Long-term intellectual and behavioral outcomes of children with febrile convulsions
ABSTRACT Hospital-based studies have reported that children with febrile convulsions have subsequent mental retardation and behavior problems. In contrast, population-based studies have reported a better outcome.
We identified 398 children with febrile convulsions among 14,676 children enrolled in the Child Health and Education Study, a national population-based study in the United Kingdom of children born in one week in April 1970. The children were comprehensively assessed at the age of 10. After excluding 16 children who had neurodevelopmental problems before their first febrile convulsion and 1 child whose case was atypical, we studied 381 children, 287 with simple febrile convulsions and 94 with complex febrile convulsions. We compared them with the rest of the cohort using measures of academic progress, intelligence, and behavior that included questionnaires, standardized tests, and formal tests.
At the 10-year assessment, only 4 of 102 measures of academic progress, intelligence, and behavior differed significantly between the entire group of children with febrile convulsions and the group without febrile convulsions -- no more than would be expected by chance. Similar results were found when children with simple febrile convulsions and those with complex febrile convulsions were analyzed separately. The children with recurrent episodes of febrile convulsions had outcomes similar to those of the children with only one episode each. Special schooling was required for more children who had febrile convulsions in the first year of life than for those who had had them later in life (5 of 67, or 7.5 percent, vs. 4 of 265, or 1.5 percent; P=0.02), but these numbers were small.
Children who had febrile convulsions performed as well as other children in terms of their academic progress, intellect, and behavior at 10 years of age.
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ABSTRACT: PURPOSE: Convulsive status epilepticus (CSE) is the most common pediatric neurologic emergency and is often associated with unfavorable neurodevelopmental outcomes. The early developmental trajectory of children following CSE has not been previously investigated, leaving a gap in our understanding of how these adverse long-term outcomes emerge. METHODS: We prospectively recruited children aged between 1 and 42 months from a predefined geographic region of North London who had at least one episode of CSE and classified them as prolonged febrile seizures (PFS) or nonfebrile CSE. Neuropsychological and imaging investigations were conducted within 6 weeks of CSE (baseline) and were repeated a year later (follow-up). Neurodevelopment was assessed using the Bayley Scales of Infant Development III and compared to normally developing children. Predictors of neurodevelopmental scores at baseline and follow-up were investigated using regression analyses. KEY FINDINGS: Of the 54 children that underwent investigations a mean of 38 days following CSE, 27 had PFS (mean age 18.4 months) and 27 had nonfebrile CSE (mean age 15.5 months). In addition, 17 healthy controls were assessed (mean age 20.49 months). Children with nonfebrile CSE had a worse developmental outcome than children with PFS (p < 0.002), despite there being no differences in seizure characteristics. In contrast to expectations, the PFS group had a worse developmental outcome than controls (p = 0.002). There were no significant differences in performance from baseline to 1-year follow-up for the 70.4% of children who provided data. Seizure characteristics were not shown to be significant predictors of performance. SIGNIFICANCE: CSE is associated with developmental impairments within 6 weeks of the acute event that continue to be present a year onward. This is also true of PFS cases that under-perform relative to controls despite mean scores within the clinically normal range. The absence of a change in performance from baseline to follow-up as well as the lack of a relationship between seizure characteristics and developmental outcomes supports the notion that premorbid abilities may be overshadowing any direct effects of CSE itself on outcome.Epilepsia 04/2013; 54(6). DOI:10.1111/epi.12136 · 4.58 Impact Factor
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ABSTRACT: To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders. We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first-degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9-year follow-up. Clinical cutoffs for CBCL problem and Diagnostic and Statistical Manual of Mental Disorders (DSM)-Oriented scales were examined. The association between first-degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first-degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, was adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations. In probands with uncomplicated epilepsy, first-degree family history of unprovoked seizure was significantly associated with clinical cutoffs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cutoffs for Withdrawn/Depressed, and DSM-Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cutoffs for Aggressive Behavior and Delinquent Behavior, and DSM-Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first-degree family history of unprovoked seizure and Total Problems and Aggressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed, and Anxiety Disorder. There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First-degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy. Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it.Epilepsia 12/2011; 53(2):301-7. DOI:10.1111/j.1528-1167.2011.03351.x · 4.58 Impact Factor
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ABSTRACT: Clinical studies have suggested that children experiencing a febrile seizure (FS) before the age of 1year have persistent deficits, but it is unknown whether these seizures lead to permanent cortical reorganization and alterations in function. A FS on the background of increased genetic seizure susceptibility may also lead to negative long-term consequences. Alterations in neocortical motor map expression provide a measure of neocortical reorganization and have been reported in both adults with frontal lobe epilepsy and following seizure induction in experimental models. The objectives of the present study were to determine whether (1) an infantile FS leads to changes to motor map expression in adulthood; (2) long-term cortical reorganization is a function of the age at FS or genetic seizure susceptibility; and (3) different levels of GABA(A) or glutamate receptor subunits or cation-chloride-co-transporters (CCCs) at the time of FS correlate with alterations to motor map expression. FSs were induced in postnatal day 10 (P10) or P14 Long-Evans (LE) rats or in P14 seizure-prone FAST rats by the administration of the bacterial endotoxin lipopolysaccharide (LPS) and a subconvulsant dose of kainic acid. Ten weeks later intracortical microstimulation was performed to generate motor maps of forelimb movement representations. Sensorimotor neocortex samples were also dissected from naïve P10 FAST and P10 and P14 LE pups for western blotting with antibodies against various GABA(A), NMDA, and AMPA receptor subunits and for CCCs. Adult FAST rats had larger motor maps with lower stimulation thresholds after a FS at P14, while adult LE rats had significantly lower map stimulation thresholds but similar sized maps after a FS at P10 compared to controls. There were no differences in neocortical motor map size or stimulation thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had significantly lower levels of the GABA(A) receptor α1 subunit, higher levels of the α2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the P14 LE rats. A single infantile FS can have long-term effects on neocortical reorganization in younger individuals and those with underlying seizure susceptibility. These changes may be related to an increased level of excitability in the neocortex of younger or genetically seizure-prone rats, as suggested by immaturity of their GABAergic and CCC systems. Given the high incidence of FSs in children, it will be important to gain a better understanding of how age and genetic seizure predisposition may contribute to the long-term sequelae of these events.Neurobiology of Disease 10/2011; 45(2):692-700. DOI:10.1016/j.nbd.2011.10.013 · 5.20 Impact Factor