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

Vagal Nerve Stimulation in Super-Refractory Status Epilepticus

Vagal nerve stimulation (VNS) should be considered as an adjunctive treatment for super-refractory status epilepticus (SRSE) when conventional pharmacological approaches have failed, with evidence showing successful termination of status epilepticus in multiple case reports. 1, 2, 3

Mechanism and Efficacy in SRSE

VNS works by delivering intermittent electrical stimulation to the vagus nerve through implanted electrodes connected to a pulse generator. In the context of epilepsy:

• VNS has demonstrated efficacy in refractory epilepsy with approximately 51% of patients experiencing a ≥50% reduction in seizure frequency 4, 1
• For SRSE specifically, VNS has shown promising results in terminating seizure activity when conventional treatments fail 2, 3
• The mechanism appears to involve alteration of cortical synchronization and modulation of brain activity 4

Implementation in SRSE

When considering VNS for SRSE, the following approach is recommended:

1. Timing of implantation:

   • Consider VNS after failure of standard pharmacological approaches (benzodiazepines, antiseizure medications, anesthetic agents)
   • Case reports show successful implantation between 8-58 days after status epilepticus onset 2, 3

2. Stimulation parameters:

   • Implement rapid parameter titration after implantation 3, 5
   • Higher duty cycle and/or frequency may improve response rates based on preclinical evidence 4
   • Both continuous stimulation and on-demand stimulation (via magnet swiping) can be utilized 1

3. Expected response:

   • Successful cases report termination of status epilepticus within 7-14 days after VNS implantation 3, 6
   • Some patients have shown complete resolution of status epilepticus for extended periods (e.g., 72 hours in one case) 2

Clinical Evidence in SRSE

The evidence for VNS in SRSE comes primarily from case reports and small case series:

• A 25-year-old male with NORSE showed significant reduction in seizure activity following VNS implantation on day 8 of hospitalization, with no seizures for 72 hours after implantation 2
• Two patients with genetic epilepsy and SRSE achieved stable remission of status epilepticus by day 7 and day 10 after VNS implantation 3
• A 23-year-old man in status epilepticus for 3 weeks made a full recovery after VNS implantation 7
• In pediatric patients, VNS has shown efficacy in resolving SRSE in approximately 2 weeks in most cases 6

Advantages and Limitations

Advantages:

• Non-pharmacological approach that may reduce medication burden and associated toxicities 2, 6
• Can be effective when multiple antiseizure medications and anesthetic agents have failed 2, 3, 7
• Both continuous and on-demand stimulation options 1
• Potential anti-inflammatory effects that may be beneficial in certain etiologies like FIRES 5, 6

Limitations:

• Invasive procedure requiring surgical implantation
• Limited large-scale evidence specifically for SRSE
• Potential complications including infection risk and rare cardiac complications 1
• Battery depletion requiring eventual replacement 1

Alternative Neuromodulation Approaches

If VNS is not feasible or unsuccessful, deep brain stimulation (DBS) may be considered:

• DBS offers more precise targeting of epileptic networks 1
• Potentially higher efficacy rates (60-78% vs 51% with VNS) 1
• Anterior thalamic nucleus stimulation shows strongest evidence for focal seizures 1

Important Clinical Considerations

• VNS should be considered earlier rather than later in the course of SRSE, as prolonged status epilepticus is associated with worse outcomes
• Rapid parameter titration appears safe and may lead to faster seizure control 3, 5
• VNS may be particularly beneficial in specific etiologies like FIRES or genetic epilepsies 3, 5
• The decision to implant VNS should be made in conjunction with a multidisciplinary team including neurologists, neurosurgeons, and critical care specialists

VNS represents a valuable adjunctive treatment option for SRSE when conventional approaches have failed, with multiple case reports demonstrating successful termination of status epilepticus and improved outcomes.