Reduction In Seizure Duration Research Articles

Magnesium sulfate versus phenytoin for seizure prevention in amygdala-kindled rats

Objective: Magnesium sulfate is widely used for seizure prophylaxis in preeclampsia-eclampsia. However, its anticonvulsant effects in other types of seizures have not been proved. Diphenylhydantoin has been widely characterized as the “gold standard” of anticonvulsants. In this study we compared the anticonvulsant effects of therapeutic blood levels of magnesium sulfate and phenytoin in seizures generated in amygdala-kindled rats.Study Design: Eighteen male rats had a bipolar electrode stereotaxically implanted into the central nucleus of the amygdala. After recovery an electrical seizure threshold was determined for each rat. Rats were stimulated twice daily at their seizure thresholds (i.e., kindling) until three consecutive generalized tonic-clonic seizures occurred. Kindled rats randomly received one of the following intravenous injections in a volume of 1.5 ml/kg: saline solution, magnesium sulfate (30, 60, or 90 mg/kg), or phenytoin (12.5, 25, or 50 mg/kg). Fifteen minutes after injection rats were stimulated at their seizure thresholds, and electrical and behavioral seizure activity was assessed. Statistical comparisons were made by analysis of variance and post hoc comparisons where appropriate.Results: Magnesium sulfate had no effect on any of the seizure parameters assessed. Phenytoin significantly reduced seizure duration (p < 0.01), duration of postictal depression (p < 0.01), and behavioral seizure stage (p < 0.01).Conclusion: Amygdala-kindled seizures are more potently inhibited by phenytoin than by magnesium sulfate.

A comparison of propofol and methohexital as anesthetic agents for ECT: Effects on seizure duration, therapeutic outcome, and memory

The effects of the anesthetic agents propofol and methohexital on seizure duration, clinical outcome, recovery, and memory in electroconvulsive therapy (ECT) were studied in a double-blind trial. The study comprised 53 patients, 47 patients with major depression and six patients with other diagnoses according to DSM-III. Several recent clinical studies with a crossover design have shown a reduced seizure duration for anesthesia with propofol in comparison with both methohexital and thiopental. Propofol significantly reduced the seizure duration in this study without reducing the therapeutic outcome as measured by the Montgomery-Åsberg Depression Rating Scale. Propofol did not significantly alter the length of the course of ECT; however, a slightly prolonged course for women cannot be completely ruled out. There were no significant differences between the two agents in effects on recovery times after anesthesia and on anterograde memory. In general, it seems that propofol is as effective as methohexital as an induction agent for ECT.

Lack of changes in seizure susceptibility during the estrous cycle in kindled rats

The threshold and pattern of focal and generalized seizures in fully kindled rats during the estrous cycle were investigated. Two groups of rats were studied; one was kindled from stimulation of the basolateral amygdala, the other from stimulation of the anterior portion of the posterior piriform cortex. Determinations of the threshold for focal afterdischarges were either carried out in the morning (between 8 and 9 a.m.) or in the afternoon (between 2 and 3 p.m.). In all experiments, stable and reproducible afterdischarge thresholds were obtained during the different stages of the estrous cycle. The only significant alteration was a reduced seizure duration during metestrus and/or the first day of diestrus in amygdala kindled rats. The data indicate that the natural changes in sex hormone levels during the estrous cycle in rats do not affect seizure susceptibility, at least in the kindling model of epilepsy.

Prevention of the Cardiovascular and Neuroendocrine Response to Electroconvulsive Therapy

Electroconvulsive therapy (ECT) under anesthesia is associated with hypertension and tachycardia. The cardiovascular effects of ECT were studied after pre-treatment of 10 patients with esmolol (1.0 mg/kg), fentanyl (1.5 micrograms/kg), labetalol (0.3 mg/kg), lidocaine (1.0 mg/kg), and saline solution (control), using a double-blind, randomized block-design. Each patient received all five pretreatment regimens over the course of five ECT sessions. During control studies, arterial blood pressure and heart rate increased significantly in all patients after ECT (P less than 0.05 and P less than 0.01, respectively). The rate-pressure product increased by an average of 336% +/- 14% (P less than 0.01). There were appreciable individual differences in the cardiovascular response to ECT, independent of pretreatment (P less than 0.01). Pretreatment with esmolol and labetalol significantly reduced the hemodynamic response to ECT, compared with fentanyl, lidocaine, or saline solution (P less than 0.05). Esmolol attenuated arterial blood pressure to a larger extent than did labetalol (P less than 0.05). Compared with saline solution (control), pretreatment with labetalol, fentanyl, or lidocaine significantly reduced seizure duration (P less than 0.05) and increased the frequency with which a second electrical stimulus was required. In contrast, esmolol pretreatment did not significantly affect seizure duration. Esmolol (1 mg/kg), administered 1 min before induction of anesthesia, produced significant amelioration of the cardiovascular response to ECT with minimal effect on seizure duration.

Propofol as an Anaesthetic Agent for Ect: Effect on Outcome and Length of Course

Recent reports of reduced seizure duration with ECT under propofol anaesthesia have led to concerns that propofol may diminish the efficacy of this treatment. To investigate the effect of propofol on the response to ECT, we reviewed records of 66 patients with primary depression treated with ECT, 37 of whom had been assessed prospectively with pre- and post-ECT Hamilton and Zung depression severity ratings. Despite demonstrating that the individual seizure duration was significantly reduced with propofol compared to thiopentone we found no evidence of reduced ECT efficacy with propofol. Courses under propofol anaesthesia were on an average two treatments longer than with thiopentone. Although this difference was not statistically significant this may have been due to a type II error. These results suggest that it is premature to abandon the use of this new anaesthetic agent in ECT without controlled prospective outcome studies.

Sleep deprivation and kindled seizures

Total sleep deprivation in a treadmill, and REM sleep and partial slow-wave sleep deprivation by the platform technique led to reduced seizure threshold in kindled rats. After treadmill deprivation there was also a reduction in seizure duration. Arousing aspects of the sleep deprivation procedures counteracted the sleep deprivation effect. In the treadmill experiment this led to an increase in seizure threshold in the control group. In the platform experiment the reduction in seizure threshold was delayed for 24 h after the deprivation because of these short-acting processes. Seizure thresholds remained low for at least 72 h.

Effect of amino-oxyacetic acid (AOAA) on focal penicillin seizures

The biochemical and behavioral effects of the anticonvulsant amino-oxyacetic acid (AOAA) have been studied in a model of focal penicillin seizures in rats. At 20 mg/Kg AOAA treatment results in a progressive 11 fold increase in GABA levels in cortex over three hours. There is a decrease in aspartate, ketoglutarate, alanine and glutamine, and an initial decrease followed by an increase in pyruvate and glutamate. These results reflect a functional inhibition of several B-6 dependent aminotransferase enzymes. When rats are pretreated 30 min before the onset of focal penicillin seizures there is a 60% reduction in the number of discharges and a 34% reduction in seizure duration. Pretreatment beyond 75 min results in progressively less anticonvulsant effect, such that seizures eventually become more severe than control. There is an increase in the number and duration of discharges, seizure spikes become complex, and tonic-clonic events develop. Penicillin seizures do not cause a change in levels of GABA, but result in a decrease in glutamate within the focus. AOAA pretreatment initially prevents this decrease in glutamate but later accentuates it. The biochemical effects of AOAA are complex, but biphasic anticonvulsant properties coincide in time with a change in the balance of excitatory and inhibitory amino acids in the seizure focus.

ANTIMALARIALS AND OTHER ANTICONVULSANT DRUGS: PREDICTIVE VALIDITY OF LABORATORY TESTS.

SummaryThe antimalarials quinacrine, chloroquine and hydroxychloroquine were investigated for their anticonvulsant activities against maximal electroshock seizures, maximal and minimal metrazol seizures and electrogenic psychomotor seizures. Phenobarbital, trimethadione diphenylhydantoin, and phenacemide were employed as reference standards. 1. All 3 antimalarials were ineffective in protecting mice from maximal electro-shock tonic extensor seizures, both after single oral doses and after 4 daily doses. 2. Hydroxychloroquine was effective against maximal metrazol seizures after a single oral dose. Quinacrine and chloroquine exhibited activity after 4 daily medications. 3. Quinacrine and chloroquine (low doses) enhanced psychomotor seizure duration while hydroxychloroquine and chloroquine (high doses) slightly reduced seizure duration. 4. Difficulties in predicting clinical efficacy from laboratory data are discussed.

Stimulus intensity and duration of electroshock seizure response

This investigation proposes a simple mathematical model for electroshock seizure responses in terms of an operational definition of excitatory state based on the relationship between stimulus intensity and seizure duration. Two parameters, the decay constant, a, and the minimal threshold for seizure activity, h K , are derived from this model as the slope and intercept, respectively, of the line drawn on the plot of log stimulus intensity against seizure duration. Preliminary experimental evaluation indicates that h K is not affected by repeated stimulation. On the other hand, changes in a are observed after a conditioning stimulus. It is tentatively concluded that these changes in a persisted for at least 300 seconds following a stimulus, and may partially explain the reduction in seizure duration which occurs after a conditioning stimulus.