Stress sensitivity of childhood epilepsy is related to experienced negative life events *yJolien S. van Campen, *Floor E. Jansen, *Laurie C. Steinbusch, yMarian Joe ¨ ls, and *Kees P. J. Braun Departments of *Pediatric Neurology and yNeuroscience & Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands SUMMARY Purpose: To evaluate the effect of stress on seizure fre- quency in childhood epilepsy, and to assess possible differ- ences between children in whom seizures are precipitated by stress and those in whom they are not. Methods: Parents or caregivers of children with active epilepsy (aged 2–16 years) were sent questionnaires on developmental and epilepsy characteristics, life-time stress exposure, and the effect of stressful periods and moments of acute stress on seizure frequency in their child. Further information was extracted from patient files. Key Findings: Parents or caregivers of 153 children with a median age of 8.8 years responded to the questionnaires. Thirty-nine percent reported an increase in seizure fre- quency during periods of stress, with a median increase of 2.5 times the frequency compared to nonstressful periods. Thirty-seven percent reported that seizures were precipi- tated by acute stress, with stress being a precipitating factor in 33% (median value) of the seizures. Overall, 51% of the patients reported stress sensitivity of seizures. A higher number of negative life events experienced in total life was related to an increase in seizure frequency in stressful periods (odds ratio [OR] 1.3, p = 0.01) as well as to the precipitation of seizures by acute stress (OR 1.3, p = 0.02). Significance: Stress sensitivity is reported in half of the children with epilepsy. Results of this study suggest a rela- tion between experienced negative life events and stress sensitivity of childhood epilepsy. One possible explanation could be that experiencing negative life events may cause a larger response to daily stressors, thereby increasing the likelihood to induce epileptic activity. KEY WORDS: Epileptic, Seizures, Pediatric, Children, Life event. In patients with epilepsy, stress is one of the most fre- quently self-reported precipitants for seizures (Cull et al., 1996; Spatt et al., 1998; Frucht et al., 2000; Spector et al., 2000; Da Silva Sousa et al., 2005; Nakken et al., 2005; Haut et al., 2007; Sperling et al., 2008; Pinikahana & Dono, 2009; Lunardi Mdos et al., 2011). Emotional stress is the precipitant most often reported (Nakken et al., 2005), but acute physical stressors can exacerbate seizures as well (Arida et al., 2009). The relationship between stress and sei- zures was shown to be independent of sleep deprivation or medication noncompliance (Haut et al., 2007). Prospective explorative studies revealed a higher seizure frequency in children with epilepsy in areas of war compared to children in nonwar areas (Bosnjak et al., 2002), an increase in sei- zure frequency in patients with epilepsy during natural disasters (Swinkels et al., 1998), and a higher incidence of seizures in soldiers who experience more occupational stress (Moshe et al., 2008). Although stress has been shown to influence seizure sus- ceptibility in patients with epilepsy, the evidence was so far mostly obtained in adults. Other types of seizure precipit- ants such as fever, hot water, and photic stimulation have been shown to be more common in children compared to adults (Satishchandra, 2003; Lu et al., 2008; Reid et al., 2009). However, the prevalence and characteristics of stress-sensitive epilepsy have never been studied in a pediat- ric population. Therefore, the aim of our study was to assess the effect of stress on seizure frequency in children with epi- lepsy and to evaluate which characteristics of these children relate to their stress sensitivity. Patients and Methods Patients In this consecutive cohort study, we retrospectively selected all children, aged 2–16 years, with active epilepsy (i.e., a definite clinical diagnosis of epilepsy and seizures within 2 years prior to data collection), who consulted one Accepted May 10, 2012; Early View publication June 27, 2012. Address correspondence to Jolien S. van Campen, Department of Pedia- tric Neurology KC03.063.0, University Medical Center Utrecht, PO Box 85090, 3508 AB, The Netherlands. E-mail: j.s.vancampen-4@umcutrecht.nl Wiley Periodicals, Inc. ª 2012 International League Against Epilepsy Epilepsia, 53(9):1554–1562, 2012 doi: 10.1111/j.1528-1167.2012.03566.x FULL-LENGTH ORIGINAL RESEARCH 1554