VNS significantly improves seizure control, cognitive outcomes, and quality of life, with a favorable safety profile, and support VNS as an effective and safe alternative for this specific TSC population.
Abstract
Objective
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with a high prevalence of drug-resistant epilepsy (DRE), significantly affecting patients' quality of life. For patients with TSC lacking localizing epileptogenic tuber, resective surgery is often not feasible. Vagus nerve stimulation (VNS) has been proposed as an alternative surgical therapy, although robust evidence in TSC-related DRE remains limited.
Methods
A prospective cohort study was conducted between December 2019 and July 2024 across multiple epilepsy centers in China. Seventy patients with TSC-related DRE were enrolled, all lacking resectable epileptogenic tubers on multidisciplinary evaluation and ineligible for resective surgery. Participants were divided into VNS (n = 20) and medication-only (n = 50) groups based on actual treatment, and followed for up to 3 years. Seizure outcomes, anti-seizure medication use, IQ, and quality of life were evaluated longitudinally.
Results
The VNS group demonstrated significantly higher response rates at 1-, 2-, and 3-year follow-ups (65%-75%) compared to the medical treatment group (31%-36%). Median and average seizure frequency reductions were also greater in the VNS group. VNS was associated with significantly higher treatment response than medication, with the relative risk (RR) of response being 1.81 (95% confidence interval [CI]: 1.22-2.67), 2.21 (95% CI: 1.42-3.44), and 2.42 (95% CI: 1.49-3.93) at 1-, 2-, and 3-year follow-ups (p < 0.01). Seizure recurrence was significantly lower in the VNS group (p < 0.01). Moreover, VNS treatment led to significant reductions in anti-seizure medication (ASM) use and improvement in intelligence quotient and quality of life at the 2-year follow-up. Treatment modality was the only independent predictor of clinical response. VNS was well tolerated, with only mild surgical complications and no permanent adverse events reported.
Significance
VNS significantly improves seizure control, cognitive outcomes, and quality of life, with a favorable safety profile. These findings support VNS as an effective and safe alternative for this specific TSC population. Future randomized controlled trials are warranted to further validate these results.
Vagus nerve stimulation (VNS) has been proven as an effective and safe adjunct therapy for epilepsy, but real-world evidence is limited. This study aimed to evaluate outcomes of VNS and its cumulative effect through a prospective, multicenter, real-world survey in China, with dynamic follow-up. A total of 83 sites in China participated and 124 epilepsy patients enrolled. Visits were scheduled at 1, 3, 6, 9, and 12 months after VNS. Primary outcomes included seizure response rate (≥ 50% frequency reduction) and seizure-free rate. Secondary outcomes assessed changes in the 31-item Quality of Life in Epilepsy Inventory (QOILE-31) score, overall anti-seizure medication (ASM) load, and adverse events. The responder rates were 35.5%, 41.6%, 62.2%, 64.2%, and 76.6% at 1, 3, 6, 9, and 12 months after VNS, respectively. Seizure-free rates were 2.4%, 2.7%, 9.2%, 8.6%, and 10.9% at 1, 3, 6, 9, and 12 months, respectively. No significant differences were observed in overall ASM load between baseline and any follow-up visit. Significant improvements were noted in QOLIE-31 from baseline to each follow-up visit, with mean (± SD) score improvements as follows: 1 month (2.93 ± 8.65), 3 months (4.27 ± 9.84), 6 months (4.69 ± 11.5), 9 months (6.68 ± 12.5), and 12 months (9.32 ± 13.8). A significant trend toward improved seizure outcomes and change in quality of life was observed with longer treatment durations. Adverse events occurred in 34 patients (27.4%). VNS is an effective and safe adjunctive treatment for epilepsy, reducing seizure frequency and significantly improving quality of life, with a cumulative effect over time.
It is suggested that repeat sEEGs may help guide effective treatment in children with multifocal epilepsy, while multifocal networks may necessitate additional sEEG evaluations and subsequent surgeries, favorable seizure outcomes can be achieved.
J. Uchitel, Olubunmi A. Fariyike, Samantha Steeman et al.· Epilepsia Open· 0 citations
Abstract Introduction 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. Objective and Material 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. Results 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. Conclusion 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.
Naoki Nakano, J.C. Takahashi· Asian Journal of Neurosurger...· 0 citations
Childhood drug-resistant epilepsy was the strongest predictor of persistent adult seizures and disability and TSC2 mutations were linked to a more severe phenotype but does not predict the course of epilepsy in adulthood, supporting early, optimized seizure management.
Q. Calonge, A. Hanin, Maëlle Dade et al.· Journal of Neurology· 0 citations
Palliative surgical procedures for pediatric DRE are safe and associated with seizure reduction, decreased medication burden, and gradual improvement in adaptive functioning and early surgical intervention may help minimize developmental decline and improve long-term adaptive outcomes.
Ana Valeria Duarte Oliveira, H. Machado, Ú. Thomé et al.· Child's Nervous System· 0 citations
