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.     

Complex Febrile Seizures

In the context of a prospective cohort study, we examined the associations between individual complex features of both first (n = 428) and recurrent (n = 240) febrile seizures and factors shown to predict outcome in children with febrile seizures. Thirty-five percent of first and 33% of recurrent febrile seizures had one or more complex features (focal onset, duration ≥10 min, or multiple seizures during the illness episode). There were strong correlations between focality and prolonged duration for both first and recurrent febrile seizures. A low fever at the time of the seizure was marginally associated with prolonged duration. Most factors associated with either recurrent febrile seizures or subsequent unprovoked seizures were not associated with either the initial seizure being complex or the likelihood that a recurrence would be complex. However, in children with recurrent febrile seizures, complex features tended to repeat. This factor was statistically significant and particularly striking for prolonged duration. Genetic or other constitutional factors may explain why the prolonged feature recurs. Eleven (2.5%) children had three or four risk factors for recurrent febrile seizures and a first febrile seizure that was prolonged. Eight (72.7%) of them experienced a recurrent febrile seizure that was prolonged. This very small group of children may be candidates for abortive therapy to be administered at the onset of a recurrent seizure.     

A comparative study of febrile and afebrile seizures associated with mild gastroenteritis

Purpose: Seizures associated with mild gastroenteritis have been increasingly reported. We analyzed the clinical characteristics of febrile and afebrile seizures associated with mild gastroenteritis, and attempted to determine the influence of fever in these two groups. Methods: We reviewed the medical records of 59 children presenting with seizures during a mild gastroenteritis episode. They were classified into an afebrile group (n = 27) and a febrile group (n = 32). We compared the age of onset, sex, seizure semiology, frequency, duration, family history, and prior history of seizures between the two groups. Results: The mean age, family history, seizure semiology, and frequency of seizures were not significantly different between the two groups. However, more patients in the afebrile group experienced ?2 seizures/day than in the febrile group (63% vs. 38%, p = 0.051). The febrile patients had a tendency of experiencing prolonged seizures lasting ?5 min compared with the afebrile group (34% vs. 11%, p = 0.063). Prior febrile seizures were noted in 5 of the 32 patients (15.6%) in the febrile group, while none of the 27 patients in the afebrile group had a history of prior seizures (p = 0.056). Conclusions: It seems that the presence of fever may influence the clinical characteristics of seizures associated with mild gastroenteritis. We suggest that afebrile seizures associated with gastroenteritis may be regarded as a distinct condition from those associated with fever, and it needs to be clarified by a further large sample study.     

Nonfebrile Illness Seizures: A Unique Seizure Category?

PURPOSE: To describe the clinical characteristics of children with a first-time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea. METHODS: This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first-time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0 degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present). RESULTS: Of the 323 children with first-time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group. CONCLUSIONS: Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.     

How long do new‐onset seizures in children last?

Although there are data on the duration of seizures in patients with refractory epilepsy, little is known about the duration of seizures in nonrefractory epilepsy populations. In a prospective study, seizure duration was determined in 407 children with a first unprovoked seizure using a structured interview and review of medical and ambulance records. Analysis focused on the distribution of seizure duration and on the conditional probability that a seizure would stop once it had already lasted for a specified time. Seizures lasted > or = 5 minutes in 50% of cases, > or = 10 minutes in 29%, > or = 20 minutes in 16%, and > or = 30 minutes in 12%. Seizure duration data were best fit as the sum of two exponential distributions, one with a mean of 3.6 minutes accounting for 76% of cases and the other with a mean of 31 minutes accounting for 24% of cases. The longer a seizure lasted, the less likely it was to stop within the next few minutes. In the 182 children with 2 or more seizures, the durations of the first and second seizures were highly correlated (r = 0.395, p < 0.0001). We conclude that the distribution of seizure duration in children with a first unprovoked seizure differs markedly from that observed in patients with refractory epilepsy. A subgroup of patients are predisposed to prolonged seizures. The data suggest that, once a seizure lasts for more than 5-10 minutes, it is unlikely to stop spontaneously within the next few minutes, and intervention is therefore indicated. These findings also support the continued use of the current definition of status epilepticus as a seizure lasting for 30 minutes or longer for epidemiologic studies.     

Characteristic phasic evolution of convulsive seizure in PCDH19‐related epilepsy

PCDH19‐related epilepsy is a genetic disorder that was first described in 1971, then referred to as “epilepsy and mental retardation limited to females”. PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video‐EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19‐related epilepsy. To do this, ictal video‐EEG recordings of 26 convulsive seizures in three girls with PCDH19‐related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: “jerk”, “reactive”, “mild tonic”, “fluttering”, “mild clonic”, and “postictal”. Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic‐clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19‐related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19‐related epilepsy when occurring in clusters with or without high fever in girls. [Published with video sequences online]     

Serum sodium does not correlate with seizure length or seizure threshold in electroconvulsive therapy

Disorders of sodium balance can result in seizures. In electroconvulsive therapy (ECT) practice, it is customary to obtain electrolytes, including sodium, before treatment. A question that arises is whether the patient with mild disturbances of sodium can safely be treated with ECT or whether normalization of serum sodium is needed first. In this series, 207 patients were treated with ECT and had a serum sodium performed within a week before the first treatment. A few patients were mildly hypernatremic or hyponatremic. We found no correlation between baseline sodium and seizure threshold or seizure duration at the first treatment session. We conclude that although it is ideal to have normal sodium values before ECT, mild abnormalities do not necessarily presage prolonged seizures or lower seizure thresholds in ECT.     

Influenza A and febrile seizures in childhood

The aims of the present study are to identify predisposing factors of febrile seizures in influenza A infection and to clarify the special characteristics of febrile seizures in children with influenza A infection. Between January and July 2005, children hospitalized because of febrile seizures and subsequently confirmed influenza A infection were enrolled as subjects. Age-matched control subjects were those admitted as a result of influenza A infection but no febrile seizures (control 1) and children who developed febrile seizures with negative viral studies (control 2). Significant factors for the development of febrile seizures include: history of febrile seizures, family history of seizure disorders, and coexisting gastroenteritis. Independent risk factor for febrile seizures was history of febrile seizures (odds ratio 7.58, 95% confidence interval CI 1.48 to 38.84, P = 0.015). When compared with children who developed febrile seizures with negative virus studies, children who developed febrile seizures in influenza A infection had a significantly higher maximum body temperature, shorter duration of fever before seizure onset, and more frequent occurrence of partial seizures. Current episode represented first seizure in 26.5% of children infected with influenza A as compared with 50% of children whose virus studies were negative (P = 0.04). The findings suggest that effective vaccination may prevent development of febrile seizures, especially in those patients with past history of febrile seizures. Rapid diagnostic testing for influenza infection in the management of complex febrile seizures, especially during influenza season, is cost-effective.     

Peripheral leukocytosis in children with febrile seizures

Peripheral blood leukocytosis has been reported following febrile seizures as a result of infection, the seizure, or both. To examine this relationship, 238 consecutive children < 5 years of age who experienced their first febrile seizure were evaluated. Lumbar punctures were electively done on 128 of the children to rule out central nervous system infection. Total leukocyte counts and duration of fever before the seizure were negatively correlated (r = - .175, P < .05). In logistic regression analysis, the logarithm of fever duration before the seizure was negatively associated with leukocytosis (leukocyte count > or = 15,000 cells/microL [odds ratio: 0.117, P < .05]). Cerebrospinal fluid glucose concentrations were significantly correlated with increased body temperature (r = .230, P < .05) and increased leukocyte counts (r = .255, P < .01). No significant association was found between leukocyte counts and the characteristics of the febrile seizure event. By all indications, changes in leukocyte counts appear more likely to be related to the length and underlying etiology of the fever than to the seizure itself.     

Analysis of cerebrospinal fluid glial fibrillary acidic protein after seizures in children

PURPOSE: To evaluate pediatric seizure patients for astrocytic injury by measuring cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP), determine risk factors for GFAP elevation after seizures, and compare seizure-induced astrocyte injury with neuronal injury by concurrent measurement of CSF neuron-specific enolase (NSE). METHODS: CSF obtained from pediatric patients (n = 52) within 24 h of seizure was assayed for GFAP and NSE. Retrospective chart review was performed for seizure type, duration, and etiology. RESULTS: Overall, children with seizures had elevated CSF GFAP compared with controls (p = 0.0075), but no elevation of NSE (p = 0.1437). No effect of seizure type or etiology was found, but a significant positive effect of seizure duration (p = 0.0010) and status epilepticus (p = 0.0296) was seen on CSF GFAP. Individually, seven children (13%) had elevated GFAP (>440 pg/ml); in five children, the increased GFAP was not accompanied by elevations in NSE (<12 ng/ml). Five children with elevated GFAP had symptomatic etiologies for their seizures, but the etiology of one child with elevated GFAP was cryptogenic, and one had febrile seizures. CONCLUSIONS: Elevation of CSF GFAP after seizures suggests that astrocytic injury may occur in a subgroup of children, primarily in the context of prolonged seizures and symptomatic etiologies. Increased GFAP levels may occur in patients with normal NSE, suggesting that GFAP may be a more sensitive marker of brain injury in some cases.     

Afebrile benign convulsions with mild gastroenteritis: a new entity?

Afebrile seizures in children usually necessitate investigations in order to determine the etiology and estimate the prognosis. Recently, convulsions that are described as benign but afebrile have been documented in children, in association with diarrhea, and are now recognized as a distinct entity. Benign afebrile seizures with mild gastroenteritis are defined as convulsions accompanying symptoms of mild diarrhea without dehydration or electrolyte derangement and without fever before and after the seizures in healthy children without meningitis, encephalitis or encephalopathy. The convulsions are short, symmetrical, generalized tonic–clonic seizures, occurring in clusters. Laboratory studies (full blood count, blood glucose, creatinine, serum electrolytes, cerebrospinal fluid, bacterial and viral cultures) are usually normal, and other investigations (neuroimaging and electroencephalogram) are not necessary. Prognosis is always favorable (normal psychomotor development, no recurrences of seizures), and anticonvulsant therapy is not warranted. Recognition of this benign infantile convulsion avoids extensive evaluation and long‐term anticonvulsant therapy; physicians may reassure the parents regarding the lack of long‐term sequelae. In conclusion, this type of seizure seems to be a new entity, but it awaits a correct place in the large group of infantile convulsion disorders.     

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...     

Comparison between febrile and afebrile seizures associated with mild rotavirus gastroenteritis

PurposeWe aimed on identifying the differences of febrile and afebrile seizures associated with mild rotavirus gastroenteritis (RVGE) in the pediatric population.MethodMedical charts of pediatric patients who had been admitted between July 1999 and June 2011 due to RVGE were retrospectively reviewed. Subjects were ultimately divided into three groups; ‘no seizure’ (NS: patients without seizure), ‘febrile seizure’ (FS: patients with fever during seizure), ‘afebrile seizure’ (AFS: patients without fever during seizure). Comparisons between groups were carried out on demographic and clinical characteristics, laboratory test results, electroencephalogram findings, brain magnetic resonance imaging findings, antiepileptic treatment, and prognosis.ResultsAmong the 755 subjects who had been admitted due to mild rotavirus enteritis, 696 (90.3%) did not have any seizures, 17 (2.2%) had febrile seizures, 42 (5.5%) had afebrile seizures. The duration of gastrointestinal symptoms before the onset of seizures were significantly shorter in the FS group compared to the AFS group (1.3 ± 0.8 vs. 2.8 ± 1.0 days; p < 0.0001). A single seizure attack was significantly higher in the AFS group (3.0 ± 1.6 vs. 1.7 ± 1.0 episodes; p = 0.0003), and the frequency of seizures that were of focal type with or without secondary generalization were significantly higher in the AFS group (33.3% vs. 6.0%; p = 0.0139). All patients among the FS and AFS group had not received further antiepileptic treatment after discharge, and none developed epilepsy during follow up period.ConclusionDespite some differences in seizure characteristics, both febrile and afebrile seizures associated with mild RVGE were mostly benign with a favorable prognosis.     

Cerebrospinal fluid neuron-specific enolase following seizures in children: role of etiology

Neuron-specific enolase, a marker for neuronal injury, is elevated following seizures in adults, but relatively few data exist on postictal neuron-specific enolase levels in children. This study measured cerebrospinal fluid (CSF) neuron-specific enolase levels after seizures in 49 consecutive pediatric patients and investigated the role of seizure type, duration, and etiology in influencing neuron-specific enolase. Overall, there was no significant difference in neuron-specific enolase levels between patients with seizures and a control group. However, 4 of the 49 seizure patients (8%) had neuron-specific enolase levels clearly above the normal range. Seizure patients with symptomatic etiologies had significantly increased neuron-specific enolase compared to cryptogenic/idiopathic or febrile seizures. The four individual patients with elevated cerebrospinal fluid neuron-specific enolase all had identified metabolic or genetic etiologies and presented with medically refractory status epilepticus. No individuals with cryptogenic/idiopathic or febrile seizures had abnormal neuron-specific enolase. There was no significant effect of seizure duration or type on cerebrospinal fluid neuron-specific enolase. In contrast to adults, acute seizure-induced neuronal injury in children as detected by neuron-specific enolase is rare and may occur primarily with severe symptomatic etiologies. Children with cryptogenic, idiopathic, or febrile seizures, including status epilepticus, are at relatively low risk for neuronal damage following seizures.     

Unconsciousness and delirious behavior in children with febrile seizures

The aim of this study is to clarify the incidence and clinical features of prolonged unconsciousness and delirious behavior in children with febrile seizures. We studied 213 consecutive febrile seizures during 208 febrile episodes in 203 patients. The seizure manifestations, the duration of seizures, the duration of unconsciousness, and the presence or absence of delirious behavior were determined on the basis of interviews with the parents with the assistance of medical records. The duration of seizures was less than 5 minutes in 90.2% of the seizures. The duration of unconsciousness was less than 30 minutes in 93% of the seizures. Delirious behavior was observed in 2.0% of the patients. Delirious behavior appeared before febrile seizures, and its duration was not long. On multiple regression analysis, nongeneralized seizures, seizures of ≥5 minutes, and intravenous diazepam were demonstrated to be independently associated with prolonged unconsciousness. In conclusion, prolonged unconsciousness and delirious behavior are rare in children with febrile seizures. Careful diagnostic evaluation is necessary when a child with febrile seizures has associated prolonged unconsciousness or delirious behavior. Okumura A, Uemura N, Suzuki M, Itomi K, Watanabe K. Unconsciousness and delirious behavior in children with febrile seizures.     

Total or partial withdrawal of antiepileptic drugs

Total withdrawal of antiepileptic drugs leads to a mean relapse rate of approximately 50 p. 100 in adults and 25 p. 100 in children. The relapse rates are lowest in patients with benign epilepsies of childhood and epilepsies with absence seizures only and those with a short duration of epilepsy. Relapse rates are higher in patients with complex partial seizures, absences with generalized tonic-clonic seizures, juvenile myoclonic epilepsy, patients with several types of seizures, high seizure frequency prior to control, in patients with neurological, psychiatric or social handicaps and in those with emotional ambivalence towards the reduction. Guidelines for slow and safe withdrawal are given. Reduction should be actively encouraged only in patients with absence seizures or benign focal epilepsy and those with epilepsy of short duration. Slow partial withdrawal is recommended in uncontrolled epilepsy because in 80 p. 100 of the patients it results in a decrease in seizure frequency and side effects or both.     

A detailed analysis of frontal lobe seizure semiology in children younger than 7 years

PURPOSE: We sought to analyze semiology of seizure onset and evolution in young children with frontal lobe epilepsy (FLE), compare this with adult reports, and assess age-related differences. METHODS: We analyzed 111 videotaped seizures from 14 patients with FLE based on focal cortical dysplasia aged 3-81 months (mean, 30 months). Ictal events were categorized into behavioral, consciousness, autonomic, and sensory features, as well as motor patterns, which included tonic, clonic, epileptic spasm, and myoclonic seizure components. We developed a time-scaled datasheet to record each epileptic event as onset, very early, early, or late manifestation. RESULTS: Patients had a high seizure frequency with up to 40 attacks/day; half of them showed a cluster tendency. Forty-seven percent of the seizures started in sleep. Mean duration of seizures was short (29 s). Most common seizure components were motor manifestations, mostly tonic-clonic seizures, and epileptic spasms. Behavioral change was frequent, and hypermotor seizures were not seen. In five patients, the motor features were contralateral to the epileptic focus, including two children with asymmetric epileptic spasms. Secondarily generalized tonic-clonic seizures (SGTCSs) were not recorded, but had been reported in the history of two patients. Complex motor automatisms were not seen, whereas oral automatism appeared in three children. CONCLUSIONS: Motor features are common in young children with FLE, as reported in adults. The characteristics, however, differ. Epileptic spasms and subtle behavioral change were frequent. Hypermotor seizures and complex motor automatisms were not seen, and SGTCSs were unusual. Our results suggest that FLE in young children shows age-related features differing from those of adults.     

Risk of seizure recurrence after a first unprovoked seizure: a prospective study among Jordanian children.

PURPOSE: There is wide variation in the reported recurrence rate after a first unprovoked seizure in children. We investigated the risk of recurrence after a first unprovoked seizure in Jordanian children and the risk factors associated with increased recurrence rate. METHODS: All consecutive patients aged 3 months-14 years who presented with their first unprovoked seizures between January 1997 and 2000, were included in a prospective study and followed up for 3 years for possible recurrence. Of the patients studied, there was slight male predominance (56.6%) and 55% of them were 2-9 years of age. Generalised seizures were reported in 75% and the remaining 25% had partial seizures. The duration of seizure was 1-4 minutes in 59%. Family history of epilepsy was positive in 31% and parental consanguinity in 32%. The role of these factors in increasing the risk of recurrence was also investigated. RESULTS: Two hundred sixty-five patients were included in the study and continued follow up for 3 years. Ninety-eight (37%) of them experienced seizure recurrence. Among the predictor factors for recurrence, partial seizure (P = 0.003) and positive family history (P = 0.000) were associated with a statistically significant increased risk. Sex, age, duration of seizure and consanguinity were not associated with increased risk of recurrence. CONCLUSION: Thirty-seven percent of the children studied experienced a second attack after a first unprovoked seizure over the 3 years follows up period. The risk of recurrence was significantly higher in children with a partial seizure (55%) and among those with a positive family history of epilepsy (59%). Age at first seizure, sex, duration of seizure and consanguinity were not significantly related to the risk of recurrence.     

Absence seizures in children: clinical and electroencephalographic features

The clinical and electroencephalographic (EEG) features of absence seizures in children were evaluated using EEG frequency modulation radiotelemetry and videotape monitoring. The only seizures evaluated were those with a spike-and-wave or multiple spike-and-wave duration lasting at least 3 seconds. A total of 926 absence seizures (426 typical, 500 atypical) were reviewed in 54 patients. Abnormal interictal EEGs, multiple seizure types, mental retardation, or developmental delay were more likely in patients with atypical absence seizures than in patients with typical absence seizures. Both types of absence seizures usually had a clear onset and cessation. Atypical absence seizures lasted significantly longer than did typical absence seizures. Automatisms occurred more frequently in typical absence seizures than in atypical ones, while decreases in postural tone or tonic activity occurred more frequently in atypical absence seizures. Receptive and expressive speech were retained in some patients during both types of seizures. This study demonstrates that typical and atypical absence seizures are not discrete entities but rather form a continuum. No single clinical feature can adequately distinguish the two seizure types.     

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.