Epilepsy in young life can produce cognitive deficits that have a significant impact on outcomes and health-related quality of life (HRQOL). Pediatric epilepsy has been specifically associated with reduced capacity for executive function, which is reported in 49% of children studied.1 Neurology Advisor spoke with Jeffrey B. Titus, PhD, director of pediatric neurosciences at the Dell Children’s Medical Center in Austin, Texas, for his insights on the impact of childhood epilepsy on cognition and strategies to prevent long-term effects on HRQOL.
Neurology Advisor: What clinical features affect the expression of cognitive impairment in epilepsy?
Dr Titus: The most predictive clinical feature of cognitive impairment in epilepsy is underlying brain malformation. Individuals with abnormal brain magnetic resonance imaging (MRI) scans are known to be at higher risk for cognitive problems due to brain dysfunction associated with an area of brain damage or malformation that is causing both cognitive problems and seizure activity.
When brain malformation is involved, cognitive problems are typically stable regardless of the status of seizure control. However, cognitive problems in epilepsy can also be state-dependent, which means that they fluctuate in concert with various states of epilepsy. For example, an individual with frequent seizures may experience cognitive problems that remit after better seizure control is achieved. Adverse events from antiepileptic drug (AED) treatment can also create state-dependent cognitive problems.
Neurology Advisor: Your study1 focused on executive function as the most impaired domain in pediatric epilepsy. Why is executive function most vulnerable?
Dr Titus: In pediatric epilepsy, impaired executive function is often the most prominent cognitive problem, but it is certainly not the only cognitive concern. Executive functioning is mediated predominantly in the frontal lobes, and does not fully develop until later in brain maturation. Because of this, executive functioning has a more protracted period of development than other cognitive functions, making it more vulnerable to the negative influence of seizures and/or seizure treatment during development.
Neurology Advisor: How much are other domains (memory, attention) affected comparatively?
Dr Titus: Our study suggested that deficits in one aspect of executive functioning — working memory — tended to result in lower HRQOL in children with epilepsy. Working memory refers to the ability to hold and manipulate multiple pieces of information in the mind at one time, which is important for comprehension, problem solving, and aspects of learning. Working memory is also closely related to attention, especially when individuals are required to focus or divide their attention in the presence of competing stimuli.
Neurology Advisor: How closely does impairment of executive function relate to HRQOL?
Dr Titus: According to research that my colleagues and I published in 2016,1 impairments in executive functioning are more predictive of lower HRQOL than intelligence and many seizure-related factors such as seizure frequency, age of seizure onset, and the number of AEDs.
Neurology Advisor: What are the effects of pharmacotherapy on cognitive impairment in children with epilepsy?
Dr Titus: AED treatment in children with epilepsy does not always cause negative cognitive adverse events. All AEDs are different, and the newer AEDs tend to have a much better adverse event profile. The older AEDs are more commonly associated with cognitive problems at higher doses and, when they occur, are traditionally manifest as global sedation and/or slow processing speed. There are a few AEDs that have specific effects on certain aspects of cognitive functioning such as verbal expression or verbal learning. When cognitive adverse events are suspected, a comprehensive neuropsychological assessment by a neuropsychologist with experience in pediatric epilepsy is recommended. Adjustments to AEDs should only be made by the child’s neurologist or physician.
Neurology Advisor: What are the best treatment strategies to address cumulative and combined effects of epilepsy and AEDs on cognition in children?
Dr Titus: Regardless of the cause, the most effective cognitive intervention is one-on-one support, which provides a scaffold to support the learning process that helps circumvent the executive function problems. Children with executive function problems can have difficulty starting, following through, and completing activities independently. One-on-one assistance provides a child with reminders about how to initiate tasks, how to move from one step to another, and how to know when the activity has been completed correctly. It is important to note that executive function problems are not necessarily related to intelligence, and children with these problems can often function at or close to expectancy for their age when given frequent or occasional one-on-one support.
Neurology Advisor: Can long-term cognitive outcomes be predicted and mitigated?
Dr Titus: Cognitive outcomes in epilepsy can certainly be maximized by focusing on all aspects of the child’s health. In the past, many epilepsy providers have focused solely on seizure control as a way to improve developmental outcomes and HRQOL. We know now that the most effective treatment for pediatric epilepsy is comprehensive. Seizure control should always be the first approach to managing the child’s health, but caregivers should remain vigilant for the presence of cognitive adverse events from medications that may impede learning, communication, mood, behavior, and socialization.
Seizure management can often be handled well by a pediatrician, especially if the condition is less severe. However, when seizures become refractory to medications or cognition or QOL has declined, consultation at a comprehensive epilepsy center is recommended. Comprehensive centers can provide input from multidisciplinary teams equipped to manage the seizures and the many other complications associated with a complex brain disorder like epilepsy.
Schraegle WA, Titus JB. Executive function and health-related quality of life in pediatric epilepsy. Epilepsy Behav.2016;62:20-26.