Epilepsy and Mental Retardation Following Febrile Seizures In Childhood

ABSTRACT. In an unselected group of children who were seen following an initial febrile convulsion, the frequency of subsequent afebrile seizures was 3.5% and of mental retardation 1%. The most common afebrile seizure type was generalized major (86%). About 3/4 of the children who developed afebrile seizures did so by three years and all by five years following the initial febrile seizure. The children with afebrile seizures differed from those without afebrile seizures in the frequency of neonatal abnormality, family history of mental retardation, focal initial febrile convulsions, and delay in psychomotor milestones before the initial febrile seizure. Only about 1/3 of the children who developed afebrile seizures ever had a recurrent febrile convulsion and none had complex recurrent febrile seizures. Half the children with mental retardation had histories of delay in psychomotor milestones prior to the initial febrile seizure, and no child with mental retardation had any seizure longer than five minutes. The administration of daily phenobarbital did not reduce the frequency of epilepsy, in spite of a significant reduction in the incidence of recurrent febrile seizures. There remains no evidence that the prevention of recurrent febrile convulsions significantly decreases the frequency of afebrile seizures or mental retardation.     

Epilepsy and mental retardation following febrile seizures in childhood

In an unselected group of children who were seen following an initial febrile convulsion, the frequency of subsequent afebrile seizures was 3.5% and of mental retardation 1%. The most common afebrile seizure type was generalized major (86%). About 3/4 of the children who developed afebrile seizures did so by three years and all by five years following the initial febrile seizure. The children with afebrile seizures differed from those without afebrile seizures in the frequency of neonatal abnormality, family history of mental retardation, focal initial febrile convulsions, and delay in psychomotor milestones before the initial febrile seizure. Only about 1/3 of the children who developed afebrile seizures ever had a recurrent febrile convulsion and none had complex recurrent febrile seizures. Half the children with mental retardation had histories of delay in psychomotor milestones prior to the initial febrile seizure, and no child with mental retardation had any seizure longer than five minutes. The administration of daily phenobarbital did not reduce the frequency of epilepsy, in spite of a significant reduction in the incidence of recurrent febrile seizures. There remains no evidence that the prevention of recurrent febrile convulsions significantly decreases the frequency of afebrile seizures or mental retardation.     

Continuous phenobarbital treatment after a 'simple febril convulsion'

In only a small proportion of young children with brief, generalized, febrile convulsions do afebrile seizures develop, but this fraction is several times the prevalence of epilepsy in an unselected population. The risk of another febrile convulsion is approximately 30%. Febrile status epilepticus during a subsequent infection is a potential source of serious morbidity and mortality. Intermittent phenobarbital administration during subsequent, febrile illnesses confers little protection against recurrent, febrile convulsions. Continuous phenobarbital administration during the preschool years is indicated for most children who have had a simple febrile convulsion.     

伴高热惊厥史的儿童癫痌病例分析

分析伴高热惊厥史的癫痌患儿的临床特点,探讨高热惊厥脑损伤及其与颞叶癫痌的关系。 方法对1996～1999年本院儿科神经病房480例住院癫痌患儿进行回顾性分析,包括首发年龄、家族史、持续时 间、癫痌发作类型、神经影像学及脑电图改变等。结果115例(23.9％)患儿有前期高热惊厥史。伴高热惊厥史 的患儿癫痌发作早且易于出现癫痌持续状态。与无高热惊厥史的患儿相比,伴高热惊厥史的患儿强直-阵挛发作 较多,复杂部分性发作较少。408例患儿曾行影像学检查,4例提示有海马硬化者均无高热惊厥史。在伴高热惊厥史 的癫痌患儿中脑电图局灶起源的异常放电显著低于无高热惊厥史的癫痌患儿。有6.08％(7/115)伴高热惊厥史的癫 痌惠儿和6.84％(25/365)无高热惊厥史的癫痌患儿脑电图表现为单纯颞叶异常放电,二组相比无明显差异。结论 在癫痌患儿中,高热惊厥可能伴有脑损伤,且可能与后期的癫痌发生有关,伴高热惊厥史者不一定发展为颞叶癫痌。     

Duration of fever prior to onset of a simple febrile seizure: a predictor of significant illness and neurologic course

This study tested the hypothesis that the duration of fever prior to the onset of a simple febrile seizure may be an important clinical variable with respect to patient outcome. The duration of fever prior to seizure according to patient history was defined as either long (greater than or equal to 24 hours) or short (less than 24 hours). We hypothesized that simple febrile seizures which occur with a history of a fever of long duration (LDF) are more likely to be associated with a significant illness at presentation or a subsequent neurologically abnormal course than are simple febrile seizures which occur with a history of a fever or short duration (SDF). Of 100 cases which met study criteria for simple febrile seizures, nine had a LDF and 91 had a SDF prior to the development of a seizure. No statistical differences in age, sex, maximum fever recorded in the emergency department, duration of seizure, WBC, or electrolytes were found between patients with SDF and LDF (P less than 0.01). Of the nine patients with a LDF, all had either a significant illness at the time of initial visit or a subsequent neurologically abnormal course. Of the 91 patients with a SDF, 88 had a good outcome, while two had a significant illness at the time of visit, and one had a subsequent neurologically abnormal course. These results suggest that children with a history of LDF prior to the occurrence of a simple febrile seizure are more likely to have a serious illness at presentation or a subsequent neurologically abnormal course than are children with seizures which occur with a history of SDF.     

Low morbidity and mortality of status epilepticus in children

In an ongoing study of status epilepticus, 193 children with status epilepticus of varying causes have been followed up for a mean period of 13.2 months. Of these, 97 patients were recruited prospectively. The patients' ages ranged from 1 month to 18 years (mean, 5.0 years). The cause of the status epilepticus was classified as idiopathic in 46 cases, remote symptomatic in 45, febrile in 46, acute symptomatic in 45, and progressive neurologic in 11. The mortality and incidence of sequelae following status epilepticus was low and primarily a function of etiology. Seven children died within 3 months of having the seizure. New neurologic deficits were found in 17 (9.1%) of the 186 survivors. All of the deaths and 15 of the 17 sequelae occurred in the 56 children with acute or progressive neurologic insults. Only two of the 137 children with other causes sustained any new deficits (P less than .001). Duration of the status epilepticus affected outcome only within the acute symptomatic group (P less than .05). Neurologic sequelae occurred in 29% of infants younger than 1 year of age, 11% of children 1 to 3 years of age, and 6% of children older than 3 years of age. However, this was a reflection of the greater incidence of acute neurologic disease in the younger age groups. Within each cause, age did not affect outcome. Of the 193 children, 61 (32%) had a history of prior unprovoked seizures. Of the 125 surviving children with no history of prior unprovoked seizures, 37 (30%) had subsequent unprovoked seizures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Children with febrile seizures do not consume excess health care resources

BACKGROUND: Febrile seizures are benign but so terrifying for parents that they may subsequently view their affected children as "vulnerable". Children viewed as vulnerable may be brought to medical attention more frequently. We examined subsequent hospitalizations and physician visits during a 6- to 7 1/2-year period for a group of children who had participated in a case-control study of initial febrile seizures. METHODS: Individual data from a regional cohort of 75 children with a first febrile seizure and 150 febrile and 150 afebrile controls were linked to 2 comprehensive provincial health services databases-a hospital admissions/ separations database and a physician services database. RESULTS: Linkage was achieved for 98% of the study cohort, with heath care utilization data for 6 to 7 1/2 years available for 96%. Children with febrile seizures had nearly identical rates of subsequent hospitalization compared with age-matched controls (chi2 test, P = .88). An excess of day-surgery visits for primarily otolaryngologic procedures was seen for the febrile seizure patients 0 to 12 months after their initial febrile seizure (chi2 test, P < .001). During the next 6 to 7 1/2 years, the febrile seizure patients had nearly identical rates of physician visits (chi2 test, P = .15); however, they had more visits to otolaryngologists in the first 3 to 9 months after the febrile seizure (chi2 test, P < .001), but fewer visits to pediatricians during the next 1 to 4 years (chi2 test, P < .001). CONCLUSIONS: Children with febrile seizures have nearly identical rates of hospital and physician services utilization compared with controls. This supports the hypothesis that febrile seizures are benign, and that parents recover from their initial anxiety and do not consider their children vulnerable to additional illness in the years that follow.     

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.     

A major role of viruses in convulsive status epilepticus in children: a prospective study of 22 children

A group of 22 previously healthy children with their first convulsive status epilepticus (SE), treated at Kuopio University Hospital, Finland, were prospectively studied. Eleven children had febrile and 11 afebrile SE. Polymerase chain reaction was used to detect specific DNA from CSF, enzyme immunoassays and immunofluorescence assays to detect specific antibodies in serum and CSF, viral cultures were obtained from CSF, throat and stool and antigen detection from throat specimens. Viral infection was identified in 10 of 11 children with febrile SE (91%) and in 7 of 11 with afebrile SE (64%). Human herpes virus 6 infection was identified in 12 children (55%), and in at least six of them the infection was primary. Single cases of human herpes virus 7, parainfluenza 3, adenovirus 1, echovirus 22, rota, influenza A and Mycoplasma pneumoniae infection were diagnosed. Conclusion Viruses, human herpes virus 6 in particular, seem to be major associated factors in convulsive status epilepticus, both febrile and afebrile. Human herpes virus 7 and Mycoplasma pneumoniae are novel agents associated with status epilepticus. Received: 3 April 2000 / Accepted: 8 August 2000     

Seizures in children after kidney transplantation: Has the risk changed and can we predict who is at greatest risk?

Abstract:  Children undergoing kidney transplantation are at increased risk for symptomatic seizures with a previously reported incidence of approximately 20%. Little data exist to help predict which children may be at risk. We retrospectively reviewed all children who underwent kidney transplantation evaluation at our center between October 1993 and August 2007 and identified 41 children who had an EEG prior to transplant. Demographic data as well as the following were collected: immunosuppressive medications, developmental status, history of seizures, family history of seizures, post-transplant seizures and EEG results. EEGs were classified as normal or abnormal. Prior to transplantation, one child had a history of febrile seizures and six experienced afebrile seizures. Nine (22%) children identified had an abnormal EEG prior to transplant. In eight cases the EEG was non-epileptiform and in one case was epileptiform. Abnormal EEGs did not correlate with a family history of seizures. Delayed development was noted in seven children and was not associated with an epileptiform EEG. Following kidney transplantation, no child experienced a seizure. Our single center study suggests that current rates of seizures following kidney transplantation are lower than previously reported and that routine EEG as part of the pretransplant evaluation in these children is of limited use to predict those at risk.     

Prolactin levels in febrile and afebrile seizures

Transient hyperprolactinaemia has been reported to follow unprovoked seizures, a finding proposed to be useful in the differential diagnosis of epilepsy. There is also evidence that patients with unprovoked seizures may have high baseline prolactin levels, which could be of value in detecting those predisposed to epilepsy after a first convulsive attack. The purpose of this study was to examine whether prolactin levels are elevated: (1) postictally in febrile seizures and (2) interictally in afebrile seizures. In 17 children with simple febrile seizures, mean postictal prolactin value (370±160 mU/l, mean±SD) was significantly higher (0.001) than the mean baseline value of 18 seizure-free controls (202±136 mU/l). The mean baseline prolactin values were not significantly different: (1) in ten children with afebrile versus ten seizure-free controls and (2) in 18 children with febrile seizures associated with high risk for subsequent afebrile seizures versus 23 children with febrile seizures but unlikely to suffer from afebrile seizures.Conclusion Postictal prolactin levels may be a useful marker of recent febrile seizures, while baseline prolactin levels do not appear to have any prognostic significance in afebrile seizures.     

Effective short-term diazepam prophylaxis in febrile convulsions

The efficacy of short-term diazepam prophylaxis in febrile convulsions was evaluated in a prospective, controlled study. A total of 289 consecutive children admitted with their first febrile seizure were randomized into two groups. One group received short-term prophylaxis for 18 months with rectally administered diazepam in solution whenever the temperature was greater than or equal to 38.5 degrees C. The control group received no prophylaxis, but diazepam rectally in the event of new seizures. The short-term prophylaxis, a mean of five doses of diazepam per child per year, afforded effective seizure control; the 18-month recurrence rate was reduced from 39% to 12% (P less than 0.001), the total number of recurrences from 77 to 23 (P less than 0.001), the long-lasting recurrences from 5.0% to 0.7% (P less than 0.05). The risk of subsequent epilepsy within the first 2 years was the same, regardless of receiving prophylaxis (3%) or not (3%); it was low after simple febrile convulsions (no cases of epilepsy in 230 children) but considerable after complex febrile seizures (20%) or seizures associated with severe interictal EEG abnormalities (50%).     

Parents'fear regarding fever and febrile seizures

In order to improve the effectiveness of information, we studied parents' perceptions and knowledge about fever and febrile seizures. A questionnaire study was carried out among the parents whose children (n = 230) participated in a randomized controlled trial of ibuprofen to prevent recurrent febrile seizures. Of the 230 parents, 181 (79%) responded to the questionnaire. Of all parents, 45% were afraid or very afraid of fever, which was strongly associated with being afraid of recurrent febrile seizures. Parents of children with a non-West European background were more afraid. The consequences of parental fear included frequent temperature measurements (25% measured five times per day or more), sleeping in the same room (24%) and 13% remained awake at night. Witnessing a febrile seizure is a frightening experience for parents; a majority thought that febrile seizures were harmful, because they look dangerous. Forty-seven percent thought that their child was dying during the initial febrile seizure. On the other hand, reassuring information may be helpful: 21% mentioned it as their reason to consider febrile seizures not harmful. We conclude that parental fear of fever and febrile seizures is a major problem with several negative consequences for daily family life. Adequate provision of information may reduce parental fear. We suggest that information about fever and febrile seizures should be provided to all parents, preferably during their contact with the providers of preventive healthcare. The parents of children with a non-West European origin need extra attention.     

Status epilepticus in children: Causes,clinical features and short‐term outcome

Background: We aimed to evaluate the cause, clinical profile, and short‐term outcome of status epilepticus cases that were admitted to our pediatric emergency unit between 1 January and 31 December 2008. Methods: We studied the clinical features of 59 seizures that occurred in 56 patients aged between 3 months and 15 years with the diagnosis of status epilepticus. We observed the clinical course and outcome of 53 cases for 6 to 18 months. The correlation between the cause of the seizure and the patient's age at the time of status epilepticus was evaluated as well as the correlation between the risk of seizure recurrence and family history of seizure, the neurological status of the patient prior to seizure and the presence of epilepsy. Results: The most common cause of status epilepticus is febrile illness in children younger than 2 years and idiopathic/cryptogenic and remote symptomatic causes in children older than 2 years. The rate of recurrence of seizure was significantly higher in cases with existing neurological abnormalities, prior epilepsy and seizures with remote symptomatic causes. The most common triggering factors of status epilepticus development in cases with epilepsy were noncompliance for anti‐epileptic drugs and infectious fever. Conclusions: In our study, the risk factors for seizure recurrence were the presence of prior epilepsy, existence of neurological abnormalities and remote symptomatic causes. We argue that improving the compliance of patients and their families to take medicine appropriately and training them in how to cope with febrile illnesses may decrease the recurrence of seizures.     

Nonfebrile seizures after febrile convulsions: possible role of chronic cytomegalovirus infection

Twelve hundred children with convulsions when feverish were studied during a period of five years. Among them 52 subjects (4.33%) developed nonfebrile seizures after a period of eight months to five years from the first febrile convulsion (group A). Twenty-three children had neither afebrile seizures nor EEG abnormalities during the period of observation (group B). The two groups were comparable for age of the first febrile convulsion onset, sex, and socioeconomic status. None had risk factors for subsequent epilepsy or clinical signs of congenital cytomegalovirus infection. The isolation rate of CMV from urine was 53.84% in patients of group A, 26.09% in children of group B, and 26.83% in healthy control children. Twelve CMV-positive children from group A were followed for one to more than three years. In five of seven children with persisting EEG abnormalities, cytomegaloviruria was still present 13 to 41 months after the first isolation, whereas none of five patients with normal electroencephalograms had viruria after a comparable period. We found that CMV-positive children generally lacked cell-mediated immunity to the virus, whereas CMV-negative patients had positive reactions. Our data suggest a correlation between persistence of neurologic abnormalities and CMV excretion in children with nonfebrile seizures and CMV infection.     

伴癫痫发作的儿童抗髓鞘少突胶质细胞糖蛋白抗体相关疾病的临床分析

目的 探讨抗髓鞘少突胶质细胞糖蛋白（anti-myelin oligodendrocyte glycoprotein,MOG）抗体相关疾病（MOG associated disorders,MOGAD）中伴癫痫发作患儿的临床特征。方法 回顾性收集2017年1月至2021年6月于首都儿科研究所附属儿童医院神经内科住院的MOGAD患儿的临床资料,分析患儿的癫痫发作特征,并比较伴或非癫痫发作MOGAD患儿临床特征的差异。结果 入组MOGAD患儿共48例,包括伴癫痫发作组13例（27.1%）,非癫痫发作组35例（72.9%）,两组患儿起病年龄及性别比无明显差异（t=-1.76,P=0.09;χ2=1.33,P=0.25）。伴癫痫发作组患儿在18例次急性发作期出现癫痫发作,其中10例次（55.6%）表现为癫痫持续状态,这18例次临床综合征符合急性播散性脑脊髓炎诊断者7例次,皮质脑炎4例次,不能分类的表型4例次,孤立性癫痫发作3例次。与非癫痫发作组相比,伴癫痫发作组皮质受累更常见（χ2=7.27,P=0.01）,脊髓、小脑受累少见（χ2=4.85,P=0.03;χ2=4.31,P=0.04）。8例（61.5%）伴癫痫发作组患儿呈复发病程,与非癫痫发作组（22.9%）相比差异具有统计学意义（χ2=4.76,P=0.03）,且两组患儿复发次数具有明显差异（Z=-2.43,P=0.02）。患儿对急性期免疫治疗敏感,至末次随访多数未遗留症状性癫痫。结论 癫痫发作是MOGAD患儿的临床表现之一,约半数出现癫痫持续状态,对免疫治疗敏感,癫痫发作多呈良性转归。伴癫痫发作患儿复发性病程多见。     

Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures

Febrile seizures are the most common seizure disorder in childhood, affecting 2% to 5% of children between the ages of 6 and 60 months. Simple febrile seizures are defined as brief (<15-minute) generalized seizures that occur once during a 24-hour period in a febrile child who does not have an intracranial infection, metabolic disturbance, or history of afebrile seizures. This guideline (a revision of the 1999 American Academy of Pediatrics practice parameter [now termed clinical practice guideline] "The Long-term Treatment of the Child With Simple Febrile Seizures") addresses the risks and benefits of both continuous and intermittent anticonvulsant therapy as well as the use of antipyretics in children with simple febrile seizures. It is designed to assist pediatricians by providing an analytic framework for decisions regarding possible therapeutic interventions in this patient population. It is not intended to replace clinical judgment or to establish a protocol for all patients with this disorder. Rarely will these guidelines be the only approach to this problem.     

Late cognitive effects of early treatment with phenobarbital.

We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures.     

Characteristics of the initial seizure in familial febrile seizures

Complex seizure characteristics in patients with a positive family history were studied to define familial phenotype subgroups of febrile seizures. A total of 51 children with one or more affected first degree relatives and 177 without an affected first degree relative were compared for history of complex characteristics of the initial febrile seizure. No difference was found in the frequency of febrile status epilepticus (OR = 1.1 (95% confidence interval (CI) 0.3 to 4.3)), multiple type (OR = 0.6 (CI 0.3 to 1.2)), and focal characteristics (OR = 0.4 (CI 0.2 to 1.2)). The presence of any complex characteristic (OR = 0.5 (CI 0.3 to 1.0)) was higher in those without an affected first degree relative, although differences did not reach significance. The familial type of febrile seizures is not associated with complex characteristics of the initial febrile seizure. Complex seizure characteristics are unlikely to help in discriminating phenotype subgroups for genetic studies of febrile seizures.     

Characteristics of the initial seizure in familial febrile seizures.

Complex seizure characteristics in patients with a positive family history were studied to define familial phenotype subgroups of febrile seizures. A total of 51 children with one or more affected first degree relatives and 177 without an affected first degree relative were compared for history of complex characteristics of the initial febrile seizure. No difference was found in the frequency of febrile status epilepticus (OR = 1.1 (95% confidence interval (CI) 0.3 to 4.3)), multiple type (OR = 0.6 (CI 0.3 to 1.2)), and focal characteristics (OR = 0.4 (CI 0.2 to 1.2)). The presence of any complex characteristic (OR = 0.5 (CI 0.3 to 1.0)) was higher in those without an affected first degree relative, although differences did not reach significance. The familial type of febrile seizures is not associated with complex characteristics of the initial febrile seizure. Complex seizure characteristics are unlikely to help in discriminating phenotype subgroups for genetic studies of febrile seizures.