Anti-seizure medication is a minor causative factor in behavioral problems of children with tuberous sclerosis complex

Abstract

Introduction: Behavioral problems in Tuberous Sclerosis Complex (TSC) are considered among the highest disease burden for both patients and caregivers, while the cause is often not clear. The current study aimed to explore the relationship between anti-seizure medication (ASM) and behavioral manifestations in children with TSC and epilepsy. Methods: 118 children referred to the University Medical Center Utrecht with definite TSC and epilepsy, aged 2–18 years, were included in a retrospective cohort study. Behavioral problems were categorized into: ‘any behavioral problem’, ‘aggressive behavior’, ‘attentional’, ‘eating’ and ‘sleeping’ problems, and ‘temper tantrums’. In a descriptive analysis, we studied the relationship between behavioral problems and exposure to specific ASMs compared to any other ASM. We looked in detail at manifestations occurring within ninety days after ASM initiation. For both time points we calculated Odds Ratios, comparing use of a specific ASM with use of any other ASMs. In addition, behavioral problems were related to disease characteristics with multivariable multinomial log-linear modeling after variable selection. Results: During a mean follow-up of nine years, 616 ASM prescriptions were made. Behavioral problems were reported in 66% of patients, with temper tantrums showing the highest prevalence (53%). However, behavioral problems were low in association with a specific ASM. From the disease-inherent factors intellectual disability and autism spectrum disorder were significantly associated with attention and sleeping problems. Conclusion: We did not find evidence for aggravation of behavioral problems with specific ASM use. In this complexity of symptoms of TSC the possible benefits of ASM, therefore, likely outweigh the risk of behavioral problems.