BUPA Foundation, The Academy of Medical Sciences, Wellcome Trust, National Institute for Health Research, and Young Epilepsy.
Summary 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.
Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal injury may be evident in human children after prolonged febrile seizures. The current study addressed this question by investigating memory abilities in 26 children soon after a prolonged febrile seizure (median: 37.5 days) and compared their results to those of 37 normally developing children. Fifteen patients were reassessed at a mean of 12.5 months after their first assessment to determine the transiency of any observed effects. We used the visual paired comparison task to test memory abilities in our group, as this task does not depend on verbal abilities and also because successful performance on the task has been proven to depend on the presence of functional hippocampi. Our findings show that patients perform as well as controls in the absence of a delay between the learning phase and the memory test, suggesting that both groups are able to form representations of the presented stimulus. However, after a 5-min delay, patients' recognition memory is not different from chance, and comparison of patients and controls points to an accelerated forgetting rate in the prolonged febrile seizure group. The patients' performance was not related to the time elapsed from the acute event or the duration of the prolonged febrile seizure, suggesting that the observed effect is not a by-product of the seizure itself or a delayed effect of medication administered to terminate the seizure. By contrast, performance was related to hippocampal size; participants with the smallest mean hippocampal volumes revealed the biggest drop in performance from the immediate to the delayed paradigm. At follow-up, children were still showing deficiencies in recognizing a face after a 5-min delay. Similarly, this suggests that the observed memory impairments are not a transient effect of the prolonged febrile seizures. This is the first report of such impairments in humans, and it is clinically significant given the links between mesial temporal sclerosis and prolonged febrile seizures. The persistence of these impairments a year onwards signals the potential benefits of intervention in these children who run the risk of developing episodic memory deficits in later childhood.
The peak latency of the Nc was slower for infants with lower regulatory capacity, independent of facial expression. The amplitude of the Nc over right fronto-central electrodes was related to both self-regulation and negative emotionality, but the effects differed by emotion: infants with better self-regulation had larger Nc responses to fearful faces, and infants scoring higher on negative emotionality had larger Nc responses to happy faces. These results are discussed in relation to the development of executive attention networks and their modulation by the amygdala.
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