Vagal Nerve Stimulation May Benefit Patients With Medically Intractable Epilepsy

A review of randomized controlled trials suggests patients with epilepsy refractory to medical management may benefit from vagal nerve stimulation.

A new review suggests that vagal nerve stimulation (VNS) can offer palliative benefit for patients with epilepsy that is refractory to medical management and not amenable to resective surgery.

This review of randomized controlled trials (RCTs) and prospective nonrandomized studies was published in Journal of Central Nervous System Disease. The final review included 6 total trials.

The authors identified 3 adult trials and 1 pediatric trial in their comprehensive literature search. Across these 4 RCTs, high-frequency VNS stimulation—defined as frequency greater than 20 Hz—consistently achieved a greater seizure frequency reduction, ranging between 23.4% and 33.1%, compared with low-frequency VNS—defined as 1 Hz—which ranged between 0.6% and 15.2%.

The authors also identified 2 RCTs that looked at whether the parameters of VNS influenced seizure control. According to the results from these 2 trials, VNS achieved seizure control comparable to that reported by the first 4 RCTs, with a reduction in seizure frequency ranging between 22% and 43%, irrespective of the parameters utilized for VNS.

“While the reduction in seizure frequency did not reach significance in every RCT, the studies that reported insignificant differences were also those with fewer patients, suggesting that inadequate sample size contributed to the variation in the reported outcome,” the authors said.

Additionally, VNS-associated morbidities were found to be consistently higher in adults who underwent high-frequency VNS, while these differences were not observed in the pediatric population.

The following VNS-related morbidities were seen in the trials, and were reduced by the associated percentages:

  • Hoarseness: 15%-66%
  • Cough: 7%-45%
  • Pain: 11%
  • Dyspnea: 6%-25%
  • Paresthesias: 7.9%
  • Nausea: 30%

The authors noted that quality of life and global well-being assessments in certain RCTs suggest the benefits of seizure control generally outweigh the risk of VNS-associated morbidities, as one trial evaluated patients’ well-being as a secondary end point and found VNS was linked to overall improvements in well-being. Further, since the initial FDA approval of VNS technology, these tools have drastically improved.

They also noted this review raised several key questions to steer future analyses, emphasizing the need for research on seizure biomarkers in patients with epilepsy to see who would benefit from VNS treatment.

“Finally, advances in wearable devices, such as smartwatches, have the potential to bypass the need for patient-reported seizure diaries in future clinical studies,” the authors wrote. “The development of 'closed-loop VNS' systems and transcutaneous VNS as adjunctive treatments for medically intractable epilepsy has the potential to further enhance the efficacy of VNS in select patients.”


Cramer SW, McGovern RA, Chen CC, Park MC. Clinical benefit of vagus nerve stimulation for epilepsy: assessment of randomized controlled trials and prospective non-randomized studies. J Cent Nerv Syst Dis. Published online January 11, 2023. doi:10.1177/11795735231151830

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