The World Health Organization defines health as “a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity.”¹ In the past, measures of success in treating medical illness have been thought of in terms of freedom of disease or identifiable quantifiable endpoints, such as serum glucose, systolic blood pressure, or seizures.² However, recently, there has been an emergence of interest in measuring health-related quality of life (HRQOL), a valid and significant indicator of health in patients with disease. This idea has been studied over the past decade and applied to develop reliable and valid measures of function and well-being for use in patients with epilepsy.³ This concept especially pertains to chronic epilepsy, where though many treating clinicians focus on treating the ictal phenomenon of the disease, namely seizures, the disease itself carries a multitude of clinically relevant interictal comorbidities that affects patients’ overall HRQOL.

Indeed, this concept is not specifically inclusive to adults, as the negative impact on quality of life in children is common, and typically manifests with impaired social functioning, peer relationships, self-esteem, mood, and academic performance.^4,5,6,7 In addition, epilepsy can have a negative impact on not only the many aspects of a child’s life but also on his or her family as well.^6,8,9,10 Issues with subjective health status can be especially challenging for children living with epilepsy, because the maturation of a healthy self-identity is recognized as a fundamental task in a child’s development.¹¹

There has been increased focus concerning HRQOL and epilepsy in children over the past decade. Most of these studies used various standardized measures to systematically investigate the various aspects that contribute to HRQOL.^{12,13,14,15,16,17,18,19,20,21,22} However, many studies did not analyze qualitative measures, and were thus unsuccessful in investigating subjective health status by direct exploration of children’s views.²³

This review will examine the contribution and impact of different forms of comorbidity on overall health status in children in epilepsy. We will discuss neurpopsychiatric comorbidity, medication effects, seizure burden, and outcomes of epilepsy surgery pertaining to overall HRQOL.

Depression is the most common comorbid psychiatric disorder in patients with epilepsy.²⁴ Extensive literature has indicated that depression is a frequent complication of chronic epilepsy.^{25,26,27,28,29} However, symptoms of psychological distress are often unrecognized by clinicians treating children with epilepsy.^28,29 There are a variety of potential causes of depression in children with epilepsy. For example, depression may be reactive and secondary to being diagnosed with a chronic, debilitating condition.³⁰ Psychosocial factors, such as perceived social stigma and parental overprotection might be related to psychopathology, but there is little empirical research on this topic and the findings are inconsistent.³¹ Studies have shown that psychiatric problems may exist prior to the identification of the diagnosis of epilepsy in children, and therefore are likely due to underlying pathophysiological disturbances of the disease.^32,33 Indeed, associations have been made between underlying brain dysfunction occurring in patients with epilepsy with depression.^{34,35,36,37,38} Different forms of psychiatric comorbidity have also been shown to be associated with different types of epilepsy in children.^39,40 For instance, thought disorder and hyperactivity are linked with different forms of localization-related epilepsy,⁴¹ while both Axis I disorders and personality disorders are associated with juvenile myoclonic epilepsy.⁴²

Epilepsy and behavior have a complex association. Particular attention should be paid to the temporal relationship of psychiatric symptoms with seizure occurrence. Psychopathology can accordingly be classified as either ictal (due to the clinical properties during the seizure), peri-ictal (clinical manifestations preceding or following the seizure), or interictal (symptoms occurring independent of seizure occurrence).⁴³ Ictal depression has been associated with partial seizures of temporal origin.⁴⁴ The most common form of peri-ictal psychiatric symptoms encountered is that seen following a seizure, and have been identified in as many as 7% of patients.⁴⁵ Symptoms may include postictal psychosis or depression.

Postictal depression may persist as long as 2 weeks following the seizure.⁴⁶

Interictal depression is by far the most common form of psychopathology in patients with epilepsy. It has a prevalence of up to 55% among adult patients with pharmacoresistant epilepsy.^47,48,49 Pediatric patients have lower rates of depression, ranging between 23% and 26%.^28,50 This may be secondary to the fact that diagnosing depression in children can be more challenging than in adults, irrespective of the patient having a diagnosis of epilepsy. Depression often manifests differently in children than adults. Children infrequently have depressive symptoms, and instead may express multiple somatic complaints. Children with mood disorders often display symptoms of irritability rather than depression, and may carry more than one psychiatric diagnosis, such as attention-deficit disorder, depressive disorder, and language disorders, further clouding the proper identification of the disorder.⁵¹ It may be for this reason that though recent studies have revealed a strong negative correlation between mood status and overall HRQOL in adults,^{28,47,48,49,52,53} there is a paucity of literature linking poor subjective health status with mood disorders in children with epilepsy.

Children with epilepsy were found to be consistently behaviorally disturbed and demonstrated lower self-esteem when compared to children with diabetes.⁵⁴ However, this was not reported to be associated with HRQOL. Older adolescents reporting poor HRQOL were more likely to perceive a greater negative impact on life and general health, and had more negative attitudes toward epilepsy than younger patients.¹⁸

Though interictal comorbid depression and epilepsy is not as common in childhood, it has a substantial effect on HRQOL. Systematic screening for depression facilitates treatment with psychotropic medications or psychotherapy, potentially improving comprehensive care.

Attention deficit hyperactivity disorder (ADHD) affects approximately 3%–7% of all children in the general population.^55,56 ADHD has a negative impact on personal and social functioning, given the relationship of ADHD with learning difficulties, school failure, poor peer relationships, as well as accompanying mood, anxiety, and conduct disorders, potentially leading to adverse effects on occupational attainment.^57,58,59

Symptoms resembling those of ADHD were first reported in 8% of children with epilepsy over 50 years ago, described as an interictal “hyperkinetic syndrome.”⁶⁰ The prevalence of ADHD in the epilepsy population in recent studies has varied widely, depending on the samples studied and the measures for ADHD used. In studies of children with chronic epilepsy, 28%–39% had symptoms of hyperactivity and impulsivity.^61,62 Forty-two percent were reported to have problems with attention.⁶³ These studies, however, did not use the standard diagnostic criteria for ADHD.

More recent studies of patients with chronic epilepsy using established measures for ADHD found a striking difference with regards to the symptoms of ADHD in primary ADHD and ADHD in children with epilepsy. The inattention component of ADHD has been found to be more prevalent than hyperactivity impulsive types, with 24%–40% and 2%–18%, respectively.^64,65 The likely explanation for the higher prevalence of the inattention subtype of ADHD in children with epilepsy is the epilepsy-specific neurologically based risk factors for disturbances in attention in these particular patients. These include the pathophysiological disturbances accounting for interictal cognitive dysfunction in patients with epilepsy, as well as medication effects.^66,67,68

Patients with epilepsy and ADHD have a two- to fourfold increase in poor HRQOL, indicating that the symptoms of ADHD have substantial effects on patients, with significant implications on overall subjective health status.⁶⁵ These findings are similar to other studies investigating the effect of ADHD on HRQOL in patients without epilepsy.^69,70,71 Once again, this study found that inattention was the main symptom in the children with epilepsy and ADHD. The fact that ADHD has a negative effect on HRQOL has particularly relevant clinical implications, namely screening and treatment of ADHD in this population.

Screening and treatment of ADHD in pediatric patients is particularly relevant given the association between ADHD symptoms and poor subjective health status. ADHD is a behavioral syndrome that is treatable, with medical intervention having a potential impact. By recognizing this interictal phenomenon, we have the opportunity to intervene with proper treatment and effect positive change in the overall HRQOL in these children.

Over the past recent years, the use of self-report rating scales has been used to screen for depression in patients with epilepsy. Though an in-depth psychiatric interview conducted directly with the patient is of great importance when assessing for psychiatric comorbidity, the rating scales assist in providing valuable information, and can help the clinician determine when referral to a psychiatrist is warranted.

Many depression scales have been developed over the years for assessing psychopathology in adults with epilepsy.

• The Beck Depression Inventory (BDI) is the most commonly used self-rating scale. It was designed to detect current (past 2 weeks) depressive symptoms. The BDI contains 21 descriptive statements regarding depressive symptoms frequently reported by individuals diagnosed with depression.⁷² The statements can be rated on a 4-point severity-rating scale. The BDI was found to have a high sensitivity and specificity as a screening instrument.^73,74

• The Structured Clinical Interview for DSM-IV: Research Version (SCID-I) and Mini International Neuropsychiatric Interview (MINI) are two effective instruments used primarily in research to screen for Axis I disorders,^75,76 but administration time is approximately 15–20 minutes and are thus impractical for use in a busy practice setting. The Center for Epidemiological Studies-Depression (CES-D) scale is a 20-item scale developed to screen for depression in primary-care settings.⁷⁷ The CES-D items focus on measuring the frequency of depressive symptoms and the scale has been shown to be a valid and a reliable instrument,⁷⁸ with significant ability to identify major depression in epilepsy.⁷⁴

• The Neurological Disorders Depression Inventory Index for Epilepsy (NDDI-E) is a relatively new tool used for a rapid screening for major depressive episodes in adults with epilepsy.⁷⁹ The 6-item questionnaire was developed for a brief, yet accurate screening technique that can easily be applied in a busy office setting.

Similarly, screening instruments have been used for children and adolescents with epilepsy.

The Child Behavior Checklist (CBCL) evaluates pathological behaviors and social competence in children and is one of the most widely used scales in clinical practice and research.⁸⁰

The Children’s Depression Inventory (CDI) is one of the most frequently used questionnaires for monitoring depression in children.⁸¹ It contains 27 descriptive items that includes three statements of increasing severity.

The Child Symptom Inventories-4 (CSI) screens for behavioral, affective, and cognitive symptoms of many DSM-IV disorders and is also widely used in research.

Families of children with epilepsy appear to have more problems with family functioning than families with healthy children.^82,83 Having a child diagnosed with epilepsy, like other chronic illnesses, likely provokes substantial stress in parents. Parental difficulty in handling and accepting their child’s diagnosis has been associated with elevated levels of parental stress.⁸⁴ This, in turn, predicts dysfunction with child–parent relationships, which becomes directly related to child psychopathology.^85,86 This idea is supported by recent reports showing that parental psychopathology, particularly anxiety and depression, has a negative effect on patients’ HRQOL,^87,88,89,90 with some authors concluding that the influence of parental emotion was stronger than the burden of the epilepsy itself.⁹⁰ Indeed, parents of children with epilepsy have their own unique set of psychiatric disorders different from their children’s. Parental anxiety may lead to them becoming overprotective, promoting a transmission of anxieties to their children. Prevalence of maternal depression was reported to be anywhere between 32% and 37% in mothers of children with epilepsy.^91,92,93