Contents lists available at ScienceDirect Epilepsy Research journal homepage: www.elsevier.com/locate/epilepsyres Special Communication Complement system dysregulation in patients affected by Idiopathic Generalized Epilepsy and the effect of antiepileptic treatment Claudio Liguori a, ⁎ , Andrea Romigi a,b , Francesca Izzi a , Fabio Placidi a , Marzia Nuccetelli b , Alberto Cordella c , Sergio Bernardini b , Mercuri Nicola Biagio a,d a Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy b Neurology Unit, San Giovanni Addolorata Hospital, Rome, Italy c Clinical Biochemistry and Molecular Biology, University of Rome “Tor Vergata”, Rome, Italy d IRCCS Fondazione Santa Lucia, Rome, Italy ARTICLE INFO Keywords: C3 C4 Complement system Anti-epileptic drugs Idiopathic Generalized Epilepsy ABSTRACT Complement system dysregulation has been hypothesized as a possible pathogenetic factor triggering epi- leptogenesis in both animal models and human studies. The aim of the present study is to evaluate the com- plement system in adult patients affected by idiopathic generalized epilepsy (IGE), either untreated or treated by antiepileptic drugs (AEDs). Thirty-seven IGE patients were compared to a population of 20 matched healthy controls. IGE patients un- derwent neurological investigation, epilepsy diary, 24-h EEG recording, and blood sample for the assessment of the complement factors C3 and C4, fibrinogen, and C-reactive protein (CRP) serum levels. We excluded patients with clinical and subclinical seizures in the 24 h before obtaining the blood sample. We observed decreased C3 and C4 serum levels in IGE patients with respect to controls (p < 0.05), and in untreated compared to treated IGE patients (p < 0.05). We found significant correlations in the IGE group linking C3 to C4 (R = 0.34), CRP (R = 0.49), and fibrinogen serum levels (R = 0.61). This study proved a significant alteration of the complement system in IGE patients not related to ictal conditions. The hyperactivation of the complement cascade was more significant in untreated than in treated IGE patients. Hence, this study documented the complement factors dysregulation in patients affected by IGE. However, the impact of complement system alteration in the epileptogenetic process needs to be clarified. 1. Introduction Converging experimental and human studies suggest that the im- mune system may play a critical role in epileptogenesis (Vezzani and Friedman, 2011). Despite progresses in pharmacological and surgical treatments of epilepsy, the complex and multifactorial mechanisms leading to the generation of seizures are not completely understood, mainly in idiopathic generalized epilepsies (IGE) (Vezzani and Friedman, 2011). Recent findings propose the involvement of in- flammatory mediators in both the origin of individual seizures and the epileptogenic process (Aronica et al., 2007). Accordingly, neuroin- flammation has been identified as a possible crucial mechanism in the pathophysiology of seizures and epilepsy (Vezzani and Granata, 2005; Riazi et al., 2010; Choi et al., 2009). In keeping with this hypothesis, several inflammatory mediators, such as interleukines, chemokines, and adhesion molecules, have been evaluated in both epileptic patients and experimental models of epilepsy (Vezzani and Friedman, 2011). Among them, also the complement cascade has been investigated in rat models of temporal lobe epilepsy (TLE) (Aronica et al., 2007). In particular, increased expression of the complement factors C1q, C3, and C4 has been proved in the hippocampal and entorhinal cortex of animal tissues (Xiong et al., 2003). Moreover, the upregulation of C1q and C3d protein expression has been documented in TLE tissues of drug-resistant epi- leptic patients affected by hippocampal sclerosis (HS) (Aronica et al., 2007). On these bases, it has been demonstrated a prominent activation of the complement cascade in patients affected by TLE due to HS (Aronica et al., 2007). Therefore, the complement system may be al- tered in patients affected by idiopathic or secondary focal epilepsies (Başaran et al., 1994; Bostantjopoulou et al., 1994). The complement system represents the backbone of the innate im- mune system (McGeer et al., 2016). It is constituted by more than 25 components working together in a clockwork way in order to dis- criminate and eliminate foes. Complement exerts its function by priming key proteins. Among them, C3 and C4 are considered central http://dx.doi.org/10.1016/j.eplepsyres.2017.09.005 Received 23 April 2017; Received in revised form 28 July 2017; Accepted 15 September 2017 ⁎ Corresponding author at: Epilepsy Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome “Tor Vergata”, Viale Oxford 81, 00133, Rome, Italy. E-mail address: dott.claudioliguori@yahoo.it (C. Liguori). Epilepsy Research 137 (2017) 107–111 Available online 21 September 2017 0920-1211/ © 2017 Elsevier B.V. All rights reserved. MARK