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(Abst. 2.141), 2019

Effect of Caffeine Consumption on Seizure Frequency and SUDEP Risk Factors in Patients with Drug-Resistant Focal Epilepsy
Authors: Julie Bourgeois-Vionnet, Hospices Civils de Lyon; Philippe Ryvlin, CHUV; Veronique Michel, University Hospital of Bordeaux; Luc Valton, University Hospital of Toulouse; Philippe Derambure, University Hospital of Lille; Vincent Navarro, APHP; Edouard Hirsch, University Hospital of Strasbourg; Louis Maillard, University Hospital of Nancy; Fabrice Bartolomei, University Hospital of Marseille; Julien Biberon, University Hospital of Tours; Didier Tourniaire, La Teppe; Arnaud Biraben, University Hospital of rennes; Arielle Crespel, University Hospital of Montpellier; Pierre Thomas, University Hospital of Lice; University Hospital of Dijon Philippe Convers, University Hospital of Saint-Etienne; Sebastien Boulogne, Hospices Civils de Lyon; Hospices Civils de Lyon
Content: Rationale: Preclinical studies have shown that caffeine increases seizure susceptibility. However, this effect depends on the dose and administration type, with data suggesting that chronic low-dose caffeine exposure can protect rodents from seizures and their complications, including risk of Sudden and Unexpected Death in Epilepsy (SUDEP). In contrast, the exact relation between caffeine consumption and seizure frequency in patients remains unclear. Methods: The SAVE study is an ongoing multicenter open-label trial, focusing on the management of antiepileptic drugs withdrawal during LTM in patients with drug resistant epilepsy (NCT02679846). Its inclusion criteria are: (i) patients (age ≥6 years) with drug-resistant focal epilepsy (ii) who undergo long term video-EEG monitoring. In the present study, we selected adults patients (age ≥18 years) included in the SAVE study between 15/02/2016 and 31/10/2018 in whom both coffee consumption and data about seizure frequency were available. We collected demographic data and detailed clinical data, including seizure frequency over the past 3 months and number of focal seizure evolving to generalized tonic-clonic seizures (sGTCS) during the past year. Coffee consumption was collected using a standardized self-questionnaire where each included patient indicated her/his usual consumption as the following: no consumption, less than 1 cup/week, between 1 et 3 cups/week, between 4 et 6 cups/week, between 1 et 3 cups/day, between 4 et 6 cups/day and more than 6 cups/day. Caffeine consumption was further classified into four groups: none, rare (from less than 1 cup/week to up 3 cups/week), moderate (from 4 cups/week to 3 cups/day) and high (more than 4 cups/day). Risk of SUDEP was evaluated using the revised SUDEP-7 inventory. Results: Overall, 616 patients were included with a mean age of 36.2 +/- 11.6 years and a mean duration of epilepsy of 18.1 +/- 12.0 years. Over the past 3 months preceding study inclusion, the median seizure frequency of any type was 4.33 per month (interquartile range (IR) 11.0). 217 patients reported sGTCS in the past year. In these latter, the median sGTCS frequency per month was 1.0 (IR 1.75). The median number of antiepileptic drugs currently used was 2.0 (IR 1.0). The revised SUDEP-7 inventory was available in 607 patients and the median score was 3.0 (IR 2.0). Overall, 192 patients (31/1%) reported no coffee consumption, 40 (6.5%) less than 1 cup/week, 109 (17.7%) between 1 et 3 cups/week, 55 (8.9%) between 4 et 6 cups/week, 121 (19.6%) between 1 et 3 cups/day, 71 (11.5%) between 4 et 6 cups/day and 29 (4.7%) more than 6 cups/day. There was no relation between caffeine consumption and seizure frequency of any type (p=0.89). In contrast, we observed a bimodal association between frequency of sGTCS and coffee consumption (p=0.014 by Kruskal-Wallis test). The mean GTCS frequency was thus 1.01 +/- 6.63 in patients who did not report coffee consumption, 1.40 +/- 7.13 in those with rare consumption (n=149), 0.48 +/- 1.81 in those with moderate consumption (n=176) and 4.13 +/- 21.5 in those with high consumption. In contrast, no significant association was observed between score of the SUDEP-7 inventory and level of caffeine consumption (p=0.078). Conclusions: As observed in animal models of epilepsy, our data suggest that effect of caffeine on seizures might depend on dose, with potential benefits at moderate doses but increased seizure susceptibility at high doses. These results and their potential relation with risk of SUDEP need to be further investigated in prospective studies. Funding: French Ministry of Health (PHRC National 2013)