Inter- and intraobserver agreement of seizure behavior scoring in the amygdala kindled rat

\u3cp\u3eIntroduction: The Racine scale is a 5-point seizure behavior scoring paradigm used in the amygdala kindled rat. Though this scale has been applied widely in experimental epilepsy research, studies of reproducibility are rare. The aim of the current study was, therefore, to assess its interobserver variability and intraobserver variability. Material and methods: A video database set was acquired in the course of amygdala kindling of 67 Wistar rats. Six blinded observers received scoring instructions and then viewed a set of 15 random videos (session #1). Next, each observer scored 379 to 1048 additional videos (session #2) and finally scored the same set of 15 videos again (session #3). Scores included the occurrence of seizures (yes or no), the total seizure time (start of stimulus until the absence of seizure behavior), and the highest Racine stage. Interobserver variability and intraobserver variability were assessed in and between sessions #1 and #3 using a 2-way mixed intraclass correlation or Cohen's kappa depending on the variable. Results: Interobserver agreement in session #1 was 0.664 for seizure occurrence, 0.861 for total seizure time, and 0.797 for the highest Racine stage. In session #3, interobserver agreement on seizure occurrence declined to 0.492, total seizure time declined to 0.625, and agreement for the highest Racine stage was 0.725. Interobserver agreement was scored insufficiently on focal R2 seizures in both sessions (0.287 and 0.182). Intraobserver agreement reached >. 0.80 agreement for seizure occurrence, highest seizure score, and total seizure time in 3 out of 4 observers. Racine's scale stage 2 seizure scores were only 0.135 in one observer but 0.650, 0.810, and 0.635 in the other observers. Discussion and conclusion: Overall, interobserver agreement and intraobserver agreement in scoring with Racine's scale were adequate. However, because interobserver agreement declined after a period of individually scoring videos, we suggest periodic repetition of the standardized instruction in the course of evaluating videos in order to ensure reproducible results.\u3c/p\u3

Analyzing EEG maturation in preterm infants:the value of a quantitative approach

\u3cp\u3eDespite increase in survival of very low birth weight infants, the number of infants who experience neuromotor or neurocognitive problems later in life is still high. Therefore, accurate documentation of the brain development in these infants is indicated. Electroencephalography (EEG) may be a valuable tool to monitor brain development during the intensive care period. However, our knowledge on EEG maturation is based on visually determined patterns. Since there are no exact reference values, conclusions on EEG maturation are difficult to establish and may vary between investigators. Also, most knowledge concerning EEG maturation is derived from relatively old studies in the pre-digital era. New digital EEG recorders provide the opportunity towards a quantitative approach of EEG maturation. This approach may lead to a more objective and uniform description of EEG maturation. In this article we review the most important aspects of EEG maturation, i.e. changes in discontinuity, development of age specific waveforms, inter-hemispheric synchrony/correlation and the development of sleep-wake cycles, and qualitative or semi-quantitative studies concerning EEG maturation and outcome. We discuss the concept of an EEG analyzing algorithm and propose several quantitative analyzing techniques which may be incorporated in such an algorithm.\u3c/p\u3

A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy

\u3cp\u3eObjective: To evaluate the efficacy and tolerability of the ketogenic diet (KD) during the first 4 months of a randomized controlled trial (RCT) in refractory epilepsy patients aged 1–18 years. Methods: Children and adolescents with refractory epilepsy, not eligible for epilepsy surgery, were included. Following 1 month at baseline, patients were randomized to either the KD or to care as usual (CAU).Primary outcome is the proportion of patients with at least 50% reduction in seizure frequency at 4 months. Secondary outcomes are mean percentage of baseline seizures, seizure severity, and side effects. Results: Fifty-seven patients were randomized; nine dropped out, leaving 48 for analysis (i.e., 26 KD, 22 CAU). In an intention-to-treat analysis, 13 patients (50%) treated with the KD and four patients (18.2%) of the CAU group were responders.Mean seizure frequency at 4 months compared to baseline, after removal of two outliers in the KD group, was significantly lower (P = 0.024) in the KD group (56%) (95% CI: 36–76) than in the CAU group (99%) (95% CI: 65–133%).Twice as many patients in the KD group had a relevant decrease in seizure severity score (P = 0.070).Patients treated with the KD had a significantly higher score for gastrointestinal symptoms (P = 0.021) without an increase in the total score of side effects. Conclusions: This trial provides class I evidence that the KD is an effective therapy in children and adolescents with refractory epilepsy compared with CAU. Most often reported side effects are gastrointestinal symptoms.The study has been registered with the Netherlands Trial Registry (NTR2498).\u3c/p\u3

A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy

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A study on the validity of a computer-based game to assess cognitive processes, reward mechanisms, and time perception in children aged 4-8 years

\u3cp\u3eBACKGROUND: A computer-based game, named Timo's Adventure, was developed to assess specific cognitive functions (eg, attention, planning, and working memory), time perception, and reward mechanisms in young school-aged children. The game consists of 6 mini-games embedded in a story line and includes fantasy elements to enhance motivation.\u3c/p\u3e\u3cp\u3eOBJECTIVE: The aim of this study was to investigate the validity of Timo's Adventure in normally developing children and in children with attention-deficit/hyperactivity disorder (ADHD).\u3c/p\u3e\u3cp\u3eMETHODS: A total of 96 normally developing children aged 4-8 years and 40 children with ADHD were assessed using the game. Clinical validity was investigated by examining the effects of age on performances within the normally developing children, as well as performance differences between the healthy controls and the ADHD group.\u3c/p\u3e\u3cp\u3eRESULTS: Our analyses in the normally developing children showed developmental effects; that is, older children made fewer inhibition mistakes (r=-.33, P=.001), had faster (and therefore better) reaction times (r=-.49, P<.001), and were able to produce time intervals more accurately than younger children (ρ=.35, P<.001). Discriminant analysis showed that Timo's Adventure was accurate in most classifications whether a child belonged to the ADHD group or the normally developing group: 78% (76/97) of the children were correctly classified as having ADHD or as being in the normally developing group. The classification results showed that 72% (41/57) children in the control group were correctly classified, and 88% (35/40) of the children in the ADHD group were correctly classified as having ADHD. Sensitivity (0.89) and specificity (0.69) of Timo's Adventure were satisfying.\u3c/p\u3e\u3cp\u3eCONCLUSIONS: Computer-based games seem to be a valid tool to assess specific strengths and weaknesses in young children with ADHD.\u3c/p\u3

The use of health care services and psychotropic medication in a community sample of 9-year-old schoolchildren with ADHD

Objective To examine the prevalence of the use of health care services and psychotropic medication within a community sample (N = 283) of 9-year-old school children and, more specifically, to evaluate the use of prescribed stimulants. Methods Data from the second follow-up phase of the "Study of Attention Deficit Maastricht" (SAM) were analysed. Assessments at age 9 included a structured psychiatric interview with parents, behaviour and family situation questionnaire, IQ estimate and global assessment scale. Use of health care services and medication was obtained by the DICA-R and from the Youth Health Care records. Results About 190 children of the selected sample had at least one child psychiatric diagnosis, 26 (14%) of them were clinically referred and 12 (6%) received stimulants. Of the children with ADHD (N = 45), 10/45 (22%) received stimulants. Conversely, 2 out of 12 children who were treated with stimulants did not meet full DSM-IV diagnostic criteria, but were subthreshold ADHD cases. The treatment status was highly dependent on being clinically referred. Conclusion The major finding of our survey is a lack of referral to child mental health services, and associated underdiagnosis and undertreatment, particularly in children with ADHD. There is a critical need to translate and implement the diagnostic and treatment guidelines to clinical practice

Towards a better understanding of cognitive deficits in absence epilepsy:a systematic review and meta-analysis

Cognition in absence epilepsy (AE) is generally considered undisturbed. However, reports on cognitive deficits in AE in recent years have suggested otherwise. This review systematically assesses current literature on cognitive performance in children with AE. A systematic literature search was performed in Pubmed, Embase, Cochrane and Web of Science. All studies reporting on cognitive performance in children with AE were considered. In total 33 studies were eligible for inclusion. Neuropsychological tests were classified into the following domains: intelligence; executive function; attention; language; motor & sensory-perceptual examinations; visuoperceptual/visuospatial/visuoconstructional function; memory and learning; achievement. Random-effect meta-analyses were conducted by estimating the pooled mean and/or pooling the mean difference in case-control studies. Full-scale IQ in children with AE was estimated at 96.78 (95%CI:94.46-99.10) across all available studies and in case-control studies IQ was on average 8.03 (95%CI:-10.45- -5.61) lower. Verbal IQ was estimated at 97.98 (95%CI:95.80-100.16) for all studies and 9.01 (95%CI:12.11- -5.90) points lower in case-control studies. Performance IQ was estimated at 97.23 (93.24-101.22) for all available studies and 5.32 (95%CI:-8.27-2.36) points lower in case-control studies. Lower performance was most often reported in executive function (cognitive flexibility, planning, and verbal fluency) and attention (sustained, selective and divided attention). Reports on school difficulties, neurodevelopmental problems, and attentional problems were high. In conclusion, in contrast to common beliefs, lower than average neurocognitive performance was noted in multiple cognitive domains, which may influence academic and psychosocial development

Pediatric frontal lobe epilepsy : white matter abnormalities and cognitive impairment

Objectives: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE). Its etiology remains unknown. With diffusion tensor imaging, we have studied cerebral white matter properties and associations with cognitive functioning in children with FLE and healthy controls. MethodsThirty children aged 8–13 years with FLE of unknown cause and 39 healthy age-matched controls underwent neuropsychological assessment, structural and diffusion-weighted brain MRI. Patients were grouped as cognitively impaired or unimpaired, and their white matter diffusion properties were compared with the controls. ResultsChildren with FLE had reduced apparent diffusion coefficients in various posteriorly located tract bundles, a reduced fractional anisotropy (FA) of the white matter tract between the right frontal and right occipital lobe, and smaller volumes of several collections of interlobar bundle tracts, compared with controls. The cognitively impaired patient group demonstrated significant increases in FA of the white matter of both occipital lobes, a reduced FA of white matter tract bundles between the right frontal and both left occipital lobe and subcortical white matter area, and smaller volumes of two collections of tract bundles connecting the frontal lobe with the temporal and parietal lobes, compared with controls. ConclusionsChildren with FLE had white matter abnormalities mainly in posterior brain regions, not confined to the area of the seizure focus. Cognitively impaired children with FLE showed the most pronounced white matter abnormalities. These possibly reflect disturbed maturation and might be part of the etiology of the cognitive impairment

Cognitive development in absence epilepsy during long-term follow-up

\u3cp\u3eAbsence epilepsy (AE) has been associated with lower than average cognitive functioning, which are clinically relevant in some and may predispose to problems later in life. This study aimed to assess cognitive development during long-term follow-up in children with AE. Thirty-one children with AE, who had undergone two neuropsychological assessments between 2010 and 2017 were analyzed retrospectively. Cognitive measurements were 1.7 ± 0.95 years apart. The difference in neurocognitive test scores was assessed on a group level and on an individual level using reliable change methodology. Results show that sustained attention was lower at the first measurement compared to the normative mean. Sustained attention improved during follow-up and 7 out of 14 children showed improvement after correction for practice effects. Receptive vocabulary showed a decline over time, but did not differ from the normative mean. Significant lower mean group scores were present for performance IQ, perceptual organization, processing speed, simple reaction times, and visual motor integration, while being stable over time in the majority of children. Cognitive development was not associated with seizure freedom. Mild-to-severe academic underachievement was present in 65% and comorbidities that might affect learning in 38%. This study in children with AE showed improvement in sustained attention during long-term follow-up while other cognitive weaknesses persisted over time, regardless of seizure freedom.\u3c/p\u3