FRANCESCA PIZZO ^1,2* Romain Carron ^1,2 Virginie Laguitton ¹ Audrey Clement ¹ Bernard Giusiano ^1,2 Fabrice Bartolomei ^1,2

• ¹ Service d'épileptologie et de neurophysiologie clinique, Hôpital de la Timone, Marseille, Provence-Alpes-Côte d'Azur, France
• ² INSERM U1106 Institut de Neurosciences des Systèmes, Faculté de Médecine, Aix Marseille Université, Marseille, Provence-Alpes-Côte d'Azur, France

Objective: This study aims to evaluate the efficacy and safety of deep brain stimulation (DBS) of the medial pulvinar nucleus (PuM) in reducing seizure frequency and addressing comorbidities in patients with drug and vagal nerve-resistant focal epilepsy. Methods: This is an open-label prospective treatment trial with planned enrollment of 12 patients suffering from medically refractory epilepsy (Clinical trial gov NCT04692701), for which the interim 12 months post-implantation results for the first 6 patients are being reported. Inclusion criteria were focal epilepsy not suitable for or after failed surgical intervention, and previous failure of neurostimulation therapies (vagus nerve stimulation or anterior thalamic nucleus DBS). Evaluations included seizure diaries, neuropsychological assessments, and scales for depression, anxiety, quality of life, and seizure severity. PuM DBS was performed using ROSA robotic assistance, with follow-ups every three months for one year. Results: Out of six patients, five completed one year of follow-up (1 patient died prematurely). A non-significant trend towards seizure reduction was observed at six months, becoming more pronounced at one year (mean reduction: 45%; responders: 2/5). Seizure severity significantly improved (p=0.02), with a reduction in the NHS3 scale scores. Quality of life improved significantly at one year (p=0.03). Psychiatric assessments indicated a non-significant trend towards improvement in depression (mean improvement: 26%) and anxiety (mean improvement: 20%) scores. Neuropsychological testing showed stable or improved cognitive performance in three out of five patients. Adverse events included one case of cerebral hemorrhage, one infection leading to device removal, and one possible SUDEP. Significance: Preliminary results suggest that PuM DBS may offer a promising therapeutic option for reducing seizure severity and improving quality of life and cognitive functions in patients with drug-resistant epilepsy. Despite the small sample size and the presence of serious adverse events, the findings warrant further investigation with larger cohorts to confirm these trends and optimize the treatment protocol.