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Convulsions in childhood shigellosis. Clinical and laboratory features in 153 children.

We studied 153 children who experienced convulsions associated with shigellosis. The male-female ratio was 1.2:1.0. Thirty-six children had a previous history of febrile convulsions, and 31 children had a family history of convulsive disorder. Most of the children were 0.5 to 3 years of age, although 49 (32%) were older than 3 years of age and 20 (13.1%) were older than 5 years of age. All children were febrile; in 75% of the children, the temperature was over 39 degrees C. The majority of the children had generalized, self-limited convulsions, which lasted less than ten minutes. In 30 children the seizures were categorized as complex; ten of them had recurrent episodes, although none had any residual neurologic deficit. The total leukocyte count was usually within normal limits, but the differential count characteristically showed a marked increase in the number of band forms. Hypocalcemia (blood calcium level, less than 9.01 mg/dL [less than 2.25 mmol/L]) was observed in four patients; hyponatremia (blood sodium level, 130 mEq/L [130 mmol/L]), in 11 patients; and hypernatremia (blood sodium level, 157 mEq/L [157 mmol/L]), in one patient. Electroencephalographic (EEG) studies were performed in ten children, and lumbar punctures were performed in 34 children; both procedures usually yielded normal results. Shigella sonnei was isolated from 69% of the children; Shigella flexneri from 25%; Shigella boydii from 5%; and Shigella dysenteriae from 1%. Due to the benign and self-limited nature of most of the convulsions, neither diagnostic procedures, nor drug therapy, are usually necessary. These measures should, however, be considered in complicated cases characterized by focal or prolonged seizures.

Blood Glucose↗

Platelet-derived growth factor B-chain homodimer suppressing a convulsion of epilepsy model mouse El.

El mouse is a mutant which has epileptic convulsions after tossing-up stimulations and has a hippocampal dysfunction. Platelet-derived growth factor B-chain homodimer has been reported to be a trophic factor of hippocampal neurons. We found that a recombinant PDGF-BB suppressed the convulsions of El mice in a dose-dependent manner. Furthermore, thrombin-treated mice manifested no convulsions, but thrombin receptor activating peptide-treated ones had convulsions. These findings suggest that an abnormality in PDGF-BB release may make El mice susceptible to tonic-clonic convulsions.

Animals↗

Amygdala-kindled convulsions in suspended rats.

Amygdala-kindled Long-Evans rats were suspended in a harness--with all four feet off the ground--and their convulsions were triggered, videotaped, and scored. In the suspended subjects, it was found that kindled convulsions involve the hindlimbs as well as the forelimbs and that they involve tonus as well as clonus. These data contradict the commonly held view that kindled convulsions consist only of face and forelimb clonus. They suggest that kindled convulsions resemble the generalized, whole-body convulsions observed in the maximal electroshock model and other "maximal" seizure models.

Amygdala↗

Sex differences in the sensitivity of CBA mice to convulsions induced by GABA antagonists are age-dependent.

The administration of the GABA-blocking agents picrotoxin and bicuculline to adult (2.5-3 months old) CBA/HZgr mice resulted in the appearance of convulsions, the occurrence and/or lethality of which was greater in males than in females. The latency of picrotoxin-induced convulsions was also shorter in male mice. Strychnine, a drug which induces convulsions by blocking glycine receptors was equally effective in producing convulsions in both male and female adult mice. Unlike adult mice, young (20 days old) or old (2 years old) mice fail to display sex differences following the picrotoxin administration. Accordingly, the observed sex differences in the sensitivity of CBA mice to administration of convulsive agents are specific for the GABA system and present only in sexually mature, but not in immature or old animals.

Aging↗

Possible mechanism of digoxin-induced convulsions.

Intraventricular (IVT) administration of digoxin (7.5 micrograms) induced 'popcorn-type' convulsions in rats. Though the convulsions looked similar to morphine-induced seizures, naloxone failed to antagonize these effects. Other anticonvulsants like phenobarbitone, ethosuximide, or GABAergic substances like piracetam and semicarbazide also had no protective effect against digoxin-induced convulsions. While calcium chloride potentiated these effects of digoxin, phenytoin, magnesium chloride, and potassium chloride treatment showed blocking actions. These observations suggest the involvement of Na/K-ATPase system in digoxin-induced convulsions. Clonidine and diazepam also provided protection against digoxin-induced convulsions through an unknown mechanism.

Animals↗

Specific action of tranylcypromine to precipitate barbital withdrawal convulsions.

This research was designed to determine whether the convulsion-eliciting action of tranylcypromine (TCP) during bartibal (B) withdrawal was specific to physical dependence on B, and to compare the findings with the action of pentetrazol (PTZ). Challenge with 15-20 mg/kg IP TCP at 48 or B withdrawal resulted in the elicitation of clonic-tonic convulsion (CTC) in all rats (n = 6) within 10 min. Another challenge with 5-20 mg/kg TCP led to the dose-related precipitation and intensification of CTC. The CTC-inducing action of TCP was relatively reduced as the B withdrawal signs were gradually mitigated. In other words, when challenge with the drug was made at 72h of B withdrawal, the time of CTC onset was prolonged, and the incidence was reduced to 50% in parallel with abolition of the other withdrawal signs. A challenge at 120 h of B withdrawal when the vital signs had almost recovered to prewithdrawal level failed to induce even the prodromal signs of convulsion. In all rats exhibiting only mild to moderate withdrawal signs (such as hyperirritability, hyper-reflexia, anorexia, weight loss), 40 mg/kg TCP was required to induce CTC during B withdrawal, which was twice the dose required in severely dependent rats. Other monoamine oxidase inhibitors, i.e., pargyline, iproniazid, and clorgyline, elicited no CTC during B withdrawal. Methamphetamine was without effect on B withdrawal convulsions. From these findings, the convulsive threshold for TCP during B withdrawal proved well correlated to the grade of B-dependence and the duration of B-withdrawal signs.

Animals↗

Serotonin reduction in the mouse neostriatum during hyperthermia-induced convulsions studied by immunohistochemistry.

Changes occurring in serotonin neurons during hyperthermia-induced convulsions were examined by means of a modified immunohistochemical method. All mice (8-12 weeks of age) exposed to the temperature of 50 degrees C had convulsions, showing a generalized tonic and/or clonic pattern. Immediately after the convulsions, the animals were perfused transcardially with a fixative. A significant reduction in serotonin immunoreactivity was observed in the neostriatum (caudate-putamen complex) of the mice which had hyperthermia-induced seizures, while the serotonin immunoreactivity remained unchanged in the neocortex and paleostriatum. These results suggest that serotonin may be an important mediator in the mechanism of hyperthermia-induced convulsions or that the susceptibility of serotonin neurons to a convulsive state is greatest in the neostriatum.

Animals↗

Convulsions and inhibition of glutamate decarboxylase by pyridoxal phosphate-gamma-glutamyl hydrazone in the developing rat.

We have previously shown that in the adult rat the inhibition of brain glutamate decarboxylase (GAD) activity by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH) administration does not result in convulsions, whereas in the adult mouse intense convulsions invariably occur. In the present study we report that, surprisingly, immature rats from 2 to 20 days of age treated with PLPGH (80 mg/kg) showed generalized tonic-clonic convulsions, whereas no convulsions at all were present in 30 days-old or older rats. GAD activity, measured by enzymic determination of GABA formed in forebrain homogenates, was inhibited by about 60% at the time of convulsions in 15 days-old and younger rats, whereas the inhibition was between 40 and 50% in older animals. The addition of the coenzyme pyridoxal 5'-phosphate to the incubation medium completely reversed this inhibition. In all treated animals GABA levels were lower compared to controls. The results indicate that the susceptibility of GAD in vivo to a diminished cofactor concentration decreases with age. It seems possible that changes in the expression of enzyme forms are reflected in developmental variations in the susceptibility to seizures induced by vitamin B6 depletion, but alterations of other B6-dependent biochemical pathways cannot be discarded.

Animals↗

Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain.

To investigate the relationship between the immune system and convulsions in an animal model, we examined the effects of repeated administration with the immunosuppressant cyclosporin A on pentylenetetrazol (PTZ)-induced convulsions and the changes in the mRNA expression of its binding protein cyclophilin in the rat brain. The consecutive administration of cyclosporin A (5 mg/kg, s.c., 14 days) significantly aggravated the severity of convulsions induced with PTZ 75 mg/kg, i.p. Furthermore, it down-regulated the levels of cyclophilin mRNA in several brain regions and inhibited the PTZ-induced increase of hippocampal cyclophilin mRNA. Compared with the group without PTZ pretreatment or the group treated with chronic vehicle administration after the PTZ-preinjection, chronic cyclosporin A administration after the initial injection of PTZ apparently aggravated convulsions after the second PTZ injection. Interestingly, the increase in hippocampal cyclophilin mRNA observed after a single PTZ injection was not found after the second PTZ injection in the group with PTZ pretreatment. Therefore, these findings suggest that cyclosporin A administered peripherally can affect the central nervous system, and that an immune response associated with the first convulsive episode plays a key role in severity during subsequent attacks.

Amino Acid Isomerases↗

An ATP-sensitive potassium channel blocker abolishes the potentiating effect of morphine on the bicuculline-induced convulsion in mice.

ICV bicuculline, a selective GABAA antagonist, dose-dependently induced clonic-tonic convulsions in mice. Coadministration of ICV morphine (mu opioid agonist) significantly potentiated ICV bicuculline-induced convulsions, and this effect of morphine was completely blocked by pretreatment with beta-funaltrexamine (beta-FNA), a mu antagonist. ICV glibenclamide, a selective ATP-sensitive potassium (KATP) channel blocker, at a dose which alone did not affect the convulsive threshold of bicuculline, was capable of blocking the exacerbation of ICV bicuculline-induced convulsions by morphine. The present data further suggest that KATP channels may play a tonic regulatory role in the potentiative effect of morphine on ICV bicuculline-induced convulsions.

Adenosine Triphosphate↗

Convulsive behaviour during alcohol dependence: discrimination between the role of intoxication and withdrawal.

Male Wistar rats were subjected to repeated weekly episodes of 2 days severe alcohol intoxication (intragastric intubation) and 5 days of withdrawal. In half of the animals the withdrawal reaction was attenuated during the first nine weekly episodes by intragastric intubations with phenobarbital. During episodes 10-14 both phenobarbital treated and phenobarbital untreated animals were allowed to develop a withdrawal reaction; all animals were video-recorded during withdrawal and the records were rated blindly for the occurrence of convulsive seizures. The results were analyzed by step-wise logistic analysis of regression including phenobarbital treatment, alcohol dose and intoxication score as explanatory variables for the occurrence of convulsive seizures. The animals that had been in withdrawal during all episodes developed significantly more convulsive seizures compared with animals that had their first nine withdrawal episodes attenuated by phenobarbital. The development of withdrawal seizures depended on repeated episodes of withdrawal, whereas repeated alcohol intoxication per se did not explain the development of seizures. There were no differences between the groups in the severity of the non-convulsive signs of alcohol withdrawal. Thus the development of seizures and the non-convulsive signs of alcohol withdrawal may result from two pathogenetically different mechanisms: 1) seizures from a cumulative kindling-like effect over long time periods and 2) physical signs of alcohol withdrawal may reflect the degree of physical dependence during the most recent drinking bout.

Alcoholism↗

Convulsive threshold differences in right unilateral and bilateral ECT.

UNLABELLED: This study examines how the convulsive threshold in electroconvulsive therapy (ECT) varies with electrode placement (bilateral [BL] versus right unilateral [RUL]), age, gender, weight, and the nasion-inion measurements of the head. METHOD: Twenty-eight subjects underwent stimulus dose titration to determine the convulsive threshold. Titration was accomplished for each subject with both electrode placements during the first and second ECT in a balanced design. Head measurements were made prior to the first ECT. Results indicated that the convulsive threshold was higher for BL than RUL, higher for men than women, increased with age, and increased with an increasing nasion-inion measurement in women but not in men. We concluded that the convulsive threshold varies according to the choice of electrode placement, gender, and age as has been reported by others. We additionally report that the convulsive threshold increases with increasing head size as reflected in the nasion-inion distance.

Adult↗

Determination of neurotransmitter release into the caudate nucleus during convulsions induced by pentylenetetrazole using in vivo differential pulse voltammetry.

In vivo differential pulse voltammetry using an electrochemically treated carbon fiber electrode was applied to the investigation of the in vivo release of indoleamine and catecholamine within the caudate nucleus of freely moving and immobilized rats during convulsions induced by pentylenetetrazole (PTZ). Two distinct oxidation peaks, on at 130 mV (3,4-dihydroxyphenylacetic acid (DOPAC] and the other at 300 mV (5-hydroxyindoleacetic acid), were observed in voltammograms obtained from the caudate nucleus. In the caudate nucleus of freely moving rats, the in vivo oxidation current that peaked at 300 mV showed almost no change during and after tonic convulsions induced by 60 mg/kg of PTZ i.p. During tonic convulsions, the amplitude of the DOPAC oxidation peak significantly decreased to 75% of the peak height recorded prior to the injection of PTZ, and the minimum lasted for about 30 min; then the mean curve slowly recovered to the control level within 60 min. These results suggest that the release of dopamine (DA) in the caudate nucleus of freely moving rats decreased during tonic convulsions induced by PTZ. In another experiment, the EEGs of immobilized rats were recorded simultaneously, and the changes in the EEG pattern were used as an index of convulsion. In voltammograms from the caudate nucleus of immobilized rat, the peak height of the 130-mV oxidation potential significantly increased during ictal seizures. The increase lasted for 3-6 min after the ictal seizures. The severe electrical activity of the brain during ictal seizures interfered with the recording of some voltammograms.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

The effects of FG 7142 upon local cerebral glucose utilization suggest overlap between limbic structures important in anxiety and convulsions.

The effects of the beta-carboline benzodiazepine receptor ligand FG 7142 upon local cerebral glucose utilization have been examined in conscious rats using the quantitative [14C]2-deoxyglucose autoradiographic technique. FG 7142 (1-10 mg/kg i.v.) produced behavioural changes consistent with an anxiogenic action. At the largest dose of FG 7142 (10 mg/kg) 30% of the animals experienced overt convulsions. In the data analysis animals were divided according to the behavioural response elicited by the drug. In animals not expressing convulsions, FG 7142 (1-10 mg/kg) effected increases in glucose utilization in 33 of the 65 regions examined. The majority of changes were confined to limbic structures with pronounced effects occurring in the mammillary body, anterior thalamic nuclei, septal nuclei and the oriens and molecular layers of the hippocampus. Glucose use in other structures associated with auditory and visual processing, such as the medial and lateral geniculate body, and associated cortical areas, was also significantly increased. However, brain regions involved in motor control were minimally affected. The patterns of local cerebral glucose use in animals expressing FG 7142-induced convulsions were contrasted with those from an equivalent non-seizure group. Some limbic structures which were significantly affected by FG 7142 (non-seizure group) displayed a further increase in glucose utilization during convulsions. These included the mammillary body and septum. Many other limbic structures (anterior thalamic nuclei, CA fields of the hippocampus and basolateral amygdala) did not display this further rise in glucose utilization. In the cortical amygdala, lateral preoptic area of the hypothalamus, nucleus accumbens and lateral elevations in glucose utilization were restricted to those animals experiencing overt convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Opioid mu-deficient CXBK mouse and the role of mu 1-receptors in electrically induced convulsions.

Studies were made on the role of mu 1-receptors on electrically induced convulsions in mice. A relatively selective mu 1-agonist, DAGO ([D-Ala2-N-methyl-Phe4-Gly-ol]-enkephalin) decreased the durations of tonic and clonic convulsions in C57BL/6 mice, but not in opioid mu-deficient CXBK mice, indicating that the activation of mu 1-receptors had an anticonvulsive effect on these convulsions in mice. The selective mu 1-antagonists naloxonazine and naltrexonazine promoted the clonic phase of electrically induced convulsion in C57BL/6 mice. Moreover, the duration of the clonic phase was longer in mu-deficient CXBK mice than in C57BL/6 mice. These data for CXBK mice confirmed, at least some proconvulsant effects of mu 1-antagonists in C57BL/6 mice. Thus, blockade of mu 1-receptors has a proconvulsant effect, and mu 1-receptors have at least some protective role against electrically induced convulsions.

Animals↗

Type I corticosteroid receptors modulate PTZ-induced convulsions of withdrawal seizure prone mice.

Corticosteroids have been shown to modulate convulsion expression in humans and animals. It is hypothesized that type I corticosteroid receptors mediate the excitatory effects of corticosteroids in vivo based on low-dose efficacy of corticosterone, and differential effects of mineralocorticoids vs. glucocorticoids on convulsions. In the present experiments, the effects of altering corticosterone levels, and the role of the type I receptor in mediating these effects, were examined using pentylenetetrazol (PTZ)-induced convulsions in ethanol withdrawal seizure prone (WSP) mice. It was hypothesized that stimulation of type I receptors partially mediates the expression of tonic hindlimb extensor (THE) convulsions produced by PTZ. Aminoglutethimide, a steroid synthesis inhibitor, increased latencies to PTZ-induced THE. This anticonvulsant effect was reversed by corticosterone and the type I agonist, deoxycorticosterone (DOC), but not by the type II agonist, dexamethasone. Furthermore, two type I receptor antagonists, spironolactone and RU26752, increased latencies to PTZ-induced THE, suggesting that they have anticonvulsant action. In summary, the results of these experiments suggest that type I corticosteroid receptors are important for expression of PTZ-induced convulsions.

Aminoglutethimide↗

Physiological function of descending noradrenaline projections to the spinal cord: role in post-decapitation convulsions.

Destruction of the descending noradrenergic innervation to the spinal cord, but not that to the cerebellum or the forebrain, by the use of intracerebral injection of 6-hydroxydopamine completely prevented the occurrence of the usual itation convulsion. Depletion of brain noradrenaline by synthesis inhibition with DDC, FLA 57 or FLA 63 g reduced the duration of the post-decapitation convulsion. Blockade of alpha-noradrenergic receptors by phentolamine or phenoxybenzamine, but not of beta-receptors by propranolol, also reduced the duration of the convulsion. The presynaptic alpha-agonist, clonidine, at either 1 mg/kg or 0.05 mg/kg also reduced the magnitude of the convulsion but either blockade of dopamine receptors with pimozide or destruction of the ascending dopamine systems by 6-hydroxydopamine was without effect. It is concluded that dopamine systems are not involved in post-decapitation convulsions and that the noradrenergic involvement is by the descending spinal projections acting on a post-synaptic alpha-receptor in the spinal cord, but also modulated by presynaptic alpha-receptors possibly on the locus coeruleus perikarya.

Animals↗

Antagonism of ethanol withdrawal convulsions in Withdrawal Seizure Prone mice by diazepam and abecarnil.

Abecarnil, a beta-carboline acting at benzodiazepine receptors, has been shown to have anxiolytic and anticonvulsant properties in a number of models. It has reduced muscle relaxant and incoordinating effects in comparison to diazepam. Given the wide clinical application of diazepam to prevent alcohol withdrawal seizures, a genetic animal model was employed to compare abecarnil with diazepam for its anti-withdrawal effects. Withdrawal Seizure Prone (WSP) mice, genetically selected to develop severe handling-induced convulsions after withdrawal from chronic ethanol treatment, were exposed to ethanol vapor for 24 h. WSP mice given doses of abecarnil or diazepam at the peak of withdrawal had significantly reduced handling-induced convulsion scores. While abecarnil was slightly more potent than diazepam, its effects were shorter-lasting. Similar results were seen in an experiment where withdrawal handling-induced convulsions were assessed after a single high-dose ethanol injection. Abecarnil and diazepam also reduced the smaller handling-induced convulsion scores seen in naive WSP mice. Single doses of abecarnil or diazepam did not lead to a rebound elevation of handling-induced convulsion scores suggestive of a withdrawal reaction.

Animals↗