Contemporary Disconnection and Neuromodulation Treatments for Generalized Drug-Resistant Epilepsy: A Narrative Review...

Background: Surgical treatment of generalized drug-resistant epilepsy (DRE), lacking a clearly resectable epileptogenic focus, presents a formidable clinical challenge. Inadequately treated generalized DRE is associated with neurological deficits, impaired neurodevelopment, poor quality of life, and lifelong educational and occupational difficulties. Over the last half-century, various neurosurgical interventions have been introduced for the management of generalized DRE. These include longstanding and well-established disconnection procedures, which have evolved over time to reduce surgical morbidity, as well as more recent options such as neuromodulation through surgically implanted devices. As technological advances and evidence for their use continue to grow, clinical decision-making has become increasingly nuanced. Summary: This narrative review synthesizes contemporary neurosurgical strategies for the management of generalized DRE, focusing on two principal categories of intervention: disconnection procedures (e.g., corpus callosotomy) and neuromodulation therapies (e.g., vagus nerve stimulation, deep brain stimulation, responsive neurostimulation). We provide an updated summary of their indications, efficacy, and complications, supported by recent clinical data. In addition, we offer an evidence-based clinical framework to assist with patient selection and presurgical counselling in specialized epilepsy centers. The review also addresses emerging technologies and ongoing innovations, including minimally invasive techniques and closed-loop stimulation systems. Key Messages: Neurosurgical intervention is a viable treatment option for patients with generalized DRE who have failed medical therapy, with evidence supporting its role in reducing seizure burden and improving overall quality of life. Disconnection procedures remain highly effective, especially for individuals with frequent drop attacks or developmental and epileptic encephalopathies, though patient selection is critical to minimize neurocognitive risks. Neuromodulation therapies are increasingly used in both pediatric and adult populations, offering less invasive and more adaptable alternatives. As treatment options expand, clinical decision-making has become more complex and must be guided by seizure characteristics, imaging findings, and individualized patient goals.