Revision and removal of vagus nerve stimulation systems: twenty-five years' experience.

BACKGROUND: Epilepsy, a disease characterized by recurrent seizures, is a common chronic neurologic condition. Antiepileptic drugs (AED) are the mainstay of treatment for epilepsy. Vagus nerve stimulation (VNS) surgery is an adjuvant therapy for the treatment of drug refractory epilepsy (DRE). VNS revision and implant removal surgeries remain common. METHODS: Using a single neurosurgeon data registry for epilepsy surgery, we retrospectively analyzed a total of 824 VNS surgeries. Patients were referred to two Level IV Comprehensive Epilepsy centers (from 08/1997 to 08/2022) for evaluation. Patients were divided into four groups: new device placement, revision surgery, removal surgery, and battery replacement for end-of-life of the generator. The primary endpoint was to analyze the reasons that led patients to undergo revision and removal surgeries. The time period from the index surgery to the removal surgery was also calculated. RESULTS: The median age of patients undergoing any type of surgery was 34 years. The primary reason for revision surgeries was device malfunction, followed by patients' cosmetic dissatisfaction. There was no statistical sex-difference in revision surgeries. The median age and body mass index (BMI) of patients who underwent revision surgery were 38 years and 26, respectively. On the other hand, the primary reason for removal was lack of efficacy, followed again by cosmetic dissatisfaction. The survival analysis showed that 43% of VNS device remained in place for 5 years and 50% of the VNS devices were kept for 1533 days or 4.2 years. CONCLUSIONS: VNS therapy is safe and well-tolerated. VNS revision and removal surgeries occur in less than 5% of cases. More importantly, attention to detail and good surgical technique at the time of the index surgery can increase patient satisfaction, minimize the need for further surgeries, and improve acceptance of the VNS technology.

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition.

Guided by computational analysis, herein we report the design, synthesis and evaluation of four novel diazine-based histone deacetylase inhibitors (HDACis). The targets of interest (TOI) are analogues of panobinostat, one of the most potent and versatile HDACi reported. By simply replacing the phenyl core of panobinostat with that of a diazine derivative, docking studies against HDAC2 and HDAC8 revealed that the four analogues exhibit inhibition activities comparable to that of panobinostat. Multistep syntheses afforded the visualized targets TOI1, TOI2, TOI3-rev and TOI4 whose biological evaluation confirmed the strength of HDAC8 inhibition with TOI4 displaying the greatest efficacy at varying concentrations. The results of this study lay the foundation for future design strategies toward more potent HDACis for HDAC8 isozymes and further therapeutic applications for neuroblastoma.