The frequency, complications and aetiology of ADHD in new onset paediatric epilepsy

Matthews Neuropsychology Lab, Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Brain (Impact Factor: 9.2). 01/2008; 130(Pt 12):3135-48. DOI: 10.1093/brain/awm227
Source: PubMed


Recent studies suggest that Attention Deficit Hyperactivity Disorder (ADHD) is a common comorbid condition in childhood epilepsy, but little is known regarding the nature, frequency and timing of associated neurobehavioural/cognitive complications or the underlying aetiology of ADHD in epilepsy. This investigation examined: (i) the prevalence of ADHD and its subtypes; (ii) the association of ADHD with abnormalities in academic, neuropsychological, behavioural and psychiatric status and (iii) the aetiology of ADHD in paediatric epilepsy. Seventy-five children (age 8-18) with new/recent onset idiopathic epilepsy and 62 healthy controls underwent structured interview (K-SADS) to identify the presence and type of DSM-IV defined ADHD, neuropsychological assessment, quantitative MR volumetrics, characterization of parent observed executive function, review of academic/educational progress and assessment of risk factors during gestation and delivery. The results indicate that ADHD is significantly more prevalent in new onset epilepsy than healthy controls (31% versus 6%), characterized predominantly by the inattentive variant, with onset antedating the diagnosis of epilepsy in the majority of children. ADHD in childhood epilepsy is associated with significantly increased rates of school based remedial services for academic underachievement, neuropsychological consequences with prominent differences in executive function, and parent-reported dysexecutive behaviours. ADHD in paediatric epilepsy is neither associated with demographic or clinical epilepsy characteristics nor potential risk factors during gestation and birth. Quantitative MRI demonstrates that ADHD in epilepsy is associated with significantly increased gray matter in distributed regions of the frontal lobe and significantly smaller brainstem volume. Overall, ADHD is a prevalent comorbidity of new onset idiopathic epilepsy associated with a diversity of salient educational, cognitive, behavioural and social complications that antedate epilepsy onset in a significant proportion of cases, and appear related to neurodevelopmental abnormalities in brain structure.

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    • "Significant ADHD symptoms are present in many patients before the onset of the first seizure. Of children newly diagnosed with epilepsy, 31% showed symptoms of ADHD [7], with 82% of these children with epilepsy and ADHD showing ADHD symptoms prior to seizure onset [7]. A bidirectional association between epilepsy and "
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    ABSTRACT: Objectives: Epilepsy in humans and rodent models of epilepsy can be associated with behavioral comorbidities including an increased prevalence of attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder symptoms and seizure frequency have been successfully reduced in humans and rodents using a ketogenic diet (KD). The aims of this study were (i) to describe the behavioral profile of dogs with idiopathic epilepsy (IE) while on a standardized nonketogenic placebo diet, to determine whether ADHD-like behaviors are present, and (ii) to examine the effect of a ketogenic medium chain triglyceride diet (MCTD) on the behavioral profile of dogs with idiopathic epilepsy (IE) compared with the standardized placebo control diet, including ADHD-like behaviors. Methods: A 6-month prospective, randomized, double-blinded, placebo-controlled, crossover dietary trial comparing the effects of the MCTD with a standardized placebo diet on canine behavior was carried out. Dogs diagnosed with IE, with a seizure frequency of at least 3 seizures in the past 3months (n=21), were fed the MCTD or placebo diet for 3months and were then switched to the alternative diet for 3months. Owners completed a validated behavioral questionnaire to measure 11 defined behavioral factors at the end of each diet period to report their dogs' behavior, with three specific behaviors hypothesized to be related to ADHD: excitability, chasing, and trainability. Results: The highest scoring behavioral factors in the placebo and MCTD periods were excitability (mean±SE: 1.910±0.127) and chasing (mean±SE: 1.824±0.210). A markedly lower trainability score (mean±SE: 0.437±0.125) than that of previously studied canine populations was observed. The MCTD resulted in a significant improvement in the ADHD-related behavioral factor chasing and a reduction in stranger-directed fear (p<0.05) compared with the placebo diet. The latter effect may be attributed to previously described anxiolytic effects of a KD. Conclusions: These data support the supposition that dogs with IE may exhibit behaviors that resemble ADHD symptoms seen in humans and rodent models of epilepsy and that a MCTD may be able to improve some of these behaviors, along with potentially anxiolytic effects.
    Full-text · Article · Feb 2016 · Epilepsy & Behavior
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    • "It is not known whether the theta/beta ratio can distinguish children with both ADHD and epilepsy from children who have epilepsy but not ADHD. Given that ADHD is especially prevalent in children with epilepsy (Hermann et al., 2007), this question is clinically relevant. "
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    ABSTRACT: Objective: To determine correlations of the EEG frequency spectrum with neuropsychological status in children with idiopathic epilepsy. Methods: Forty-six children ages 8-18years old with idiopathic epilepsy were retrospectively identified and analyzed for correlations between EEG spectra and neuropsychological status using multivariate linear regression. In addition, the theta/beta ratio, which has been suggested as a clinically useful EEG marker of attention-deficit hyperactivity disorder (ADHD), and an EEG spike count were calculated for each subject. Results: Neuropsychological status was highly correlated with posterior alpha (8-15Hz) EEG activity in a complex way, with both positive and negative correlations at lower and higher alpha frequency sub-bands for each cognitive task in a pattern that depends on the specific cognitive task. In addition, the theta/beta ratio was a specific but insensitive indicator of ADHD status in children with epilepsy; most children both with and without epilepsy have normal theta/beta ratios. The spike count showed no correlations with neuropsychological status. Conclusions: (1) The alpha rhythm may have at least two sub-bands which serve different purposes. (2) The theta/beta ratio is not a sensitive indicator of ADHD status in children with epilepsy. (3) The EEG frequency spectrum correlates more robustly with neuropsychological status than spike count analysis in children with idiopathic epilepsy. Significance: (1) The role of posterior alpha rhythms in cognition is complex and can be overlooked if EEG spectral resolution is too coarse or if neuropsychological status is assessed too narrowly. (2) ADHD in children with idiopathic epilepsy may involve different mechanisms from those in children without epilepsy. (3) Reliable correlations with neuropsychological status require longer EEG samples when using spike count analysis than when using frequency spectra.
    Full-text · Article · Aug 2015 · Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology
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    • "However, ADHD symptoms often appear before seizure onset [17], suggesting that the seizures and their treatment may not have much to do with the psychiatric comorbidity. Hermann et al. [18] reported 23 patients with ADHD and new-onset epilepsy: in 19, ADHD symptoms preceded seizure onset. An epidemiologic study showed that the risk of epilepsy was 2.5 times greater in children who had already developed ADHD symptoms [5]. "
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    ABSTRACT: Comorbidity between difficult-to-treat epilepsies and ADHD is frequent and impacts negatively on quality of life. The commonly held (yet poorly substantiated) view that stimulants may worsen seizure control has prevented studies from evaluating the impact of such treatment in this population. Our aim was to study the effect of methylphenidate on the quality of life of children and adolescents with difficult-to-treat epilepsies and comorbid ADHD. The study was an open-label, noncontrolled trial with intention-to-treat analysis following 30 patients for 6months. Subjects received methylphenidate following 3months of baseline, during which antiepileptic drugs (AEDs) were adjusted and epilepsy, ADHD, and quality-of-life variables were assessed. Multivariate regression analysis identified the main variables correlated with outcome. Only one patient withdrew because of seizure worsening. Following methylphenidate introduction, doses were titrated up to 0.40-0.50mg/kg/day. A marked improvement in quality-of-life scores and a significant reduction in seizure frequency and severity were observed. Female sex, reduction of core ADHD symptoms, and tolerability to adequate doses of methylphenidate were significantly associated with improved quality-of-life scores. These preliminary data suggest that methylphenidate treatment is safe and effective in patients with ADHD and difficult-to-treat epilepsies, positively impacting on quality-of-life scores. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · May 2015 · Epilepsy & Behavior
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