Cognitive problems among children with epilepsy are of paramount concern. Cognition includes a variety of skills such as intelligence, attention, learning, remembering, reasoning, judging, planning, and expressing and understanding language. One’s proficiency in these processes can influence other aspects of function such as behavior and social skills. During development, the maturation of cognitive processes is protracted, extending from infancy though to adolescence, and for more complex aspects of cognition such as executive function, even into young adulthood. Thus, in youth with epilepsy, seizures occur during a long window of time that is essential for the development of basic and complex cognitive skills that form the core foundation for long-term educational, vocational, and interpersonal adaptation.¹

Deficits in cognition are identified by children with epilepsy and their parents as a significant comorbidity. For example, in a study by Arunkumar et al,² parents of 80 children and adolescents with epilepsy were asked to list in order of importance their concerns about living with or caring for their children with epilepsy; children who were old enough to be interviewed were asked to express (independently of their parents) their own concerns about having epilepsy. For both parents and children, the second most common item identified was that of the cognitive effects of epilepsy. Their worries included learning disabilities, academic difficulties, poor attention and concentration, and impoverished memory.

Cognitive deficits appear to be present early on in the course of epilepsy and may even predate the onset of seizures. A study of children with idiopathic localization-related or primary generalized epilepsy approximately 10 months after seizure onset revealed a pattern of mild generalized cognitive difficulties.³ It is thought that these deficits are related to structural brain anomalies. For example, in children evaluated soon after they experienced their first seizure, those with an abnormality detected on MRI performed more poorly on cognitive tasks than children without a significant brain abnormality.⁴ These differences were widespread, and were found in the areas of intelligence, memory, language, processing speed, verbal learning and memory, and executive functions, with all these domains affected relatively equally. Cognitive deficits early in the course of epilepsy are especially pronounced in children with neurobehavioral comorbidities.⁵

The severity and duration of epilepsy are also important in determining the incidence and magnitude of cognitive deficits in children. There is evidence that childhood onset temporal lobe epilepsy is associated with adverse neurodevelopmental impact on both brain structure and function.⁶ Patients with childhood onset seizures exhibited greater compromise across domains of cognitive performance and showed a substantial reduction in brain tissue volumes in extratemporal regions compared with patients with late onset temporal lobe seizures. Those patients with structural abnormalities at onset may be especially vulnerable to the long-term adverse effects of epilepsy.⁴ Scores on neuropsychological tests were not related to EEG activity in children with recent onset epilepsy; however, in children with chronic epilepsy, the presence of slow wave activity was associated with memory impairment.⁷ The authors speculated that the differences between the recent-onset and chronic samples represent a cumulative effect of neurophysiological abnormality on cognitive development.

Although the majority of people with epilepsy have normal intelligence, the distribution of IQ scores is skewed toward lower values.^8,9,10,11 A study of 51 children with medically refractory epilepsy illustrated the wide range of cognitive functioning within this group.¹² The mean IQ was 84 (in the Low Average range, just over one standard deviation below the population mean of 100). The spread of IQ scores was considerable, spanning the Intellectually Deficient range (<1st percentile) to the Very Superior range (>99th percentile). In a community based sample of children followed for 10 years after diagnosis of epilepsy, 24% had IQs below the normal range.¹³ In a study designed to document the occurrence of disabilities in an unselected population sample of children in Finland, 4–15 years of age, Sillanpaa¹⁴ reported that the prevalence of epilepsy in the study population was 0.68%. Among the children with epilepsy, neurological deficit was found in 39.9%, the most frequent neurological impairments being mental retardation (31.4%), speech disorders (27.5%), and specific learning disorders (23.1%).

Even in individuals with normal intelligence, reports of deficits in specific aspects of neuropsychological functioning are common, particularly in the areas of attention and concentration, memory, executive function, and academic achievement. In this chapter, we review the evidence for problems in the areas of attention, memory, and executive function; we will also briefly address language function in children with epilepsy, although this area has not received as much research examination as the others. For each of these topics, we provide some practical suggestions to assist parents and teachers in the management of the cognitive dysfunction. These recommendations are not meant to be exhaustive. It must also be recognized that they will not apply to every child with epilepsy, as the patterns of cognitive strengths and weaknesses are quite individual. In the ideal situation, recommendations will be generated from an in-depth neuropsychological assessment of the child’s abilities in multiple areas. We do not cover the area of academic achievement in any depth, as it is addressed in the chapter on “ADHD and Learning Disabilities” by Dunn and Bourgeois elsewhere in this book.

There is no clear and universally accepted definition of attention. One of the most explicit definitions comes from Lezac, Howieson, and Loring¹⁵ who proposed that attention includes a collection of interrelated mechanisms underlying the organism’s receptivity to stimuli and how it processes incoming excitation (whether internal or external). There are different kinds of attention. First, selective attention directs one’s focus toward a target while ignoring nonrelevant stimulations. Sustained attention is the ability to maintain attention for a relatively long period of time in order to detect an infrequent event. Finally, divided attention is the capacity to share attentional resources into multiple and simultaneous stimuli. Based on the nature of the stimulus, attention is usually divided in terms of auditory and visual modalities. For instance, focusing on what a teacher is saying in a classroom refers to auditory attention whereas looking at graphics and figures on the blackboard would recruit visual attentional resources. Multiple cerebral regions are reported to be involved in attentional processing such as the reticular formation, prefrontal cortex, parietal regions, cingulum, and several cortical and subcortical networks.¹⁴

Attention deficits have been shown to be more frequent in the pediatric epilepsy population than in healthy children, or in other chronic pediatric ailments such as diabetes or heart disease.^17,18 Indeed, clinical studies report that 30%–40% of children with epilepsy also have attention deficit hyperactivity disorder (ADHD).^19,20 The reasons for this association are still unclear. Some hypothesis, such effects of antiepileptic medication, underlying neurodevelopmental vulnerability, effects of chronic seizures, and subclinical epileptiform activity on cognitive function and possible common genetic defect underlying both disorders, have been suggested.^21,22 Difficulties in sustaining attention are most consistently reported in the epilepsy literature.²³ For instance, children with absence seizures present with sustained attention deficits.²⁴ Patients with childhood absence epilepsy and juvenile myoclonic epilepsy (JME) have lower scores on sustained and selective attention tests than control participants.²⁵ Children with idiopathic generalized epilepsy exhibit significantly lower performance at visual and auditory attention tasks compared to healthy children.²⁶

Data on attention profiles of different epilepsy types are variable. In fact, attention problems are not only associated with generalized epilepsy but also with focal epilepsy. For example, Pinton et al²⁷ showed impairments in children with benign childhood epilepsy with centrotemporal spikes (BECTS) compared to the normal age range. Hernandez et al²⁸ investigated attention capacities in children suffering from three different types of epilepsy (frontal lobe epilepsy, temporal lobe epilepsy, and generalized absence seizures). They showed that a deficit in sustained attention was present in all three groups compared to a control group of the same age and IQ. However, children with frontal lobe epilepsy presented significantly greater sustained attention deficits, and also visual attention problems, compared to the two other epileptic groups. Furthermore, in a questionnaire, parents of children with frontal lobe epilepsy described their child as more inattentive than parents of children with temporal lobe epilepsy or generalized absence seizures. Similarly, in a case study, Boone et al²⁹ described a 13-year-old girl with bilateral frontal foci who showed considerable fluctuation in auditory attention and working memory. Moreover, Jambaqué and Dulac³⁰ observed an important attention deficit on an auditory continuous performance task and a visual cancellation task in an 8-year-old boy with an epileptic focus in the right frontotemporal region. Impaired performance on the same auditory continuous performance task has also been reported for children with benign focal childhood epilepsy.³¹ Children with frontal lobe epilepsy have more problems resisting interference from a distracter than do children with temporal lobe epilepsy or healthy children.³² The fact that frontal lobe epilepsy is frequently associated to attention deficits might be explained by the significant involvement of the prefrontal cortex in attention control.³³ Attention deficits are commonly reported in patients with frontal lesions, and appear to be attributable to a difficulty ignoring irrelevant stimuli.³⁴ Although attention deficits seem to be frequently related to frontal epilepsy, the attention profile related to epilepsy involving other cerebral regions is heterogeneous, probably because there are multiple factors that can interfere with the neuropsychological portrait (antiepileptic medication, age at the onset, and duration of epilepsy, kind of seizures, and so on.).

Thus, attention skills seem to be vulnerable to various epileptic disorders. This cognitive function is also sensitive to some anticonvulsive medication. In some cases, attention problems seem to be elicited or exacerbated by antiepileptic drugs such as phenobarbital, benzodiazepines, topiramate, valproate, and vigabatrin³⁵ whereas lamotrigine does not seem to have any negative effects on attention.³⁶ Lamotrigine as an add-on therapy has even been reported in some cases to enhance attention, alertness, and emotional stability.³⁷ Furthermore, polypharmacotherapy has been reported to induce more attention and memory problems than monopharmacotherapy.³⁸ Bennett-Levy and Stores³⁹ showed that children who no longer took antiepileptic drugs and attended regular school displayed a decreased alertness compared to healthy classmates. However, those children still under antiepileptic therapy also presented a decreased alertness and scored lower than healthy children in concentration and mental processing measures. Based on these studies, the choice of the pharmacological therapy is a concern and should be made considering possible cognitive side effects.

STRATEGIES FOR TREATMENT OF ATTENTIONAL DEFICITS

Attention deficits, without intellectual disability, constitute a significant predictor of academic difficulties in children with epilepsy.⁴⁰ Treatment and intervention plans thus are very important. Because better seizure control may be associated with cognitive improvement,⁴¹ a first step is the reevaluation of seizure control through a review of the antiepileptic drug regime. Second, some studies have shown that surgery may improve attention skills,^42,43 presumably by a reduction of seizure frequency.⁴⁴ However, Smith et al⁴⁵ did not find any cognitive changes in children who underwent epilepsy surgery. Thus, while the possibility of surgery should be investigated for appropriate candidates, one must keep in mind that the benefits to attention or other cognitive functions may be minimal. Psychostimulant medication would also be an option that should be investigated by a physician. (See Chapter of Dunn and Bourgeois in this book for a complete discussion on this topic). However, a combination of pharmacologic and behavioral approaches has been shown to be the most effective with children presenting with attention deficits.

Cognitive rehabilitation methods can also be used to improve attention in children with epilepsy. Rehabilitation programs could be designed for each patient based on their environmental and familial context, diagnosis, neuropsychological assessment, and the attention component, which is particularly impaired. In a literature review on attention rehabilitation, Sturm and Leclercq⁴⁶ presented different attention retraining interventions that have been used with adult populations (brain injury, strokes, psychosis, and so on). The programs included computerized attention tasks or behavioral tasks in a laboratory setting and the duration of the intervention varied from a few weeks to 6 years. Most of them produced a significant enhancement of attention skills in neuropsychological tests, but the impact on daily life was not always clear. The authors concluded that attention retraining treatments must be specific to the deficient attention component (e.g., selective attention, sustained attention, or divided attention), because a lack of specificity could overload the attention system and then magnify the impairment.⁴⁷

Improvement of attention skills after retraining has also been shown to improve other cognitive domains such as memory or executive functions,^48,49 probably because attention is an important element to their execution. Very few studies have been conducted on cognitive rehabilitation, however, and the populations under study, the protocols used and even the results are heterogeneous. To our knowledge, no study has yet been carried out on attention deficit rehabilitation in pediatric epilepsy, and only a few investigations have included adult epileptic patients.

In a case study, Gupta and Naorem⁵⁰ applied a neurorehabilitation program including cognitive retraining (attention, concentration, and memory), supportive therapy and relaxation therapy, to a 32-year-old man with epilepsy, and the results suggested that attention retraining and home intervention could provide substantial benefits to patients with epilepsy. The effectiveness of two methods used for rehabilitation of attention deficits, one aimed at retraining impaired cognitive function, and one aimed at teaching compensatory strategies, was evaluated in an adult population with focal epilepsy.⁵¹ Both methods enhanced attention function and quality of life in this population compared to a waiting list control group. The compensatory method was more effective in improving quality of life, especially for patients with less education (≤11 years). The authors concluded that cognitive rehabilitation programs are effective for patients with focal epilepsy and attention problems and should be incorporated into comprehensive care programs.

Further research is needed before introducing attention rehabilitation programs as part of the regular clinical interventions with children with epilepsy. Nevertheless, some compensatory methods could readily be applied by parents and teachers. In this context, information concerning epilepsy and the child’s abilities should be given early to parents and teachers.⁵² Based on an interdisciplinary assessment, including neuropsychological assessment and questionnaires, an intervention plan and tailored recommendations can be established.

Level of education may be an essential part of rehabilitation of attention deficits. In a recent study conducted with adults presenting with JME, Pascalicchio et al⁵³ showed less severe cognitive deficits including attention problems in patients with a higher educational level (>11 years) than in patients who had a lower educational level (≤11 years). Conversely, the cognitive deficits may have limited the educational attainments; sustained attention deficits are predictive of academic failure, possibly even more so than memory dysfunction or socioeconomic status.⁵⁴ It is thus very important to provide strategies and create a favorable learning environment at home and at school to maximize school achievement.

Table 40–1 presents a list of some recommendations and advices that can be provided to parents and teachers with regard to attention problems.

Executive functions represent a cognitive construct that refers to the abilities necessary to maintain an appropriate problem-solving set for the attainment of future goals.⁵⁵ These abilities include planning, self-monitoring, organized search, concept formation, attention and impulse control⁵⁶ as well as working memory.⁵⁷ Executive dysfunction is associated with behavioral disturbance, social dysfunction, and reduced educational and occupational attainment,¹⁵ and is frequently reported in the neuropsychological profile of children with epilepsy.⁶⁸

The involvement of prefrontal cortex in executive functioning has been shown in a variety of studies of normal subjects and patients with lesions to the frontal lobes.⁵⁹ Frontal lobe epilepsy can also induce executive dysfunction⁶⁰ and may be more prone to elicit it than other types of focal epilepsy. Hernandez et al⁶¹ compared the performance of children (aged between 8 and 16 years) with frontal lobe epilepsy, temporal lobe epilepsy, and generalized epilepsy on a battery of tests assessing executive functions. Children with frontal lobe epilepsy showed greater difficulties in planning, impulse control, mental flexibility, and complex motor sequence programming than children with other types of epilepsy. Younger children (8–12 years old) with frontal lobe epilepsy had greater “executive” deficits compared to the older ones (13–16 years old). They also showed limited lexical access in a verbal fluency task, a finding congruent with case studies. The 8-year-old child with frontal lobe epilepsy studied by Jambaqué and Dulac³⁰ showed impairment in verbal fluency, whereas the 13-year-old frontal lobe epilepsy patient described by Boone et al²⁹ did not. Young patients with frontal lobe epilepsy seem to have greater difficulties mobilizing their resources to initiate the verbal search. Thus, the impact of frontal lobe epilepsy on some executive functions may be greater when the frontal lobes are still at an early stage of development.

Compared to children with temporal lobe epilepsy or generalized epilepsy, children with frontal lobe epilepsy were also more sensitive to interference in a verbal learning test and showed greater working memory deficits.²⁸ Working memory refers to a capacity limited system that allows one to mentally manipulate information maintained in short-term memory. This memory function is very sensitive to interference and its perturbation is usually associated to a frontal dorsolateral cortex malfunctioning.⁶² Working memory deficits and planning difficulties have also been documented in case studies of children with frontal lobe epilepsy.^29,30

JME is a generalized epilepsy syndrome associated with thalamofrontal circuitry dysfunction⁶³ and structural thalamic and frontal abnormalities.⁶⁴ Pulsipher et al⁶⁴ recently reported that executive functioning of children with JME was significantly impaired compared to healthy control children and children with BECTS, which is not an epileptic syndrome specifically associated with frontal dysfunction.

Although deficits in executive functions are the hallmark of frontal lobe dysfunction, several studies have shown that children and adults suffering from temporal lobe epilepsy may present impairments that are similar to, albeit less severe than those seen in frontal lobe epilepsy patients on a number of “frontal” measures. Hernandez et al⁶¹ found that a relatively high proportion (38%–50%) of children with temporal lobe epilepsy performed below age norms on tasks measuring motor coordination, verbal fluency, and mental flexibility. This finding is consistent with other studies. Children with temporal lobe epilepsy and hippocampal atrophy had below-normal performance on the Wisconsin Card Sorting Test (WCST), a test that purports to assess concept formation and mental flexibility.⁶⁵ These deficits may be due to the propagation of “neural noise” associated with epileptogenic discharges in medial temporal structures to neighboring extratemporal regions, notably the frontal cortex via a temporofrontal circuit.⁶⁶ Other studies also reported executive dysfunction in JME, idiopathic generalized epilepsy, and childhood absence epilepsy,^25,42,53,67 demonstrating that “frontal lobe” dysfunction may also be present in generalized epilepsies.

Only a few studies have been conducted to assess the presence of executive dysfunction related to antiepileptic drugs. In a prospective study, Hessen, Lossius, and Gjerstad⁶⁸ showed that withdrawal of antiepileptic drugs in a large group of seizure free epileptic adults on monotherapy is associated with a significant improved performance on executive function measures. While topiramate has been known to interfere with attention skills, it also affects executive functions such as working memory, inhibition, and verbal fluency in patients with epilepsy⁶⁹ and healthy volunteers.⁷⁰ A slight improvement of executive functioning after topiramate withdrawal in partial, especially temporal lobe epilepsy has been shown.⁷¹ Considering that multiple executive function tests are often used to measure attention ability, this improvement could also be attributed, at least in part, to a gain of attention capacities. As suggested before, pharmacological therapy should be carefully chosen with regard to its possible cognitive side effects.

Considering that executive dysfunction has been shown to be a significant predictor of poor quality of life⁷² and school achievement⁷³ in children with epilepsy, the treatment of executive function deficits is of considerable importance. Surgery is an alternative solution to medication in refractory epilepsy for appropriate patients, but it may interfere with cognitive functioning. However, data regarding postoperative deficits are inconsistent. Negative effects of frontal lobe epilepsy surgery have been reported on verbal fluency, design fluency, and mental flexibility tests in adults.⁷⁴ In contrast, Lendt et al⁷⁵ noted stable executive functioning a year after frontal lobe surgery in children.

STRATEGIES FOR TREATMENT OF EXECUTIVE FUNCTION DEFICITS

Cognitive rehabilitation may have the potential to enhance executive functioning in patients with epilepsy. To date, however, no study has been carried out on executive function rehabilitation and epilepsy and very few studies have been conducted with other clinical populations. Luria⁷⁶ was the first to propose a theoretical approach for executive problems improvement. He suggested that executive rehabilitation should be based on the replacement of the absent internal structure by an external guidance. Evans, Emslie, and Wilson⁷⁷ used external aids to improve initiation and organization in daily life activities (medication intake, plant watering, laundry, and bathing) in a 50-year-old woman with bilateral frontal lesions. They used a checklist and a NeuroPage (cellular telephone with an alphanumeric screen that sent a text message to the patient to inform her that she should start an activity) to provide an external cue to start an activity, to reduce potential distracters, and to prevent impulsive actions. Derouesné, Seron, and Lhermitte⁷⁸ successfully used an external regulation blurring technique and a preorganization and segmentation strategy of an activity to enhance self-regulation capacity in neuropsychological tasks in patients with a frontal lesion. The rehabilitation was divided in six steps: (1) detailed oral instructions, (2) detailed written instructions, (3) less detailed oral instructions, (4) less detailed written instructions, (5) simple oral stimulation, and (6) no intervention. Cicerone and Wood⁷⁹ taught a self-instruction strategy to improve planning capacity in a 20-year-old man who suffered from traumatic brain injury. During the first training phase, the patient was instructed to verbalize out-loud a plan before and during the execution of the task. The second phase was similar but the participant was instructed to whisper the plan. The third step required to internally rehearse the instructions instead of loudly. This study shows that self-instruction strategies can be useful to alleviate planning and self-regulation problems, but specific training must also be provided to generalize the improvement to daily life tasks. Thus, a few studies have shown the positive impact of executive function rehabilitation but a major concern remains that of transferring the learning to other contexts and activities. Furthermore, more studies are needed to assess the efficacy of these techniques in epilepsy and to adapt them to children.