Total Seizure Duration Research Articles

Differential regulation of seizure activity in the hippocampus of male and female rats

OBJECTIVE: The aim of the current study was to directly examine and compare the susceptibility to N-methyl-D-aspartate-induced seizures in male versus female rats. We Also sought to compare the anticonvulsant effects of magnesium sulfate in these two groups. STUDY DESIGN: Eighteen female and 10 male rats were stereotaxically implanted with a chronic bipolar recording electrode in the hippocampus and an injection cannula in the lateral cerebral ventricle. After 1 week rats randomly received an intravenous injection of 90 mg/kg magnesium sulfate or saline solution control. Fifteen minutes after the infusion rats were given the convulsant N-methyl-D-aspartate at a dose of 5 μg/μl by direct intraventricular injection. Electrical seizure activity was thereafter assessed for 20 minutes. All data were analyzed by the Mann-Whitney U test and Student t test. RESULTS: In saline solution-treated rats receiving the convulsant N-methyl-D-aspartate, females had significantly lower total duration ( p < 0.01) and total number of seizures ( p < 0.05) compared with the male rats. The initial seizure was not affected by gender. In the female animals magnesium sulfate significantly reduced first seizure duration ( p < 0.01) compared with saline solution controls. In males magnesium sulfate reduced both total duration ( p < 0.05) and total seizure number ( p < 0.05) compared with saline solution-treated animals. CONCLUSION: N-methyl-D-aspartate-induced seizure activity is more severe in males versus female rats. Magnesium sulfate's effect on N-methyl-D-aspartate-induced seizures is also dependent on gender. We speculate that seizure regulation may be hormonally influenced.

Propofol Anaesthesia in Electroconvulsive Therapy

The induction agent propofol is known to reduce electroconvulsive therapy (ECT) seizure duration. It is assumed that outcome from depression is adversely affected by this agent. This study compares propofol and methohexitone as induction agents for ECT. In a prospective, randomised, double-blind study 20 subjects with major depressive disorder (DSM-III-R criteria) received propofol or methohexitone anaesthesia. The Hamilton Depression Rating Scale and Beck Depression Inventory were used to assess depression before therapy, at every third treatment, and at the end of therapy. Seizure duration was measured using the cuff technique. Mean seizure durations (P < 0.01) and mean total seizure duration (P < 0.01) were shorter in the propofol group. There was no difference in outcome. Use of propofol may not adversely affect outcome from depression and it is not necessarily contraindicated as an induction agent for ECT. Our results should be interpreted cautiously, and larger studies are needed.

A reliability study of a neonatal seizure scoring system

Two measures of reliability assessed inter-rater agreement regarding neonatal seizure scoring: coefficient of variation and intraclass correlation coefficient. Ten neonates with electrographic seizures recorded during each of 2 h of an EEG-sleep study were submitted for visual analysis. The onset, spread, and termination of seizures were coded. The number of anatomical sites with electrographic seizures as well as the durations for each of three phases of the seizure were calculated. Seven EEG scores for these 10 patients were coded independently by three different raters. The number of sites at the onset of each seizure and the duration of seizures, both at the onset and for the entire duration of the seizure, had moderate-to-excellent reliability. Lower reliability, however, was noted for the number of seizures during the phases of spread and termination. Before the development of computerized programs to detect and document the evolution of neonatal seizures, particularly in the context of treatment with different medications, practical strategies based on visual analysis need to be developed. Although the onset and total duration of seizures can be reliably scored among raters, the more variable description of spread and termination of the seizure is more problematic and requires greater attention and experience. This technique may be useful in evaluating the medication efficacy.

Stimulation and inhibition of N-methyl- D-aspartate receptors in rats: Developing a seizure model

The objective of this study was to develop an experimental rat hippocampal seizure model based on the stimulatory effects of N-methyl-D-aspartate and to determine the inhibitory effects of MK-801 on N-methyl-D-aspartate-induced seizures. Two separate experiments were performed. In the first experiment chemitrode-implanted rats were injected intracranially with increasing doses (5, 10, 20, and 30 micrograms) of N-methyl-D-aspartate into the hippocampus. Various electrophysiologic and behavioral parameters were examined to determine the dose required to reliably elicit hippocampal seizure activity without having toxic effects on the rats. In the second experiment rats were given an intraperitoneal injection of MK-801 (0.5 or 1 mg/kg), followed 20 minutes later by an intracranial injection of N-methyl-D-aspartate (20 or 30 micrograms). The ability of MK-801 to suppress N-methyl-D-aspartate-induced seizure activity was assessed in this experiment. Intrahippocampal injection of 20 micrograms of N-methyl-D-aspartate produced the shortest electrical seizure latency (193 +/- 72 seconds, p < 0.01). At this dose seizure was achieved in 80% (four of five of the animals, and the highest numbers of electrical seizures per animal were produced (2.2 +/- 0.8, p < 0.05). The group that received 30 micrograms of N-methyl-D-aspartate had a shorter latency, a longer duration of behavioral seizure and a higher number of behavioral seizures (p < 0.05). However, this group suffered a 60% (three of five) mortality rate. The addition of MK-801 significantly decreased the number of seizures per animal and the total seizure duration (p < 0.05). MK-801 also reduced the latency period. Intracranial injection of 20 micrograms of N-methyl-D-aspartate produced reliable hippocampal seizure activity without mortality. MK-801 at a dose of 1 mg/kg injected intraperitoneally had significant inhibitory effects on this seizure model.

EEG manifestations during ECT: effects of electrode placement and stimulus intensity

This study examined the ictal electroencephalographic (EEG) characteristics of four forms of electroconvulsive therapy (ECT) known to differ in efficacy. Previously, we demonstrated that titrated, low-dose right unilateral ECT reliably produces generalized seizure of adequate duration, but is remarkably weak in antidepressant effects. Using a new rating scale, we found that specific features of the ictal and immediate postictal EEG varied significantly with ECT stimulus intensity and electrode placement. The low-dose right unilateral condition differed from more effective forms of ECT in having the longest polyspike phase duration, averaging twice that of the other conditions; it was also the condition least likely to manifest bioelectric suppression immediately following seizure termination. In contrast, high-dose bilateral ECT—a treatment with particularly rapid antidepressant effects—resulted in the greatest peak slow-wave amplitude in both hemispheres. Total seizure duration did not differ among the four treatment conditions. These findings indicate that seizure duration is not a useful marker of therapeutic efficacy, and instead provide preliminary evidence that other features of the EEG may be more useful markers of treatment adequacy.

Seizures of Fronto‐Orbital Origin: A Proven Case

Distinguishing characteristics of seizures of frontal origin have not been clearly delineated. We describe a case of seizures of proven fronto-orbital origin to provide further definition of characteristics of seizures arising in that lobe. A 36-year-old man had medically intractable seizures since age 8 years. Clinically the seizures were stereotyped, with cessation of activity followed by turning of head and body to the right and then by struggling, kicking, and vocalizations indicating fear. Total seizure duration was approximately 30 s, with an apparent abrupt return of consciousness. The interictal scalp EEGs were similar to those of primary generalized epilepsy, with bisynchronous though asymmetric epileptiform activity anteriorly. Ictal scalp recordings were not localizing. Recordings from bilateral frontal and temporal subdural electrodes showed an electrical focus in the right fronto-orbital region which was confirmed by electrocorticography (ECoG) at the time of craniotomy. The right fronto-orbital cortex was resected and on pathologic examination showed gliotic tissue and intracytoplasmic neuronal inclusions of periodic acid-Schiff (PAS)-positive granules consistent with lipofuscinosis. The patient has remained seizure-free for 6 years after operation.

On the relation between seizures and brain lesions after intracerebroventricular kainic acid.

To analyze the relation between kainic acid-induced limbic seizures and the associated brain lesions, various doses of kainic acid (117-940 pmol) were administered intracerebroventricularly to unanesthetized rats. Rats which experienced status epilepticus developed lesions in several limbic, neocortical and thalamic regions. However, rats which experienced only temporally discrete seizures (less than 30 min each) suffered neuronal degeneration exclusively in the CA3-CA4 area ipsilateral to the kainic acid infusion, even when other regions exhibited the same total electrographic seizure duration. These results can best be explained by postulating that, in addition to evoking seizures, kainic acid also enhances the toxic effects of seizures on CA3-CA4 neurons.

Comparison of seizures and brain lesions produced by intracerebroventricular kainic acid and bicuculline methiodide

Intracerebroventricular kainic acid produces in rats brain lesions similar to Ammon's horn sclerosis in humans. To test the hypothesis that these lesions result indirectly from prolonged seizure activity and not from a direct action of kainic acid on the neurons that are destroyed, the effects of intracerebroventricular kainic acid and bicuculline methiodide were compared. Although bicuculline methiodide seizures differed dramatically from kainic acid seizures, both electrographically and behaviorally, the resulting brain lesions were similar for a given total limbic seizure duration. These results, in combination with other data, support the view that lesions made by intracerebroventricular administration of convulsants are indeed caused by prolonged limbic seizures. The total duration of seizure activity appears to be one important variable.

Effect of amphetamine and cocaine on seizure in lead treated mice

Mice, genetically selected for differences in brain weight were employed. Lead administration (0.5% lead acetate) from conception increased the proportion of 21 day old mice exhibiting seizures; total duration of observed seizures was also increased. Mice from the low brain weight line more frequently exhibited seizures than either mice from the high brain weight line or the Binghamton heterogenous stock. Although genome and lead administration alter bodyweight, the inability of bodyweight to predict seizure occurence and/or total duration of seizure within conditions also ws noted. Lead administration from conception through testing increased the probability and duration of transcorneally induced electroconvulsive seizures of 21 day old mice within all three genotypes, and both cocaine and amphetamine injections 15 min prior to ECS reduced the number of animals exhibiting seizures as well as the duration of seizures in both lead treated and control mice.

Seizure duration and clinical effect in electroconvulsive therapy

It is vital to understand the nature of the seizure produced during convulsive therapy as it is the seizure itself that produces the beneficial effect rather than other factors associated with the treatment. 1–5 With the advent of monitored electroconvulsive therapy (MECT) and multiple monitored electroconvulsive therapy (MMECT), 6,7 it has become possible to measure certain parameters of the seizure produced during treatment. Induced seizures can vary in duration and intensity and such variance can be produced in part by manipulations of the treatment team. For example, increasing the oxygenation of the brain by more forceful artificial ventilation just prior to and during the seizure can increase its duration. 8–10 Increasing or altering the stimulus properties can also increase duration and enhance EEG amplitude. 11,12 Seizure durations and intensities can be measured and clinical effects correlated with these parameters. It would be important to know whether there is an optimum seizure length to produce beneficial effect or whether there is a minimum total seizure duration below which benefits will not accrue. The availability of the MECT apparatus for several years has enabled us to accumulate data on 110 patients given MECT. The present study examines number of seizures, number of sessions, and seizure durations produced during ECT to determine whether such parameters are of importance in assessing clinical effects. Seizure intensity is not reported as it cannot be measured based solely upon examination of the EEG record. 13,14 Special cumulative recording apparati are necessary for such measurement; a report on this is planned in the future.

Threshold and pattern of electroshock seizures after 250 r whole-body x-irradiation in rats.

SummaryThe effects of single doses of 250 and 500 r whole-body X-irradiation on threshold and pattern of electroshock seizures were followed in rats for 20 post-irradiation days. Irradiated rats had lower electro-shock seizure thresholds than controls. Total duration of the maximal electroshock seizures was shorter in the irradiated rats than in controls. This was due to a significant shortening of the clonic phase of the seizure. These findings are interpreted as indicating that brain excitability is increased by irradiation at 250 and 500 r. However. heightened seizure activity cannot be sustained as long in irradiated rats as in controls. The magnitude of the changes in brain convulsability was the same for the 2 doses of X-irradiation while the effects on body growth were dose-dependent in this range.

Postictal recovery in normal and diphenylhydantoin (dilantin)-treated mice.

In order to study postictal recovery, groups of normal and Dilantin-treated mice were given a supramaximal electroshock and the durations of the hindleg components of the “first” seizure recorded. At various time intervals after the “first” seizure, a “second” supramaximal electroshock was given and the durations of the hindleg components of the “second” seizure recorded. This procedure was repeated, with longer time intervals between seizures, until the observed durations of the “second” seizure components were not significantly different from their “first” seizure values. In addition, the time (RT50) required for 50% of animals to recover ability to exhibit a second tonicclonic seizure after a first was determined. The data obtained may be summarized as follows: The order in which the durations of the various components and the total duration of the “second” seizure returned to their “first” seizure values were the same in both groups: total seizure duration, terminal clonus, tonic extension, and tonic flexion. The total duration of a maximal seizure is relatively independent of marked changes in duration of the individual seizure components. Dilantin prolonged the recovery time of terminal clonus, tonic extension, and tonic flexion by approximately 300%, 150%, and 170%, respectively. In addition, Dilantin prolonged RT50 by 325%. Evidence is presented which suggests that Dilantin acts to prolong the latent period before recovery of the tonic-extensor component starts, and that the recovery process per se, once initiated, is relatively unaffected by the drug.