Shorter Seizure Duration Research Articles

ECS-Induced mossy fiber sprouting and BDNF expression are attenuated by ketamine pretreatment.

Recent evidence suggests hippocampal and possibly cortical atrophy is associated with major depression. Chronic electroconvulsive seizures (ECS) induce brain-derived neurotrophic factor (BDNF) expression and sprouting of the mossy fiber pathway in the hippocampus, effects that may be related to electroconvulsive therapy's (ECT) mechanism of action. The objective of this study was to investigate the role of NMDA (N-methyl-D-aspartate) receptor in mediating the ECS-induced mossy fiber sprouting and BDNF expression. Timm histochemistry and in situ hybridization methodologies were used to determine the effect of pretreatment with ketamine, an NMDA antagonist, on ECS-induced sprouting and BDNF expression. The results demonstrate the ability of ketamine pretreatment to attenuate ECS-induced sprouting in the dentate gyrus and BDNF expression in the medial prefrontal cortex and the dentate gyrus. In addition, we found a significant decrease in seizure duration with ketamine pretreatment. These data suggest that NMDA receptor activation contributes to both the regulation of neurotrophic factor expression and the morphological changes associated with seizure activity. However, other effects resulting from shortened seizure duration and seizure intensity cannot be excluded. These findings are of increasing interest, as they relate to the use of ECT in the treatment of depression, and the specific anesthetic agents that are used.

An automated drug delivery system for focal epilepsy

Previous studies have demonstrated the ability to stop seizures in animal models with injection of antiepileptic medication directly onto the seizure focus. The present experiments describe automated detection and focal therapy for seizures in the laboratory setting. Focal seizures were created in Sprague–Dawley rats using bicuculline, a GABA antagonist. Computerized detection of seizures was linked to a programmable infusion pump to deliver either diazepam (DZP) or pH-balanced vehicle (VEH) directly onto the seizure focus. Mean numbers of seizures following initial delivery of drug were 2.9±1.45 for the VEH-treated group and 0.2±0.42 for the DZP-treated group ( P<0.0001, Student’s t-test, nonpaired, one-tailed). In another series of experiments, early injection of DZP shortened seizure duration. Three DZP-treated animals died. This model provides proof-in-principle for the development of a clinically applicable treatment for intractable partial epilepsy. Such therapy might avoid some of the problems inherent to systemic administration of antiepileptic drugs.

Surgery in epilepsy associated with focal lesions in childhood

Surgery in children with epilepsy is a new, evolving field. The important practical issues have been to define strategies for choosing the most suitable candidates, as well as the type and the optimum timing of epilepsy surgery. This study was undertaken to illustrate these points. To identify the factors that correlated with outcome, the authors analyzed a series of 200 children (aged 1–15 years, mean 8.7 years) who underwent surgery at the Hôpital Necker-Enfants Malades between 1981 and 1996. In 171 cases (85.5%) the epilepsy was medically refractory and was associated with focal cortical lesions. Surgery consisted of resection of the lesion without specifically attempting to identify and remove the "epileptogenic area." In the group of children whose seizures were medically refractory, the mean follow-up period was 5.8 years. According to Engel's classification, 71.3% of these children became seizure free (Ia), whereas 82% were in Class I. A multivariate statistical analysis revealed that among all the factors studied, the success of surgery in a patient in whom there was a good clinical-electroencephalogram-imaging correlation, depended on the patients' having undergone a minimally traumatic operation, a complete resection of the lesion, and a short preoperative seizure duration. After the surgical control of epilepsy, behavior disorders were more improved (31% of all patients) than cognitive function (25%). The patient age at onset, duration and frequency of seizures, intractability of the disease to therapy, and seizure characteristics, were correlated with cognitive, behavioral, and academic performance pre- and postoperatively. Multivariate statistical analysis revealed that cognitive dysfunction correlated highly with the duration of epilepsy prior to surgery, whereas behavioral disorders correlated more with seizure frequency. These data must be taken into account when selecting patients for surgical treatment and when deciding the timing of surgery. Early surgical intervention allows for optimum brain development.

Effect of methohexitone and propofol with or without alfentanil on seizure duration and recovery in electroconvulsive therapy

We have studied the effects of methohexitone and propofol with and without alfentanil on seizure duration and recovery in this observer-blinded, prospective, randomized, crossover study involving 24 patients undergoing electroconvulsive therapy (ECT). Each patient had four treatment sessions, and received the following four i.v. regimens in random order: methohexitone 0.75 mg kg-1, methohexitone 0.50 mg kg-1 and alfentanil 10 micrograms kg-1, propofol 0.75 mg kg-1, propofol 0.50 mg kg-1 and alfentanil 10 micrograms kg-1. Additional methohexitone or propofol was given as needed in 10-20-mg increments until loss of consciousness. Suxamethonium 1.0 mg kg-1 i.v. was given for muscular paralysis. Mean motor and EEG seizure durations were longer with methohexitone-alfentanil (44.7 (SD 15.0) and 70.5 (29.7) s) than with methohexitone (37.6 (12.6) and 52.6 (15.3) s) and similarly, seizures were longer with propofol-alfentanil (36.8 (15.2) and 54.5 (20.9) s) than with propofol alone (27.2 (11.9) and 39.2 (3.9) s). Seizures were longest with methohexitone-alfentanil and shortest with propofol. Recovery time was statistically shorter in patients receiving propofol compared with methohexitone-alfentanil and methohexitone alone. Alfentanil with a reduced dose of methohexitone or propofol provided unconsciousness and increased seizure duration in patients undergoing ECT. We conclude that the combination of methohexitone with alfentanil is a good regimen for ECT, especially for patients with short seizure duration.

Combined valproate or carbamazepine and electroconvulsive therapy.

This pharmacoepidemiological study was undertaken to determine if the combination of electroconvulsive therapy (ECT) and the anticonvulsants valproate (VPA) or carbamazepine (CBZ) is safe and efficacious. The charts of seven patients receiving ECT and VPA or CBZ (ECT-anticonvulsant group) concurrently between May 8, 1989, and May 9, 1993, were reviewed to determine the indication for each treatment, the number and type of ECT treatments, the seizure duration, adverse events, and the efficacy of the combination. The ECT-anticonvulsant group was compared to patients not treated with anticonvulsants (ECT-alone group) to determine if there were any differences in the two groups. Three patients had a marked clinical improvement, two a moderate response, one a minimal response, and one no response. The ECT-AC group, compared to the control group, had a shorter duration of seizures when unilateral treatments were used. However, there were no differences in the other variables compared. One patient had moderate confusion, and the other mild confusion and hypomania. This small case series suggests that the combination of ECT and anticonvulsants is safe and may be considered in patients for whom prophylaxis with anticonvulsant drugs is planned. Further controlled studies are needed to confirm our findings.

Flumazenil before Electroconvulsive Therapy

Elana B. Doering, M.D., Ph.D., Research Fellow, Department of Anesthesia.William A. Ball, M.D., Ph.D., Inpatient Medical Director, Department of Psychiatry, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104.To the Editor:--We were very interested to read Hanania's report of flumazenil administration before electroconvulsive therapy (ECT). [1]In his two cases, flumazenil, given immediately before ECT, reversed the sedative effects of benzodiazepine premedication; seizures of acceptable duration followed. This report raises several issues that deserve further consideration, regarding the seizures and the therapeutic outcome of ECT.Regarding the seizures, the effects of flumazenil are unclear. In Hanania's cases, flumazenil was given before any ECT stimulus was delivered. We do not know what the outcome would have been without flumazenil in these two patients. Furthermore, in one case, extra flumazenil was given after an unsuccessful ECT attempt; however, Hanania does not note whether the stimulus current was increased at the same time, as is usually done when the first seizure is inadequate. So, we cannot surely attribute the subsequent success to the extra flumazenil. On the other hand, acute benzodiazepine administration has been shown to raise seizure threshold and shorten seizure duration. [2](In this context, it is interesting that flumazenil did not cause unacceptably long seizures.) We may guess that flumazenil led to better seizure outcomes than otherwise might have occurred after benzodiazepine administration, but this remains to be demonstrated.Clinically, of course, the most important issues concern the effects of flumazenil and benzodiazepines on the therapeutic outcome of ECT. Several questions arise here. First, do benzodiazepines affect clinical outcome, independent of seizure duration? Second, do acute versus chronic benzodiazepines have different effects? Third, does flumazenil reverse benzodiazepines' effects on ECT outcome? Finally, does flumazenil have relevant psychoactive effects of its own?Several authors have raised the question of benzodiazepine interference with therapeutic effects of ECT. In one study in humans, the authors determined that unilateral ECT was less effective in patients who were receiving chronic benzodiazepines, despite adequate seizures. [2]A study in mice investigated behavioral responses to serial electroshocks. Behavioral changes that usually followed the shocks did not occur when diazepam was given, despite apparently identical seizures. This was noted whether diazepam was given before or after the shocks, suggesting that diazepam's antitherapeutic effects are independent of its effects on the seizures. [3].The question of chronic versus acute benzodiazepine administration in this setting remains largely unaddressed. Hanania's patients received lorazepam only once, immediately before ECT. In contrast, the patients in the human study cited above received chronic benzodiazepine treatment. Because long-term psychoactive effects of medications often require chronic treatment, we might suppose that one-time dosing is relatively benign. However, the mouse study suggests that the presence of benzodiazepines after ECT, even from one dose of a long-acting agent, may alter the behavioral response.The effects of flumazenil on ECT outcome remain unexplored. Of note, some authors have implicated benzodiazepine receptors and enhancement of the effects of gamma-aminobutyric acid in recovery from depression. [4]Will flumazenil reverse benzodiazepine effects on ECT outcome? Will it turn out to have its own clinical effects in patients receiving ECT or in other depressed patients? Answering these questions may clarify the mechanism of ECT therapeutic effects and illuminate the biochemical features of depression as well.In the meantime, we may consider benzodiazepine sedation and flumazenil reversal in ECT patients who will not otherwise accept treatment. However, we should be prepared for the possibility of a reduced clinical antidepressant response.Elana B. Doering, M.D., Ph.D., Research Fellow, Department of Anesthesia.William A. Ball, M.D., Ph.D., Inpatient Medical Director, Department of Psychiatry, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104.(Accepted for publication May 31, 1995.)

Combined use of labetalol and nifedipine in controlling the cardiovascular response from ECT.

Serious cardiac complications have been reported to occur in elderly depressed patients during a course of electroconvulsive therapy (ECT). As a result, cardiac medications are being used more often to dampen the cardiovascular response that occurs during an ECT treatment. Specifically, labetalol (a mixed alpha- and beta-blocker) has been shown to effectively control the heart rate during ECT. However, on occasion, patients may still exhibit sustained elevations of blood pressure during ECT when receiving labetalol. The optimum clinical management of these patients is unclear. The authors report on the safety and efficacy of combining nifedipine with labetalol to control blood pressure during ECT in ten elderly patients whose blood pressures were not adequately controlled by labetalol alone. No adverse effects were noted, nor did nifedipine appear to shorten seizure duration.

Analysis of Foramen Ovale Electrode‐Recorded Seizures and Correlation with Outcome Following Amygdalohippocampectomy

We report a detailed electroclinical analysis of 320 seizures recorded by foramen ovale electrodes in 77 potential candidates for selective temporal lobe surgery because of antiepileptic drug-resistant seizures. The exact localization of the origin of seizure discharges, the electroencephalographic (EEG) seizure onset patterns, transhemispheric propagation, propagation time, duration of discharge, laterality of discharge termination, postictal focal slowing, correspondence between foramen ovale recordings and the scalp EEG, and the influence of antiepileptic drug modifications were studied and correlated with the clinical seizure semiology and with postoperative outcome following selective amygdalohippocampectomy. In general, the foramen ovale electrode technique provided good neurophysiological information in candidates for selective amygdalohippocampectomy. The following ictal signs predicted a good surgical outcome: (a) unilateral and anterior mediobasal temporal lobe seizure onset, (b) short seizure duration, (c) no or infrequent contralateral seizure discharge propagation, and (d) if propagation to the contralateral mediobasal temporal lobe occurred, the postoperative outcome was better the later the contralateral mediobasal temporal lobe was affected. Postoperative outcome was also better the less frequently contralateral interictal spikes occurred. No direct predictive value could be attributed to the presence of an initial arrest reaction.

Comparison of two esmolol bolus doses on the haemodynamic response and seizure duration during electro-convulsive therapy

Twelve ASA physical status I-III patients were enrolled in a double-blind, prospective, randomized, three-way, within-patient crossover study designed to determine the effect of two standard esmolol bolus doses (100 and 200 mg) on the haemodynamic response and seizure duration during electro-convulsive therapy (ECT). Esmolol or placebo was administered one minute prior to induction of anaesthesia and exactly two minutes before ECT. Both the 100 and 200 mg bolus doses significantly blunted the maximum increase in heart rate (HR) and mean arterial pressure (MAP) following ECT in comparison with placebo. Compared with placebo, esmolol 100 mg decreased maximum HR by 23 +/- 3%, maximum MAP by 17 +/- 7% and maximum rate-pressure product (RPP) by 40 +/- 9%. Esmolol 200 mg decreased maximum HR by 25 +/- 3%, maximum MAP by 19 +/- 3% and maximum RPP by 42 +/- 5%. No significant difference was found between the two esmolol doses at corresponding measurement points before and after ECT. Treatment with esmolol 200 mg resulted in a significantly shorter mean seizure duration than with placebo. As the 200 mg dose caused a shorter seizure duration and the haemodynamic effects of 100 mg and 200 mg doses were similar, it was concluded that the 100 mg esmolol bolus dose was the better dose for ECT.

Studies of dosage, seizure threshold, and seizure duration in ECT

Seizure threshold, defined as the minimal electrical dosage necessary to elicit adequate generalized seizure, was determined throughout the course of electroconvulsive therapy (ECT) in depressed patients randomly assigned to bilateral and right unilateral treatment, with brief pulse, constant current stimulation. In Study 1, it was found that seizure threshold may be more accurately measured using the unit of charge compared to the traditional unit of watt-second. In Study 2, it was found that seizure threshold was associated with seizure duration. Patients with high thresholds had shorter seizure durations. This indicated that the seizure threshold measure assesses in part functional neural activity. In Study 3, it was found that failure for seizure threshold to increase substantially over the course of ECT was associated with poor clinical outcome. In Study 4, it was found that electrical dosage at threshold was not related to magnitude of acute cognitive impairments. This suggested that the degree to which dosage exceeds threshold may be more strongly tied to adverse effects than the absolute dosage administered to patients. Implications of the data are discussed, particularly in relation to a hypothesized link between the anticonvulsant properties of ECT and its mechanism of therapeutic action.

Pro- and anticonvulsant action of morphine in rats

Rats were pretreated either with saline or with various doses of morphine. Thirty minutes following this pretreatment animals received an injection of either naltrexone (5 mg/kg) or saline. Motility was measured following the second injection. All animals then received 40 mg/kg pentamethylenetetrazol (PTZ). Morphine, but not naltrexone, showed anticonvulsant action by increasing the latencies to the first preclonic jerk and seizure onset. In addition, morphine tended to shorten seizure duration, whereas naltrexone tended to lengthen it. However, at the most effective anticonvulsant dose morphine-treated animals showed significantly more convulsive seizures than did the saline-treated controls. The continuation of these multiple seizures was blocked by naltrexone. At doses which did not lower preseizure motility but rather increased it, morphine significantly enhanced the duration of the behavioral post-ictal depression (PID). Naltrexone, though effecting preseizure motility when administered after morphine, did not effect PID. These results are taken as evidence, that morphine possesses both pro- and anticonvulsant properties, depending on the prior occurrence of a PTZ-induced seizure. The possibility that seizures cause increased sensitivity of the organism to morphine is discussed.

Effect of Major Motor Seizure Frequency upon Cognitive‐Intellectual Functions in Adults

Wechsler Aandult Intelligence Scale and Halstead neuropsychological performances were investigated in three groups of adult subjects with major motor epilepsy classified according to low, moderate, and high seizure frequency. The groups were equated on seizure duration and age at onset variables. On 7 of the 14 psychological measures employed, significant between-group differences were obtained, with poorest, intermediate, and best test scores associated with the high, moderate, and low seizure frequency groups, respectively. Similar performance comparisons were made on two additional groups: a "high risk" group characterized by early onset age, long seizure duration, and high seizure frequency, and a "low risk" group characterized by late onset age, short seizure duration, and low seizure frequency. Highly significant differences were obtained between the high risk and low risk groups on 12 of 14 variables, with the high risk subjects demonstrating severe cognitive and adaptive impairment in comparison to the low risk subjects. The results support the conclusion that increased frequency of major motor seizures is associated with increasing levels of adaptive impairment, and that the probability of severe cognitive-adaptive dysfunction is further and substantially increased when high seizure frequency is accompanied by a history of early onset and long duration of the disorder.