Febrile convulsions in a national cohort followed up from birth. I--Prevalence and recurrence in the first five years of life.

Of 13 135 children followed up from birth to the age of 5 years, 303 (2.3%) had febrile convulsions. Prior neurological abnormality had been noted in 13. Of the 290 remaining children, 57 (20%) presented with a complex convulsion, and 103 children (35%) went on to have further febrile convulsions. The risk of further febrile convulsions varied with the age at first convulsion and the presence of a history of convulsive disorders in relatives. There were no significant differences between the sexes.     

Primary immunisation and febrile convulsions in Oxford 1972-5.

A three-year study of febrile convulsions in Oxford with comprehensive notification from general practice and hospitals showed a 3% risk for all children of suffering at least one febrile convulsion by the age of 5 years. Children were most at risk between 6 and 27 months, and febrile convulsions were most likely to be prolonged in children aged 9-15 months. The association between febrile convulsions and primary immunisations in the preceding 28 days was compared in case and control children, matched for age and sex. Results suggested that such association was a chance relationship with age. If association was direct, the febrile convulsion rates per 1000 immunisation doses were estimated as follows: diphtheria, pertussis, tetanus--0-09 per 1000; poliomyelitis--0-6 per 1000; and measles--0-9 per 1000. Hence if any of these vaccines had a secific causal relationship with febrile convulsions, these rates would probably have been much higher.     

Failure of phenobarbitone to prevent febrile convulsions.

One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage.     

Are all born equal? Incidence of febrile convulsions by seasons of birth.

To test whether the seasons of birth had an effect on subsequent experience of illness, details were obtained of all Sheffield children born between 1973 and 1977 who were admitted to hospital before their second birthday with a first febrile convulsion. Analysis by date of birth in consecutive 28-day cohorts showed that the incidence of febrile convulsions ranged from 2.5 per thousand live births to 30.2 per thousand in different "month" cohorts. Statistically significant variations were noted in the incidence rates in relation to season and year of birth. The implication is that even large scale epidemiological studies which have been confined to children born in a particular week or month may not be representative of the whole child population.     

Occult pneumococcal bacteraemia and febrile convulsions.

Over two years 29 children had bacteraemia due to Streptococcus pneumoniae at this hospital. In 15 previously healthy children the site of infection could not be identified, and in most of them, bacteraemia was not suspected clinically. All 15 had high total white cell (greater than or equal to 17 x 10(9)/1) and neutrophil (greater than or equal to 11 x 10(9)/1) counts. Twelve children were under 4 years of age, and of these, 10 had been admitted because of a simple febrile convulsion and one had a prolonged febrile convulsion. Occult pneumococcal bacteraemia has been reported in the USA for more than 10 years, but no series has been reported from the United Kingdom. Occult pneumococcal bacteraemia may be an important cause of febrile convulsions. Persisting bacteraemia and the development of focal infections, including pneumococcal meningitis, have been reported. Meningitis did not occur after occult bacteraemia in our patients. Studies to date have been retrospective, and thus the true incidence of the complications and the best treatment are not clear. A prospective study of children with febrile convulsions could provide answers.     

Outcome of childhood status epilepticus and lengthy febrile convulsions: findings of national cohort study.

OBJECTIVE--To study outcome after lengthy febrile convulsions and status epilepticus in children. DESIGN--Population based birth cohort study. SETTING--The child health and education study (16,004 neonatal survivors born in one week in April 1970). SUBJECTS--Information available for 14,676 children. OUTCOME MEASURES--Clinical information and tests of intellectual performance at five and 10 years after birth. RESULTS--19 children had lengthy febrile convulsions and 18 had status epilepticus. Two children with status epilepticus died (one at 5 years old); neither death was directly due to the status epilepticus. Four of the 19 (21%) developed afebrile seizures after lengthy febrile convulsions compared with 14 of the 17 (82%) survivors after status epilepticus. Measures of intellectual performance were available for 33 of the 35 survivors: 23 were normal and 10 were not normal but eight of them had preceding developmental delay or neurological abnormality. CONCLUSION--The outcome in children after lengthy febrile convulsions and status epilepticus is better than reported from studies of selected groups and seems determined more by the underlying cause than by the seizures themselves.     

Complex segregation analysis of febrile convulsions.

Complex segregation analysis was performed on 467 nuclear families ascertained through febrile-convulsion probands. The probands were identified as having their first febrile convulsion while residents of Rochester, MN, during the years 1935-64. Parents and first- and second-degree relatives of probands were identified through the Olmsted County, MN, record-linkage system. Diagnoses of convulsive activity were made from review of medical records. The genetic models investigated included both single-major-locus and polygenic models, with likelihoods computed jointly on children and parents as well as being conditioned on parental phenotype. Possible heterogeneity was investigated by means of analyses of frequency of febrile convulsions in the proband. Analyses of the entire data set indicated that the single-major-locus models could be rejected. The most parsimonious model for these data was the pure polygenic (or common familial environment) model with a large heritable component (68% +/- 7%). However, when families were partitioned on the basis of frequency of febrile convulsions in the proband, significant heterogeneity was present. Our results indicated that the polygenic model was strongly corroborated in families of probands with a single febrile convulsion. In families of probands with multiple febrile convulsions, evidence was consistent with a single-major-locus model with nearly dominant seizure susceptibility.     

Genetic aspects of febrile convulsions

Summary A total of 6706 children 3 years of age (3491 boys, 3215 girls) in a particular geographical area in Fuchu (population approximately 182 000), Tokyo, was investigated. Some 654 children (9.8%; 10.5% for male, 9.0% for female) had had at least one convulsion, and the incidence of febrile convulsions was 6.7% (7.2% for male, 6.2% for female). The 450 FC children with febrile convulsions and 620 randomly selected control children were analyzed on the mode of inheritance.The incidence of the disease among siblings was 21.9% (29.7% after age correction), which rose greatly with increasing numbers of affected family members, and the segregation ratio among siblings was higher (36.5%) with one FC parent, and lower (18.5%) if neither parent had had a seizure. The more severe the illness in FC children, the larger the incidence among siblings.Population and family studies indicated that heredity plays an important role in febrile convulsions and that multifactorial inheritance is most likely.     

Epilepsy in childhood: findings from the National Child Development Study.

By the age of 11 years 1043 children (6.7%) in an unselected national sample had a history of seizures or other episodes of loss of consciousness; 322 (20.8/1000) had a history of febrile convulsions without other epileptic problems. A clear-cut diagnosis of non-febrile epilepsy was established in 64 children (4.1/1000) by the age of 11 on the basis of confirmatory information supplied by family doctors and paediatricians. A further 39 (2.6/1000) were reported as having epilepsy but did not fulfil the study criteria. The progress of 59 of the 64 children with estabished epilepsy was reviewed again when they were aged 16. Of the 37 educated in normal schools eight (22%) had one or more seizures in their 16th year compared with 13 out of 22 (59%) who received special education. A possible cause for epilepsy was found in 17 of the 64 (27%) children, but for the majority there was no obvious reason.     

Successful prophylaxis against febrile convulsions with valproic acid or phenobarbitone.

A total of 184 six-month periods were analysed during which feverish illnesses occurred in children aged 6-42 months with a history of a febrile convulsion. Fits occurred in 34 out of 100 such periods when no treatment was being given, in six out of 45 periods when the serum phenobarbitone concentration was 69.0 mumol/l (1.6 mg/100 ml) or more, and in five out of 39 periods when the plasma valproic acid concentration was 416.4 mumol/l (6.0 mg/100 ml) or more. Thus in adequate dosage both phenobarbitone and valproic acid were significantly better than no treatment in preventing febrile convulsions (p less than 0.02). The two drugs were of comparable efficacy. It is concluded that with improved compliance valproic acid, which is relatively free from side effects, might be an effective prophylactic agent against febrile convulsions.     

Functional development of the altitude convulsion mechanism in mice and rabbits

Fifty one young mice from 6 litters and 17 young rabbits from 3 litters at different ages were used for determining their functional maturation of the altitude convulsion mechanism. It was found that none of the 1 to 9-day-old mice exhibited convulsion when they were subjected to severe hypoxia. The frequency of altitude convulsions at ages of 10, 11, 12 and 13 days was 9%, 53%, 71% and 100% respectively. On the other hand, altitude convulsion was observed in 2 of 6 19-day-old (33%), 5 of 8 21-day-old (63%), 5 of 6 23-day-old (83%) and all of 24-day-old rabbits (100%). The average functional maturation period of the altitude convulsion mechanism in young mice and rabbits was shown to be 12 and 22 days of age respectively. It is clear that such a mechanism matures at different rates in different species.     

Effects of central monoamine compounds on tranylcypromine-induced barbital-withdrawal convulsions

Challenge with tranylcypromine (Tcp) during barbital (B) withdrawal induces doserelated clonic-tonic convulsion (C-TC), which is also related to the severity of withdrawal signs and their changes with the passage of time. The effects of neuropharmacological agents on the Tcp-induced convulsions were observed. dl-Propranolol, phentolamine, phenoxybenzamine and methysergide had been administered intraperitoneally 20≈30 minutes before Tcp challenge. B-withdrawn rats had been pretreated with α-methyl-p-tyrosine, 5-hydroxytryptophan, p-chlorophenylalanine or reserpine, or with the combination of iproniazid and reserpine (5 hrs after iproniazid administration) before Tcp challenge. α-MT and dl-propranolol inhibited B withdrawal convulsion markedly, though high doses of dl-propranolol rather tended to show a less inhibitory effect on the convulsion. α-Adrenoceptor blockers scarely inhibited the convulsion. Methysergide or 5-HTP failed to inhibit, but PCPA intensified the convulsion. Reserpine, when administered alone, aggravated the convulsion, but when administered after iproniazid, inhibited it significantly. These findings suggested that the balance between the activities of noradrenergic and serotonergic neurons might be of importance in the manifestation of B withdrawal convulsions, the former probably being excitatory and the latter, inhibitory.     

Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits.

Febrile (fever-induced) seizures affect 3-5% of infants and young children. Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial. Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood. The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions.     

Adult outcome of normal children who are short or underweight at age 7 years.

OBJECTIVES--To evaluate the adult growth outcome (at age 23) of children who are short or underweight at age 7 years in whom no identifiable pathological cause exists for their poor growth. DESIGN--Longitudinal follow up of a birth cohort. SETTING--The national child development study (1958 birth cohort) of Great Britain. SUBJECTS--523 children with a height or a weight below the fifth centile at age 7. Of these, 70 (13.4%) were excluded because they had a longstanding illness that could account for their poor growth. The remaining 453 subjects, who were followed to age 23, provided the base group from which those with additional data, such as parental height, were obtained. RESULTS--55/174 (31.6%) boys who were short at age 7 became short men; 60/211 (28.4%) girls who were short at age 7 became short women. Among boys who were underweight at age 7, 46/160 (28.7%) were still underweight at age 23, while 61/200 (30.5%) girls underweight at age 7 became underweight women. Having short parents did not increase the probability of being small as an adult. Children with delayed puberty were as likely to remain small as those in whom puberty was not delayed. CONCLUSIONS--One in three normal children who was short or underweight at age 7 became a short or underweight adult. This informs the management of short children and may be valuable when prolonged growth hormone treatment for short stature is being considered.     

Serum Trace Element Levels in Febrile Convulsion

Febrile convulsion is the most common disorder in childhood with good prognosis. There are different hypotheses about neurotransmitters and trace element changes in biological fluids which can have a role in pathogenesis of febrile convulsion. In this study, serum selenium, zinc, and copper were measured by atomic absorption spectrometry in the children with febrile convulsion (n?=?30) and in the control group (n?=?30). The age and sex of the subjects were registered. Selenium and zinc were found to be significantly lower in febrile convulsion cases than in the control group (p?<?0.0001 and p?<?0.0001, respectively). There was no significant difference in the value of copper between the two groups (p?=?0.16). While selenium and zinc levels were 44.92?±?10.93 μg/l and 66.13?±?18.97 μg/dl in febrile convulsion, they were found to be 62.98?±?9.80 μg/l and 107.87?±?28.79 μg/dl in healthy children. Meanwhile, copper levels were 146.40?±?23.51 μg/dl in the patients and 137.63?±?24.19 μg/dl in the control group, respectively. This study shows that selenium and zinc play an important role in the pathogenesis of febrile convulsion.     

Study of intellectual performance of children in ordinary schools after certain serious complications of whooping cough. Swansea Research Unit of the Royal College of General Practitioners.

In a case-control study 27 index children from ordinary schools who had had convulsions or apnoea as a complication of whooping cough about eight years previously were compared with 27 children who had never had whooping cough and 15 who had had whooping cough without complications. Other factors likely to cause intellectual impairment after conception were considered. The index group had a significantly lower median intelligence quotient and poorer school attainment than either of the control groups. The results support the hypothesis that convulsions or apnoea as a complication of whooping cough may be associated with subsequent intellectual impairment.     

Maternal age at last birth in Egypt

To assess the effects of women's education, residence, and marital experience on their age at the birth of their last child, a proportional hazards regression model was applied to 1980 Egyptian Fertility Survey (EFS) data. The detailed data include the date of birth of each child for every women interviewed, and the woman's date of birth and age at interview. Age at last birth was examined by regression analysis on birth history and socioeconomic information. 4 hypotheses were tested: women who are well educated have a greater probability of ending childbearing earlier than women with less education; women in rural areas have a higher probability of having their last child at older ages than urban women; marital disruption without remarriage lowers the probability of older maternal age at last birth; and marital disruption with remarriage increases the probability that a woman stops reproducing at an older age. The overall chi-square indicates a significant regression. All coefficients were significant, except the coefficient for women with intact 1st marriages. Women with more education had a greater probability of ending childbearing earlier than women with less education. Rural women tended to have their last children at ages significantly older than overall age at last birth. Current residence in urban areas had the opposite effect. The coefficient for those with intact 1st marriages was insignificant, meaning that the mean age at last birth for this group of women was not much different from the overall mean. Remarried women tended to end childbearing at ages significantly older than the overall average age at last birth, suggesting that these women tended to have children by their new husbands. Those with dissolved 1st marriages who had not remarried had a higher probability of ending childbearing earlier than did older women. Marriage age and final parity had highly significant negative coefficients; as marriage age and number of children born increased, so did the "survival" time or the age at last birth. Results from the hazards model indicate that the effects were as anticipated. The median age at last birth for the total sample of women aged 45-49 was 45-49 years. The median age at last birth was about 2 years older for rural compared to urban women. Illiterate women had the oldest median age at last birth of the education groups. There was little differences between median ages at last birth for women with intact 1st marriages and those whose 1st unions were dissolved and who had remarried. The median age at last birth increased with final parity.     

Serum and cerebrospinal fluid nitrite/nitrate levels in patients with rotavirus gastroenteritis induced convulsion

Nitric oxide (NO) is a highly reactive free radical that is involved in a variety of different biological process. In recent reports, the putative role of NO in the neuropathogenesis of brain inflammation has been demonstrated. And then the relation between neuronal NO and convulsive seizures induced by virus has been suggested. However, there are few reports about NO in vivo under viral neurological infections. In order to evaluate the relation between NO production and neurological disorders induced by viral infection, sixty-six cases including 11 patients with rotavirus gastroenteritis admitted for convulsions were examined in this study. NO metabolites (NOx) levels in both serum and cerebrospinal fluid obtained from rotavirus gastroenteritis patients with convulsion were much higher than in those of patients with purulent meningitis, encephalitis, febrile convulsion or in the control group. There was a relative correlation between IL-6 and NOx in some cases. These results indicated that NO may have a pathophysiological role in convulsions associated by rotavirus infection either through indirect or direct effects of NO. Consequently, NOx inhibitors might be helpful for the treatment of rotavirus encephalopathy.     

13例SCN2A 基因突变相关儿童神经系统疾病表型分析

摘要 目的：总结并分析SCN2A基因突变引起的儿童神经系统疾病相关表型谱特点。方法：采用回顾性研究,收集2018年6月至2021年6月在上海交通大学医学院附属上海儿童医学中心神经内科诊治的患儿,并经二代基因测序检测,纳入SCN2A基因突变者,研究并总结患儿神经系统临床表型特点。结果：共纳入13例SCN2A突变患儿,包括新生突变9例和遗传性突变4例。其中11例患儿伴有癫痫发作,发作年龄为1日龄~1岁11月龄,4例在新生儿期起病 （36%）,1~3 月龄起病2例（18%）,4~12月龄起病2例（18%）,1岁后起病3例（27%）;发作类型中强直阵挛发作、痉挛发作、局灶性发作均各有4例（36%）,阵挛发作1例（9%）。另有2例无癫痫发作的患儿,1例表现为全面性发育迟缓,另一例表现为发育迟缓合并孤独症谱系疾病。11例癫痫患儿中,丛集性发作患儿10例。遗传性突变4例患儿中2例智力、运动发育正常;9例新生突变的患儿中8例伴有运动、智力发育落后,1例发育正常。11例癫痫患儿表型中良性家族性新生儿癫痫1例,新生儿惊厥2例,婴儿痉挛症2例,不能分类的早发性癫痫性脑病3例,儿童期起病的癫痫性脑病2例,热厥附加症1例。结论：SCN2A基因突变引起的儿童神经系统疾病以癫痫表现居多、癫痫表型谱广,少数表现为不伴癫痫发作的发育迟缓和孤独症谱系疾病。     

The interaction between spontaneous convulsions and tolerance to hexobarbital in the abstinence after chronic barbital treatments in the rat.

An earlier study had shown a decreased tolerance to hexobarbital after electrically induced convulsions in the abstinence after chronic barbital treatments in the rat. The effect of spontaneous convulsions was investigated in the present study.In two experiments tolerance was induced by treatment with barbital in the drinking water. Two treatment periods with a total duration of about 55 weeks were given in each experiment. The average consumption of barbital was approximately 200 mg/kg/day during the last part of the treatments. In the abstinence after the second treatment period tolerance was measured with a hexobarbital threshold method. Convulsions were recorded with a jiggle cage. Records were obtained from all barbital treated animals during the first three days of abstinence.In both experiments the hexobarbital thresholds were reduced in barbital treated animals if a convulsion had occurred within the 25 hour period prior to a threshold determination performed on the third abstinent day. If no convulsion had occurred there was a more marked tolerance to hexobarbital.The convulsion which is regarded as a sign of physical dependence can thus reduce the tolerance to hexobarbital in the abstinence after chronic barbital treatments. The convulsion could not only be the sign but also the means to at least temporarily decrease physical dependence.