Neuromodulation for Refractory Epilepsy

Abstract

Three neuromodulation therapies, all using implanted device and electrodes, have been approved to treat adults with drug-resistant focal epilepsy, namely, the vagus nerve stimulation in 1995, deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) in 2018 (2010 in Europe), and responsive neurostimulation (RNS) in 2014. Indications for VNS have more recently extended to children down to age of 4. Limited or anecdotal data are available in other epilepsy syndromes and refractory/super-refractory status epilepticus. Overall, neuromodulation therapies are palliative, with only a minority of patients achieving long-term seizure freedom, justifying favoring such treatments in patients who are not good candidates for curative epilepsy surgery. About half of patients implanted with VNS, ANT-DBS, and RNS have 50% or greater reduction in seizures, with long-term data suggesting increased efficacy over time. Besides their impact on seizure frequency, neuromodulation therapies are associated with various benefits and drawbacks in comparison to antiseizure drugs. Yet, we lack high-level evidence to best position each neuromodulation therapy in the treatment pathways of persons with difficult-to-treat epilepsy.

Responsive Thalamic Neurostimulation: A Systematic Review of a Promising Approach for Refractory Epilepsy

“…The question of whether responsive stimulation is more efficacious than continuous thalamic DBS remains to be addressed, as the two techniques have not been directly compared in the same subjects ( Burdette et al, 2020 ). There currently are no biomarkers which would predict the efficacy of RNS system for any approved or off-label applications ( Ryvlin and Jehi, 2022 ).…”

“…It is also challenging to make deductions from these studies regarding the effects of thalamic responsive stimulation on neurocognitive wellbeing, as only 1 out of 10 publications included formal neurocognitive testing at follow-up ( Burdette et al, 2021 ). Furthermore, whereas larger studies utilize responsive stimulation for several years before assessing the impact on seizure frequency, ( Ryvlin and Jehi, 2022 ) follow-up data for 12/29 of the subjects described in this review was obtained within 12 months from starting thalamic stimulation ( Osorio et al, 2005 ; Kokoszka et al, 2018 ; Burdette et al, 2020 , 2021 ; Kwon et al, 2020 ; Welch et al, 2021 ; Beaudreault et al, 2022 ). Finally, although seizure frequency was a primary outcome in all 10 studies, the RNS system cannot record for extended periods of time and does not track all data relating to seizure frequency ( Thomas and Jobst, 2015 ).…”

“…Approved in 1995, vagal nerve stimulators (VNS) were the first implantable neuromodulation devices for epilepsy ( Ryvlin and Jehi, 2022 ). While there are some reports of success, most patients with TRE who receive VNS do not achieve adequate seizure relief ( Zhong et al, 2011 ).…”

Neurostimulation as a Method of Treatment and a Preventive Measure in Canine Drug-Resistant Epilepsy: Current State and Future Prospects

“…Despite the growing amount of human clinical data and the increasing interest in ANT deep brain stimulation for management of DRE, there a still various open questions concerning the mechanisms, patient selection, electrode placement techniques, and optimal programming ( 106 , 107 ). In line with the role of the ANT as a network hub in limbic circuits, evidence exists that patients with temporal lobe epilepsy show a favorable response as compared to patients with frontal lobe epilepsy and epilepsies with other locations.…”

Centromedian thalamic neuromodulation for the treatment of idiopathic generalized epilepsy

“…VNS received FDA approval in 1997 for the treatment of focal-onset seizures ( DeGiorgio et al, 2000 ), which was then extended to children age 4 and older in 2017 ( Jain and Arya, 2021 ). In the United States, responsive neurostimulation (RNS) was approved by the FDA in 2013 for the treatment of focal epilepsy, while deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) was approved for the treatment of focal epilepsy in 2018 (2010 in Europe) ( Ryvlin and Jehi, 2022 ).…”