Children with epilepsy show a diminished capacity for sustained attention (Besag, 2002; Sanchez-Carpentero & Neville, 2003; Torres et al., 2008). Permanent factors, such as structural brain abnormality or genetic factors, may underlie the reduced attention in some cases (Kolk et al., 2001; Sanchez-Carpentero & Neville, 2003; McLellan et al., 2005; Hermann et al., 2007; Torres et al., 2008; Bechtel et al., 2009). Yet, there is also a large number of patients in whom easily modifiable factors that impair attention can be identified. Common factors include: the use of particular antiepileptic drugs (AEDs), frequent periictal periods, and dysphoric emotional states (Weinberg & Emslie, 1991; Neville, 1999; Besag, 2002; Sanchez-Carpentero & Neville, 2003; Torres et al., 2008; Hamoda et al., 2009). Optimal management therefore addresses seizure-related, AED-related, and psychological factors that impair attention. It is advisable to use an AED that combines effectiveness with a low risk for inducing inattention, and to avoid polypharmacy (National Institute for Health & Clinical Excellence, 2008, 2012). Where attention difficulties persist despite the above strategies, behavioral and pharmacologic treatment for attention deficit hyperactivity disorder (ADHD) should be considered.
ADHD is an important cause of inattention and reduced quality of life in children with epilepsy, affecting 12–20% (Steffenburg et al., 1996; Davies et al., 2003; see Kaufmann et al., 2009 for review). Among children with epilepsy, ADHD is more common and more severe in the subset who have complex epilepsy, defined as epilepsy associated with additional neurologic impairments (Hoare, 1993; Sherman et al., 2007). Making the diagnosis of ADHD in children with epilepsy is clinically important, as it is now recognized that specifically treating ADHD improves attention in children with epilepsy (see Torres et al., 2008 for review). The treatment of ADHD comprises behavioral intervention and, if needed, a stimulant such as methylphenidate (MPH) or dexamphetamine; or a noradrenaline re-uptake inhibitor such as atomoxetine (MTA Co-operative group, 1999; Barkley, 2003; National Institute for Health & Clinical Excellence, 2008, 2012; Baptista-Neto et al., 2008; Gonzalez-Heydrich et al., 2010). The most commonly used stimulant, MPH, appears to improve ADHD symptoms in 70–80% of children with well-controlled epilepsy and ADHD (Gross-Tsur et al., 1997; for review see: Tan & Appleton, 2005; Koneski et al., 2011)—a similar efficacy to that found in the general population. There are case series in which seizure exacerbation has been reported with use of MPH (Gross-Tsur et al., 1997; Hemmer et al., 2001; Gonzalez-Heydrich et al., 2004). There are, however, no randomized controlled trials that show an increased seizure frequency or severity in patients with epilepsy who are treated for ADHD with MPH. Current evidence from retrospective chart studies, open-label trials, and controlled trials does not support the view that MPH increases seizure frequency in well-controlled epilepsy (Gross-Tsur et al., 1997; Baptista-Neto et al., 2008; Torres et al., 2008).
There is, however, less evidence regarding the use of MPH in children with difficult-to-control epilepsy and learning disability (LD) (Simonoff et al., 2006) (LD refers to permanent impairments of cognitive function having onset in childhood, a term equivalent to ‘mental retardation’ Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] or intellectual ‘disability’ [DSM V] in the North American usage). Population prevalence studies of ADHD in this patient group are unavailable, but in tertiary clinic populations of children with epilepsy that is difficult-to-control and associated with LD, ADHD may be present in 30–40% (Hempel & Frost, 1995; Semrud-Clikeman & Wical, 1999; Dunn et al., 2003). There is clinical uncertainty regarding the efficacy of the pharmacologic management of this patient group (Torres et al., 2008). There are no published randomized controlled trials (RCTs) or cohort studies specifically addressing the use of MPH in this group. These patients are commonly excluded from major MPH treatment studies (MTA Co-Operative group, 1999; Abikoff et al., 2004). There are concerns about MPH aggravating seizures, and whether adverse effects are increased in children with complex epilepsy (Gross-Tsur et al., 1997; Gonzalez-Heydrich et al., 2010). This group of children with difficult-to-control epilepsy has additional impairments including psychiatric syndromes, neurologic deficits, and LD.
This study helps to bridge this gap. The clinical experience with MPH for treating ADHD in children with severe LD and difficult-to-control epilepsy over a 7-year period (1998–2005) at a national center for epilepsy and LD was reviewed. MPH treatment efficacy was assessed, and the incidences of deterioration of seizure frequency and medication discontinuation due to adverse effects were monitored.
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- Supporting Information
There is overwhelming evidence for the benefit of MPH in ADHD in the literature (MTA Co-Operative Group, 1999) and significant evidence that such benefits apply to those with a LD (Handen et al., 1990, 1992) and in general to children with epilepsy (Gonzalez-Heydrich et al., 2010). This small study of children with intractable epilepsy and severe LD fills a gap in showing, perhaps not surprisingly, that similar benefits apply to this group, with a minority incurring adverse effects. The response rate to MPH treatment was 61% in this pediatric sample with ADHD, severe epilepsy, cognitive impairment, and a high rate of psychiatric comorbidity. The rate of adverse effects leading to discontinuation of medication was comparable to that reported in children with primary ADHD. There was no statistical evidence that the treatment of ADHD with MPH directly increased the seizure rate for the majority of patients with refractory epilepsy.
The treatment of ADHD in young people with learning disability and complex epilepsy under specialist care using behavioral interventions and MPH may improve ADHD symptoms without causing a clinically significant increase in seizure frequency. The lack of use of MPH in this group would seem to result from lack of recognition of ADHD and an exaggeration of original concerns that MPH might aggravate seizures. We suggest that, although this is a small study, there is not a strong case for a larger one but that these patients should have the benefit of consideration of this treatment. Children with epilepsy and LD should be evaluated for ADHD, as this may be underrecognized; meanwhile they stand to benefit from multimodal treatment for ADHD. The available data do not exclude a small number of children with epilepsy experiencing an increase in seizures. This study, although not an RCT, would be helpful to clinicians and parents concerned about possible adverse reactions.