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Seizures rapidly become self‐sustaining and pharmacoresistant to benzodiazepines during status epilepticus (SE). A decrease in the number of postsynaptic γ‐aminobutyric acid (GABA)A receptors with SE causes a loss of synaptic inhibition, whereas increases in postsynaptic glutamatergic receptors further upset the balance between excitation and inhibition. Although extracellular GABA levels may increase...
Prevention of epileptogenesis is an unmet need in medicine. During the last 3 years, however, several preclinical studies have demonstrated remarkable favorable effects of novel treatments on genetic and acquired epileptogenesis. These include the use of immunosuppressants and treatments that modify cellular adhesion, proliferation, and/or plasticity. In addition, the use of antiepileptic drugs in...
Convulsive status epilepticus (CSE) is the most common medical neurologic emergency in childhood. It is associated with significant mortality and morbidity. The estimates for the frequencies of adverse outcomes have a very wide range, but even the lower estimates are clinically important. The major predictor of outcomes following CSE is etiology. The characteristics of the episode of CSE itself, for...
Pretreatment with the endocannabinoid‐receptor antagonist, SR141716, has been reported to suppress the long‐lasting hyperexcitability and increased seizure susceptibility present after 30 min of hyperthermia‐induced convulsions in immature rats, an animal model of complex febrile seizures in children, which may be a cause of temporal lobe epilepsy. The present experiments tested the hypothesis that...
Although multiple genes drive epileptogenesis, uncovering the mechanisms controlling expression of GABAA receptors (GABAARs), the brain’s major inhibitory receptors, may have far‐reaching therapeutic implications. In this review, we describe how seizure‐induced changes in GABAARs result from brain‐derived neurotrophic factor (BDNF)‐induced changes in Janus kinase/Signal Transducer and Activators of...
Purpose: To determine long‐term survival in patients with status epilepticus (SE).
Methods: We prospectively followed patients admitted for the first (69.6%) or recursive episode of SE between January 1, 1989 and December 31, 1997 at the Institute of Neurology, Belgrade, Serbia, until death or study termination (December 31, 2006). Data were obtained for cause of death; etiology of SE—acute symptomatic...
Purpose: Benzodiazepines such as diazepam may fail to effectively treat status epilepticus because benzodiazepine‐sensitive GABAA receptors are progressively internalized with continued seizure activity. Ionotropic glutamate receptors, including AMPA receptors, are externalized, so that AMPA receptor antagonists, which are broad‐spectrum anticonvulsants, could be more effective treatments for status...
Rectal diazepam is established as a standard rescue or emergency treatment for seizure or status epilepticus; however, the rectal route of administration has not been universally accepted. To determine if an alternative route of administration of a benzodiazepine was equally effective, we compared a novel midazolam HCl concentrated nasal spray (MDZ‐n) with diazepam rectal solution (DZP‐r) in the treatment...
Theophylline‐associated seizures (TAS) often progress to prolonged or treatment‐resistant convulsions. Theophylline is a nonselective adenosine receptor antagonist. Adenosine is an endogenous anticonvulsant that can terminate seizures. Fever and young age have been reported to be risk factors for TAS. To elucidate the mechanism of TAS, we investigated the effect of theophylline and adenosine receptor...
Purpose: Tolerance to drug treatment is a serious problem in the treatment of epilepsy. We previously showed that tolerance to levetiracetam (LEV) developed within 4 days after the start of the treatment in a rat model for spontaneous seizures after electrically induced status epilepticus. In the current study we tested whether the development of tolerance to LEV could be prevented by alternating...
Purpose: Early life status epilepticus (SE) could enhance the vulnerability of the immature brain to a second SE in adulthood (two‐hit seizure model). Naloxone has been proved to possess inflammation inhibitory effects in nervous system. This study was designed to evaluate the dose‐dependent protective effects of naloxone in kainic acid (KA)–induced two‐hit seizure model.
Methods: After KA‐induced...
Purpose: To evaluate the effects of high‐frequency electrical stimulation (HFS) in both ventral hippocampi, alone and combined with a subeffective dose of antiepileptic drugs, during the status epilepticus (SE) induced by lithium‐pilocarpine (LP).
Methods: Male Wistar rats, stereotactically implanted in both ventral hippocampi, were injected with pilocarpine (30 mg/kg, i.p.) 24 h after lithium (3...
Purpose: Nonconvulsive status epilepticus (NCSE) is clinically difficult to diagnose, especially in old patients without epilepsy, and requires electroencephalography (EEG) for diagnosis. Its incidence among elderly patients with confusion of unknown origin (CUO) remains undetermined.
Methods: A 1‐year prospective study was conducted in patients aged 60 years or older, for whom EEG was requested...
Purpose: We intended to elucidate the whole clinical course of Dravet syndrome (DS) comprehensively, from infancy through adulthood.
Methods: Subjects were 31 patients with DS (14 with typical DS, and 17 with borderline DS) who were followed from childhood to at least 18 years of age. Their seizures, abilities, and electroencephalography (EEG) findings were investigated and statistically analyzed...
Prolonged status epilepticus (SE) can be refractory to conventional interventions, with high rates of subsequent morbidity and mortality. A high fat, low protein, low carbohydrate ketogenic diet (KD) has been used successfully to treat intractable epilepsy. However, its possible role in prolonged SE has not been well described. We report successful use of the KD in two adult patients with prolonged...
Purpose: Epilepsy is a commonly reported but rarely described clinical hallmark of mitochondrial respiratory chain defects (RCDs) with encephalopathy.
Methods: From 1990–2006 we collected data about 56 children with RCD (single, n = 24 or multiple, n = 20 mitochondrial complex deficiencies; mtDNA mutation, n = 11; mtDNA depletion n = 10 of 21; and nuclear gene mutation n = 11). Epileptic features...
The distribution of bone marrow cells in brain areas during the acute period after pilocarpine‐induced status epilepticus (SE) was investigated here. To achieve this, we generated chimeric mice by engrafting bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic mice. GFP+ bone marrow–derived cells were found throughout the brain, predominantly in the hippocampus. As expected,...
Purpose: Appropriate treatment of generalized convulsive refractory status epilepticus (RSE) requires general anesthesia in the intensive care unit (ICU) with continuous electroencephalography (cEEG) monitoring. During out of office hours and weekends, cEEG monitoring is not always available. The Bispectral Index (BIS) monitor can be used to assess the hypnotic component of general anesthesia. We...
Purpose: Exposure to toxic levels of organophosphorus (OP) nerve agents can lead to seizures, respiratory failure, and, if untreated, death. The cholinesterase inhibitor soman belongs to the class of OP nerve agents and can cause status epilepticus (SE) and brain damage due to neuroexcitotoxicity. In the present study, electroencephalographic seizures are characterized through telemetry implants...
A girl aged 1 year 9 months had recurrent episodes of febrile status epilepticus. She recovered completely after the first three episodes. However, at 9 months she developed acute encephalopathy resulting in severe neurologic sequelae. Diffusion‐weighted magnetic resonance imaging revealed diffuse high‐intensity signals over the cortex and subcortical white matter in the acute phase and severe diffuse...
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