Personalized Neuromodulation Therapy Reduces Seizures Safely in Drug-Resistant Epilepsy

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Microburst stimulation was also found to be more tolerable than standard stimulation in patients with drug-resistant epilepsy.

Kristl Vonck, MD, PhD, professor of neurology, laboratory for clinical and experimental neurophysiology, Ghent University

Kristl Vonck, MD, PhD

Data from a patient enrolled in a prospective multicenter trial, the Microburst Study (NCT03446664), suggest that individualized titration of stimulation parameters based on individual brain activation patterns resulted in a decrease in seizure frequency and severity following vagus nerve stimulation (VNS) in a patient with drug-resistant epilepsy (DRE).1

These findings were presented virtually at the American Epilepsy Society (AES) Annual Meeting, December 4–8, 2020, by Kristl Vonck, MD, PhD, professor of neurology, laboratory for clinical and experimental neurophysiology, Ghent University. Vonck and colleagues found that personalized, novel microburst stimulation resulted in reduction of seizures with minimal side effects.

“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,” Vonck and colleagues commented on VNS. “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.”

Patients enrolled in Microburst were investigated with fMRI using a series of standard and microburst stimulation parameters with titrated increases in output current. Stimulation parameters associated with the strongest thalamic activation when comparing VNS on/off fMRI microburst responses were selected post-implantation at 2 weeks, 1 month, 3 months, and 6 months based on immediate post-scanning fMRI analysis. Data presented at AES were from a 54-year-old patient with drug resistant juvenile myoclonic epilepsy with generalized tonic-clonic and myoclonic seizures.

READ MORE: Noninvasive Vagus Nerve Stimulation Shows Promise for Acute Vestibular Migraine

VNS was first initiated 2 weeks after implantation of the VNS device. The parameters were associated with the strongest thalamic blood-oxygen-level-dependent (BOLD)-signal change: 1mA output current, 300Hz frequency, 250µsec pulse width, 7 pulses and 0.5 seconds interburst intervals. VNS was cycled 30 seconds on and 5 minutes off. At the subsequent 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 microburst intervals. At 6-month follow-up, generalized tonic-clonic seizures (GTCc) decreased by 91.5% (from 4.7 to 0.4) and myoclonic seizures decreased 52.0% (from 41.7 to 20.0) from baseline.

The overall Quality of Life in Epilepsy (QOLIE) score decreased by 7.4% (from 71.9 to 66.6) but mood parameter score improved by 57.5% (from 40.0 to 63.0). The patient reported a transient dizziness that was resolved by 6 months follow-up and better tolerability to microburst stimulation vs. standard stimulation.

“This personalized medicine approach of neuromodulation is unique and may further improve seizure control in patients treated with VNS,” Vonck and colleagues concluded.

NeurologyLive has previously covered an investigation into the safety and efficacy of vagus nerve stimulation conducted by Sandipan Pati, MD, assistant professor, department of neurology, University of Alabama at Birmingham, and colleagues. They found that 44% (n = 12) of patients with DRE treated with VNS self-reported a ≥60% reduction in seizures at follow-ups, 8+ months post-implantation, though none were seizure-free. Of that cohort, 15% (n = 4) were non-responders. The most tolerated stimulation current was between 1.5 and 2.25 mA.2

For more coverage of AES 2020, click here.

REFERENCES
1. Vonck K, Mertens A, Gadeyne S, et al. Personalized neuromodulation therapy in drug resistant epilepsy patients treated with vagus nerve stimulation. Presented at AES 2020 Annual Meeting; December 4–8, 2020. Abstract 451.
2. Jamy, R, Kaur, M, Pizarro, D, Toth, E, Pati, S. Practice trends and the outcome of neuromodulation therapies in epilepsy: A single‐center study. Epilepsia. 2019; 4: 493– 497. doi:10.1002/epi4.12345
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