Children with Epilepsy and Comorbid Conditions by Liu Lin Thio, MD, PhD

Introduction

All parents want their children to have the highest quality of life possible. The same is true of parents who have a child living with a chronic condition such as epilepsy. Obviously, these children will attain this goal only if the symptoms of their condition are eliminated or at least minimized. However, the symptoms of comorbid conditions can have an equal or even greater impact on their quality of life. Comorbid conditions refer to conditions that co-occur more frequently than expected by chance. Unfortunately, children who live with epilepsy are at risk for having multiple comorbid conditions.

The comorbidities of epilepsy may arise by four distinct mechanisms.1 In some cases, the epilepsy and the comorbid condition have the same cause. For example, a genetic abnormality is responsible for both the epilepsy and intellectual disability often seen in tuberous sclerosis. In other cases, a comorbid condition such as a stroke or a tumor has caused the epilepsy. Comorbid conditions in epilepsy also may result from the seizures or the medications used to treat the seizures. For instance, nocturnal seizures can cause daytime sleepiness by disrupting sleep, and valproate can cause weight gain. Lastly, the relationship between epilepsy and the comorbid condition may not be known.

The comorbidities that children with epilepsy may face not only have several causes, but they involve multiple organ systems.2,3 Some of the most common ones involve the brain such as the psychiatric, cognitive, and social comorbidities.4 The presence of these brain comorbidities in children with epilepsy is not surprising because some conditions are known to cause both epilepsy and these brain disorders. Examples of such conditions include Fragile X syndrome, Down syndrome, and cerebral palsy. Migraine headaches are another brain comorbidity that can share an underlying cause with epilepsy. The organs affected by other epilepsy comorbidities in children include the eyes, ears, and lungs.2,3 The comorbidities involving other organs may indirectly lead to epilepsy or they may result from the seizures or the medications used to treat the seizures.1

The recognition of comorbidities by parents of children with epilepsy and their child’s healthcare providers is an important step in improving the lives of these children. The comorbidities of epilepsy are challenging to recognize because they are numerous and not always obviously related to epilepsy. Although this article will largely focus on a few epilepsy comorbidities involving the brain, it hopefully will raise awareness of all comorbidities, lead to their treatment when present, and the adoption of preventative strategies when possible.

Psychiatric Comorbidities
Psychiatric comorbidities are extremely common among children with epilepsy and may afflict more than 25%.2-6 They are far more common in children with epilepsy than in children with other chronic conditions that do not affect the brain and spinal cord. The comorbidities include mood disorders such as depression, anxiety disorders, attention deficit hyperactivity disorder, and conduct disorder. They can occur regardless of epilepsy type or how well controlled the seizures are.

Depression. This comorbidity occurs in 8-33% of children with epilepsy2-4,6 and can occur in very young children. It is especially important to recognize in adolescents because the associated risk of suicide makes it a potentially life-threatening comorbidity. The hallmarks of this common comorbidity are altered mood and a loss of pleasure that interferes with daily activities. Alterations in mood include irritability and anger. The causes of depression in children with epilepsy likely are multifactorial and consist of neurobiological and psychological factors. The neurobiological factors may include the underlying cause of the epilepsy, the seizures themselves, the abnormal electrical discharges that occur in the brain between seizures, and the drugs used to treat seizures. The psychological factors may include the stress that accompanies living with epilepsy. The psychological stress of epilepsy probably is unique because seizures are unpredictable and uncontrollable once one begins. Although the optimal treatment for depression in the setting of epilepsy is unknown, it should address both the neurobiological and psychological factors. Thus, antidepressant medications and psychotherapeutic approaches such as cognitive behavioral therapy should be mainstays of treatment.6,7

Anxiety. This comorbidity encompasses a group of disorders including panic disorder, obsessive-compulsive disorder, generalized anxiety disorder, social phobia and separation anxiety disorder.5Though anxiety disorders are common among children and adolescents in general, they are even more common in those with epilepsy affecting 15-50%.3,5 Like depression, the causes of anxiety probably are multifactorial and include psychological and neurobiological factors. The psychological factors that contribute to experiencing anxiety include the fear of a seizure, the embarrassment of having a seizure in public, and the fear of having a seizure in the absence of a parent.5,7 Of note, fear and anxiety may be symptoms of a seizure, especially a complex partial seizure arising from the temporal lobe. Research establishing the most effective treatment for anxiety disorders in children with epilepsy is lacking, but a treatment plan including both medication and psychotherapeutic approaches is reasonable.

Depression, anxiety, and other behavioral disorders are common in children and adolescents with epilepsy and negatively affect quality of life. These comorbidities are important for parents and healthcare providers to identify because treating these disorders can improve quality of life for these children. However, the treatments are complex and require the expertise of pediatric neurologists, psychiatrists, and psychologists.

Neurological Comorbidities
Neurological comorbidities occur very frequently in children with epilepsy. As mentioned above, the presence of these comorbidities in the setting of epilepsy is not surprising as many disorders that predispose children to epilepsy also increase their risk for other neurological conditions. Neurological comorbidities include learning disabilities and developmental delay, which occur in 40-50% of children with epilepsy.2,3 These comorbidities are similar to the psychiatric comorbidities in that they occur even in children with epilepsy who do not have active seizures.

Intellectual disabilities. Children with epilepsy are much more likely than those without epilepsy to have school difficulties resulting in school-based interventions such as repeating a grade and needing extra help.3,4 These problems arise, in part, from the intellectual disabilities that accompany epilepsy. As a group, children with epilepsy have a lower intelligence quotient (IQ) than those who do not. About 25% of children with epilepsy have an intelligence quotient below 70 or 80, with a score below 70 indicating an intellectual disability. These deficits occur in a variety of epilepsy types and span several cognitive domains including language, processing speed, and executive function. Although some children with epilepsy have normal cognitive function, children with mild forms of epilepsy can have intellectual disabilities, which may be present at the time of the first seizure.8,9 This observation indicates that other factors besides seizure medications contribute to the difficulties children with epilepsy have in learning.10

Attention deficit hyperactivity disorder and executive function. Children with epilepsy have deficits in executive function, which includes attention, working memory, and sequencing.8,9 Attention deficit hyperactivity disorder is very common in general but is far more prevalent in children with epilepsy occurring in 20-39%.2,3,11 The characteristics of the disorder include hyperactivity, impulsivity, and inattention in several settings. Similar to depression and anxiety disorders, neurobiological and psychological factors probably contribute to its presence in children with epilepsy. Accordingly, medications and classroom accommodations are useful in treating attentional problems.7,10Specifically, several studies indicate that stimulant medications such as methylphenidate are safe to use in children with epilepsy.7,11

Neurocognitive comorbidities are prevalent among children with epilepsy and have a negative impact on quality of life. Neuropsychologists can identify these comorbidities through a battery of tests, and they can formulate an effective educational plan based on the results. These strategies are important towards maximizing cognitive development especially because these comorbidities are not amenable to treatment with medication except for attentional difficulties. Though medical therapy may not be able to treat the majority of these deficits, pediatric neurologists can help by minimizing the untoward effects of seizures and seizure medications.

Social Comorbidities
Children and adolescents with epilepsy can have significant social comorbidities that impair daily life.4,7 Over half report limited activities, and nearly half report low social competence, which refers to forming productive and mutually satisfying relationships with others.3 These social comorbidities arise in part from the poor self-concept and low self-esteem found in children and adolescents with epilepsy. Naturally, the psychiatric comorbidities of depression and anxiety have a role in these issues of self-worth, but the persistent stigma associated with epilepsy also contributes. The social comorbidities are important to address in childhood and adolescence because of their potential impact on their quality of life later as adults. Psychotherapeutic approaches may be particularly helpful in this regard.

Other Comorbidities
Children and adolescents with epilepsy are at risk for additional comorbidities. Other neurological comorbidities include migraine, sleep disorders, and cerebral palsy. Non-neurological comorbidities include osteopenia, which seizure medications may exacerbate, and asthma, which does not have a clear relationship to epilepsy.

Conclusions
In summary, children and adolescents with epilepsy are susceptible to multiple comorbidities. Many are neurobehavioral and fall into a psychiatric, neurological, or social category. These comorbidities include depression, anxiety disorders, and intellectual disabilities that share a common underlying cause with epilepsy, result directly or indirectly from the seizures, reflect the psychological stress of epilepsy, or are exacerbated by seizure medications. Regardless of the mechanism by which they arise, they have a negative impact on quality of life. Some are responsive to treatment, which may be challenging to implement and likely requires a multidisciplinary approach including pediatric neurologists, psychiatrists, psychologists, and neuropsychologists. Parents of children with epilepsy should be aware of the many epilepsy comorbidities and monitor their children for them with the help of their healthcare provider. Once the comorbidity is identified, parents can enlist the appropriate help to address the comorbidity with the goal of maintaining a high quality of life for their child.

Dr. Thio is associate professor of neurology, pediatrics and neurobiology in the Washington University School of Medicine Department of Neurology; director of the Pediatric Epilepsy Center and neurologist-in-chief at St. Louis Children’s Hospital and chair of the Epilepsy Foundation of Missouri & Kansas professional advisory board.

References

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