This is the first longitudinal study to examine HRQOL over time in children newly diagnosed with epilepsy and beginning AED therapy. The current study utilized quantitative, validated measures of both HRQOL and side-effects to examine changes in HRQOL within the context of standard clinical care. Contrary to our hypothesis, HRQOL remained relatively stable from diagnosis to 7-months post-AED initiation across most scales. This is in contrast to a prior study where adults diagnosed with epilepsy demonstrated HRQOL improvements when initiated on lamotrigine (Gillham, Kane, Bryant-Comstock, & Brodie, 2000
). Our study only detected a statistical trend for improvements in emotional functioning over time. This may be attributed to the fact that children and parents received extensive education regarding diagnosis, prognosis, and the benefits of AED therapy. Such education likely lessened the anxiety and fear often associated with even a single seizure (Modi et al., 2009
) and receiving a diagnosis of epilepsy (Li, Ji, Qin, & Zhang, 2008
; Williams et al., 2003
The lack of significant HRQOL changes across other domains may be explained by several factors. First, physical, social, school, and total functioning remain constant over time based on group means. However, individual trajectories did vary and some patients improved while others declined over time. Although no group effects were noted, individual HRQOL data can yield patient specific clinically-relevant information for healthcare providers. Second, children with newly diagnosed epilepsy are at high risk for identification of previously undetected neurological, attentional and behavioral co-morbidities (Austin & Caplan, 2007
; Loring & Meador, 2009
). The assessment and identification of these comorbidities may influence how parents view their children’s overall functioning. Finally, as demonstrated by prior studies and our current analyses, several important covariates may account for individual differences in HRQOL over time, including seizure presence/absence and AED side-effects.
Overall, seizure presence/absence was differentially associated with HRQOL domains over time. Specifically, children who achieved complete seizure control over a seven-month period exhibited improvements on the PedsQL Physical Functioning Scale and a trend was noted for the PedsQL Total scale. Since physical recovery from the effects of one or more seizures is variable between patients, impairments in the Physical domain are not surprising. Furthermore, as children attain seizure control, caregivers may feel more comfortable allowing children to participate in sports/hobbies, chores, and physical activities of daily living, thereby increasing this aspect of HRQOL. Such findings are consistent with prior studies demonstrating that seizure severity/activity negatively affects HRQOL in children and adults (Bautista & Tannahill, 2009
; Leidy, Elixhauser, Vickrey, Means, & Willian, 1999
; Sabaz et al., 2003a
). For example, it is well documented that continued seizures and intractability are associated with the worst HRQOL outcomes. These data reinforce that achieving complete seizure control must be one of the primary goals of epilepsy management.
AED side-effects were globally and negatively associated with all aspects of HRQOL. Our findings build upon prior studies in both adult (Jacoby, Snape, & Baker, 2009
) and pediatric (Benavente-Aguilar et al., 2004
; Jakovljevic et al., 2008
) populations by demonstrating the negative relationship of side-effects starting at AED initiation and HRQOL. Common side-effects endorsed by the current sample and associated with carbamazapine and valproic acid included: Fatigue/drowsiness, hyperactivity, attention difficulties, memory problems, and headaches. Such side-effects would affect physical, emotional, social, and school functioning for children with newly diagnosed epilepsy. The persistence of side-effects relative to a discrete seizure event may play a larger role in children’s overall functioning. This has significant clinical implications as providers determine which AED to initiate and how long to maintain children on a specific AED.
Exploratory analyses revealed a three-way interaction between time, side-effects, and AED type on PedsQL Emotional functioning scores. Children prescribed carbamazepine with higher initial side-effects (+1SD) had declining emotional functioning across seven months compared to those reporting no side-effects or the mean level of side-effects initially. The decrease in HRQOL scores exceeded the MCID, suggesting that parents perceived a significant decline in their children’s emotional health. In contrast, children prescribed valproic acid demonstrated relative improvements in emotional functioning scores over time, regardless of their initial side-effects. While children on valproic acid demonstrate variable emotional HRQOL after treatment initiation, the potential mood enhancing nature of this drug appeared to affect the upward trajectories and converging of all three side-effect groups. This implies that consideration should be given for changing AEDs in children taking carbamazepine who experience more severe side-effects initially (since the HRQOL is projected to deteriorate over time) while children prescribed valproic acid can be reassured that their HRQOL will likely improve over time. It is important to note that carbamazepine is used to primarily treat partial seizures while valproic acid is used to treat generalized and unclassified seizures; thus, these AEDs cannot be used interchangeably.
Although this is the first longitudinal study to examine HRQOL over time in a newly diagnosed cohort of children with epilepsy, there were several limitations. First, despite seven months of follow-up, this study does not address the long-term prognosis and functioning of these children; however, 7-months represent a period of time when changes in HRQOL are likely to occur due to AED treatment initiation. It is possible that a subset of children who continue to experience seizures and develop intractability will have different HRQOL trajectories one to two years following treatment compared to those who have good seizure control and minimal side effects. Thus, future studies are needed to examine the long-term (e.g., 2 years) effects of seizures and side effects on HRQOL. Second, since children had both partial and generalized seizures and variable seizure frequency, seizure presence/absence was treated as a dichotomous variable. Future studies could examine a subpopulation of children with partial epilepsy and define seizures as a continuous variable to better clarify the impact of multiple seizures on HRQOL. Third, while the PedsQL is a well-validated generic measure of HRQOL, study findings may have differed if an epilepsy-specific measure was utilized because it assesses more salient domains (e.g., cognitive functioning, behavioral symptoms). However, unlike the PedsQL measure, epilepsy-specific measures are time consuming and not feasible in a busy clinic due to length [e.g. 79 items for the United States Quality of Life in Childhood Epilepsy Questionnaire (Sabaz et al., 2003b
)]. Forth, due to the age range of children in this study, only parent proxy-reported HRQOL was used. Prior literature suggests that both parent and child reports of HRQOL are correlated (Varni, Seid, & Skarr, 2001
); however, children provide a unique perspective on their own functioning, especially in emotional/social functioning domains (Eiser & Morse, 2001
). Use of multi-method reporting of HRQOL over time in a larger and older sample of children with epilepsy is warranted, especially given our non-random missing data (n
49) at Time 1. Because parental functioning may also impact reporting of their child’s functioning (Janicke et al., 2007
; Quittner, Davis, & Modi, 2003
) and parents and children are adjusting to a new diagnosis of epilepsy (Eiser, 1993
; Modi, 2009
), future studies should attempt to tease apart the influence of these factors on HRQOL changes over time. Furthermore, it is possible that younger children in our sample were unable to report side effects similar to children who were older and more verbal; thus, our data may represent an underestimation of side effects. Fifth, although this study represents an initial step in examining the relations of seizures and side-effects with HRQOL of young children with epilepsy, future studies should investigate other potential correlates of HRQOL, including medical comorbidities, family functioning, and adherence to AED therapy. Finally, children were not randomized by medication type; medication was prescribed according to standard clinical practice at one institution. Children with intractable epilepsy (e.g., continued seizures and failure on two or more AEDs) or those initiated on other AEDs may experience greater/lesser adverse effects or higher/lower QOL than participants in the current study. A future, randomized trial testing medication type will help to fully clarify this issue and determine if current results generalize to other clinical settings.
The results of this study have important implications for clinical care. Although complete seizure control is a primary goal for epilepsy treatment, AED side-effects play a key role in the HRQOL of this population. Healthcare providers should provide anticipatory guidance (i.e., to help individuals know what to expect) to children and their families around the possible impact of AED side-effects; this may help patients feel more comfortable communicating whether side-effects are tolerable or intolerable. Engaging in communication around these issues will enable shared-decision making around the next steps for treatment. Healthcare professionals of children with epilepsy should routinely assess HRQOL to provide optimal therapy for their patients by ascertaining the relative impact of seizures and side-effects on their’s patient quality of life.