What is the role of vagal nerve stimulation (VNS) in treating supra-refractory status epilepticus?

Vagal Nerve Stimulation for Supra-Refractory Status Epilepticus

Vagal nerve stimulation (VNS) should be strongly considered as a treatment option for supra-refractory status epilepticus (SRSE) with evidence showing it can terminate status epilepticus in approximately 74% of cases. 1

Definition and Context

• Refractory status epilepticus (RSE): Persistence of status epilepticus despite second-line treatment
• Super-refractory status epilepticus (SRSE): Status epilepticus that continues despite 48 hours of anesthetic treatment
• Mortality rates: 16-39% in RSE, with higher rates in SRSE

Evidence for VNS in SRSE

• Systematic review identified 38 cases of acute VNS implantation for RSE/SRSE with:
  • 74% (28/38) success rate in terminating status epilepticus
  • 82% (31/38) positive outcomes overall
  • 11% mortality rate (4 patients), attributed to underlying disease rather than VNS 1
• Median duration of RSE/SRSE:
  • Pre-VNS implantation: 18 days (range: 3-1680 days)
  • Post-VNS implantation: 8 days (range: 3-84 days) 1

Mechanism and Implementation

VNS works by:

• Altering cortical synchronization
• Increasing or decreasing EEG synchronization depending on stimulation parameters
• Potentially providing anti-inflammatory effects in certain etiologies 2, 3

Optimal VNS Parameters for SRSE

Based on available evidence, the following parameters should be considered:

1. Duty Cycle:

   • Higher duty cycles show improved efficacy
   • Consider reducing OFF time to ≤1.1 minutes from standard 5 minutes 2

2. Frequency:

   • Optimal range: 20-30 Hz based on preclinical studies
   • Higher frequencies (130-180 Hz) may provide greater seizure attenuation 2

3. Stimulation Approach:

   • Rapid titration protocol after implantation 3
   • Consider closed-loop stimulation when available 2

Clinical Implementation Timeline

• Consider VNS implantation when status epilepticus persists despite standard treatments
• In pediatric cases, resolution of SRSE occurred in approximately two weeks after implantation 3
• Case reports show successful termination of status epilepticus within 7-10 days after implantation 4

Caveats and Considerations

• Evidence is primarily from case reports and small case series (Level IV evidence)
• Risk of reporting bias is high 1
• VNS may be more effective for generalized RSE (76% success) than focal RSE (26% success) 1
• Consider as an adjunctive therapy alongside pharmacological management
• Deep Brain Stimulation (DBS) may be an alternative with potentially higher efficacy rates (60-78% vs 51% with VNS) for certain epilepsy types 5

Practical Approach to VNS in SRSE

1. Consider VNS when status epilepticus persists despite:

   • Benzodiazepines
   • Second-line antiepileptic drugs
   • Anesthetic agents

2. Implement rapid parameter titration:

   • Start stimulation immediately after implantation
   • Increase duty cycle beyond standard parameters
   • Monitor EEG for response

3. Use magnet swiping for acute seizure termination when breakthrough seizures occur 6

4. Continue monitoring for at least 72 hours after apparent seizure cessation, as recurrence is possible 6

VNS represents a promising neuromodulation approach for SRSE that may reduce the need for prolonged anesthetic coma and its associated complications. While more prospective studies are needed, current evidence supports its consideration in the management algorithm for this life-threatening condition.