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Dai Miyawaki,1 Yoshihiro Iwakura,1 Toshiyuki Seto,2 Hiroto Kusaka,1 Ayako Goto,1 Yu Okada,1 Nobuyoshi Asada,1 Erika Yanagihara,1 Koki Inoue1 1Department of Neuropsychiatry, 2Department of Pediatrics, Osaka City University Graduate School of Medicine, Asahi-machi, Abeno-ku, Osaka, Japan Abstract: Psychogenic nonepileptic seizures (PNES) are observable changes in behavior or consciousness that are similar to epileptic seizures but are not associated with electrophysiologic changes. PNES occur in children with underlying psychological distress and are especially frequent in those with epilepsy. Because PNES are heterogeneous, comprehensive treatment tailored to each patient is required to reduce psychosocial stress. Currently, reports regarding children with PNES concomitant with autism spectrum disorder (ASD) do not exist, and effective treatment strategies for these children are lacking. In this case report, we describe a 10-year-old Japanese girl with undiagnosed ASD who developed PNES while undergoing treatment for benign childhood epilepsy with centrotemporal spikes. She exhibited hypersensitivity to sound and interpersonal conflicts caused by social communication deficits. The PNES symptoms improved shortly after our intervention, which was designed to reduce her distress caused by auditory hypersensitivity and impaired social communication, both characteristics of ASD. To the best of our knowledge, this is the first report describing PNES in a child with ASD. Our findings suggest that PNES can result from psychological distress in children with undiagnosed ASD and highlight the importance of examining ASD traits in patients with PNES. Keywords: pseudoseizures, autism spectrum disorders, undiagnosed, children

IL-18 is a powerful inducer of IFN-γ production, particularly in collaboration with IL-12. IL-18, like IL-12, also augments NK activity. Here we investigated the molecular mechanism underlying the up-regulation of killing activity of NK cells by IL-18. IL-18, like IL-12, dose dependently enhanced NK activity of splenocytes. This action was further enhanced by costimulation with IL-12. Treatment with anti-IL-2R Ab did not affect IL-18- and/or IL-12-augmented NK activity, and splenocytes from IFN-γ-deficient mice showed enhanced NK activity following stimulation with IL-12 and/or IL-18. Splenocytes from the mice deficient in both IL-12 and IL-18 normally responded to IL-18 and/or IL-12 with facilitated NK activity, suggesting that functional NK cells develop in the absence of IL-12 and IL-18. IL-18R, as well as IL-12R mRNA, was constitutively expressed in splenocytes from SCID mice, which lack T cells and B cells but have intact NK cells, and in those from IL-12 and IL-18 double knockout mice. NK cells isolated from SCID splenocytes expressed IL-18R on their surface. IL-18, in contrast to IL-12, did not enhance mRNA expression of perforin, a key molecule for exocytosis-mediated cytotoxicity. However, pretreatment with concanamycin A completely inhibited this IL-18- and/or IL-12-augmented NK activity. Furthermore, IL-18, like IL-12, failed to enhance NK activity of splenocytes from perforin-deficient mice. These data suggested that NK cells develop and express IL-12R and IL-18R in the absence of IL-12 or IL-18, and that both IL-18 and IL-12 directly and independently augment perforin-mediated cytotoxic activity of NK cells.