Risk of unprovoked seizure after acute symptomatic seizure: effect of status epilepticus

The dehydration effect is suggested as a mechanism of anesthetic action of magnetic fields. After half an hour of in vivo exposure in constant magnetic field of white male rats to SMF 0.2 T the dehydration of brain, kidney and liver tissues were detected, the decrease of ouabain binding in 5.10(-9) M concentration was detected in brain, heart, spleen and liver tissues and it was increased in kidney tissue. With prolongation of the exposure time the dehydration of the whole organism was observed.     

Anxiogenic-like consequences in animal models of complex partial seizures

Extracellular adenosine triphosphate (ATP) plays an important role in the regulation of endothelial function. However, its receptors and their signal-transduction pathways in major cerebral arterial endothelial cells are largely unknown. This study was undertaken functionally to classify the P2 purinoceptors in cultured bovine middle cerebral artery endothelial cells by using [Ca2+]i microfluorimetry. The rank order of potency to increase [Ca2+]i was 2-methylthio-ATP approximately ATP approximately uridine triphosphate (UTP) > adenosine diphosphate (ADP) > adenosine monophosphate (AMP) > alpha,beta-methylene-ATP > adenosine, suggesting that the effect was mediated by both P2y and P2u receptors. ATP, 2-methylthio-ATP, and UTP mobilized Ca2+ from intracellular stores and triggered Ca2+ entry. The effects of ATP, 2-methylthio-ATP, and UTP were reduced by phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), but only the effects of ATP and UTP were attenuated by pertussis toxin, indicating that P2y and P2u receptors may activate the same effector mechanisms by coupling to different G proteins. The [Ca2+]i entry caused by UTP was significantly reduced by the receptor-regulated Ca2+ channel blocker SK&F 96365, by P-450 inhibitor econazole and by inorganic Ca2+ entry blocker lanthanum. P2-receptor antagonists suramin, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), and reactive blue 2 reduced the effects of ATP and 2-methylthio-ATP, but not those of UTP, in a concentration-dependent manner. These studies suggest a coexistence of P2y and P2u receptors in cultured bovine middle cerebral artery endothelial cells.     

Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus

A novel antiepileptic drug, tiagabine ((R)-N-[4,4-di-(3-methylthien-2-yl) but-3-enyl] nipecotic acid hydrochloride), was studied in rats in order to determine its efficacy in preventing seizures, seizure-induced neuronal damage and impairment of spatial memory in the perforant pathway stimulation model of status epilepticus. In pilot experiments, administration of tiagabine (50, 100 or 200 mg/kg/day) with subcutaneously implanted Alzet osmotic pumps led to a dose-dependent increase in tiagabine concentrations in the serum and brain. Two days of tiagabine treatment at a dose range of 50-200 mg/kg/day did not change the levels of gamma-aminobutyric acid (GABA), glutamate or aspartate in cisternal cerebrospinal fluid (CSF) compared to the controls. In the pentylenetetrazol test, the maximal anticonvulsive effect of tiagabine administered via osmotic pumps was achieved already with a dose of 50 mg/kg/day. In the perforant pathway model of status epilepticus, subchronic treatment with tiagabine (Alzet pumps, 50 mg/kg/day) completely prevented the appearance of generalized clonic seizures during stimulation (P < 0.001). In the same rats, tiagabine treatment reduced the loss of pyramidal cells in the CA3c and CA1 fields of the hippocampus (P < 0.05) but not the loss of somatostatin immunoreactive neurons in the hilus. Two weeks after perforant pathway stimulation, the tiagabine-treated rats performed better in the Morris water-maze test than the vehicle-treated rats did (P < 0.001). Our results show that tiagabine treatment reduces the severity of seizures in the perforant pathway stimulation model of status epilepticus. Possibly associated with the reduction in seizure number and severity, tiagabine treatment also reduced seizure-induced damage to pyramidal cells in the hippocampus as well as the impairment of the spatial memory associated with hippocampal damage.     

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus

BACKGROUND AND OBJECTIVE: Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend. METHODS: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. RESULTS: ESES and drop attack seizures appeared between the ages of 2 and 5 years (mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. CONCLUSIONS: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.     

Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice

Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans.     

Management of status epilepticus in children

Treatment of SE is based on the age of the patient and the possible underlying etiology. Initial treatment should include a benzodiazepine (lorazepam 0.1 mg/kg or diazepam 0.5 mg/kg). Specimens for laboratory tests should be drawn early in the event of a prolonged seizure and geared toward the clinical presentation and age of the patient. If a seizure lasts longer than 10 minutes, phenobarbital 20 mg/kg dose should be administered with strict adherence to the proper rate of administration. Further seizure activity during drug administration can be treated with additional doses of lorazepam or diazepam. If a seizure lasts longer than 10 minutes, a second long-acting anticonvulsant should be administered, followed by induction of general anesthesia.     

The EEG and prognosis in status epilepticus

To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.     

Prolonged and monosymptomatic dysphasic status epilepticus

Dysphasic seizures are an infrequent form of epilepsy, and their serial appearance as a partial status epilepticus is quite exceptional. The young patient reported here had a partial dysphasic status epilepticus of 3 weeks' duration without other temporal lobe seizures. Simultaneous serial electroencephalograms, tape recordings of the seizures, and repeated neuropsychologic ictal examinations permitted studies of increased impairment of neuropsychologic function on testing and the appearance of new irritative discharges on encephalography.     

Disseminated intravascular coagulation and status epilepticus

Status epilepticus has been associated with disseminated intravascular coagulation (DIC), but little is known regarding the pathogenesis of this uncommon association. We describe a 41-year-old woman with status epilepticus resulting in death in whom laboratory data demonstrated profound activation of the coagulation and fibrinolytic systems; autopsy findings were consistent with DIC. The occurrence of DIC in status epilepticus may be related to widespread endothelial damage secondary to seizure-induced hyperpyrexia. Body temperature should be closely monitored in patients with prolonged seizures.     

Role of propofol in refractory status epilepticus

OBJECTIVE: To provide a review of the proposed mechanism of action, clinical efficacy, adverse effects, and therapeutic considerations associated with the use of propofol in the management of patients with refractory status epilepticus. DATA SOURCES: A MEDLINE database (January 1966-April 1998) was searched for literature pertaining to status epilepticus and propofol. Additional literature was obtained from the references of selected articles identified in the search. Information from all articles published in English was considered for inclusion in the article. DATA SYNTHESIS: Propofol is a unique, nonbarbiturate, anesthetic agent possessing anticonvulsant properties, although the exact anticonvulsant mechanism is unknown. Several case reports and two small, open, uncontrolled studies have described the efficacy of propofol in refractory status epilepticus. Most of these clinical reports discuss the utility of propofol after traditional treatment regimens have failed or are not tolerated. Initiation of propofol usually resulted in termination of seizure activity and/or electroencephalographic burst suppression within seconds that was sustained during the drug's use. Additionally, propofol was well tolerated. Advantages of propofol compared with traditional barbiturate anesthetic agents include better cardiovascular tolerability and a more favorable pharmacokinetic profile, allowing for rapid assessment of efficacy and neurologic assessment upon drug withdrawal. Propofol has been associated with a variety of neuroexcitatory adverse events such as opisthotonos, muscle rigidity, and choreoathetoid movements. Additionally, although the data are inconclusive, propofol has also been reported to cause seizures. CONCLUSIONS: Propofol has shown promising results in the management of refractory status epilepticus when traditional therapies have failed or were not tolerated; however, controlled clinical trials are needed to better assess the comparative efficacy, neurologic adverse effects, and clinical outcome to better define its role in refractory status epilepticus.     

Cat-scratch disease causing status epilepticus in children

The ingestion of iron-containing products is a potential toxicologic emergency. The total iron binding capacity (TIBC) has been used widely as a predictor of end-organ toxicity and a guide to the need for deferoxamine therapy. When the TIBC is greater than the serum iron concentration (SIC), it is held that no free iron is present to cause toxicity. The TIBC fails as a marker of toxicity for several reasons. First, the laboratory methods used to measure TIBC are inaccurate in the setting of iron overload. Second, the presence of deferoxamine, the antidote for iron poisoning, has been shown to make the TIBC measurement inaccurate. Third, TIBC measurements have been shown to be variable. Finally, studies and case reports demonstrate toxicity even when the TIBC is greater than the SIC. These shortcomings of the TIBC invalidate it as a predictor of toxicity in iron poisoning.     

GABA(B) modulation improves sequence disambiguation in computational models of hippocampal region CA3

Computational models of hippocampal region CA3 were used to study the role of theta rhythm in storage and retrieval of temporal sequences of neuronal activity patterns. Retrieval of multiple overlapping temporal sequences requires a mechanism for disambiguation, e.g., for choosing between two sequences with the same starting pattern but different final patterns (forked sequences). Modulatory input to the hippocampus from the medial septum may enhance the disambiguation of pattern sequences by causing phasic changes in the relative strength of afferent input and recurrent excitation. In the models, the strength of recurrent synaptic transmission is modulated by activation of GABA(B) receptors. Theta frequency inputs from the medial septum cause oscillations in the levels of GABA in the model, producing phasic changes in the strength of synaptic potentials during a theta cycle similar to those observed experimentally (Wyble et al., Soc Neurosci Abstr 1997;23: 197.7). These phasic changes in GABA(B) suppression improve sequence disambiguation in the simulations, as previously shown with analysis of a simpler model (Sohal and Hasselmo, Neural Comp 1998;10:889-902). In addition, tonic changes in levels of cholinergic modulation enhance the storage of forked sequences by preventing a strong influence of recurrent synapses during storage.     

Selective reduction of GluR2 protein in adult hippocampal CA3 neurons following status epilepticus but prior to cell loss

Kainic acid (KA) induces status epilepticus and delayed neurodegeneration of CA3 hippocampal neurons. Downregulation of glutamate receptor 2 (GluR2) subunit mRNA [the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) subunit that limits Ca2+ permeability] is thought to a play role in this neurodegeneration, possibly by increased formation of Ca2+ permeable AMPA receptors. The present study examined early hippocampal decreases in GluR2 mRNA and protein following kainate-induced status epilepticus and correlated expression changes with the appearance of dead or dying cells by several histological procedures. At 12 h, in situ hybridization followed by emulsion dipping showed nonuniform decreases in GluR2 mRNA hybridization grains overlying morphologically healthy-appearing CA3 neurons. GluR1 and N-methyl-D-aspartate receptor mRNAs were unchanged. At 12-16 h, when little argyrophilia or cells with some features of apoptosis were detected by silver impregnation or electron microscopy, single immunohistochemistry with GluR2 and GluR2/3 subunit-specific antibodies demonstrated a pattern of decreased GluR2 receptor protein within CA3 neurons that appeared to predict a pattern of damage, similar to the mRNA observations. Double immunolabeling showed that GluR2 immunofluorescence was depleted and that GluR1 immunofluorescence was sustained in clusters of the same CA3 neurons. Quantitation of Western blots showed increased GluR1:GluR2 ratios in CA3 but not in CA1 or dentate gyrus subfields. Findings indicate that the GluR1:GluR2 protein ratio is increased in a population of CA3 neurons prior to significant cell loss. Data are consistent with the "GluR2 hypothesis" that reduced expression of GluR2 subunits will increase formation of AMPA receptors permeable to Ca2+ and predict vulnerability to a particular subset of pyramidal neurons following status epilepticus.     

Grouped crises and status epilepticus in complex partial epilepsy

INTRODUCTION: In complex partial crises (CPC) some characteristics of the way in which they occur may be helpful in localizing the focus of origin in the cerebral cortex. Thus, the appearance of any kind of status epilepticus will not predominate depending on the origin of the epileptic focus, but the complex partial state will be rare when the origin is temporal and more frequent when the origin is frontal. The appearance of CPC in a cluster form is, on the other hand, characteristic of crises originating in the frontal lobe. MATERIAL AND METHODS: We review the clinical history of 151 epileptics with CPC, evaluating the way in which the crises appear, together with other clinical data. We define the start of the crisis in a specific lobe, when this was the site of maximum voltage of the epileptic anomaly or of maximum phase opposition. RESULTS: 10% of the patients showed grouping of their CPC; in the remainder the appearance was isolated, 15% showed status epilepticus at some point in their illness. We found a statistical difference when relating this to the anomalous topography of the EEG; between 15% and 42% more patients with status epilepticus were counted when the topography of the anomaly in the EEG was extratemporal. There was also between 37.2% and 76.4% more patients with cluster crises in the cases with an extratemporal focus.     

Galanin inhibits long-term potentiation at Schaffer collateral-CA1 synapses in guinea-pig hippocampal slices

CNSs AND OTHER Master's-prepared nurses are usually expected to lead research utilization (RU) efforts in organizations, but they often feel unprepared to do so. In this article, the need for clinical RU is discussed and ideas for implementation, using an adaptation of the Conduct and Utilization of Research in Nursing model, are described. The RU process is applied to research about once-a-day temperatures in afebrile patients. To assist nurses who are implementing research-based practice, we list studies that were used for the practice change, summarize the research base on the topic, and offer an example of clinical use of practice guidelines.     

Midazolam in the treatment of status epilepticus in children

OBJECTIVE: To determine the efficacy and safety of midazolam given as a continuous infusion in the treatment of status epilepticus in children. DESIGN: Prospective, open study. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-four children with seizures, in whom three repeated intravenous doses of 0.3 mg/kg of diazepam, 20 mg/kg of phenobarbital, and 20 mg/kg of phenytoin failed to bring the episode under control. INTERVENTIONS: All patients received a bolus of midazolam (0.15 mg/kg iv) followed by a continuous infusion at 1 microgram/kg/min. The dose was increased every 15 mins until the episode of seizure was brought under control. Time to control seizures, infusion rate, and side-effects were monitored. MEASUREMENTS AND MAIN RESULTS: The mean age of the patient population was 2.2 yrs (range 2 months to 12 yrs; 14 female and 10 male). In all patients, seizures were controlled in a mean time of 0.78 hrs (range 15 mins to 4.5 hrs). The mean infusion rate was 2.3 micrograms/kg/min (range 1 to 18). None of the patients had clinically important changes in blood pressure, heart rate, oxygen saturation, or respiratory status attributable to the use of midazolam. The mean time to full consciousness for patients after stopping the infusion was 4.2 hrs (range 2 to 8.5). CONCLUSION: Midazolam is an effective and safe drug to control refractory seizures in children with status epilepticus.     

Nonconvulsive status epilepticus in the critically ill elderly

PURPOSE: To describe the electrographic and clinical features of nonconvulsive status epilepticus (NCSE) in the critically ill elderly and to identify potential predictors of outcome. METHODS: We prospectively identified 25 episodes of altered mentation and NCSE in 24 critically ill elderly patients associated with generalized, focal, or bihemispheric epileptiform EEG patterns. Patients with anoxic encephalopathy were excluded. RESULTS: Of 25 hospitalizations, 13 (52%) resulted in death, and 12 (48%) patients survived to discharge. Death was associated with the number of acute, life-threatening medical problems on presentation (survivors, 1.8; fatalities, 2.8; p = 0.013) and with generalized EEG pattern (p = 0.017). Higher doses or greater number of antiepileptic drugs (AEDs) did not improve outcome. Treatment with intravenous benzodiazepines was associated with increased risk of death (p = 0.033). Ten patients with advance directives were managed outside the intensive care unit (ICU). Mean hospitalization was 39 days in the ICU group and 22 for those with advance directives (p = 0.017). CONCLUSIONS: Severity of illness correlates with mortality in critically ill elderly patients with NCSE. Treatment with intravenous benzodiazepines may increase their risk of death. Aggressive ICU management may prolong hospitalization at considerable cost, without improving outcome. It is unclear whether NCSE affects outcome in the critically ill elderly or is merely a marker for severity of disease in predisposed patients. The benefits of aggressive therapy are unclear. Carefully controlled, prospective trials will be necessary to determine the best therapies for NCSE in the critically ill elderly and the appropriate role of the ICU in their management.     

An animal model of hypoxia-induced perinatal seizures

Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure activity. Here we describe a rodent model of cerebral hypoxia in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute seizure activity during a window of development between postnatal day (P5-17), peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had long term decreases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) transmission appear to be superior to benzodiazepines in suppressing the acute and long term effects of perinatal hypoxia, suggesting involvement of the EAA system in these phenomena. No significant histologic damage occurs in this model, suggesting that functional alterations take place in neurons when exposed to an hypoxic insult at a critical developmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptibility produced by this model.