Rationale:
Vagus nerve stimulation is a successful treatment for drug resistant epilepsy (DRE). The optimal stimulation parameters for seizure control are unknown and may differ between patients. Novel stimulation paradigms such as microburst stimulation have been developed following previous preclinical research. In this study we aimed to investigate the approach of individualized titration of stimulation parameters based on the effects of different stimulation parameters on central nervous system structures by means of functional imaging.
Method:
Patients implanted with the most recently developed VNS-device were included in a prospective multicenter trial i.e. the Microburst Study (NCT03446664). Patients were investigated with fMRI using a series of standard and microburst stimulation parameters with stepwise increases in output current. At 2 weeks, 1, 3 and 6 months post-implantation, stimulation parameters associated with the strongest thalamic activation when comparing VNS ON/OFF fMRI microburst responses were selected based on immediate post-scanning fMRI analysis. Patients filled out a quality of life questionnaire (QOLIE-31). A first 54-year old patient with drug resistant juvenile myoclonic epilepsy with generalized tonic-clonic and myoclonic seizures treated at Ghent University Hospital is presented.
Results:
Two weeks after implantation, VNS was initiated following a first fMRI session using parameters associated with the strongest thalamic BOLD-signal change: 1mA output current, 300Hz frequency, 250µsec pulse width, 7 pulses and 0.5 seconds interburst intervals (i.e. microburst parameters, figure 1). Duty cycle was 30s on/5min off. During the following fMRI sessions at 1 month, 3 months and 6 months, stimulation parameters were further adjusted based on the post-scan fMRI analysis. At 3 months, stimulation parameters were 2mA output current, 300Hz frequency, 250µsec pulse width, 7 pulses and 0.5 seconds interburst intervals resulting in seizure outcome at maximum follow-up of 6 months reported here. Generalized tonic-clonic seizures and myoclonic seizures decreased with 91.5% (from 4.7 to 0.4) and 52.0% (from 41.7 to 20.0) respectively compared to baseline. The overall QOLIE score decreased by 7,4% (from 71.9 to 66.6) but improved by 57.5% for mood parameter (from 40.0 to 63.0). The patient reported a transient dizziness that was resolved by 6 months follow-up. The patient mentioned better tolerability when microburst vs standard stimulation was tested during fMRI visits (less hoarseness).
Conclusion:
The choice of stimulation parameters based on individual brain activation patterns resulted in a decrease in seizure frequency and severity following VNS in a patient with DRE. The novel microburst stimulation parameters resulted in low side effects and successful outcome. This personalized medicine approach of neuromodulation is unique and may further improve seizure control in patients treated with VNS.
Funding:
:This study was funded by Livanova, Houston, Texas. Ann Mertens is supported by Research Foundation Flanders.
FIGURES
Figure 1