Should cognitive assessment be performed on children newly diagnosed with epilepsy?

Seizures and epilepsy are frequent chronic neurologic disorders in children with varying degrees of severity and a variety of associated disorders or comorbidities. The psychosocial impact of epilepsy on the affected child’s and family’s function in everyday life may be significant and far-reaching. Chronic uncontrolled epilepsy in children is a significant risk for deficits in cognitive, emotional, behavioral, social and family functioning.

In an ideal world with unlimited resources and expertise the answer to the above question is simply ‘yes’. All children with epilepsy should have at least one cognitive assessment (CA), preferably early after seizures have started, in addition to follow-up assessments, when clinically indicated, in order to track changes from baseline that require intervention. However, we do not live in an ideal world and resources and suitably qualified psychologists are in all too limited supply. So, why should we even ask the question? The short answer is that there are sufficient data showing that epilepsy is a chronic condition of the brain, putting children at significant risk for developing a number of cognitive, behavioral, psychiatric, academic and social difficulties. However, not every child is at equal risk and so testing every child would squander valuable resources that are needed for patients who will truly benefit from CA. Therefore, we cannot afford to use CA as a fishing expedition, but need to use a targeted approach based on risks and probabilities.

Therefore, begging the question – is there a way that we can stratify the risk for cognitive and psychosocial dysfunction for the individual child in the daily clinical setting, short of waiting for a child with epilepsy to develop difficulties at school, in the family or functioning with peers? Are there any tools that can guide us to screen early for comorbidities and earmark the at-risk child to facilitate early referral to suitably qualified experts? The successful management depends on a well-orchestrated interdisciplinary group of experts, which may include the pediatrician, child neurologist and epileptologist, social worker, psychologist, psychiatrist, educators and other therapists, who can treat and guide the patient and family longitudinally to ultimately improve on the long-term prognosis and quality of life of children with epilepsy.

Currently when children present with new-onset seizures, the evaluation usually focuses on the EEG and MRI to diagnose the underlying etiology and the epilepsy syndrome the child may have. This aids appropriate medical management with antiepileptic medication and early selection for surgical treatment in suitable cases. Defining the epilepsy syndrome early on gives us some idea of treatability, as well as risks for refractoriness to therapy and points to the indication for other forms of therapy, such as the ketogenic diet or vagal nerve stimulation.

Routine CAs are not performed regularly in children with epilepsy that are managed medically and there is no expert agreement on the timing and circumstances in which CA should be ordered.

Cognitive assessment is an important tool in the presurgical evaluation of pediatric and adult patients with refractory epilepsy to assess baseline function and surgical risks for additional cognitive deficits. Studies in pediatric surgical cohorts have shown that early-onset and longer duration of epilepsy are over-riding risk factors for low preoperative general cognitive ability, as well as long-term recoverability after successful surgical seizure remission. These detrimental prognostic factors have become a driving force for early patient selection for surgery in infants and young children who have surgically remediable epilepsy to specialized epilepsy surgery centers [1].

In their recent article entitled ‘Should every child with epilepsy undergo a neuropsychological evaluation’, Buelo and McNelis address the question of this editorial with the following ‘rational’ arguments [2].

Cognitive assessment in every child with epilepsy allows us to screen for early detection of cognitive dysfunction and pick up children that are at risk; to diagnose children who are slow learners due to borderline or low IQ or learning disability; to define the reasons for learning problems by identifying specific learning disabilities, which may be subtle but have significant influence on academic achievement; to implement educational interventions in addition to modifying medical management where possible to improve cognitive outcome; to understand social adaptation problems associated with cognitive dysfunction; and to identify special educational needs to facilitate early and appropriate referral within special educational assistance programs of the school system.

In some epilepsies, cognitive changes may fluctuate and increase over the disease course, for example, patients with catastrophic epilepsy, electrical status epilepticus, so that the use of CA offers important tracking information. Early CA will give the clinician, family and educators a point of reference, particularly in cases where we may expect progressive cognitive decline. School failure reinforces a negative sense of self and early identification and intervention may result in a more positive and effective learning experience. Some of the comorbidities associated with epilepsy, including depression, particularly in adolescents, may go undetected even by parents and CA may uncover this, in addition to issues of poor self-esteem and a sense of being stigmatized in school. A systematic behavioral assessment offers the basis for appropriate management.

This being said, however, are there are also arguments in favor of limiting CA in children with epilepsy, especially with new-onset seizures? There is the issue of substantial costs and finite resources, as well as the short supply of suitably qualified personnel who usually work in the setting of an epilepsy center. In addition, there is a real concern for parents that routine testing may lead to labeling and overdiagnosing problems that may not turn out to have clinical significance. This would add an unnecessary and additional burden for the patient and family and needs to be avoided at all costs. Most children with epilepsy do not fail at school so that detailed CA is not clearly indicated in this type of setting. However, children who have epilepsy syndromes associated with cognitive decline should be targeted for early and repeated CA to track changes in cognitive and behavioral profile. We could not agree more with the authors when they state that we can only ensure appropriate referrals for CA by convincing medical providers of the usefulness of CA for children that need it and will benefit from referrals to address the individual areas of dysfunction.

A number of recent studies have given us surprising and unexpected data about behavioral difficulties and lower cognitive abilities in children with new-onset seizures compared with age-matched peers without seizures [3–5]. A recently published prospective study by Fastenau et al. has shown that 27% of children may exhibit neuropsychological deficits at or near the onset of a first seizure [3]. The risk may increase up to 40% in children with multiple seizures who have a symptomatic or cryptogenic etiology, are on antiepileptic medication and have abnormal electroencephalograms due to epileptiform discharges. These data may have important implications for clinical management and are a strong argument for CA in children with new-onset seizures who have multiple risk factors for neuropsychological deficits, which may include deficiencies in attention, executive function, memory and language. This study did not confirm differences in academic achievement between the epilepsy cohort and the control siblings, as some other studies have shown. These earlier studies, however, included younger patients with more severe catastrophic epilepsies associated with developmental delay (all patients with IQ ≤70 were excluded in the Fastenau et al. study) and later testing after onset, representing changes across a timeframe after onset of seizures. Therefore, these data may imply a window of opportunity for early diagnosis and intervention to reduce the cumulative effect of neuropsychologic dysfuction on academic performance. In our judgment, this is very compelling data supporting the argument that cognitive assessment should be performed on children with newly diagnosed epilepsy that have the aforementioned risk profile for cognitive difficulties.

What do we know about the impact of childhood-onset epilepsy for adulthood? A large population-based longitudinal study by Sillanpää et al. has shown that childhood-onset epilepsy may have a persistent long-term adverse impact on health-related quality of life into adulthood [6]. This includes adverse consequences on employment, obtaining a driver’s license and prospects of marrying and having children. In particular the need for continued use of antiepileptic medication as opposed to the epilepsy diagnosis per se appears to impact most on social functioning later in life [6]. What can we do to minimize the potential for the acute and long-term negative impact of antiepileptic drugs (AEDs) on cognitive and social functioning in children with epilepsy?

Antiepileptic drugs exert their pharmacologic effect of preventing seizures by reducing neuronal hyperexcitability. In addition, unwanted adverse effects are known to occur through a number of direct and indirect mechanisms, which may be dose-dependent or idiosyncratic. Cognitive, psychiatric and behavioral side effects of AEDs have been extensively reported in children with epilepsy treated with AEDs, but reviewing the literature it is difficult to determine the actual incidence of AED psychiatric and behavioral side effects, as direct comparisons are often not possible. However, for the newer generation drugs that have been released since 1993, including felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate and zonisamide, side-effect data are more comprehensive from rigorous clinical trial evaluations, although few studies are actually randomized controlled clinical trials for monotherapy or adjunctive therapy AED use [7]. In general terms, behavioral and psychiatric side effects are less likely to occur in patients receiving AED monotherapy, which obtains good seizure control and has minimal clinical evidence of other neurologic dysfunction. Higher rates of negative behavior and depression have been noted with AEDs that have a strong GABAergic component as the mechanism of action, for example, phenobarbitol and benzodiazepines. Similarly, higher rates of positive behavior are seen with AEDs that do not have a GABAergic component to their mechanism of action, for example, carbamazepine, lamotrigine and valproic acid. A rare but dramatic type of idiosyncratic cognitive and psychiatric side effect is acute psychosis with delusions, mood changes, hypomania and mania, anxiety with depersonalization or even conversion reactions.

Indirect effects of AEDs on behavior may be potentiated via the P450 enzyme system, which may be induced by AEDs, such as phenobarbitol, primidone, phenytoin and carbamazepine, resulting in an increased clearance of many medications, including tricyclic antidepressants. Therefore, children with epilepsy and drug-controlled depression may have worsening comorbidity due to a previously effective antidepressant dose losing effectiveness via interaction between the enzyme-inducing AED and tricyclic antidepressant. By contrast, inhibitors such as valproate may result in toxic levels of anxiolytics, such as diazepam or alprazolam, which rely on the P450 enzyme pathway for their metabolism. These interactions may be minimized using nonenzyme-inducing newer generation drugs, such as gabapentin or levetiracetam [7].

All these considerations need to impact on the choice and dosage regimen of AEDs used in children with epilepsy, in addition to considering the specifics of the epilepsy, which may include the seizure types that need primary treatment, the syndromic features and associated comorbidities that may be risk factors for aggravation of cognitive and psychiatric side effect profiles. CA is extremely helpful in this clinical setting and should be utilized to avoid long-term chronic toxicity.

As mentioned above, recent studies have shown that children with new-onset epilepsy may have significant cognitive deficits and are highly vulnerable for academic and school difficulties [3–5].

The impact of epilepsy on a child’s and family’s everyday life may depend on several factors, including the severity and type of seizures, the efficacy and adverse reactions of clinical management, the restriction of activities due to illness, the coping abilities and the level of social support and resources available to deal with the impact of illness issues [8].

In general terms, 80% of children with new-onset epilepsy will have good seizure control on medication; however, they will need to take medication regularly.

These children will have epilepsy only, without associated symptoms, and are generally well adjusted in distinction to children with ‘epilepsy plus’ [9]. Children with continued seizures form a subgroup of children (epilepsy plus) that will have significantly more problems with cognitive function, behavior and neurologic dysfunction, earlier age of onset, higher seizure frequency, more medication use and increased physician visits, surgery and ketogenic diet.

How can we screen for these problems without doing a full CA in every patient, but pick up on the at-risk child?

A recently developed scoring instrument reported by Camfield and coauthors is brief and well validated to rate the impact of epilepsy and is helpful in determining the ‘burden’ of illness on various domains, including relationships with siblings, peers, self-esteem, restrictions and family coping [9]. This information can be utilized to select patients for more detailed and costly CA to address therapeutic needs with targeted resources for intervention.

In addition, information that monitors medication side effects, school difficulties, intrafamilial tensions and social economic problems affecting quality of life may be useful to help children and their families cope with the burden of epilepsy [8].

“The chief business of the chronically ill person is not just to stay alive and to keep his symptoms under control, but to live as normally as possible, despite the symptoms and the disease” [10].

As healthcare providers this is also our chief business in caring for children with epilepsy. By appropriately screening children with epilepsy who are at risk for cognitive and behavioral dysfunction and referring them early for CA, we strongly believe that we may improve the social prognosis of each individual child.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.