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Lower degree of fever at the initial febrile convulsion is associated with increased risk of subsequent convulsions.

We studied 132 children admitted consecutively with their first febrile convulsion to assess whether the degree of fever at the onset of the convulsion can predict the risk of subsequent convulsions. The children studied were reviewed at least 2 years after the initial febrile convulsion to determine the number of children who had recurrences of febrile convulsions and/or afebrile convulsions. Children with body temperatures below 39 degrees C at the onset of their initial febrile convulsion (Group 1) were two and half times more likely to experience multiple convulsions within the same illness than those with body temperatures above 39 degrees C (Group 2). This occurred when the body temperature rose above that which had triggered the initial febrile convulsion. Children in Group 1 were also over three times more likely to experience recurrent febrile convulsion in subsequent illnesses than those in Group 2. As for subsequent development of afebrile convulsion or epilepsy, although the risk was low, it only occurred in Group 1. It is suggested that the known association between multiple convulsions, recurrent febrile convulsions and epilepsy may be due to the single predisposing factor of a low degree of fever at the onset of febrile convulsion. Each child with febrile convulsion may have his own threshold for eliciting a convulsion with fever; the lower this threshold is, the more likely are subsequent convulsions.

Acute Disease↗

Febrile convulsions in children: relationship of family history to type of convulsions and age at presentation.

BACKGROUND: Febrile Convulsions are the commonest cause of convulsions in children under five years of age. Present study was conducted to know relationship of positive family history of convulsions to the type of febrile convulsions and age of presentation. METHODS: This study was carried out in the Department of Paediatrics, Hayat Shaheed Teaching Hospital Peshawar from June 1999 to June 2000. Data of all children with febrile convulsions were recorded on special proforma. Convulsions were labelled as febrile by excluding infections of central nervous system in developmentally normal children on the basis of history, examination and relevant laboratory investigations. RESULTS: In 30% children there was positive family history of febrile convulsions and febrile convulsions occurred at earlier age in these children. Febrile convulsions were complex in 35% of cases and out of these there was positive family history of convulsions in 29% of children. As a whole 44% of children had first febrile convulsions below 12 months of age and 56% above 12 months of age. CONCLUSION: Majority of febrile convulsions occurred in first two years of life. Initial febrile convulsions of simple type are more common in children with positive family history of convulsions, in whom first febrile convulsions tend to occur at earlier age. Further, complex febrile convulsions are more common when age at presentation is less than 12 months.

Age of Onset↗

Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children.

BACKGROUND: Tonic-clonic (grand mal) convulsions and convulsive status epilepticus (currently defined as a grand mal convulsion lasting at least 30 minutes) are medical emergencies and demand urgent and appropriate anticonvulsant treatment. Diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde may all be regarded as drugs of first choice. OBJECTIVES: To review the evidence comparing diazepam, lorazepam, phenobarbitone, phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status epilepticus in children. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's specialized register (4 July 2002); the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2002); MEDLINE (28 May 2002) and EMBASE (January 2002). SELECTION CRITERIA: Randomized controlled trials comparing lorazepam and other anticonvulsant drugs used for the treatment of convulsive status epilepticus in children. DATA COLLECTION AND ANALYSIS: This was a review of published, aggregate data. The main outcome measures included cessation of the presenting tonic-clonic convulsion/episode of convulsive status epilepticus; the number of additional drugs required to stop the convulsion; people demonstrating respiratory depression and people requiring admission to the intensive care unit because of respiratory depression. MAIN RESULTS: Only one trial was found, in which children were allocated lorazepam or diazepam. The main results are as follows. (1) One or two intravenous doses stopped the convulsion in 19 of 27 (70%) lorazepam and 22 of the 34 (65%) intravenous diazepam-treated children. The relative risk (RR) with 95% confidence intervals (CIs) was 1.09(95% CI 0.77 to 1.54). A single dose of rectal lorazepam stopped the convulsion in six of six, compared to six of 19 children treated with rectal diazepam, RR 3.17(95% CI 1.63 to 6.14). (2) Six of the 27 (22%) intravenous lorazepam and 12 of the 34 (35%) intravenous diazepam-treated children respectively, experienced a further convulsion within 24 hours after presentation RR 0.63(95% CI 0.27 to 1.46). (3) Only one of 27 children (4%) who received intravenous lorazepam compared to five of 34 children (15%) who received intravenous diazepam required additional antiepileptic drugs to terminate the presenting seizure RR 0.25(95% CI 0.03 to 2.03). (4) A lower incidence of respiratory depression occurred in the lorazepam-treated group: one of 27 (4%) children compared to seven of 34 in the diazepam-treated group (21%), RR 0.21(95% CI 0.02 to 1.37). REVIEWER'S CONCLUSIONS: This review provides no evidence to suggest that intravenous lorazepam should be preferred to diazepam as the first-line drug in treating acute tonic-clonic convulsions including convulsive status epilepticus in children. There was some evidence from this review that rectal lorazepam may be more effective and safer than rectal diazepam, but the data were insufficient to indicate that lorazepam should replace diazepam as the first choice rectal drug in treating acute tonic-clonic convulsions and convulsive status epilepticus.

Administration, Rectal↗

Experimental febrile convulsions: long-term effects of hyperthermia-induced convulsions in the developing rat.

The susceptibility of infant rats to experimental febrile convulsions was investigated. Rats were subjected to a single hyperthermia convulsion at 5, 10, 15, or 20 days of age or the a series of convulsions from 5 to 20 days of age. Susceptibility to the experimental febrile convulsion decreased with age in all rats except those subjected to multiple convulsions. In this group, susceptibility tended to increase. This results is discussed in terms of its similarity to the kindling phenomenon and to the incidence of recurrent febrile convulsions in the human infant. Sex differences in susceptibility to the convulsion were examined, but none were found. Mature rats that had been subjected to experimental febrile convulsions as infants were found to be significantly more susceptible to a convulsive dose of pentylenetetrazol than controls. The results of this study indicate that even a single experimental febrile convulsion during infancy can exert a long-lasting, if not permanent, enhancement in seizure susceptibility. The similarities between the present findings and human infantile febrile convulsions are discussed.

Age Factors↗

Genetic correlations among inbred strain sensitivities to convulsions induced by 9 convulsant drugs.

Inbred mouse strains differed significantly in sensitivity to convulsions induced by 9 convulsant drugs administered using a timed infusion procedure. Some strains (e.g. BALB/cJ, A/J) were generally seizure-susceptible, while some were generally seizure resistant (e.g. C57BL/6J, SWR/J). However, the overall pattern of strain sensitivities was complex, and depended upon drug and convulsant sign. Five of the drugs (bicuculline, DMCM, picrotoxin, TBPS and pentylenetetrazol (PTZ] produce convulsions, at least in part, through their interactions with the GABA receptor, while the other 4 (strychnine, CHEB, 4-aminopyridine and kainic acid) act through independent mechanisms. We predicted that responses to drugs with similar mechanisms of action would be genetically correlated. However, strains sensitive to picrotoxin-induced convulsions were not necessarily sensitive to convulsions elicited by PTZ or TBPS. Furthermore, different convulsant signs produced by a single drug were not always strongly correlated. Instead, genetic correlations were found among inbred strains for sensitivity to similar convulsant signs produced by different drugs. This suggests that genetic variation in sensitivity to these convulsant drugs arises primarily from variation in systems important for the expression of the convulsion.

Animals↗

[Febrile convulsions and other occasional convulsions in children].

Febrile convulsions are the main etiology of the occasional convulsions. They occur between 6 months and 5 years. They are short, bilateral, clonic or tonico-clonic. Febrile convulsions are classified in 2 groups: benign febrile convulsions and complicated febrile convulsions. When it exists, the genetic predisposition is a significant factor recurrent of febrile convulsions, but their prognosis remains good. Treatment depends on the diagnosis of simple or complicated febrile convulsions. The treatment of febrile convulsions is intra-rectal diazepam (0.5 mg/kg). The risks of recurrence of convulsions are inversely proportional to the intensity and duration of the fever episode before the convulsion.

Anticonvulsants↗

Effect of dihydroergotoxine on the susceptibility of rats to convulsions produced by different convulsant agents.

The study was undertaken to test further whether diminished GABAergic transmission might be responsible for the increased susceptibility of rats to picrotoxin-induced convulsions. In rats kept individually in cages in a noise-free room, the time between the intraperitoneal injection of the convulsant agent and the onset of convulsions was measured. Acute and subacute treatment with low doses of dihydroergotoxine (0.01-1.0 mg/kg) increased the occurrence and decreased the latency of picrotoxin-induced convulsions. Acute administration of dihydroergotoxine, 1.0 mg/kg, caused convulsions in animals injected with the subconvulsive dose (3 mg/kg) of bicuculline and of 10.0 mg/kg dihydroergotoxine in animals injected with the subconvulsive dose (1.5 mg/kg) of strychnine. Some of the animals injected with the 100% convulsive dose of strychnine were protected by dihydroergotoxine pretreatment (1.0 mg/kg) as evidenced by the lower occurrence of convulsions and fewer animals dying, as well as by a delay in the appearance of convulsions at 10.0 mg/kg. These results together with the previous findings on the GABA system suggest that dihydroergotoxine potentiates the appearance of picrotoxin and bicuculline-induced convulsions by a diminution of GABAergic transmission.

Animals↗

[Recurrence of febrile convulsions after the first diphtheria-pertussis-tetanus vaccination and measles vaccination in children with febrile convulsions: a questionnaire survey in Takamatsu City].

A questionnaire about convulsions and other adverse events after vaccination was sent to doctors who administered a diphtheria-pertussis-tetanus (DPT) vaccine (the first dose) or a measles vaccine between April 1, 1995 and December 31, 1997 in Takamatsu City to children with convulsions. DPT and measles vaccines were administered to 300 and 339 such children, respectively. Many of them had febrile seizures, the last of which had occurred before more than 1 year. Among them, 175 cases were administered with DPT and 180 with measles vaccine. There were recurrences of febrile convulsions after immunization in 2 (1.1%) of the cases given DPT and 3 (1.7%) of those given measles vaccination. According to the data of the Monitoring System for Adverse Events Following Immunization (the Ministry of Health and Welfare of Japan), the incidence of convulsion after immunization in healthy children between April 1, 1996 and September 30, 1997 was 0.4% after the first dose of DPT vaccination and 0.3% after measles vaccination. In comparison, the incidence was higher in children who had had febrile convulsions before more than one year. Especially, the rate of convulsions after measles vaccinations was significantly higher (p < 0.05) in children with febrile convulsions. These results suggest that the measles vaccination should be administered with caution to the children with previous febrile convulsions.

Child↗

Altitude convulsion threshold and time to altitude convulsion in gold thioglucose obese mice.

Gold thioglucose-induced hypothalamic obesity caused a higher altitude convulsion threshold and a decrease in the time to altitude convulsion. The average altitude convulsion threshold for the obese mice was 151 torr (38,500 ft). In contrast, the average value for the controls was 131 torr (41,500 ft). It was also observed that at 206 torr (32,000 ft), the average time until altitude convulsion of the obese mice was 69 s; at 179 torr (35,000 ft), 27 s; at 141 torr (40,000 ft), 17 s; at 111 torr (45,000 ft), 10 s; at 87 torr (50,000 ft), 9 s; and at 69 torr (55,000 ft), 8 s. On the other hand, the average control time until altitude convulsion at the above-mentioned altitudes was 97, 37, 26, 11, 9, and 8 s, respectively. Moreover, the average accumulation of fat between pleura and lungs in obese mice was 154 (Table I) or 181 mg (Table II), while the value of the control group was only 72 to 67 mg. Such an increase of fat accumulation in the thoracic cage could decrease the tidal volume. The altitude convulsion threshold and the time until altitude convulsion might thus be changed. The time until altitude convulsion may be regarded as a convenient objective measure of altitude tolerance in mice.

Altitude↗

Binding of [3H]muscimol to calf cerebrocortical synaptic membranes and the effects of sulphur-containing convulsant and non-convulsant compounds.

Endogenous and xenobiotic sulphur-containing convulsant and non-convulsant compounds containing structural moieties of, or bearing a structural resemblance to, GABA and homocysteine were tested in binding studies for their potency in displacing the GABA-mimetic [3H]muscimol from specific, high-affinity sites (Kd = 3.6 nM; Bmax = 3.94 pmol/mg protein) on freeze-thawed, Triton-treated calf-brain synaptic membranes. The xenobiotic convulsants, 4-mercaptobutyric acid (MBA), 3-mercaptopropionic acid (3-MPA) and 2-mercaptopropionic acid (2-MPA) were found to be two-site competitive inhibitors exhibiting apparent inhibition affinity constants (Kiapp) of 5000 microM, 3750 microM, and 4800 microM, respectively; while homocysteic acid (Kiapp = 4800 microM) was shown to be a one-site partial competitive inhibitor. Intermediary metabolites of methionine: S-adenosyl-L-homocysteine, L-cysteine, the convulsant L-homocysteine, and its non-convulsant disulphide oxidation product, homocystine, were found to be one-site partial competitive inhibitors exhibiting Kiapp values of 5750 microM, 8350 microM, 5000 microM, and 510 microM, respectively. The endogenous anticonvulsant neuroeffector, taurine, and the tripeptide, reduced glutathione (GSH) were shown to be, respectively, one-site (Ki = 20 microM) and two-site (Kiapp = 4300 microM) competitive inhibitors of [3H]muscimol binding. These findings are discussed with regard to a previously proposed mechanism for the convulsant action of homocysteine.

Animals↗

Drug withdrawal convulsions and susceptibility to convulsants after short-term selective breeding for acute ethanol withdrawal.

High Alcohol Withdrawal (HAW) and Low Alcohol Withdrawal (LAW) mice were selectively bred from a foundation population of C57BL6/J (B6) x DBA/2J (D2) F2 intercross progeny for display of intense or mild handling-induced withdrawal convulsions, respectively, following a single injection of a hypnotic dose of ethanol (alcohol; 4 g/kg). The HAW line had significantly greater alcohol withdrawal severity scores compared to the LAW line after only a single generation of selection; the magnitude of the line difference was 8-fold by the fourth selected generation. We tested these lines for severity of withdrawal convulsions following the benzodiazepine, diazepam; the gaseous anesthetic, nitrous oxide; the imidazopyridine, zolpidem and the barbiturate, pentobarbital. In all cases, HAW mice had significantly greater withdrawal severity than mice of the LAW line. These results indicate that some genes influencing withdrawal convulsion severity following ethanol also affect withdrawal from other CNS depressants. D2 mice are more sensitive to a variety of convulsants than B6 mice (and have more severe withdrawal convulsions). We, therefore, tested separate groups of mice of both selectively bred lines for threshold sensitivity to pentylenetetrazol (PTZ), N-methyl-D-aspartate (NMDA) and kainic acid (KA). No line differences were detected. These results indicate that genes influencing severity of withdrawal from several depressant drugs are largely different from those affecting susceptibility to GABAergic or glutamatergic convulsants.

Animals↗

Febrile convulsions followed by nonfebrile convulsions: analysis based on a maximum likelihood method and discriminant function.

Two hundred sixty-two nontreated patients with febrile convulsions only and 107 with later nonfebrile convulsions were analyzed based on a maximum likelihood method and discriminant function. The formula for discrimination is as follows: y = 2.9193 x (basic EEG abnormality at the first examination) + 2.2134 x (more than 20 minutes in duration of convulsion) + 1.7358 (fever under 38.4 degrees C before convulsion) + 1.7005 x (specific EEG abnormality at the first examination) + 1.6703 x (more than 5 recurrences) + 1.5610 x (over 4 years of age at the last convulsion) + 1.4921 x (exogenous causes) + 0.3741 x (family histroy of febrile convulsions among second or third relatives)--3.0397. If an item is positive, coefficient x 1 is to be used, and if it is negative, coefficient x 0 is to be applied. When one classifies patients with y greater than 0 as the FCC group, and those with y less than 0 as the FC group, misclassification may be theoretically expected in 18.9% of cases (accuracy in 81.1%).

Age Factors↗

Febrile convulsions followed by nonfebrile convulsions. A clinical, electroencephalographic and follow-up study.

103 patients with febrile convulsions followed by nonfebrile convulsions and 512 patients with febrile convulsions only (FC group) under 5 years of age at the first examination were analyzed from many aspects. A trimodal curve in distribution by age at onset of nonfebrile convulsions was seen: 2--3 years of age with occasional grand mal, 5--6 years of age with absence, and 12 years of age with awakening grand mal. Specific EEG abnormality was observed in 40% at the first examination (29% in FC group). Typical or atypical spike-and-wave complex, polyspikes, or continuous EEG abnormality were characteristic (slow wave burst with spike for FC group). Development from febrile convulsions into nonfebrile convulsions was detected in 17% among male and female patients. To identify an effective sign for the prediction of this development, the ratio between correct and incorrect prediction rates was analyzed. Specific paroxysmal EEG abnormality was increased over 3 years of age. EEG change due to aging and the significance of EEG reexamination were indicated.

Age Factors↗

Effects of malaoxon on phosphatidylinositol signaling in convulsing and non-convulsing non-pregnant and pregnant female rats and their offspring.

Phosphatidylinositol (PI) signaling during organophosphate (OP) induced convulsions and tissue Ca2+ changes in 10 weeks old male, and 14 weeks old non-pregnant and pregnant female rats, and the offspring of the latter were explored. Brain inositol and inositol-1-phosphate (Ins1P) served as indices of alterations in brain PI signaling, and brain tissue Ca2+ as an index of early neuronal injury. A dose of malaoxon OP, which produced convulsions in about 60% of the exposed rats in different rat groups, was 39.2 for male, and 8.2 mg/kg for pregnant female rats, respectively. Malaoxon (8.2 mg/kg) did not produce convulsions in non-pregnant female rats. All the rats were followed for 1 or 4 hr subsequent to malaoxon. Malaoxon decreased cerebral inositol in both male and female rats, and the decrease was similar in spite of the dose difference. The decrease was larger in the convulsing than in the non-convulsing rats. A tendency towards a decrease of brain inositol also occurred in the offspring. Ins1P levels were markedly increased in male, and also in non-pregnant female rats, but not in the brains of pregnant female rats. Ins1P was not markedly changed in the brains of the offspring. Malaoxon elevated brain tissue Ca2+ in male but not in female rats or their offspring. Cholinergic systems and PI signaling in the brain seem to be associated with OP-induced convulsions both in male and female rats; females seem to be more sensitive than males. Malaoxon may also have slightly modified PI signaling in the offspring brain. Hormonal factors are likely to modify OP CNS toxicity and cholinergic stimulation of brain PI signaling.

Animals↗

Malaoxon-induced brain phosphoinositide turnover and changes in brain calcium levels by female gender in pregnant and non-pregnant convulsing and non-convulsing rats.

Alterations in malaoxon-(MO)-induced brain regional phosphoinositide (PI) turnover and in brain calcium levels were studied in female non-pregnant and pregnant rats, and in their offspring. The adult rats were followed for 1 or 4 h after MO for tonic-clonic convulsions. A dose of 8.2 mg kg-1 of MO caused similar convulsions in 74% of the pregnant rats as we have reported in young male rats with a dose of 39.2 mg kg-1. However, convulsions did not occur in non-pregnant female rats. Inositol and inositol monophosphate levels were similar in all control rats. MO decreased brain inositol both in pregnant and non-pregnant female rats, and in the cerebellum of the offspring. In contrast to the findings in male rats, MO only randomly increased brain inositol-1-phosphate in female rats, or in their offspring. However, cerebral inositol-4-phosphate levels were similarly increased both in the non-pregnant and the pregnant rats irrespectively of convulsions. MO did not elevate cerebral Ca2+ in female rats or their offspring, in contrast to the male rats. The present results suggest that female rats are more sensitive than male rats to MO-induced PI signalling, and during pregnancy, also to MO-induced overt convulsions, but not to changes in cerebral Ca2+.

Animals↗

Comparison of folate levels in convulsing and non-convulsing febrile children.

The relationship between folic acid levels and occurrence of convulsion in febrile subjects was studied in thirty-two children aged 8 months to 5 years. Both the serum and red cell folate levels were significantly higher in the febrile children who convulsed than in those who did not convulse. When the period of convulsion was more than thirty minutes, there was a significant rise in the red cell folate. These results suggest that the accumulation of folate in the serum and red cell may be causally related to the development of the convulsing state in febrile children.

Body Temperature↗

Ketamine: convulsant or anti-convulsant?

Ketamine hydrochloride in doses producing narcotic-cataleptic effects (50--100 mg/kg, IP) reduced the intensity of picrotoxin convulsions and eliminated seizures caused by metrazol administration. Subcataleptic doses (5--20 mg/kg) increased the duration of mitigated convulsive symptoms (abortive grand mal fits, jerks) especially those evoked by picrotoxin. Narcotic-cateleptic doses of ketamine considerably increased the duration of the period of single and multiple jerks produced by picrotoxin administration. Both convulsants transformed 1--2 Hz "ketamine complexes" into 2--4 Hz Wave spike discharges which appeared in a quasi-periodic fashion alternating with periods of relatively suppressed electrocortical activity. Electroencephalographic grand mal patterns were typically dissociated from behavioral manifestations under 50--100 mg/kg of ketamine, followed by a short period of postictal depression and a rapid recovery of preseizure electrographic patterns. Findings suggest that mechanisms involved in seizure alleviation may be responsible for sustaining mitigated convulsive phenomena. Neuro-chemical processes underlying antiepileptic ketamine potency remain unknown.

Animals↗

The effects of a single neonatally induced convulsion on spatial navigation, locomotor activity and convulsion susceptibility in the adult rat.

The effect of a single neonatal convulsion on subsequent behaviour was investigated in the male rat. Convulsions were induced by heat or pentylenetetrazol on days 1, 10 or 21. As adults, locomotor activity, spatial ability and convulsion susceptibility were measured. Significant differences were seen in some measures and some groups but a single neonatal convulsion did not induce a consistent and significant pattern of behavioural change, despite the persistent change in hippocampal physiology shown in a previous study.

Aging↗