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.     

Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction

Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in febrile children by qualitative and quantitative polymerase chain reaction (PCR) assays. Diagnosis was based on the differential detection of viral DNA in peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile infants, but none of seven non-febrile controls, were identified with primary infections (three HHV-6, three HHV-7). These children had significantly higher viral loads in PBMC (HHV-6, median 24213 genomes/10(6) PBMC; HHV-7, median 6,040,000 genomes/10(6) PBMC) than DNA-aemic, saliva PCR positive children (HHV-6, median 1606 genomes/10(6) PBMC, p < 0.01; HHV-7, median 7089 genomes/ 10(6) PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary infections. All three children with primary HHV-7 infection had febrile convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6 and HHV-7 infections when an appropriate combination of clinical specimens is used.     

Diagnosis of primary human herpesvirus 6 and 7 infections in febrile infants by polymerase chain reaction

Accepted 16 April 1997
Primary human herpesvirus 6 (HHV-6) and 7 (HHV-7) infections were identified in febrile children by qualitative and quantitative polymerase chain reaction (PCR) assays. Diagnosis was based on the differential detection of viral DNA in peripheral blood mononuclear cells (PBMC), but not in saliva. Six of 41 febrile infants, but none of seven non-febrile controls, were identified with primary infections (three HHV-6, three HHV-7). These children had significantly higher viral loads in PBMC (HHV-6, median 24 213 genomes/10⁶ PBMC; HHV-7, median 6 040 000 genomes/10⁶ PBMC) than DNA-aemic, saliva PCR positive children (HHV-6, median 1606 genomes/10⁶ PBMC, p < 0.01; HHV-7, median 7089 genomes/10⁶ PBMC, p < 0.05). Viral DNA was detected in serum by PCR in only 50% of primary infections. All three children with primary HHV-7 infection had febrile convulsions. Thus PCR, including quantitative assays, may identify primary HHV-6 and HHV-7 infections when an appropriate combination of clinical specimens is used.

     

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.     

Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland.

BACKGROUND: Primary human herpesvirus-6 and -7 (HHV-6/-7) infections cause febrile illness sometimes complicated by convulsions and rarely encephalopathy. AIMS: To explore the extent of such HHV-6 and -7 induced disease in young children. METHODS: In a three year prospective study in Britain and Ireland, 205 children (2-35 months old) hospitalised with suspected encephalitis and/or severe illness with fever and convulsions were reported via the British Paediatric Surveillance Unit network. Blood samples were tested for primary HHV-6 and -7 infections. RESULTS: 26/156 (17%) of children aged 2-23 months had primary infection (11 HHV-6; 13 HHV-7; two with both viruses) coinciding with the acute illness; this was much higher than the about three cases expected by chance. All 26 were pyrexial; 25 had convulsions (18 status epilepticus), 11 requiring ventilation. Median hospital stay was 7.5 days. For HHV-6 primary infection the median age was 53 weeks (range 42-94) and the distribution differed from that of uninfected children; for HHV-7, the median was 60 weeks (range 17-102) and the distribution did not differ for the uninfected. Fewer (5/15) children with primary HHV-7 infection had previously been infected with HHV-6 than expected. CONCLUSIONS: Primary HHV-6 and HHV-7 infections accounted for a significant proportion of cases in those <2 years old of severe illness with fever and convulsions requiring hospital admission; each virus contributed equally. Predisposing factors are age for HHV-6 and no previous infection with HHV-6 for HHV-7. Children with such neurological disease should be investigated for primary HHV-6/-7 infections, especially in rare cases coinciding by chance with immunisation to exclude misdiagnosis as vaccine reactions.     

The relationship between drug treatment and the clinical characteristics of febrile seizures

Background  Drugs such as theophylline, antihistamines, and antiallergics with anti-histaminic actions have been shown to induce febrile seizures. The relationship between febrile seizures and medications has not been actively investigated. The present study aimed to investigate the relationship between the clinical characteristics of febrile seizures and the use of medications. Methods  Two hundred and sixty-five children treated at our emergency room due to febrile seizures were studied to investigate the relationship between the clinical characteristics of febrile seizures, such as the type and duration of convulsions, and the drug treatment. Results  The duration of convulsions was longer among children who took theophylline and antihistamines than among children who did not take these medications. Of the antihistamines, mequitazine did not prolong the duration of convulsion. Conclusions  Theophylline should not be used in febrile children, particularly infants. Cautions should be taken in using histamine H1 antagonists in young infants because such drugs could potentially disturb the anticonvulsive central histaminergic system. However, mequitazine appears to be a suitable antihistamine for use in children with febrile seizures, since it does not prolong convulsions.     

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.     

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.     

Evaluation of Selenium Levels and Mean Platelet Volume in Patients with Simple Febrile Convulsion

Objective: This study aimed to evaluate serum selenium levels and mean platelet volume in children who experience simple febrile convulsion. Methods: The study comprised 42 patients diagnosed with simple febrile convulsions and a control group of 30 healthy children. Blood samples were taken following a febrile convulsion. Selenium levels in the serum of both the patients and control subjects were measured with the hydride formation method on an atomic absorption spectrometry device and mean platelet volume was evaluated. Findings: When the mean values of the febrile convulsion patients were compared with those of the control group, the mean selenium levels and thrombocyte count were found to be statistically significantly low (P=0.002, P=0.01 respectively) and the mean platelet volume values were statistically significantly high (P=0.002). Conclusion: While low serum selenium levels cause the onset of a febrile seizure in patients with simple febrile convulsion, it is thought that the increased mean platelet volume shows infection activity causing febrile convulsion.Key Words: Febrile Convulsion, Selenium, Platelet: Mean Platelet Volume, Antioxidant     

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.     

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.     

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.     

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.     

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.     

Cerebrospinal fluid acid-base status and lactate and pyruvate concentrations after short (less than 30 minutes) first febrile convulsions in children.

Twenty-nine infants and children with short (less than 30 minutes) first febrile convulsions were studied between 3 and 22 hours after convulsive episodes. Arterial and CSF acid-base variables, lactate and pyruvate concentrations, and lactate/pyruvate ratios were measured. Biochemical signs of cerebral hypoxia were found in only 2 patients, one of whom had short, repeated convulsions. Our findings indicate that hypoxic damage is unlikely to result from a short-duration febrile convulsion.     

Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions

Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections (p less than 0.001), viral infections (p less than 0.005) or no infection (p less than 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL-1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions.     

Increased Interleukin-1 (IL-1) Production from LPS-Stimulated Peripheral Blood Monocytes in Children with Febrile Convulsions

ABSTRACT. Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections ( p < 0.001), viral infections ( p < 0.005) or no infection ( p < 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL-1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions.     

Human herpesvirus 6 infection in febrile infants ninety days of age and younger

BACKGROUND: The importance of human herpesvirus 6 (HHV-6) as a pathogen in febrile infants 相似文献   

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。     

The first febrile convulsion: an analysis of 108 children in Saudi Arabia

In 108 children admitted to the Maternity and Children's Hospital, Riyadh with their first febrile convulsion, clinical course, management and underlying causes were analysed. There was a preponderance of boys (69%) and a mean age of 18.6 months with a peak incidence (82%) between six months and three years. The commonest precipitating conditions were upper respiratory infection and gastroenteritis. Physical findings were confined to those of the primary disease. Routine investigations, including CSF analysis were not helpful. Convulsions were mainly of the simple type, single and symmetrical, and did not last for more than 30 minutes. Two thirds of the children reached hospital within two hours of the onset of their first convulsion, and the remainder up to ten hours after the convulsion had ceased. In only 18 patients did the parents take measures to lower the temperature or revive the child. Management of febrile convulsions is discussed. Since the condition is common and, if repeated, may have serious effects, methods of educating parents are suggested.