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.     

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.     

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.     

Febrile status epilepticus

As part of a study of status epilepticus in children (Maytal J, Shinnar S, Moshe SL, Alvarez LA. Pediatrics. 1989; 83:323-331); 44 children with febrile convulsions lasting more than 30 minutes were followed for a mean of 28 months (range 4 to 72). Thirty children were followed prospectively. Children with prior afebrile seizures or evidence of acute central nervous system infection were excluded. Nine (20%) children had prior neurological deficits. The duration of the febrile seizure was 0.5 to 1 hour in 41 cases (85%), 1 to 2 hours in 5 (10%), and greater than 2 hours in 2 children (5%). No child died or developed new neurological deficits following the seizures. The risk of recurrent seizures was increased, but only in the group with prior neurological abnormality. Six (66%) of these children had subsequent febrile seizures compared with 12 (34%) of the normal children (P = .08). Three (33%) had recurrent febrile status epilepticus compared with only 1 (3%) normal child (P = .023). The 2 children in the prospective arm of the study with recurrent febrile status epilepticus were both neurologically abnormal (P = .035). All 3 of the children who subsequently had afebrile seizures (2 prospective) were neurologically abnormal (P = .006 overall, P = .035 for prospective only). It is concluded that the occurrence of febrile status epilepticus in a neurologically impaired child is a risk factor for subsequent febrile as well as afebrile seizures. The occurrence of febrile status epilepticus in an otherwise normal child does not significantly increase the risk for subsequent febrile (brief or prolonged) or afebrile seizures in the first few years following the episode.     

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.     

Retrospective study of 160 children with febrile convulsions]

In a retrospective study of 411 children with cerebral convulsions over a period of 4 years, 160 patients with febrile seizures were found. This group consisted of 94 boys and 66 girls. The main purpose of this study was to establish the age of the first convulsive fit in each child. Febrile convulsions started in the first half year, increased in the second half year and culminated in the second year of life. This age dependent appearance was explained with passive immunization by maternal antibodies so that febrile convulsions appear when these antibodies decrease. The first occurrence of febrile convulsions appeared on an average of 22.9 months, in children with recurrent febrile convulsions a little earlier with 18.2 months. The most interesting fact was that children with a family history of febrile seizures showed an even earlier occurrence of the first seizure with 14.5 months. This tendency of early incidence of febrile convulsion in the group with family history and in the group of recurrent febrile convulsions could be shown as statistically significant respectively nearly significant in comparing with the group of retarded patients. A peculiar tendency for febrile convulsions seems to be documented by recurrent seizures in the patient himself, but also by a history of febrile convulsions in other family members. Both facts may lead to a very early incidence of febrile convulsions.     

Viral infections and recurrences of febrile convulsions

To determine whether complicated febrile seizures occur more often in children with a proven viral infection, we performed viral examinations on 144 children with febrile convulsions, of whom 112 had simple and 32 had complicated seizures. A diagnosis of virus infection was verified in 46% of the former patients and 53% of the latter. Three adenoviruses, one parainfluenza virus type 2 and one type 3, one respiratory syncytial virus, one echovirus type 11, one herpes simplex virus type 2, and one influenza B virus were isolated from the cerebrospinal fluid. A simple febrile convulsion occurred in seven children with a positive cerebrospinal fluid viral isolation, and two had a complex febrile seizure. In a follow-up of 2 to 4 years (mean 3.3 years), 21 of the 107 children with simple seizures (19.6%) and 3 of the 32 children with complicated seizures (9.4%) had recurrent febrile seizures. The children with positive evidence for a viral infection, even with a virus isolated from the cerebrospinal fluid, had no more recurrences than those without any proven viral infection. We conclude that children with a proven viral infection have no worse prognosis than those without.     

Thalassemia major may decrease the frequency of febrile convulsions in children

Aim: We aimed to determine the relative frequency of febrile convulsion in children with major thalassemia to theorize that higher serum iron levels could reduce the incidence of febrile convulsion. Background: Febrile convulsion is the most common type of seizure in childhood that its causes are not fully understood. However, some risk factors have been cited such as the serum iron level. Materials and methods: Three hundred and fifty-nine children aged more than 5 years with major thalassemia who were receiving blood were enrolled as the case group. The control group consisted of 357 children without thalassemia aged 4–7 years (151 boys, 206 girls) who were referred to healthcare centers for routine health monitoring. Included data were the history of febrile convulsion, age of onset and type and the frequency of convulsions. Results: Children in control group significantly experienced more febrile convulsions than thalassemic children [4/359 (1.1%) in the thalassemic children and 14/357 (3.9%) in the control group had experienced febrile convulsions (P = 0.017)]. Conclusion: The frequency of febrile convulsion in children with major thalassemia is less than that of normal children. Children with thalassemia major may have higher serum levels of iron and such high serum iron levels might have a protective role in the children who have a vulnerability for febrile convulsions.     

婴儿良性癫癎的临床观察和远期随访研究

目的 研究婴儿良性癫痫的发作特征,脑电图及治疗反应,探讨早期诊断方法。方法 对出生后3-24个月内起病,排除热性惊厥,症状性癫痫及发育异常的婴儿惊厥进行临床观察及寻像脑电图（VEEG）监测,并随访治疗效果和远期预后,结果 42例经2年以上随访确诊为婴儿良性癫痫,其中3例有良性婴儿惊厥家族史,19%惊厥伴有轻微腹泻,67%为短期内频繁发作,无癫痫持续状态,3例VEEG监测证实分别为起源于颞区,枕区及多灶性的部分性发作,发作间期脑电图背景正常,24%睡眠中有Rolandic区小棘波,39例接受抗癫痫单药治疗,平均用药时间9个月,3例未用药物治疗,起病1年内发作均消失,结论 起病早期具有以下特征应考虑有婴儿良性癫痫的可能;（1）起病年龄在3-12个月,不超过24个月,可有婴儿良性惊厥家族史;（2）发病前后精神运动发育正常;（3）发作无诱因,或仅有轻度腹泻等非特异性感染;（4）以部分性发作为主,可继发全身性发作,起病时发作可以很频繁,但无癫痫持续状态;（5）发作间期脑电图背景正常,无典型癫痫样放电,可有睡眠期Rolandic区小棘波;（6）神经影像学正常。     

Febrile convulsions and later development of epilepsy

A group of 172 epileptic children who had had prior febrile convulsions was compared with a group of 674 who had not. Children with epilepsy and prior febrile convulsions were similar in some respects (sex ratio, positive family history for seizures) to children with pure febrile convulsions and in most respects (type of epilepsy, mental status, initial EEG, and two- and four-year remission rates in the long-term outcome) to epileptic children without prior febrile convulsions. Our data do not support the current view that febrile convulsions, per se, are the main cause of mesial temporal sclerosis, le, temporal lobe epilepsy. Thus, our clinical findings support previously expressed doubts on the role of febrile seizures in temporal lobe epilepsy that were based on pathohistologic findings.     

Theophylline-associated seizures and their clinical characterizations

BACKGROUND: To elucidate the basic mechanism of theophylline-associated seizures (TAS), the clinical symptoms, electroencephalogram (EEG) and neuroradiological imaging of eight pediatric patients were all retrospectively evaluated. METHODS: Patients whose seizures represented their first episode were selected, while patients with cerebrospinal fluid abnormalities including pleocytosis and protein elevation, present illness of head trauma, epilepsy, febrile convulsion or any psychomotor retardation were excluded although they were given theophylline. RESULTS: Eight patients, 3.5 +/- 1.7 years of age, thus fulfilled the definition of TAS in the past 5 years. Based on their seizure patterns, EEG findings, brain single-photon emission computed tomography and head magnetic resonance imaging, a total of seven of eight patients had either localized or unilateral dominant lesions. They all had fever, > or =38 degrees C, and six of eight patients had a family history of febrile convulsions and/or idiopathic epilepsy. Thereafter none of them had convulsions after the cessation of theophylline administration. Through the TAS event, a 6-year-old female patient was found to have a right deep lateral cerebral venous angioma. CONCLUSION: In infants with idiopathic low seizure threshold and fever, theophylline administration might possibly trigger a seizure. Moreover, based on these patients' clinical findings, some kind of cerebral vascular involvements is speculated to be related with TAS.     

The prognosis of convulsions during childhood shigellosis

We examined the long-term outcome in 111 children who had convulsions during shigellosis and were followed for 3–18 years after the incident. No deaths or persistent motor deficits occurred as sequellae. Poor coordination of fine hand movements were noted in 3.3% of the 92 children who had no pre-existing neurological abnormality. Only 1 child developed epilepsy by the age of 8 years. Of the children 15.7% had recurrent febrile seizures. The only risk factor identified for febrile seizures following convulsions in shigellosis was a previous history (P<0.01). These observations suggest that convulsions in shigellosis have a favourable prognosis, and do not necessitate long-term follow up.     

Clinical characteristics of febrile convulsions during primary HHV-6 infection.

OBJECTIVE: To clarify clinical characteristics of children with febrile convulsions during primary human herpesvirus 6 (HHV-6) infection. SUBJECTS AND METHODS: The clinical characteristics of first febrile convulsion were compared between those with and without primary HHV-6 infection in 105 children. HHV-6 infection was verified by culture or acute/convalescent anti-HHV-6 antibody titres. RESULTS: Primary infection with HHV-6 was seen in 21 of 105 patients with febrile convulsions (3 upper respiratory infection, 1 lower respiratory infection, and 17 exanthem subitum). 13 of 23 patients < 1 year, 19 of 79 patients with first febrile convulsion, and 2 of 15 with second convulsion were infected with HHV-6. The median age of patients with first febrile convulsion and HHV-6 was significantly lower than those without infection. The frequency of clustering seizures, long lasting seizures, partial seizures, and postictal paralysis was significantly higher among those with primary HHV-6 infection than among those without. The frequency of atypical seizures in 19 patients with first febrile convulsion associated with primary infection was significantly higher than in 60 patients without primary infection. The frequency in infants younger than 1 year of age was also significantly higher than that in 10 age matched infants without primary infection. CONCLUSIONS: These findings suggest that primary infection with HHV-6 is frequently associated with febrile convulsions in infants and young children and that it often results in the development of a more severe form of convulsions, such as partial seizures, prolonged seizures, and repeated seizures, and might be a risk factor for subsequent development of epilepsy.     

Spontaneous fits after convulsions with fever.

112 of an original sample of 134 children with febrile convulsions were reviewed between 8 years and 9 years 10 months after their initial attack. 17% of those followed up had had at least one spontaneous fit. A significant correlation was found with perinatal abnormalities. 12% had continuing recurrent fits. Persisting grand mal occurred most commonly in lower social class children who had had perinatal abnormalities and continued to have long-term neurological disorders. Psychomotor epilepsy correlated significantly with a prolonged or repeated initial convulsion with unilateral features. It is suggested that the development of grand mal and temporal lobe epilepsies after convulsions with fever are determined by different mechanisms.     

Clinical characteristics of febrile convulsions during primary HHV-6 infection

OBJECTIVE—To clarify clinical characteristics of children with febrile convulsions during primary human herpesvirus 6 (HHV-6) infection.SUBJECTS AND METHODS—The clinical characteristics of first febrile convulsion were compared between those with and without primary HHV-6 infection in 105 children. HHV-6 infection was verified by culture or acute/convalescent anti-HHV-6 antibody titres.RESULTS—Primary infection with HHV-6 was seen in 21 of 105 patients with febrile convulsions (3 upper respiratory infection, 1 lower respiratory infection, and 17 exanthem subitum). 13 of 23 patients < 1 year, 19 of 79 patients with first febrile convulsion, and 2 of 15 with second convulsion were infected with HHV-6. The median age of patients with first febrile convulsion and HHV-6 was significantly lower than those without infection. The frequency of clustering seizures, long lasting seizures, partial seizures, and postictal paralysis was significantly higher among those with primary HHV-6 infection than among those without. The frequency of atypical seizures in 19 patients with first febrile convulsion associated with primary infection was significantly higher than in 60 patients without primary infection. The frequency in infants younger than 1 year of age was also significantly higher than that in 10 age matched infants without primary infection.CONCLUSIONS—These findings suggest that primary infection with HHV-6 is frequently associated with febrile convulsions in infants and young children and that it often results in the development of a more severe form of convulsions, such as partial seizures, prolonged seizures, and repeated seizures, and might be a risk factor for subsequent development of epilepsy.     

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.     

肌阵挛失张力癫(癎)的临床和脑电图特点

目的 总结肌阵挛失张力癫(癎)(MAE)的临床和脑电图特点.方法 分析MAE患儿的临床和视频脑电图及同步肌电图资料,并对治疗效果进行随访.结果 收集MAE患儿共47例,其中25例有热性惊厥史,20例有热性惊厥和(或)癫(癎)家族史,发病前智力运动发育均正常.起病年龄1.4～5.8岁,首次发作为无热的全面强直-阵挛发作(GTCS)41例(87.2%),肌阵挛发作4例,失张力发作2例.病程中均有多种发作类型,包括GTCS46例(97.9%)、肌阵挛失张力发作34例(72.3%)、肌阵挛发作47例(100%)、失张力发作32例(68.1%)、不典型失神36例(76.6%)和强直发作3例(6.4%).出现多种类型的发作时脑电图背景均为弥漫性慢波或顶区为主的θ节律,发作间期呈全导1～4 Hz(以2～3 Hz为主)棘慢波、多棘慢波发放.所有患儿均首选抗癫(癎)药物(AEDs)治疗,41例(87.2%)应用AEDs发作控制,其中37例单用或合用丙戊酸,26例联合应用拉莫三嗪.10例(21.3%)发病后出现智力落后.结论 MAE的临床特点包括:发病前发育正常,多数以GTCS起病,病程中具有多种全面性癫(癎)发作类型,肌阵挛失张力发作是其特征性发作类型;脑电图呈全导棘慢波、多棘慢波发放.早期明确诊断并合理选择AEDs是取得良好预后的关键.

Abstract：

Objective To summarize the electroclinical characteristics of myoclonic atonic epilepsy (MAE) in children. Method The clinical data, video electroencephalogram (EEG) and simultaneous electromyography (EMG) of MAE patients were analyzed. The treatment and its effects were followed up.Result In 47 MAE patients, 25 had a history of febrile seizures ( FS), 20 had a family history of FS or epilepsy. All patients had a normal development before the illness. The age of afebrile seizure onset was between 1.4 years to 5.8 years. The first seizure was generalized tonic-clonic seizure (GTCS) in 41 patients (87.2%). All patients had multiple seizure types, including 47 GTCS (97.9%), 34 myoclonic atonic seizures (72. 3% ), 47 myoclonic seizures ( 100% ), 32 atonic seizures (68. 1% ), 36 atypical absences (76. 6% ) and 3 tonic seizures (6. 4% ). EEG backgrounds were slow or parietal θ rhythm, interictal EEG showed 1-4 Hz (predominant 2-3 Hz) generalized spike and wave or poly spike and wave discharges in all cases. Seizures were controlled by antiepileptic drugs (AEDs) in 41 patients (87.2%). Valproate was used in 37. Lamotrigine was used in 26. Mild mental retardation was observed in 10 children after the onset of the illness. Conclusion The clinical features of MAE included the following: the development was normal before the onset of the illness; the onset of seizure type was often GTCS. All patients had multiple generalized seizure types. Myoclonic atonic seizure was its characteristic seizure type. EEG showed generalized discharges. Early diagnosis and rational choice of AEDs are important for getting a better prognosis.     

Phenobarbital compared with carbamazepine in prevention of recurrent febrile convulsions. A double-blind study

In a double-blind trial, children who had recurrent and/or complex febrile convulsions were treated with either phenobarbital sodium or carbamazepine. Forty children were suitable for analysis; 19 were receiving carbamazepine, and 21 were receiving phenobarbital. Of the carbamazepine-treated patients, nine (47%) had recurrent convulsions despite therapeutic levels of the drug, while only two (10%) of the phenobarbital-treated patients suffered further seizures. These results confirm previous findings suggesting that carbamazepine is not as effective in the prophylactic treatment of febrile convulsions as phenobarbital.     

Risk of recurrent seizures after the first afebrile grand mal seizure in childhood]

A cohort of 74 children three months to 16 years-old who presented with a first unprovoked seizure were followed for five years to assess the risk of recurrence. Children with febrile convulsions, immediate posttraumatic seizures, meningitis and encephalitis were not included. The risk of recurrence was 68% for a second seizure. 47% of the patients developed an epilepsy. 85% of recurrences occurred within the first 6 months and 100% within 2 1/2 years. A history of epilepsy in a first degree relative, age at first seizure, duration of seizure, initial EEG or neurologic status were not associated with significantly higher risk of recurrence.