Neurostimulation as a promising epilepsy therapy

Abstract

SummaryThe revolution in theory, swift technological developments, and invention of new devices have driven tremendous progress in neurostimulation as a third‐line treatment for epilepsy. Over the past decades, neurostimulation took its place in the field of epilepsy as an advanced treatment technique and opened up a new world. Numerous animal studies have proven the physical efficacy of stimulation of the brain and peripheral nerves. Based on this optimistic fundamental research, new advanced techniques are being explored in clinical practice. Over the past century, drawing on the benefits brought about by vagus nerve stimulation for the treatment of epilepsy, various new neurostimulation modalities have been developed to control seizures. Clinical studies including case reports, case series, and clinical trials have been booming in the past several years. This article gives a comprehensive review of most of these clinical studies. In addition to highlighting the advantages of neurostimulation for the treatment of epilepsy, concerns with this modality and future development directions are also discussed. The biggest advantage of neurostimulation over pharmacological treatments for epilepsy is the modulation of the epilepsy network by delivering stimuli at a specific target or the “hub.” Conversely, however, a lack of knowledge of epilepsy networks and the mechanisms of neurostimulation may hinder further development. Therefore, theoretical research on the mechanism of epileptogenesis and epilepsy networks is needed in the future. Within the multiple modalities of neuromodulation, the final choice should be made after full discussion with a multidisciplinary team at a presurgical conference. Furthermore, the establishment of a neurostimulation system with standardized parameters and rigorous guidelines is another important issue. To achieve this goal, a worldwide collaboration of epilepsy centers is also suggested in the future.

Brain‐responsive neurostimulation treatment in patients with GAD65 antibody–associated autoimmune mesial temporal lobe epilepsy

“…In addition to neuromodulation, VNS therapy has been speculated to have a modulatory effect on immune cell reactivity 13 . The mechanisms mediating the effects of RNS System treatment on seizures may be due to depolarization blockade, synaptic inhibition, and long‐term pathologic network modulation 14 . Currently, it is unknown whether direct brain‐responsive neurostimulation exerts a local modulatory effect on inflammatory mediators.…”

Intracranial interictal functional networks predict the effect of subacute cortical stimulation in focal epilepsy

“…Combining these insights with the recent proposal by [18] that such network analysis techniques may be informative for identifying suitable neurostimulation targets, we propose to use the SCS dataset in a retrospective functional network analysis. Specifically, we will investigate if interictal functional networks at baseline (before stimulation) can predict the success of the stimulation location in suppressing seizures.…”

Cortical GABAergic Interneuron/Progenitor Transplantation as a Novel Therapy for Intractable Epilepsy

“…Two alternatives are neurosurgical resection of the seizure focus ( Kneen and Appleton, 2006 ) and neurostimulation ( Lin and Wang, 2017 ). Compared to current drug therapies, patients that undergo surgical removal of seizure foci are more likely to become seizure free with better quality of life ( Liu et al, 2018 ).…”

“…Moreover, many patients relapse after an initial seizure-free phase ( de Tisi et al, 2011 ). The major advantages of neurostimulation over surgical resections and AEDs are that this approach does not require removal of brain tissue, and it can be applied into a specific target region to modulate affected neural circuity ( Lin and Wang, 2017 ). Electrical neurostimulation is reported to be effective and acceptably safe ( Heck et al, 2014 ), but it is currently useful only in a fraction of patients with drug-refractory seizures ( Pais-Vieira et al, 2016 ).…”

“…Electrical neurostimulation is reported to be effective and acceptably safe ( Heck et al, 2014 ), but it is currently useful only in a fraction of patients with drug-refractory seizures ( Pais-Vieira et al, 2016 ). Transcranial magnetic stimulation is non-invasive, but there is no powerful evidence to support its efficacy ( Lin and Wang, 2017 ). These limitations in the currently available treatment options for epilepsy, especially for those for refractory epilepsy, call for the development of more effective and restorative therapeutics.…”