The effect of oral and subcutaneous meperidine on the maximal electroshock seizure (MES) in mice.

The likely effect of oral and subcutaneous meperidine on maximal electroshock seizure (MES) in mice was studied. Convulsive current fifty (CC50) was assessed to be 46m A, an electrical pulse causing seizure in 50% of test animals. Doses of 15, 30, 60, or 120 mg/kg meperidine given orally or subcutaneously increased the convulsion threshold of MES as evidenced by a significant dose-dependent reduction of MES below control value (p < .05). An initial hyperactivity reaction that was worsened by noisy and tactile stimuli and tail erection followed by sedation was observed after s.c. injection of 60 or 120 mg/kg meperidine. No significant difference was found between meperidine-induced reductions of control MES values obtained one and two hours after oral doses; the depressed MES values obtained one hour after oral administration of meperidine were significantly different and more powerful than those obtained two hours after s.c. drug administrations (p < .05). Combining previous literature information with the present results, we conclude that such an effect of meperidine can be attributed to cerebellar stimulation.

GABA and L-glutamic acid release in en bloc resection slices of human hippocampus: an in vitro microdialysis study.

The interaction of neurotransmitters has been a major interest in pathophysiological conditions like epilepsy. In vivo microdialysis has recently gained much validity in measuring neurotransmitter release in experimental animals. However, there is a paucity of data concerning its use in humans on the grounds of safety considerations. Microdialysis experiments were performed using the hippocampal head region removed from patients with medically intractable seizures, who underwent surgery for mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Following en bloc resection, the tissues were immediately transferred to the essential in vitro milieu. Slices were incubated in lactated Ringer's solution and microdialysis probes inserted into the slices were perfused with artificial cerebrospinal fluid (aCSF). When the K+ concentration of aCSF was elevated to 100 mM, GABA and L-glutamic acid levels increased by 293% and 177%, respectively. This method may serve as an experimental model for human brain, to throw more light on the interactions between GABA and L-glutamic acid in hippocampal tissues obtained from patients with MTLE-HS.

Cost minimization analysis of antiepileptic drugs in newly diagnosed epilepsy in 12 European countries.

A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drug's side-effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an "intent-to-treat" basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Ictal spitting during a left emporal lobe-originated complex partial seizure: a case report.

We present a 35-year-old male patient with intractable temporal lobe epilepsy in whom spitting automatism was documented by ictal recordings during seizures. Spitting is an uncommon automatism and occurs mainly with right-sided, nondominant, temporal focus. However, our patient had left mesial temporal sclerosis with nonverbal memory impairment, but intracarotid amobarbital test demonstrated language and memory dominance on the right hemisphere. The authors feel that this case supports the hypothesis of a nondominant, temporal lobe origin for the spitting automatism.

Surgical outcome of epilepsy patients evaluated with a noninvasive protocol.

Surgery is now an accepted treatment for some medically intractable epilepsies. Presurgical evaluation is particularly important for the localization of the epileptogenic zone, which may necessitate sophisticated imaging techniques and intracranial electroencephalogram (EEG) recordings. If patients are carefully selected, however, successful results can be achieved with noninvasive evaluation methods. Seventy-seven patients were operated on for intractable seizures. All patients underwent EEG, neuropsychological, psychiatric, and magnetic resonance imaging investigations. Ictal EEG-video recording was performed in all nonlesional and in some lesional cases that had discordant data. Selective amygdalo-hippocampectomy was performed on patients with mesial temporal lobe epilepsy (MTLE), an extended or a limited lesionectomy was performed on patients with structural lesions, and a lesionectomy with deafferentation was performed on two patients with West syndrome. Electrocorticography was not used. Temporal lobe directed surgery was performed in 63.6% of the cases. The pathological examinations of all cases showed hippocampal sclerosis (HS) in 43%, tumor or tumor-like lesions in 36%, and cortical dysplasia in 5% of patients. After a mean follow-up of 17 months (range, 2-53), 75% of the patients were seizure-free with or without aura and 15% had a marked improvement, whereas 10% did not benefit from surgery. Neuropsychological outcome of patients with MTLE and HS also showed worthwhile results. Our patients, who were evaluated without pre- and perioperative intracranial recordings and other sophisticated techniques, had an outcome comparable to those in other series from more experienced centers. Our experience indicates that successful results, especially for patients with MTLE-HS and lesion-related epilepsies, can be obtained at centers with limited resources if the diagnoses and evaluation procedures are performed carefully.

Effect of pirenzepine, a muscarinic M1 receptor antagonist, on amygdala kindling in rat.

Kindling, an animal model of complex partial seizures with secondary generalization, is performed by daily application of low-intensity electrical brain stimulation. The purpose of this study was to investigate the role of muscarinic M1 receptors on amygdala kindling in the rat. Bipolar nichrome stimulation and recording electrodes were stereotaxically implanted into the right and left basolateral amygdala. Extradural recording electrodes were also placed bilaterally in the skull over the cortex. Amygdala stimulation was applied twice daily at the current intensity of afterdischarge threshold. Seizure intensity was graded by using Racine's standard five-stage scale. In the first group of experiments, saline or pirenzepine (10, 25, 50 and 100 nmol), a muscarinic M1 receptor antagonist, was injected intracerebroventricularly 1 h before the electrical stimulation. In the second group of experiments, rats were kindled to full stage 5 seizures. After a recovery period, 50 nmol of pirenzepine was administered intracerebroventricularly to kindled animals. In the first group of experiments, none of the animals pretreated with the doses of 50 and 100 nmol of pirenzepine reached a stage 5 seizure. Pirenzepine significantly retarded kindling seizure development and increased the total number of stimulations required to reach the first stage 5 seizure. Afterdischarge duration was also reduced in the pirenzepine 10 nmol group as compared with that in the saline-pretreated group. In the second group, seizure stage and afterdischarge duration were not affected by pirenzepine in fully-kindled animals. The findings of this study suggest that muscarinic M1 receptors may have a critical role in the development of kindling epileptic activity, but not in already kindled seizures.

The effect of tizanidine on maximal electroshock seizures (MES) in mice.

Tizanidine, an alpha-2 adrenergic agonist, is a centrally active muscle relaxant and a spasmolytic drug. The aim of our study was to investigate the activity of tizanidine on maximal electroshock seizures (MES) in mice. In the first part of the study, convulsive current 50 (CC 50) value to produce seizures was found. Then, tizanidine was given intraperitoneally (IP) at the doses of 0.5, 1, and 2 mg/kg, and orally (PO) at the doses of 5, 10, 20, 40 mg/kg. We found that tizanidine at the doses of 1 and 2 mg/kg IP and 40 mg/kg PO caused a significant protection against MES. In the second part of the study, after pretreatment with yohimbine, an alpha-2 adrenergic receptor blocker, at the dose of 2 mg/kg, anticonvulsant effect of tizanidine is diminished. We concluded that the mode of action of the anticonvulsant effect of tizanidine may be mediated by the central alpha-2 adrenergic receptors.

Therapeutic strategies against epilepsy in Mediterranean countries: a report from an international collaborative survey.

A collaborative survey was performed to compare prescribing strategies for the treatment of epilepsy in Mediterranean countries, based on analysis of 500 questionnaires compiled by physicians in 14 different countries. For partial seizures, carbamazepine was the drug of choice in most countries, whereas the second choice of drug differed widely. For primarily generalized tonic-clonic seizures, valproic acid was usually preferred, but other drugs used widely in some countries included phenobarbital, phenytoin and carbamazepine. Lamotrigine was the most popular second-line drug for primarily generalized tonic-clonic seizures in the European countries. In patients where the initial drug failed, switching to an alternative monotherapy was usually the preferred strategy, but advocates of early use of combination therapy exceeded 30% in the respondents of seven countries. Most respondents, in all countries except Turkey, did not prescribe drugs to prevent recurrence of febrile seizures; however, intermittent prophylaxis with a benzodiazepine was advocated by a considerable number of physicians, and continuous prophylaxis was prescribed by a significant minority of respondents in France, Syria and Tunisia. New drugs were rarely used as first-line treatment due to high cost and inadequate experience. Overall, this survey indicates that there is a wide variability in therapeutic practices between and within countries. This information may be useful for the implementation of national educational activities and for the design of pragmatic trials aimed at comparing different therapeutic strategies.

Antiepileptic therapy and teratogenicity in Turkey.

In this study 170 children born to 116 epileptic mothers are evaluated for the presence of congenital malformations. In one group, the mothers of 104 children were administered with one or more antiepileptic drugs (AEDs) during their pregnancies. In the control group, the mothers of 66 children received no therapy throughout or during the first trimester of their pregnancies. Twelve of the 104 children who were exposed to antiepileptic drugs in utero, had various major congenital malformations. On the other hand, 66 children who were not exposed to AEDs in utero had no malformations. The incidence of congenital malformations in children born to epileptic mothers was found to be significantly higher compared to the incidence observed in other studies (0.48-2%) among the general population of Turkey.

The effect of propranolol on maximal electroshock seizures in mice.

The aim of this study was to determine the possible effect of propranolol, a beta-adrenoceptor blocker, on maximal electroshock seizures (MES) in mice. It was found that doses of 5, 10 and 20 mg/kg propranolol caused an increase in the convulsion threshold of maximal electroshock seizures (MES) proportional to the dose and, that the mode of the anticonvulsant action of propranolol used doses in this study is related to membrane stabilization.