfalo/anormalidades , Eletroencefalografia , Evolução Fatal , Feminino , Hepatite C , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Transtornos Relacionados ao Uso de SubstânciasRESUMO
This study was carried out during the second phase of the project "Video Technologies for Neonatal Seizures" and aimed at the development of a seizure detection system by training neural networks, using quantitative motion information extracted by motion tracking methods from short video segments of infants monitored for seizures. The motion of the infants' body parts was quantified by temporal motion trajectory signals extracted from video recordings by robust motion trackers, based on block motion models. These motion trackers were developed to autonomously adjust to illumination and contrast changes that may occur during the video frame sequence. The computational tools and procedures developed for automated seizure detection were evaluated on short video segments selected and labeled by physicians from a set of 240 video recordings of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). This evaluation provided the basis for selecting the most effective strategy for training neural networks to detect neonatal seizures as well as the decision scheme used for interpreting the responses of the trained neural networks. The best neural networks exhibited sensitivity and specificity above 90%. The best among the motion trackers developed in this study produced quantitative features that constitute a reliable basis for detecting myoclonic and focal clonic neonatal seizures. The performance targets of the second phase of the project may be achieved by combining the quantitative features described in this paper with those obtained by analyzing motion strength signals produced by motion segmentation methods.
Assuntos
Movimento/fisiologia , Redes Neurais de Computação , Convulsões/diagnóstico , Convulsões/fisiopatologia , Processamento de Sinais Assistido por Computador , Gravação em Vídeo/métodos , Diagnóstico por Computador , Humanos , Lactente , Recém-Nascido , Sensibilidade e Especificidade , Análise EspectralRESUMO
This article reviews the ictal and interictal EEG findings associated with a select group of generalized seizures. These include absence seizures, myoclonic seizures seen in juvenile myoclonic epilepsy, idiopathic generalized tonic clonic seizures, infantile spasms, and atypical absence, tonic, and atonic seizures associated with the Lennox Gastaut syndrome.
Assuntos
Eletroencefalografia/métodos , Convulsões/classificação , Convulsões/diagnóstico , Diagnóstico Diferencial , Humanos , Guias de Prática Clínica como Assunto , Padrões de Prática MédicaRESUMO
PURPOSE: This study aimed at the development of a seizure-detection system by training neural networks with quantitative motion information extracted from short video segments of neonatal seizures of the myoclonic and focal clonic types and random infant movements. METHODS: The motion of the infants' body parts was quantified by temporal motion-strength signals extracted from video segments by motion-segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The motion of the infants' body parts also was quantified by temporal motion-trajectory signals extracted from video recordings by robust motion trackers based on block-motion models. These motion trackers were developed to adjust autonomously to illumination and contrast changes that may occur during the video-frame sequence. Video segments were represented by quantitative features obtained by analyzing motion-strength and motion-trajectory signals in both the time and frequency domains. Seizure recognition was performed by conventional feed-forward neural networks, quantum neural networks, and cosine radial basis function neural networks, which were trained to detect neonatal seizures of the myoclonic and focal clonic types and to distinguish them from random infant movements. RESULTS: The computational tools and procedures developed for automated seizure detection were evaluated on a set of 240 video segments of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). Regardless of the decision scheme used for interpreting the responses of the trained neural networks, all the neural network models exhibited sensitivity and specificity>90%. For one of the decision schemes proposed for interpreting the responses of the trained neural networks, the majority of the trained neural-network models exhibited sensitivity>90% and specificity>95%. In particular, cosine radial basis function neural networks achieved the performance targets of this phase of the project (i.e., sensitivity>95% and specificity>95%). CONCLUSIONS: The best among the motion segmentation and tracking methods developed in this study produced quantitative features that constitute a reliable basis for detecting neonatal seizures. The performance targets of this phase of the project were achieved by combining the quantitative features obtained by analyzing motion-strength signals with those produced by analyzing motion-trajectory signals. The computational procedures and tools developed in this study to perform off-line analysis of short video segments will be used in the next phase of this project, which involves the integration of these procedures and tools into a system that can process and analyze long video recordings of infants monitored for seizures in real time.