The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.     

The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.     

Febrile convulsions in a Serbian region: a 10-year epidemiological study

The first population-based study in the central region of the Republic of Serbia (total population 283,103) was carried out to assess some epidemiological features of febrile convulsions among children of between 6 months and 5 years of age. During the 10-year period, 1986 to 1995, there were 570 cases of the first febrile convulsions (287 males and 283 females). The average annual incidence rate was 3/1000 (2.9/1000 in males and 3.0/1000 in females), with the highest in 1995. During the study period, a significantly increased linear regression trend was observed. During the follow-up period of 5 years for children who had their first febrile convulsions in 1989 and 1990 (total 154 cases), 27 (17.5%) had a recurrence of the disorder, and ten (6.5%) had one or more afebrile seizures, of whom seven children (4.5% of total sample) developed epilepsy (recurrent afebrile seizures).     

Recurrent seizures in children with Shigella-associated convulsions

Fifty-five children with Shigella-associated convulsions were followed prospectively to investigate their risk of subsequent febrile or nonfebrile seizures. The duration of the follow-up period was between 6.9 and 14.1 years (9.7 +/- 3.1 years). No case of nonfebrile seizures and only 2 cases (3%) of subsequent febrile seizures were observed during this period. We conclude that although febrile and Shigella-associated convulsions share many clinical features, the natural history of these two conditions seems to be distinctly different. Shigella-related convulsions are not associated with an increased incidence of subsequent febrile or nonfebrile convulsions.     

Temporal lobe epilepsy in childhood: reappraisal of etiology and outcome

This article reports the neurologic and psychologic findings, seizure characteristics, family histories, and etiology of clinically and electroencephalographically defined temporal lobe epilepsy in 63 children who were studied retrospectively. Subsequent data were available for 53 patients (84%), 15 of whom had undergone temporal lobectomies; 38 patients had been managed conservatively for at least 2 years. Previous, complicated febrile convulsions were the most common predisposing factor, occurring in 13 patients (21%), while 6 patients had tumors (10%). Of the 10 children whose onset of temporal lobe seizures occurred before 2 years of age, 5 had tumors. The presence of emotional or behavioral problems was related significantly to the presence of borderline or low intelligence, but not to the frequency of seizures. Although there was a tendency for a reduction in seizure frequency over time, only 10% of those managed by medical therapy alone were seizure-free at a mean subsequent examination interval of 6.6 years.     

热性惊厥持续状态复发的危险因素分析

目的探讨儿童热性惊厥持续状态(FSE)复发的危险因素。方法收集138例FSE患儿的临床资料,并于出院后进行2个月至8.3年的随访。根据随访结果,将患儿分为热性惊厥复发组、癫痫进展组及无惊厥复发组,分析FSE复发的相关因素。结果根据随访结果,热性惊厥复发30例(21.7%)(热性惊厥复发组),8例(5.8%)进展为癫痫(癫痫进展组),100例(72.5%)无复发(无惊厥复发组)。与无惊厥复发组比较,热性惊厥复发组低热时出现惊厥、既往有热性惊厥病史、阳性惊厥家族史及异常EEG的比率显著升高(P<0.05~0.01)。多因素Logistic回归分析显示,低热时出现惊厥、既往有热性惊厥病史及阳性惊厥家族史为FSE热性惊厥复发的独立危险因素(P<0.05~0.01)。FSE进展为癫痫的危险因素为低热时出现惊厥、既往有热性惊厥病史、异常EEG及异常头颅MRI(P<0.05~0.01)。结论低热时出现惊厥、既往有热性惊厥病史及阳性惊厥家族史为FSE热性惊厥复发的独立危险因素。低热时出现惊厥、既往有热性惊厥病史、异常EEG及异常头颅MRI为FSE进展为癫痫的危险因素。对于有危险因素的FSE患儿,应早期合理选择预防用药,改善预后。     

Retrospective study of late febrile seizures.

This retrospective study documents the clinical features, electroencephalographic data, and outcome of 50 children with a history of seizures with fever that occurred after 5 years of age. Children with afebrile seizures before the onset of febrile seizures were excluded. Outcome was based on a cross-sectional survey and the follow-up period was 1-13 years. Of the 50 children, 40 had two or fewer febrile seizures after 5 years of age, and febrile seizures did not occur after 10 years of age. Twenty had complex febrile seizures, and 16 had a first-degree relative with febrile seizures. Five developed afebrile seizures, and 18 had educational difficulties. Epileptiform electroencephalographic abnormalities were observed in 22 but were not predictive of later afebrile seizures. Febrile seizures that occur after 5 years of age recur infrequently and cease by 10 years of age. The risk of developing afebrile seizures in this group is small.     

Seizure recurrence after reduction of an antiepileptic drug in patients with unprovoked seizures and severe neurological abnormalities

A prospective study of antiepileptic drug (AED) reduction in patients with unprovoked seizures and severe neurological abnormalities after a seizure-free period of more than 5 years was performed. From a hospital for severely handicapped children (150 patients) and an institution for mentally handicapped people (89 persons), 13 patients were enrolled to this study after informed consent was obtained. All patients had experienced a seizure-free period of more than 7 years (median, 10 years). The patients had IQs of less than 50 and were almost dependent in their life. Five patients had additional motor deficits. The patients had been taking one to three AED (mean, 1.9) before reduction and only one AED was withdrawn. During the following 2years, four of the 13 patients (31%) showed a recurrence of seizures. The age at the time of the last seizure was lower in the seizure-free patients. As to the 10 patients with onset ages of 10 or less, a significant factor as to seizure recurrence was whether or not seizures were controlled before the age of 11 years (P < 0.05, Fisher's exact probability test). It is suggested that a patient with severe neurological abnormalities, in whom epilepsy or unprovoked seizures are controlled before the age of 11 years (i.e. before adolescence) could be a candidate for the reduction of AED.     

Febrile seizures in southern Chinese children: incidence and recurrence

This study investigates the incidence, recurrence, and risk factors of febrile seizures in southern Chinese children. A retrospective study of a 5-year period (March 1998 through February 2003) was conducted for all children admitted with first febrile seizure to a university teaching hospital of Hong Kong, serving a population of 31,700 under 6 years. A total of 565 Chinese children (329 males, 236 females) were identified with mean age of 2.1 +/- 1.1 years. The annual incidence was 0.35%. Among them 16% (91/565) had complex febrile seizures. Family history of febrile and afebrile seizures was present in 17.5% and 2.7% respectively. The mean follow-up period was 2.33 +/- 1.69 years. Altogether 103 children (18%) had recurrence, and the cumulative rates by 1, 2, and 3 years were 12.7%, 18.7%, and 20.5% respectively. Three significant factors were identified for higher risk of recurrence: early age of onset, family history of febrile seizure, and complex febrile seizure. The incidence of first febrile seizure in Chinese children is low compared with the Western world and relatively similar to mainland China. Recurrence is also lower despite similarities in the predictive factors. Further epidemiologic and genetic studies will be necessary to confirm and explain this interethnic variation.     

Unprovoked seizures after complex febrile convulsions

Children with complex febrile convulsions bear a higher risk of developing epilepsy than children with simple febrile convulsions. Complex febrile convulsions are defined by the presence of prolonged seizures, partial seizures and multiple seizures occurring during the same day. The aim of this study is to delineate the relative significance of each of the three criteria defining complex febrile convulsions. Fifty-seven out of 477 children (12%) admitted for febrile convulsions had complex febrile convulsions and normal neurological examination. Follow-up was available for 48 (84%) of them. Thirteen of these 48 (27%) had epilepsy at follow-up. The mean age of seizure onset among the patients with subsequent afebrile seizures was significantly lower than the rest (10.8 months versus 16.8 months). The patients with partial febrile convulsions showed a trend toward a higher risk (45%) of developing epilepsy than the patients with multiple febrile convulsions (21%).     

Afebrile seizures associated with minor infections: comparison with febrile seizures and unprovoked seizures

This study aimed to demonstrate that afebrile seizures provoked by minor infections constitute a distinct epilepsy syndrome different from febrile seizures and unprovoked afebrile seizures. Of the children who were admitted to hospitals for their first seizure, 1170 had febrile seizures, 286 had provoked seizures, and 125 had unprovoked afebrile seizures. Children with provoked seizures were afebrile at the time of seizure but manifested definite symptoms or signs of minor infection, for example, cough, coryza, vomiting or diarrhea, normal metabolic and cerebrospinal fluid investigations, and no obvious cause for their seizures. The average follow-up was 6.1 years. The Kaplan-Meier estimate of risk at 5 years for subsequent unprovoked afebrile seizures after a first febrile seizure, provoked seizure, or unprovoked afebrile seizure was 1.6%, 5.7%, and 65.7% respectively. All differences were statistically significant (P < 0.0014). In conclusion, afebrile seizures provoked by minor illnesses constitute a distinct type of situation-related seizures, which have not been previously described. Children with provoked seizures have a much lower risk of subsequent unprovoked afebrile seizures than patients with the first afebrile seizure. Careful inquiry for symptoms of minor infections when children present with their first afebrile seizure will help determine the risk for subsequent seizures and the need for antiepileptic drugs.     

Temporal Lobe Epilepsy After Prolonged Febrile Convulsions: Excellent Outcome After Surgical Treatment

We studied 47 consecutive patients who underwent temporal resection for seizure control. Nineteen (40%) had febrile convulsions preceding onset of their habitual seizures. In 17 of 18 patients whose disease duration was known, the febrile convulsions were prolonged (mean 4 h). As compared with patients without preceding febrile convulsions, patients with antecedent febrile convulsions had a significantly higher prevalence of positive family history of febrile convulsions, an increased incidence of retrospectively identified gestational or perinatal complications, and no foreign tissue lesions. Pathologic studies showed gliosis and cell loss in mesiotemporal structures, usually moderate, in addition to usually mild gliosis in lateral temporal cortex. These patients had an excellent outcome after temporal resection: 84% were seizure-free, had residual auras only, or occasional convulsions with medication discontinuation. One patient (5%) had >90% improvement. Two patients (11%) in whom the hippocampus was totally spared continued to have complex partial seizures: in both, seizures stopped after reoperation and hippocampal resection. Thus, 95% of these patients had an excellent result. Only 16% required invasive preoperative studies to confirm lateralization. These results were significantly better than those of the group without preceding febrile convulsions (p= 0.0013).     

Intermittent prophylaxis in febrile convulsions with oral diazepam]

Intermittent prophylaxis with oral diazepam is presented as an optional treatment for febrile seizures. This proposition is justified by the severe side effects of the currently used chronic anticonvulsant drug therapy in febrile seizures (phenobarbital and valproate). Nineteen patients aged between 3 months and 5 years were treated. They had either simple or complex febrile seizures. Sixteen patients had at least one prognostic factor for recurrence of febrile seizures: first febrile seizure before 15 months of age, positive family history for epilepsy or febrile seizures, occurrence of a complex febrile seizure or abnormal neurological examination. Three patients had none (cases 8, 12 and 13). We recommended 2.5mg b.i.d. for children younger than 12 months, 5mg b.i.d. for children older than 12 months and younger than 3 years, and 7.5 b.i.d. for children older than 3 years. The results showed that only one patient had febrile convulsions while taking adequate diazepam dosage. Transient side effects occurred in 36.8% of the cases.     

Seizures with Fever After Unprovoked Seizures: An Analysis in Children Followed from the Time of a First Febrile Seizure

Summary: Purpose: To determine how the onset of unprovoked seizures influences recurrence of seizures with fever in children followed from the time of a first febrile seizure.
Methods: In a prospective cohort of children (n = 428) identified at the time of a first febrile seizure, predictors of a second seizure with fever were identified. The occurrence of a first unprovoked seizure was treated as a time-dependent covariate in a Cox regression model rather than as a censoring point as it traditionally has been in the past.
Results: One hundred forty-three (33.4%) children had further seizures. Seven had further seizures with fever only after onset of unprovoked seizures. After adjustment was made for the four previously described predictors of recurrent febrile seizures (age at onset, family history, height of fever, and duration of fever), the onset of unprovoked seizures was associated with a rate ratio of 3.47 (p = 0.0015), indicating a large increase in the risk of further seizures with fever after onset of unprovoked seizures.
Conclusions: Young children who develop unprovoked seizures after a febrile seizure are at substantial risk for further seizures with fever. This may represent part of the spectrum of benign febrile seizures or it may represent the so-called "epilepsy triggered by fever" spectrum. It affects only a small proportion of children with febrile seizures; however, in some children, it may be useful information to consider when making treatment decisions.     

INFANTILE FEBRILE STATUS EPILEPTICUS: RISK FACTORS AND OUTCOME

The medical records of 68 children who had had infantile febrile status epilepticus (FSE) were examined. Follow-up periods ranged from three to 28 years (mean 8 years 10 months). Details were abstracted of relevant medical events prior to FSE, diagnosis of the febrile illness, age at onset and main characteristics of FSE, and outcome (subsequent febrile convulsions and/or epilepsy, neurological and psychiatric disorders). Neither medical events prior to FSE nor aetiology of fever were associated with subsequent febrile convulsions, epilepsy, or neurological or psychiatric abnormalities. There was a significant association between age at onset of FSE and both subsequent epilepsy and CNS disorders. 12 of the 13 children who had had transient or persistent post-ictal hemiparesis subsequently developed epilepsy. Of the 46 children who later developed epilepsy, 34 had partial seizures and 12 had generalized seizures. The latter were more common among children who had had FSE before the age of one year. Likewise, all those who developed severe myoclonic epilepsy in infancy had their first FSE before age one. These findings suggest that age at onset of FSE is the most important feature determining long-term outcome.     

Is the long-term outcome of children following febrile convulsions favorable?

The study comprised 80 children aged 6 to 9 years with a history of febrile convulsions. A neurological examination, an interview to assess psychiatric anomalies, and a series of neuropsychological tests were performed on patients with previous febrile convulsions and on matched healthy controls. Children with non-febrile seizures or CNS infections were excluded. Recurrence of febrile seizures in the study group was 41% ( N =33), 18 children (22%) had prolonged febrile convulsions, six (7.5%) patients and two controls showed discrete neurological abnormalities. Behavioral anomalies were exhibited by 22% of the patients and 6% of the healthy children. The neuropsychological test results did not demonstrate significant differences between the children with febrile convulsions and the healthy controls. However, in children with prolonged febrile convulsions, non-verbal intelligence was found to be significantly lower as compared with children with simple febrile seizures and with controls. None of the other parameters tested yielded any differences between patients and controls. Children with multiple recurrences of febrile convulsions performed poorer in all tests when compared with children with only one febrile seizure or with controls. Other factors such as a positive family history of epilepsy, age at onset of febrile convulsions, or duration of the seizure were not found to be of prognostic significance.     

The Risk of Nonfebrile Seizures in Children Who Have Experienced Febrile Convulsions

Abstract: (1) The frequency of development of nonfebrile seizures in 116 children who had experienced at least one febrile convulsion and were followed for more than five to eight years was 4.3% (5 cases). Of these, three cases had prolonged generalized convulsions of the clonic or tonic-clonic type and two had brief generalized fits of the tonic-clonic type. (2) The risk factors identified as nonfebrile seizures after febrile convulsions were the preexisting neurological abnormality or developmental retardation, focal features and more than a 10-minute duration of the first febrile convulsions, and abnormal paroxysmal discharges at the initial interictal EEG recordings.     

Plasma interleukin-1beta levels in children with febrile seizures

Proinflammatory and anti-inflammatory cytokines regulate the febrile response during infection. In this study, the role of cytokines in the pathogenesis of febrile seizures was investigated, through comparing levels of interleukin-1beta in the peripheral blood of children with febrile seizures and in a matched control group of children with febrile illnesses without seizures. The study included 33 children with febrile seizures (mean +/- SD, 29.94 +/- 14.9 months) and 38 controls with comparable age, sex, and type of infection. A laboratory workup for the diagnosis of infection was performed, and interleukin-1beta levels were assessed by enzyme-linked immunosorbent assay for the patients and the control groups immediately on arrival at the hospital. The plasma levels of interleukin-1beta were comparable in the patients and the control group (mean +/- SD, 7.321 +/- 3.123 and 8.087 +/- 4.8 pg/mL, respectively). Furthermore, there was no significant difference when comparing the plasma levels of interleukin-1beta in patients with simple and complex types of febrile seizures. Plasma interleukin-1beta levels did not show a significant correlation to either the duration of the last seizure, the number of the previous attacks of febrile convulsion, or the degree of temperature. However, interleukin-1beta levels were negatively correlated to the duration from the last seizure attack (r = -.8). Thus, the results of the present study do not support the hypothesis that increased production of interleukin-1beta is involved in the pathogenesis of febrile seizures in children.     

Exogenous causes of seizures in children: A population study

Of many exogenous causes, difficult birth, neonatal asphyxia, and coiling of the umbilical cord might be identified as risk factors predicting an initial febrile convulsion. Children with febrile convulsions and exogenous causes are likely to have affected family members, and have a risk of recurrence of seizures on 5 occasions or more. Exogenous causes alone barely raise the risk of recurrence of febrile convulsions after 3 years of age or development of afebrile convulsions. The incidence of exogenous causes is highest in children who develop afebrile convulsions after febrile convulsions, and lowest in children who experience only febrile convulsions, although a little higher than in normal controls.     

Clinical evaluation of the patients with epilepsy following febrile convulsions

We studied clinical, EEG and developmental features of 46 epileptic children following febrile convulsions. Incidence of developing epilepsy was 9.9 percent. Eleven patients (group G) out of 46 had generalized epileptic seizures, and 34 patients (group P) had partial seizures. Febrile convulsions of early onset, partial seizures and postictal neurological symptoms were more striking in group P (p less than 0.05), whereas febrile convulsions of late onset and prolonged seizures were slightly dominant in group G. And EEG abnormalities were more frequent in group P (p less than 0.05). Group P patients had significant number of risk factors (complex features of febrile convulsions) than group G patients (p less than 0.01). The interval between the last febrile convulsion and subsequent epileptic seizures was shorter in group G (p less than 0.01). Although subsequent epileptic seizures were well controlled in the both groups (91% in group G and 82% in group P), intractable seizures were recognized in 9% of group P patients. The patients who had risk factors of prolonged seizures, postictal neurological symptoms and early onset manifested poor controlled epileptic seizures (p less than 0.01). Motor or mental deficits were more frequently associated with group P: in some patients they had been observed before the onset of febrile convulsions. These results suggest that pathogenesis of epilepsy following febrile convulsions may be different among various seizure types of subsequent epilepsy. And the risk factors during febrile convulsions may be related to the prognosis of subsequent epileptic seizures as well as the incidence of developing epilepsy.