Long-Term Seizure Outcomes Between Combined Vagus Nerve Stimulation and Corpus Callosotomy and Corpus Callosotomy Alone in Patients with Refractory Multifocal or Generalized Epilepsy: A Comparative Study

Abstract Epilepsy surgery is considered an established therapeutic modality for achieving seizure control in patients with drug-resistant epilepsy. Surgical interventions are broadly categorized as either curative or palliative, which depend on the identification or absence of a well-defined epileptogenic focus amenable to surgical treatment. Palliative surgical interventions are indicated for patients with medically refractory multifocal or generalized epilepsy who are not suitable candidates for resective surgery. These therapeutic modalities include corpus callosotomy (CC), vagus nerve stimulation (VNS), deep brain stimulation (DBS), and other neuromodulatory strategies. Several studies have reported that the combined application of VNS and CC is associated with favorable seizure outcomes in patients with drug-resistant epilepsy. In this study, the long-term efficacy of the combined application of these two surgical interventions and CC alone in patients with multifocal or generalized epilepsy was assessed over a follow-up period exceeding 10 years. Moreover, 11 patients who underwent the combined treatment of CC and VNS, as well as 7 patients who underwent CC alone, were included; all of whom received surgical treatment through our institution's epilepsy surgery program between 2004 and 2015. All 11 patients initially underwent CC, followed by subsequent implantation of VNS. The clinical outcomes following the combined therapeutic approach showed a progressive increase in the proportion of patients achieving a ≥80% reduction in seizure frequency compared with CC alone. Moreover, the therapeutic benefits of the combined intervention were maintained throughout long-term follow-up. The combined treatment of CC and VNS has shown considerable efficacy in the management of multifocal and generalized epilepsy. In recent years, palliative surgical approaches have progressively evolved toward neuromodulation-based therapies, driven by advances in emerging technologies. However, further research is needed to establish the potential therapeutic benefit of integrating next-generation neuromodulatory modalities, including VNS, DBS and responsive neurostimulation, which is expected to expand the therapeutic landscape for patients with drug-resistant epilepsy.