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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    • "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.
    Epilepsy & Behavior 05/2015; 46. DOI:10.1016/j.yebeh.2015.02.019 · 2.26 Impact Factor
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    • "The amygdala has previously been reported to show either no significant changes in gray matter volume [Castellanos et al., 1996; Filipek et al., 1997] or a decrease in volume [Lim et al., 2013; Plessen et al., 2006]. There are fewer known group level abnormalities in white matter as it is less frequently investigated using structural MRI [Hermann et al., 2007]. Although no differences in white matter volume were reported in one small study [Carmona et al., 2005], a larger study described significantly reduced total white matter volume and significant reductions in the frontal, parietal, temporal, and occipital lobes in ADHD [Castellanos et al., 2002]. "
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    ABSTRACT: Despite extensive research, psychiatry remains an essentially clinical and, therefore, subjective clinical discipline, with no objective biomarkers to guide clinical practice and research. Development of psychiatric biomarkers is consequently important. A promising approach involves the use of machine learning with neuroimaging, to make predictions of diagnosis and treatment response for individual patients. Herein, we describe predictions of attention deficit hyperactivity disorder (ADHD) diagnosis using structural T1 weighted brain scans obtained from 34 young males with ADHD and 34 controls and a support vector machine. We report 93% accuracy of individual subject diagnostic prediction. Importantly, automated selection of brain regions supporting prediction was used. High accuracy prediction was supported by a region of reduced white matter in the brainstem, associated with a pons volumetric reduction in ADHD, adjacent to the noradrenergic locus coeruleus and dopaminergic ventral tegmental area nuclei. Medications used to treat ADHD modify dopaminergic and noradrenergic function. The white matter brainstem finding raises the possibility of “catecholamine disconnection or dysregulation” contributing to the ADHD syndrome, ameliorated by medication. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2014; 35(10). DOI:10.1002/hbm.22542 · 5.97 Impact Factor
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    • "Up to 70% of ASD cases (74) and 38% of children with epilepsy exhibit ADHD (75–77). ADHD is significantly more common among children with newly diagnosed epilepsy than among controls suggesting that there is a common antecedent for both conditions (78, 79). "
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    ABSTRACT: Numerous neurological disorders including fragile X syndrome, Down syndrome, autism, and Alzheimer's disease are co-morbid with epilepsy. We have observed elevated seizure propensity in mouse models of these disorders dependent on diet. Specifically, soy-based diets exacerbate audiogenic-induced seizures in juvenile mice. We have also found potential associations between the consumption of soy-based infant formula and seizure incidence, epilepsy comorbidity, and autism diagnostic scores in autistic children by retrospective analyses of medical record data. In total, these data suggest that consumption of high levels of soy protein during postnatal development may affect neuronal excitability. Herein, we present our theory regarding the molecular mechanism underlying soy-induced effects on seizure propensity. We hypothesize that soy phytoestrogens interfere with metabotropic glutamate receptor signaling through an estrogen receptor-dependent mechanism, which results in elevated production of key synaptic proteins and decreased seizure threshold.
    Frontiers in Neurology 09/2014; 5:169. DOI:10.3389/fneur.2014.00169
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