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SYMPOSIUM
Year : 2020  |  Volume : 68  |  Issue : 8  |  Page : 249-258

Role of Neuromodulation for Treatment of Drug-Resistant Epilepsy


1 Department of Neurology, Lady Harding Medical College, New Delhi, India
2 Department of Neurosurgery, AIIMS, New Delhi, India
3 Department of Neurology, AIIMS, New Delhi, India

Date of Web Publication5-Dec-2020

Correspondence Address:
Dr. Manjari Tripathi
Professor, Department of Neurology, Room 705, 7th Floor, CN Center, AIIMS, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.302476

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 » Abstract 


The choice of neuromodulation techniques has greatly increased over the past two decades. While vagal nerve stimulation (VNS) has become established, newer variations of VNS have been introduced. Following the SANTE's trial, deep brain stimulation (DBS) is now approved for clinical use. In addition, responsive neurostimulation (RNS) has provided exciting new opportunities for treatment of drug-resistant epilepsy. While neuromodulation mostly offers only a ‘palliative’ measure, it still provides a significant reduction of frequency and intensity of epilepsy. We provide an overview of all the techniques of neuromodulation which are available, along with long-term outcomes. Further research is required to delineate the exact mechanism of action, the indications and the stimulation parameters to extract the maximum clinical benefit from these techniques.


Keywords: Deep brain stimulation, drug-refractory epilepsy, neuromodulation, outcome, responsive neurostimulation, vagal nerve stimulation
Key Message: Epileptologists and epilepsy surgeons have a plethora of neuromodulation devices and targets to choose from. It is important to have a working knowledge of the mechanism, efficacy and complications of each modality to choose the best possible device to suit individual patient needs.


How to cite this article:
Parihar J, Agrawal M, Samala R, Chandra P S, Tripathi M. Role of Neuromodulation for Treatment of Drug-Resistant Epilepsy. Neurol India 2020;68, Suppl S2:249-58

How to cite this URL:
Parihar J, Agrawal M, Samala R, Chandra P S, Tripathi M. Role of Neuromodulation for Treatment of Drug-Resistant Epilepsy. Neurol India [serial online] 2020 [cited 2021 Mar 4];68, Suppl S2:249-58. Available from: https://www.neurologyindia.com/text.asp?2020/68/8/249/302476




Drug-resistant epilepsy (DRE), defined as the “failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapy or in combination) to achieve sustained seizure freedom”,[1],[2],[3] is a chronic debilitating condition accounting for nearly 30% of epilepsy cases. It's also clear now that DRE may be diagnosed quite early in the course of illness especially when there is a failure of the first anti-epileptic drug (AED).[4],[5],[6] Currently the only effective treatment for DRE is surgery in both adult and paediatric population.[7],[8],[9],[10] Class I evidence in the form of RCTs is available (for both adult and paediatric population) to support surgical over medical management.[7],[8],[9],[10]

It is very important that neuromodulation should only be considered in those patients where a resection or disconnection surgery is not possible. These may include (1.) temporal resection surgery (e.g. temporal lobectomy with amygdalo hippocampectomy, (2.) extra temporal resections, lesionectomies) or a (3.) disconnective surgery (hemispheric surgery, temporal parietal occipital (TPO) disconnection, parietal occipital (PO) disconnection. The possible exception may be corpus callosotomy where a vagal nerve stimulation (VNS) may be considered as an option. In our centre, we prefer performing an endoscopic guided corpus callosotomy with anterior, hippocampal and posterior commissurotomy.[11],[12] Likewise, for hemispheric disconnections, we have introduced the procedure of endoscopic hemispherotomy.[13],[14],[15],[16]

It is thus important that patients with DRE are evaluated properly at a centre routinely dealing with epilepsy surgery so that the above possibilities are excluded. The concept of neuromodulation is best understood if this is treated like “an additional drug” in a patient with DRE where all options of resection or disconnection surgery are exhausted. Thus, providing neuromodulation provides a “booster” option to control epilepsy. Likewise, a complete work up is required specially performing an epilepsy protocol MRI and video EEG (recording at least 3 habitual ictal events). The evaluation of MRI must be done by a radiologist experienced in dealing with epilepsy substrates as subtle lesions like a bottom of sulcus dysplasia may be easily missed out. Likewise, a video EEG is necessary to rule out non-epileptic events as these may occur even in persons with DRE (in our series up to 25%). Thus, the whole workup is not just to rule out an operable substrate for epilepsy but also to rule out PNES (psychogenic non-epileptic seizures) and other causes of DRE. The latter may include drug non-compliance, seizures precipitated by events like lack of sleep, fasting etc.[8],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29]

Temporal lobe epilepsy and hemispherotomy have been seen to have the best long-term seizure-free outcomes (60-70%), with outcome after extratemporal epilepsy observed to be around 30-50%.[30],[31] The dilemma lies in the management of cases in whom seizures appear to be originating from multiple sources, or the EZ is localized to an eloquent cortex which cannot be sacrificed, or patients in whom multiple complex networks appear to be the cause of DRE. About 40-50% of patients fall under this category.[32] These patients may be offered palliative surgery, in the form of neuromodulation, in an effort to decrease the seizure burden.

The term “neuromodulation” is essentially electrical stimulation of the nervous system to modulate or modify a specific function (as in movement disorders, pain, epilepsy). It can be delivered in different ways: through stimulation over the skin surface, peripheral nerve stimulation, cortical stimulation, or deep brain stimulation. The origin of the idea of using electrical current to stimulate the brain dates back more than a century to Sir Victor Horsley utilizing it to map neural functions to aid resection surgery in a patient with focal epilepsy.[33] The field of cortical stimulation was further expanded by Penfield and Jasper at Montreal.[34] Electrical stimulation for the treatment of human epilepsy was first described in the 1970s with the targeting of the cerebellum.[35] Since then, the field has grown exponentially with rapid technological advances. Breakthroughs in neurophysiology, enhanced imaging modalities, robotics and computer devices have allowed rapid progress in this field. This is reflected in the explosion of research on the topic in the past two decades.[36],[37] Epilepsy has recently been postulated to be due to a maldeveloped network in which the normal neurophysiological parameters of the brain get abnormally re-organized.[38] This recognition of has led to efforts to modulate the network to the patients’ benefit.[39]

At present, there are multiple neuromodulator devices available in the physician's armamentarium. They may be classified in multiple forms. [Figure 1] They can be implanted inside the body or used to reduce cerebral excitability non-invasively. Based on the mechanism, they may be an open loop (stimulation only, no feedback) or a closed loop (feedback-based stimulation) device. Several intracranial areas and peripheral nerves have been targeted and shown promising results. When the stimulation site is the peripheral part of the cranial nerves, the stimulation ascends through brainstem nuclei and affects the cortex's excitability diffusely. However, the exact indication and the situation when it would be appropriate to use each device is not well defined. The underlying mechanism of action of each therapy, optimal stimulation settings and variables to predict the efficacy and effect on seizure frequency is still a work in progress. Here, we review the role of neuromodulation in DRE. We discuss the most common forms of neuromodulations used in DRE, their mechanism of actions, the evidence related to the process and the outcome.
Figure 1: Classification of Neuromodulation Devices for Epilepsy

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Vagal Nerve Stimulation (VNS)

This was the first neuromodulator device approved for use by the Food and Drug Administration (FDA) of USA in 1997. It was initially approved for use in patients older than 12 years, but recently in 2017, approval has also been given for use in children more than 4 years of age with partial seizure with DRE. It's an invasive, open-loop device. A generator implanted in the chest wall intermittently stimulates the vagus nerve with pre-programmed current and timing. It is one of the most widely available techniques worldwide.

Mechanism

One proposed rationale of using VNS in DRE is that seizure activity in the brain is associated with venous hyperemia and electrical stimulation of the vagus nerve is associated with a decrease in the hyperemia and hence, the seizure abortion.[40] Another hypothesis suggests that VNS causes desynchronization of the seizure network activity, modulate the neurotransmitter release with increase in gamma-aminobutyric acid (GABA) levels and decreased glutamate levels.[41],[42] More recently, vagal nerve afferents have been postulated to have a role in seizure modulation.[43] Vagus nerve synapses intracranially on the nucleus of tractus solitarius (NTS), which in turn projects to the locus coeruleus (LC) and dorsal raphae. An increase in norepinephrine (NE) and serotonin has been observed which is thought to subserve the clinical effects of VNS.[44] An animal study showed decreased responsiveness in rats in whom the LC was iatrogenically lesioned.[45] Widespread network changes have been observed after VNS, most importantly in the limbic circuit, probably through the NTS and its projections to the amygdala.[46]

Efficacy

The efficacy of VNS was demonstrated by two RCTs – EO3 and EO5,[47],[48] which formed the basis for the subsequent FDA approval. They recruited patients older than 12 years with focal epilepsy with history of more than five seizures per month. Patients were randomized to receive high (3 mA, 20- to 50-Hz, “on” times 30–90s, “off” times 5–10 min) or low (up to 2.75 mA, 1–2 Hz, “on” times of 30 sec, “off” times 1–3 hour) stimulation. This was followed by a 3-month blinded evaluation. A mean seizure frequency reduction of 24.5% and 27.9% in the high stimulation group was seen in the EO3 and EO5 studies respectively as compared to 6.1% and 15.2% in the low stimulation groups. A point of criticism of these trials was that there was no real blinding due to the high incidence of stimulation related hoarseness of voice (as high as 66%), as even the control group was stimulated at a lower setting.[49]

Long-term analysis has shown VNS to be efficacious in focal, generalized as well as syndromic epilepsy.[50] A study assessing outcomes in 440 patients showed a responder rate (patients attaining >50% reduction in seizure frequency) of 36.8% at one year. This subsequently improved to 43.2% at two years and 42.7% at three years.[51] A large meta-analysis was published in 2011 on VNS efficacy in epilepsy that included 74 clinical studies (3 blinded, RCTs; 2 nonblinded, RCTs; 10 prospective studies; and numerous retrospective studies) with 3321 patients with DRE. Its result showed an average 45% reduction in the seizure frequency with a 36% reduction in seizures at 3-12 months after surgery and a 51% reduction after >1 year of therapy indicating a better long-term neuromodulation in the seizure circuits with VNS than immediate suppression of seizure activity. Posttraumatic epilepsy and tuberous sclerosis were found to be the positive predictors of a favorable outcome after VNS in this metanalysis.[52] Patients with generalized epilepsy were seen to respond better. Similar outcomes were seen in a Japanese database of 362 patients, with responder rate of 57.7% and 58.8% at two and three years respectively.[53]

VNS has also been effective in children younger than 12 years of age. A study compared the outcomes of 86 children less than 12 years to adolescents.[54] They found no difference in efficacy or complication rate between the groups. A recent retrospective analysis of VNS implanted in 99 children less than six years of age reported 55%, 60% and 52% responder rate one, two and four years after implantation. The overall complication rate was also comparable to adult series at 5.6%.[55] Evidence of its therapeutic effect in children less than three years is also emerging.[56]

There are case reports and studies suggesting benefit of VNS in status epilepticus[56],[57] and epileptic syndromes like tuberous sclerosis,[52],[58] Lennox-Gastaut syndrome,[59] generalized epilepsy with febrile seizures plus,[60] and absence epilepsy.[61]

A significant improvement in drug-refractory depression has also been reported.[62] FDA approval for the same was received in 2007. The effect of VNS on the rate of sudden unexpected death in epilepsy (SUDEP) is debatable with one study showing a significant decline in death rate at long-term follow-up up to 10 years as compared to the initial two years of follow-up.[63] However, another study has failed to corroborate this finding.[64]

Quality of Life (QoL)

A multicenter prospective trial (PuLsE) concluded that VNS with best medical therapy had significant improvement in health-related QoL, as compared to the medical management group alone.[65] Overall improvement in attention, cognitive ability, memory, creativity and decision-making has been observed.[66],[67] An improvement in quality-adjusted life years of 5.96 (patients aged 1-11 years) and 4.82 years (in patients aged 12-17 years) has been reported.[68] Epilepsy has a significant economic burden.[69] Reduction in total health care costs by as much as 3000USD per patient per year and decreased emergency room visits has been found after VNS implantation, even in patients not having a significant reduction in seizures.[68],[69],[70]

Adverse effects

Many studies have shown that VNS implantation is a relatively safe operation. However, there are a few complications that the epileptologist should be aware of. It is an expensive procedure and may have mechanical equipment-related complications including lead fracture, or malfunction with interruption of the wire-electrode circuitry and need for battery replacement at regular intervals.[50] Stimulation based side effects such as hoarseness of voice, coughing and laryngeal paresthesia are thought to be because of the efferent nerve fibers supplying the larynx. These are the most common side effects, the incidence of which has been reported to be as high as 60%.[48],[50],[51],[52] Fortunately, they have been seen to improve with time and device parameter adjustment.[71] Bradycardia has infrequently been observed due to the stimulation of the sinoatrial and atrioventricular nodes in the heart. Worsening of preexistent (50%) or development of new onset (57.9%) sleep apnea has been reported in small series of patients.[72] Surgical complications such as infections (3-6%) and lead damage (3%) have rarely been seen.[48],[50],[51],[52],[72]

Recent advances

Transcutaneous VNS (tVNS) has been introduced as a non-invasive technique, targeting either the auricular branch or the cervical branch of the vagus in the neck. A pilot study conducted on 10 patients showed reduction in seizure frequency in 50% of the patients.[73] A controlled trial (n = 60) demonstrated significant reduction (p < 0.001) in seizure rate and intensity at twelve months follow-up.[74] Improvement in mood and QoL was also noted.

A form of closed-loop VNS has been introduced in 2015, wherein the device detects tachycardia due to seizure onset and then delivers automatic stimulus.[75],[76] Another model detects bradycardia and prone positioning of the patient and differs the stimulation accordingly to offset the risk of SUDEP.[50],[77] Despite these ancillary benefits, significant improvement in seizure outcome of these devices over and above the regular VNS is debatable.[78],[79]

Ongoing attempts to predict clinical response to VNS have shown interesting results. A study analyzed outcomes in 82 patients with and without cognitive deficits receiving VNS.[80] They found patients without cognitive defects had improved seizure-free outcome, although secondary benefits like improved alertness were more in the group of patients with cognitive deficits. An improved synchronization of EEG waveforms has been seen in patients who respond to VNS.[81] A recent review on the biomarkers of VNS response reported connectomics-based studies utilizing diffusion tensor imaging, magneto encephalography and functional MRI as the most promising avenues to predict seizure outcome.[82] Further research in this field may improve preoperative decision making.


 » Conclusion Top


VNS device ushered in the modern age of neurostimulation. It is the only neuromodulation device approved for use in children. Epileptologists have extensive experience with the device and implantation is relatively simpler. It can be used to treat both focal and generalized epilepsy. Additional unique benefits include mood elevation and is the device of choice for patients with co-existent depression. Some disadvantages include poorer efficacy as compared to other modalities, MRI incompatibility and difficulty in device removal due to adhesion formation.

Deep Brain Stimulation (DBS)

In DBS the electrodes are directly implanted into the deeper epileptogenic targets in the brain to abort the episode. It is an invasive, open-loop neuromodulator device. Although many targets were studied for use by DBS, efficacy in anterior nucleus (AN) of thalamus was the first to be established by an RCT which led to the approval of the technique in Europe in 2010, followed by the USFDA in 2018. Direct targeting of the anteroventral AN near the mammillothalamic tract has been shown to be most efficacious.[83],[84]

Mechanism

AN is well connected to the limbic circuit. It also sends projections to various cortical structures such as the orbito frontal, cingulate and mesial frontal cortices.[85] Animal studies in the 1960s showed the effect of subcortical lesioning in achieving seizure control.[86],[87] Subsequently, high-frequency stimulation was seen to prevent seizure activity in rats.[88] The first studies in human subjects were performed by Cooper and Upton et al. who showed chronic stimulation was efficacious in seizure control.[89],[90]Low-frequency stimulation was seen to synchronize the EEG pattern and cause seizures. On the other hand, high-frequency stimulation was seen to disrupt the same and thus abort seizure activity. Stimulation induced changes in the ion channels, synaptic levels of neurotransmitters and subsequent glial changes leading to overall network modulation have been proposed as the mechanism of action.[91],[92],[93]

Efficacy

A multicenter RCT (stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy – SANTE) included 109 adults.[94] A 40.4% seizure reduction was reported in the stimulation group (14.5% in the control group) at the end of the blinded phase of evaluation (12 weeks). The responder rate at the end of one year was 43%, which improved to 54% at two years post-implantation. A criticism pointed out was that almost half (44.6%) of the study population had received prior VNS implantation,[49] although recent reports have observed favorable outcomes in this subset of patients.[95] Five year follow-up of the patients in the RCT revealed 69% seizure reduction and 68% responder rate, with 16% of patients reporting seizure freedom of at least six months.[96] Post hoc analysis suggested improved seizure reduction for temporal lobe epilepsy in comparison to other lobes.[97],[98]

A recent systematic review of DBS for DRE in children found 40 patients aged 4-18 years.[98] Various areas were targeted, with eight patients receiving bilateral AN-DBS. Overall, 85% of patients showed seizure reduction. Case reports also suggest that DBS may have limited use in patients with refractory status epilepticus.[99]

Quality of Life (QoL)

Significant improvement in the QoL has been reported at long-term follow-up.[96] A relatively high rate of depression (14.8%) and memory decline (13.0%) was initially reported in the stimulation group of the SANTE trial.[94] However, long-term studies with seven years of follow-up have allayed these concerns with objective measures reporting no significant decline in the two parameters. Additionally, an improvement in attention and executive function was noted.[100]

Other targets

Several other intracranial targets for DBS have been tried with varying success rates. DBS of the centromedian nucleus of thalamus (CMNT) seems to be effective in reducing generalized as compared to focal seizures.[101] Good response has been seen in patients with Lennox Gastaut syndrome.[102] In a study, only one of five patients with frontal lobe epilepsy showed a worthwhile reduction in seizures, as compared to all six of the patients with generalized epilepsy.[103]

Targeting the hippocampus is indicated in patients with bilateral mesial temporal sclerosis, in MRI negative temporal lobe epilepsy, in patients with risk of memory deficits and in cases of previous temporal lobectomy with a contralateral relapse of seizures.[104],[105] Long-term follow-up in nine patients showed >95% seizure reduction in patients with a normal MRI, while 50-70% reduction was seen in substrate positive patients.[104] In a recent RCT, seven out of eight patients in the control group had more than 50% reduction in seizures, and four of them became seizure free.[105] Hippocampal DBS has been shown to be a safe procedure without any neuropsychological adverse effects.[104] However, resection is still the procedure of choice in patients with a recognized unilateral seizure substrate.

Cerebellum was the oldest targets of DBS,[35] although recent research targeting it is sparse. Electrodes are placed on the superomedial surface of the cerebellum.[106] An RCT showed significant reduction in generalized seizure frequency in the stimulation group and overall reduction of seizure rate to 41% of baseline at the end of six months.[106]

Adverse effects

The most common adverse event noted has been paresthesia and implant site pain noted in 23% of patients on long-term follow-up.[96] Implant site infection has been noted in 12.7% of cases. Lead mis targeting rate of 8.2% shows the importance of postoperative imaging to confirm lead position. Rate of hemorrhage has been comparable to the experience with implantation of DBS electrodes for other indications (2.4%).[107]


 » Conclusion Top


DBS seems to be effective for both focal and generalized seizures, although maximum benefit seems to be in temporal lobe epilepsy. Although the efficacy seems to be slightly higher than VNS, DBS requires more frequent battery changes due to higher stimulation parameters and its more expensive. Other disadvantages are the risk of target mismatch and a more elaborate surgical procedure as compared to VNS.

Responsive Neurostimulation (RNS)

RNS is a form of invasive, closed loop device. It includes a set of recording electrocorticogram electrodes, the feedback of which is used to deliver electrical stimulus to the seizure focus upon the detection of epileptiform activity. The threshold at which the device responds is predetermined, and it does not require any further human setting. The stimulus thus delivered is expected to abort the seizure right at its onset. Additionally, the device provides valuable chronic electrophysiological data for research purpose. RNS has been approved by the USFDA in 2013 for adult patients with refractory focal epilepsy, with upto two identified seizure foci on preoperative evaluation.

Mechanism

It was observed by researchers in patients undergoing intracranial monitoring that stimulation in response to a seizure could reduce its frequency.[108] They also reported that such a stimulus has to be delivered right at the onset of abnormal epileptiform recording.[109] Acute stimulation has been observed to disrupt synchronization associated with epileptiform activity by upregulation of local GABA activity.[110] Additionally, depletion of neurotransmitters has been reported at synaptic terminals causing depression of activity. Long-term effects have been postulated to be mediated via induced changes in gene expression with chronic stimulation.[110]

Efficacy

The pivotal trial which established the efficacy of RNS included 191 patients assessed over a 12-week blinded period to receive stimulation vs no stimulation in response to seizure detection.[111] The treatment group had a significant reduction in seizure frequency (n = 97, 37.9%), as compared to the control group (n = 94, 17.3%, P = 0.012). No significant difference was observed in the adverse effects and favorable outcome was seen in both the groups in the unblinded phase. Further follow-up demonstrated 44% seizure reduction at one year, and a significant improvement to 53% at the end of two years.[112]

Subset analysis showed that at an average of 6.1 years of follow-up, the best response (70% median percent seizure reduction) was seen in patients with frontal and parietal seizure foci, while it was seen to be 58% with temporal neocortical onset and 51% with multilobar foci. Authors further demonstrated that eloquent cortex stimulation could be performed with no stimulation related adverse effects. Visible MRI abnormality was a predictor of better response (p = 0.02).[113] There was no effect of prior surgery or VNS implantation on the seizure response. Another subset of patients with mesial temporal onset of epilepsy (n = 111, 72% of which had bilateral mesial temporal onset) were observed for a mean follow-up of 6.1 ± 2.2 years.[114] Patients had a mean seizure reduction of 70% with 29% of them experiencing seizure free periods of longer than six months. More recently, a 9-year follow-up of all the patients (n = 230) enrolled in multicenter open label trials of RNS showed encouraging results.[115] A significant median seizure reduction of 75% was reported, while the responder rate was 73%. Additionally, the SUDEP rate was found to be significantly reduced with RNS (p < 0.05).[115] The efficacy of RNS in pediatric patients as an off-label therapy is restricted to case reports as of now.[116],[117]

Quality of Life (QoL)

In the pivotal trial, in addition to the benefit with respect to seizure reduction, there were significant improvements seen in QoL following treatment.[111] Analysis performed at two years in a subset of patients enrolled in the trial with temporal onset of seizures showed significant improvement in naming in patients with neocortical onset (p < 0.0001), while significant improvement in verbal learning was observed in patients with mesial temporal onset (p = 0.005).[118] Long-term follow-up of nine years has also shown significant improvement in cognition and overall QoL.[115] No definite adverse effect on mood has been reported.[111],[115]

Adverse effects

The rate of hemorrhage and infection has been found to be similar to other invasive neuromodulation devices.[113],[114] The risk of infection has been found to be 4.1%, with approximately half of them requiring explantation. The rate of hemorrhage has been seen to be 2.7%, with none causing any neurological deficit. A recent analysis of the manufacturer database between 2013 to 2020 reported overall 241 complications. 40% of these complications were infection related, while the second most common were lead breakage (12%).[119]


 » Conclusion Top


RNS is a promising therapy for refractory partial seizures, especially in bitemporal epilepsy. The use of RNS is currently restricted to cases wherein two seizure foci are recognized, and thus requires extensive evaluation to identify the correct epileptogenic zone. It is the most expensive neuromodulator device available, although a longer battery life has been reported as compared to other modalities.[109] Chronic long-term electrical recordings made available through this device are a unique advantage in increasing understanding of epilepsy networks.[109] Recognition of the exact biomarkers of abnormal seizure activity would further improve the efficacy.

Other techniques

Trigeminal Nerve Stimulation (TNS) involves non-invasive bilateral stimulation of the supra orbital nerves. In an RCT (n = 50) patients either received high frequency (120 Hz) or low frequency (2 Hz) stimulation.[120] A 30.2% responder rate was observed in the former as compared to 21.1% in the latter. Although this difference was not significant, significant within group improvement was seen with high frequency stimulation. Another recent RCT comparing TNS with medical management was able to show a 50% responder rate with TNS at 12 months follow-up.[121] Overall, TNS is a relatively economical technique with easy applicability.

Repetitive Transcranial Magnetic Stimulation (rTMS) uses external magnetic fields to induce electrical currents which affect neurons to cause seizure reduction. Repetition causes longer lasting effects. An RCT of 21 patients with cortical dysplasia showed significant reduction in seizure frequency, with the beneficial effect maintained for two months.[122] Headache was the most common adverse effect (25%).

Transcranial Direct Current Stimulation (tDCS) is a portable, non-invasive mode of treatment, wherein changes in cortical excitability are induced using weak direct current (2 mA) to influence resting membrane potentials.[123] Twelve patients with mesial temporal sclerosis underwent tDCS and showed a responder rate of 83.33% at one month.[124] In a randomized double-blind trial including 28 patients, 48% mean seizure frequency reduction was seen at two months.[125]

Although these techniques are promising, further long-term experience in terms of sustained efficacy are required.

Concerns for low- and middle-income countries

There are several special considerations for the use of neuromodulation in developing countries. Even though these devices have been shown to reduce the long-term economic burden of epilepsy, the upfront cost of the device is still out of reach for many of the economically weaker section of patients.[50] Additionally, some of the devices like RNS are currently not available in developing countries. There is a dearth of medical personnel in many of these countries.[126] The availability of trained experts in neuromodulation is even rarer. Many patients travel from far off places for specialized treatment. Thus, regular follow-up for device programming is a big issue and is simply not possible for many. Lastly, there is a great potential for misuse of these devices. Patients as well as physicians need to be educated as to the risks and benefits of these techniques. Regulatory control to prevent implantation for improper indications is required. It is for all these reasons, that relatively more invasive palliative procedures such as corpus callosotomy are still used in several institutes.


 » Conclusion Top


Neuromodulation techniques are emerging as effective and relatively safe treatment options for DRE not amenable or not responsive to resection. Overall, these devices provide a significant added seizure reduction without typical medication side effects and their efficacy continues to improve over years. Several ancillary benefits have been noted including improvement of quality of life and overall reduced economic burden of epilepsy. However, the complete seizure freedom is rarely achieved using these techniques and there still are a subgroup of DRE patients who do not benefit from these therapies, leaving a scope for further advancement. Disadvantages such as hardware related complications, need for battery replacement and frequent parameter adjustment have been noted. The recent trend towards development of closed loop devices is an effort to offset some of these disadvantages. Currently there are no head-to-head trials comparing the different neuromodulation devices. The choice of device therefore depends on the type of epilepsy, whether the seizure focus can be identified, age of the patient, and other factors like availability and cost. Evolution in hardware and technology have continuously improved device longevity and performance.[127] Advanced imaging and analysis of electrophysiological data including machine learning have shown promise in improving accuracy and predicting response to therapy. All this has led to the blossoming of neuromodulation for epilepsy into a promising area filled with exciting possibilities.

Acknowledgements

The paper has been partially funded by Dept of Biotechnology, Ministry of Science and Technology, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Brodie MJ, Barry SJ, Bamagous GA, Kwan P. Effect of dosage failed of first antiepileptic drug on subsequent outcome. Epilepsia 2013;54:194-8.  Back to cited text no. 1
    
2.
Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, et al. Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE commission on therapeutic strategies. Epilepsia 2010;51:1069-77.  Back to cited text no. 2
    
3.
Kwan P, Schachter SC, Brodie MJ. Drug-resistant epilepsy. N Engl J Med 2011;365:919-26.  Back to cited text no. 3
    
4.
Brodie MJ, Barry SJE, Bamagous GA, Norrie JD, Kwan P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012;78:1548-54.  Back to cited text no. 4
    
5.
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342:314-9.  Back to cited text no. 5
    
6.
Tripathi M, Padhy UP, Vibha D, Bhatia R, Padma Srivastava MV, Singh MB, et al. Predictors of refractory epilepsy in north India: A case-control study. Seizure 2011;20:779-83.  Back to cited text no. 6
    
7.
Dwivedi R, Ramanujam B, Chandra PS, Sapra S, Gulati S, Kalaivani M, et al. Surgery for drug-resistant epilepsy in children. N Engl J Med 2017;377:1639-47.  Back to cited text no. 7
    
8.
Chandra PS, Ramanujam B, Tripathi M. Surgery for drug-resistant epilepsy in children. N Engl J Med 2018;378:399.  Back to cited text no. 8
    
9.
Engel J Jr, McDermott MP, Wiebe S, Langfitt JT, Stern JM, Dewar S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: A randomized trial. JAMA 2012;307:922-30.  Back to cited text no. 9
    
10.
Wiebe S, Blume WT, Girvin JP, Eliasziw M, Effectiveness, efficiency of surgery for temporal lobe epilepsy study G. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001;345:311-8.  Back to cited text no. 10
    
11.
Chandra SP, Kurwale NS, Chibber SS, Banerji J, Dwivedi R, Garg A, et al. Endoscopic-assisted (through a mini craniotomy) corpus callosotomy combined with anterior, hippocampal, and posterior commissurotomy in Lennox-Gastaut syndrome: A pilot study to establish its safety and efficacy. Neurosurgery 2016;78:743-51.  Back to cited text no. 11
    
12.
Chandra SP, Tripathi M. Endoscopic epilepsy surgery: Emergence of a new procedure. Neurol India 2015;63:571-82.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Girishan S, Tripathi M, Garg A, Doddamani R, Bajaj J, Ramanujam B, et al. Enhancing outcomes of endoscopic vertical approach hemispherotomy: Understanding the role of “temporal stem” residual connections causing recurrence of seizures. J Neurosurg Pediatr 2019:1-9. doi: 10.3171/2019.8.PEDS19148.  Back to cited text no. 13
    
14.
Chandra PS, Tripathi M. Letter to the editor: Endoscope-assisted hemispherotomy and corpus callostomy. J Neurosurg Pediatr 2016;18:141-4.  Back to cited text no. 14
    
15.
Chandra PS, Subianto H, Bajaj J, Girishan S, Doddamani R, Ramanujam B, et al. Endoscope-assisted (with robotic guidance and using a hybrid technique) interhemispheric transcallosal hemispherotomy: A comparative study with open hemispherotomy to evaluate efficacy, complications, and outcome. J Neurosurg Pediatr 2018;23:187-97.  Back to cited text no. 15
    
16.
Baumgartner JE, Blount JP, Blauwblomme T, Chandra PS. Technical descriptions of four hemispherectomy approaches: From the pediatric epilepsy surgery meeting at Gothenburg 2014. Epilepsia 2017;58(Suppl 1):46-55.  Back to cited text no. 16
    
17.
Doddamani RS, Tripathi M, Samala R, Agarwal M, Ramanujan B, Chandra SP. Posterior quadrant disconnection for sub-hemispheric drug refractory epilepsy. Neurol India 2020;68:270-3.  Back to cited text no. 17
[PUBMED]  [Full text]  
18.
Bajaj J, Chaudhary K, Chandra PS, Ramanujam B, Girishan S, Doddamani R, et al. Left temporal lobectomy using functional MRI in a math genius: A case report. Neurol India 2020;68:170-2.  Back to cited text no. 18
[PUBMED]  [Full text]  
19.
Swami P, Bhatia M, Tripathi M, Chandra PS, Panigrahi BK, Gandhi TK. Selection of optimum frequency bands for detection of epileptiform patterns. Healthc Technol Lett 2019;6:126-31.  Back to cited text no. 19
    
20.
Bajaj J, Tripathi M, Dwivedi R, Sapra S, Gulati S, Garg A, et al. Does surgery help in reducing stigma associated with drug refractory epilepsy in children? Epilepsy Behav 2018;80:197-201.  Back to cited text no. 20
    
21.
Kumar S, Ramanujam B, Chandra PS, Dash D, Mehta S, Anubha S, et al. Randomized controlled study comparing the efficacy of rapid and slow withdrawal of antiepileptic drugs during long-term video-EEG monitoring. Epilepsia 2018;59:460-7.  Back to cited text no. 21
    
22.
Ramanujam B, Bharti K, Viswanathan V, Garg A, Tripathi M, Bal C, et al. Can ictal-MEG obviate the need for phase II monitoring in people with drug-refractory epilepsy? A prospective observational study. Seizure 2017;45:17-23.  Back to cited text no. 22
    
23.
Tripathi M, Ray S, Chandra PS. Presurgical evaluation for drug refractory epilepsy. Int J Surg 2016;36:405-10.  Back to cited text no. 23
    
24.
Chandra PS, Vaghania G, Bal CS, Tripathi M, Kuruwale N, Arora A, et al. Role of concordance between ictal-subtracted SPECT and PET in predicting long-term outcomes after epilepsy surgery. Epilepsy Res 2014;108:1782-9.  Back to cited text no. 24
    
25.
Tripathi M, Jain DC, Devi MG, Jain S, Saxena V, Chandra PS, et al. Need for a national epilepsy control program. Ann Indian Acad Neurol 2012;15:89-93.  Back to cited text no. 25
[PUBMED]  [Full text]  
26.
Chandra PS, Tripathi M. Epilepsy surgery: Recommendations for India. Ann Indian Acad Neurol 2010;13:87-93.  Back to cited text no. 26
[PUBMED]  [Full text]  
27.
Chandra PS, Bal C, Garg A, Gaikwad S, Prasad K, Sharma BS, et al. Surgery for medically intractable epilepsy due to postinfectious etiologies. Epilepsia 2010;51:1097-100.  Back to cited text no. 27
    
28.
Thapa A, Chandra SP, Sinha S, Sreenivas V, Sharma BS, Tripathi M. Post-traumatic seizures-A prospective study from a tertiary level trauma center in a developing country. Seizure 2010;19:211-6.  Back to cited text no. 28
    
29.
Tripathi M, Singh MS, Padma MV, Gaikwad S, Bal CS, Tripathi M, et al. Surgical outcome of cortical dysplasias presenting with chronic intractable epilepsy: A 10-year experience. Neurol India 2008;56:138-43.  Back to cited text no. 29
[PUBMED]  [Full text]  
30.
Tellez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: A systematic review and meta-analysis. Brain 2005;128:1188-98.  Back to cited text no. 30
    
31.
Tellez-Zenteno JF, Hernandez Ronquillo L, Moien-Afshari F, Wiebe S. Surgical outcomes in lesional and non-lesional epilepsy: A systematic review and meta-analysis. Epilepsy Res 2010;89:310-8.  Back to cited text no. 31
    
32.
Wiebe S, Jette N. Pharmacoresistance and the role of surgery in difficult to treat epilepsy. Nat Rev Neurol 2012;8:669-77.  Back to cited text no. 32
    
33.
Vilensky JA, Gilman S. Horsley was the first to use electrical stimulation of the human cerebral cortex intraoperatively. Surg Neurol 2002;58:425-6.  Back to cited text no. 33
    
34.
Penfield WJHH WP. Epilepsy and the functional anatomy of the human brain. In: Brown L, editor. Epilepsy. XV ed. Boston; 1954. p. 896.  Back to cited text no. 34
    
35.
Cooper IS, Amin I, Riklan M, Waltz JM, Poon TP. Chronic cerebellar stimulation in epilepsy. Clinical and anatomical studies. Arch Neurol 1976;33:559-70.  Back to cited text no. 35
    
36.
Ibrahim GM, Snead OC, 3rd, Rutka JT, Lozano AM. The most cited works in epilepsy: Trends in the “Citation Classics”. Epilepsia 2012;53:765-70.  Back to cited text no. 36
    
37.
Kutluk MG, Danis A. Bibliometric analysis of publications on pediatric epilepsy between 1980 and 2018. Childs Nerv Syst 2020. doi: 10.1007/s00381-020-04897-9.  Back to cited text no. 37
    
38.
Dixit AB, Banerjee J, Tripathi M, Chandra PS. Presurgical epileptogenic network analysis: A way to enhance epilepsy surgery outcome. Neurol India 2015;63:743-50.  Back to cited text no. 38
[PUBMED]  [Full text]  
39.
Foit NA, Bernasconi A, Bernasconi N. Functional networks in epilepsy presurgical evaluation. Neurosurg Clin N Am 2020;31:395-405.  Back to cited text no. 39
    
40.
Fan JJ, Shan W, Wu JP, Wang Q. Research progress of vagus nerve stimulation in the treatment of epilepsy. CNS Neurosci Ther 2019;25:1222-8.  Back to cited text no. 40
    
41.
Hammond EJ, Uthman BM, Wilder BJ, Ben-Menachem E, Hamberger A, Hedner T, et al. Neurochemical effects of vagus nerve stimulation in humans. Brain Res 1992;583:300-3.  Back to cited text no. 41
    
42.
Zabara J. Inhibition of experimental seizures in canines by repetitive vagal stimulation. Epilepsia 1992;33:1005-12.  Back to cited text no. 42
    
43.
Krahl SE, Clark KB. Vagus nerve stimulation for epilepsy: A review of central mechanisms. Surg Neurol Int 2012;3(Suppl 4):S255-9.  Back to cited text no. 43
    
44.
Dorr AE, Debonnel G. Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J Pharmacol Exp Ther 2006;318:890-8.  Back to cited text no. 44
    
45.
Krahl SE, Clark KB, Smith DC, Browning RA. Locus coeruleus lesions suppress the seizure-attenuating effects of vagus nerve stimulation. Epilepsia 1998;39:709-14.  Back to cited text no. 45
    
46.
Cao J, Lu KH, Powley TL, Liu Z. Vagal nerve stimulation triggers widespread responses and alters large-scale functional connectivity in the rat brain. PLoS One 2017;12:e0189518. doi: 10.1371/journal.pone. 0189518.  Back to cited text no. 46
    
47.
A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. The Vagus Nerve Stimulation Study Group. Neurology 1995;45:224-30.  Back to cited text no. 47
    
48.
Handforth A, DeGiorgio CM, Schachter SC, Uthman BM, Naritoku DK, Tecoma ES, et al. Vagus nerve stimulation therapy for partial-onset seizures: A randomized active-control trial. Neurology 1998;51:48-55.  Back to cited text no. 48
    
49.
Rolston JD, Englot DJ, Wang DD, Shih T, Chang EF. Comparison of seizure control outcomes and the safety of vagus nerve, thalamic deep brain, and responsive neurostimulation: Evidence from randomized controlled trials. Neurosurg Focus 2012;32:E14.  Back to cited text no. 49
    
50.
Wheless JW, Gienapp AJ, Ryvlin P. Vagus nerve stimulation (VNS) therapy update. Epilepsy Behav 2018;88S: 2-10.  Back to cited text no. 50
    
51.
Morris GL 3rd, Mueller WM. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology 1999;53:1731-5.  Back to cited text no. 51
    
52.
Englot DJ, Chang EF, Auguste KI. Vagus nerve stimulation for epilepsy: A meta-analysis of efficacy and predictors of response. J Neurosurg 2011;115:1248-55.  Back to cited text no. 52
    
53.
Kawai K, Tanaka T, Baba H, Bunker M, Ikeda A, Inoue Y, et al. Outcome of vagus nerve stimulation for drug-resistant epilepsy: The first three years of a prospective Japanese registry. Epileptic Disord 2017;19:327-38.  Back to cited text no. 53
    
54.
Elliott RE, Rodgers SD, Bassani L, Morsi A, Geller EB, Carlson C, et al. Vagus nerve stimulation for children with treatment-resistant epilepsy: A consecutive series of 141 cases. J Neurosurg Pediatr 2011;7:491-500.  Back to cited text no. 54
    
55.
Muthiah N, Zhang J, Remick M, Welch W, Sogawa Y, Jeong JH, et al. Efficacy of vagus nerve stimulation for drug-resistant epilepsy in children age six and younger. Epilepsy Behav 2020;112:107373. doi: 10.1016/j.yebeh. 2020.107373.  Back to cited text no. 55
    
56.
Fernandez L, Gedela S, Tamber M, Sogawa Y. Vagus nerve stimulation in children less than 3 years with medically intractable epilepsy. Epilepsy Res 2015;112:37-42.  Back to cited text no. 56
    
57.
Shen Y, Xia F, Feng G, Liu L, Lin W, Liu Y, et al. Seizure freedom in epilepsia partialis continua (EPC) through vagus nerve stimulation (VNS) therapy: A case report. Epilepsy Behav Case Rep 2013;1:50-1.  Back to cited text no. 57
    
58.
Grioni D, Landi A. Does vagal nerve stimulation treat drug-resistant epilepsy in patients with tuberous sclerosis complex? World Neurosurg 2019;121:251-3.  Back to cited text no. 58
    
59.
Braakman HM, Creemers J, Hilkman DM, Klinkenberg S, Koudijs SM, Debeij-van Hall M, et al. Improved seizure control and regaining cognitive milestones after vagus nerve stimulation revision surgery in Lennox-Gastaut syndrome. Epilepsy Behav Case Rep 2018;10:111-3.  Back to cited text no. 59
    
60.
Hanaya R, Niantiarno F, Kashida Y, Hosoyama H, Maruyama S, Otsubo T, et al. Vagus nerve stimulation for generalized epilepsy with febrile seizures plus (GEFS+) accompanying seizures with impaired consciousness. Epilepsy Behav Case Rep 2017;7:16-9.  Back to cited text no. 60
    
61.
Arya R, Greiner HM, Lewis A, Mangano FT, Gonsalves C, Holland KD, et al. Vagus nerve stimulation for medically refractory absence epilepsy. Seizure 2013;22:267-70.  Back to cited text no. 61
    
62.
Conway CR, Kumar A, Xiong W, Bunker M, Aaronson ST, Rush AJ. Chronic vagus nerve stimulation significantly improves quality of life in treatment-resistant major depression. J Clin Psychiatry 2018;79:18m12178. doi: 10.4088/JCP. 18m12178.  Back to cited text no. 62
    
63.
Annegers JF, Coan SP, Hauser WA, Leestma J. Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia 2000;41:549-53.  Back to cited text no. 63
    
64.
Granbichler CA, Nashef L, Selway R, Polkey CE. Mortality and SUDEP in epilepsy patients treated with vagus nerve stimulation. Epilepsia 2015;56:291-6.  Back to cited text no. 64
    
65.
Ryvlin P, Gilliam FG, Nguyen DK, Colicchio G, Iudice A, Tinuper P, et al. The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia 2014;55:893-900.  Back to cited text no. 65
    
66.
Tsai JD, Chang YC, Lin LC, Hung KL, Vns T. The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS--A 24-month follow-up in Taiwan. Epilepsy Behav 2016;56:95-8.  Back to cited text no. 66
    
67.
Englot DJ, Hassnain KH, Rolston JD, Harward SC, Sinha SR, Haglund MM. Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data. Epilepsy Behav 2017;66:4-9.  Back to cited text no. 67
    
68.
Helmers SL, Duh MS, Guerin A, Sarda SP, Samuelson TM, Bunker MT, et al. Clinical outcomes, quality of life, and costs associated with implantation of vagus nerve stimulation therapy in pediatric patients with drug-resistant epilepsy. Eur J Paediatr Neurol 2012;16:449-58.  Back to cited text no. 68
    
69.
Marras CE, Colicchio G, De Palma L, De Benedictis A, Di Gennaro G, Cavaliere M, et al. Health technology assessment report on vagus nerve stimulation in drug-resistant epilepsy. Int J Environ Res Public Health 2020;17:6150.  Back to cited text no. 69
    
70.
Ben-Menachem E, Hellstrom K, Verstappen D. Analysis of direct hospital costs before and 18 months after treatment with vagus nerve stimulation therapy in 43 patients. Neurology 2002;59 (6 Suppl 4):S44-7.  Back to cited text no. 70
    
71.
Morris GL 3rd, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C. Evidence-based guideline update: Vagus nerve stimulation for the treatment of epilepsy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2013;81:1453-9.  Back to cited text no. 71
    
72.
Zambrelli E, Saibene AM, Furia F, Chiesa V, Vignoli A, Pipolo C, et al. Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy. Epilepsia 2016;57:e24-7.  Back to cited text no. 72
    
73.
Stefan H, Kreiselmeyer G, Kerling F, Kurzbuch K, Rauch C, Heers M, et al. Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: A proof of concept trial. Epilepsia 2012;53:e115-8.  Back to cited text no. 73
    
74.
Aihua L, Lu S, Liping L, Xiuru W, Hua L, Yuping W. A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy. Epilepsy Behav 2014;39:105-10.  Back to cited text no. 74
    
75.
Boon P, Vonck K, van Rijckevorsel K, El Tahry R, Elger CE, Mullatti N, et al. A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation. Seizure 2015;32:52-61.  Back to cited text no. 75
    
76.
Schneider UC, Bohlmann K, Vajkoczy P, Straub HB. Implantation of a new Vagus Nerve Stimulation (VNS) Therapy (R) generator, AspireSR (R): Considerations and recommendations during implantation and replacement surgery--comparison to a traditional system. Acta Neurochir (Wien) 2015;157:721-8.  Back to cited text no. 76
    
77.
Wong S, Mani R, Danish S. Comparison and selection of current implantable anti-epileptic devices. Neurotherapeutics 2019;16:369-80.  Back to cited text no. 77
    
78.
Datta P, Galla KM, Sajja K, Wichman C, Wang H, Madhavan D. Vagus nerve stimulation with tachycardia detection provides additional seizure reduction compared to traditional vagus nerve stimulation. Epilepsy Behav 2020;111:107280. doi: 10.1016/j.yebeh. 2020.107280.  Back to cited text no. 78
    
79.
Cukiert A, Cukiert CM, Mariani PP, Burattini JA. Impact of cardiac-based vagus nerve stimulation closed-loop stimulation on the seizure outcome of patients with generalized epilepsy: A prospective, individual-control study. Neuromodulation 2020. doi: 10.1111/ner. 13290.  Back to cited text no. 79
    
80.
Pipan E, Apostolou A, Bograkou M, Brooks P, Vigren P, Gauffin H. Vagal nerve stimulation in epilepsy: Experiences of participants with cognitive deficits. Neuropsychiatr Dis Treat 2020;16:1181-8.  Back to cited text no. 80
    
81.
Sangare A, Marchi A, Pruvost E, Soufflet C, Crepon B, Ramdani C, et al. The effectiveness of VNS in drug-resistant epilepsy correlates with VNS induced EEG desynchronization. Brain Connect 2020. doi: 10.1089/brain. 2020.0798.  Back to cited text no. 81
    
82.
Workewych AM, Arski ON, Mithani K, Ibrahim GM. Biomarkers of seizure response to vagus nerve stimulation: A scoping review. Epilepsia 2020. doi: 10.1111/epi. 16661.  Back to cited text no. 82
    
83.
Guo W, Koo BB, Kim JH, Bhadelia RA, Seo DW, Hong SB, et al. Defining the optimal target for anterior thalamic deep brain stimulation in patients with drug-refractory epilepsy. J Neurosurg 2020:1-10. doi: 10.3171/2020.2.JNS193226.  Back to cited text no. 83
    
84.
Krishna V, King NK, Sammartino F, Strauss I, Andrade DM, Wennberg RA, et al. Anterior nucleus deep brain stimulation for refractory epilepsy: Insights into patterns of seizure control and efficacious target. Neurosurgery 2016;78:802-11.  Back to cited text no. 84
    
85.
Child ND, Benarroch EE. Anterior nucleus of the thalamus: Functional organization and clinical implications. Neurology 2013;81:1869-76.  Back to cited text no. 85
    
86.
Mullan S, Vailati G, Karasick J, Mailis M. Thalamic lesions for the control of epilepsy. A study of nine cases. Arch Neurol 1967;16:277-85.  Back to cited text no. 86
    
87.
Kusske JA, Ojemann GA, Ward AA Jr. Effects of lesions in ventral anterior thalamus on experimental focal epilepsy. Exp Neurol 1972;34:279-90.  Back to cited text no. 87
    
88.
Mirski MA, Rossell LA, Terry JB, Fisher RS. Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat. Epilepsy Res 1997;28:89-100.  Back to cited text no. 88
    
89.
Cooper IS, Upton AR. Effects of cerebellar stimulation on epilepsy, the EEG and cerebral palsy in man. Electroencephalogr Clin Neurophysiol Suppl 1978:349-54.  Back to cited text no. 89
    
90.
Upton AR, Cooper IS, Springman M, Amin I. Suppression of seizures and psychosis of limbic system origin by chronic stimulation of anterior nucleus of the thalamus. Int J Neurol 1985;19-20:223-30.  Back to cited text no. 90
    
91.
McIntyre CC, Savasta M, Kerkerian-Le Goff L, Vitek JL. Uncovering the mechanism(s) of action of deep brain stimulation: Activation, inhibition, or both. Clin Neurophysiol 2004;115:1239-48.  Back to cited text no. 91
    
92.
Zumsteg D, Lozano AM, Wennberg RA. Rhythmic cortical EEG synchronization with low frequency stimulation of the anterior and medial thalamus for epilepsy. Clin Neurophysiol 2006;117:2272-8.  Back to cited text no. 92
    
93.
Witcher MR, Ellis TL. Astroglial networks and implications for therapeutic neuromodulation of epilepsy. Front Comput Neurosci 2012;6:61.  Back to cited text no. 93
    
94.
Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010;51:899-908.  Back to cited text no. 94
    
95.
Park HR, Choi SJ, Joo EY, Seo DW, Hong SB, Lee JI, et al. The role of anterior thalamic deep brain stimulation as an alternative therapy in patients with previously failed vagus nerve stimulation for refractory epilepsy. Stereotact Funct Neurosurg 2019;97:176-82.  Back to cited text no. 95
    
96.
Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, et al. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology 2015;84:1017-25.  Back to cited text no. 96
    
97.
Medtronic DBS therapy for epilepsy: Summary of safety and ef- fectiveness. Editor, editor: In: Administration USFD; 2018.  Back to cited text no. 97
    
98.
Yan H, Toyota E, Anderson M, Abel TJ, Donner E, Kalia SK, et al. A systematic review of deep brain stimulation for the treatment of drug-resistant epilepsy in childhood. J Neurosurg Pediatr 2018;23:274-84.  Back to cited text no. 98
    
99.
Sobstyl M, Stapinska-Syniec A, Rylski M. Deep brain stimulation for the treatment of refractory and super-refractory status epilepticus. Seizure 2020;81:58-62.  Back to cited text no. 99
    
100.
Troster AI, Meador KJ, Irwin CP, Fisher RS, Group SS. Memory and mood outcomes after anterior thalamic stimulation for refractory partial epilepsy. Seizure 2017;45:133-41.  Back to cited text no. 100
    
101.
Velasco F, Velasco M, Jimenez F, Velasco AL, Brito F, Rise M, et al. Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus. Neurosurgery 2000;47:295-304; discussion -5.  Back to cited text no. 101
    
102.
Velasco AL, Velasco F, Jimenez F, Velasco M, Castro G, Carrillo-Ruiz JD, et al. Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with Lennox-Gastaut syndrome. Epilepsia 2006;47:1203-12.  Back to cited text no. 102
    
103.
Valentin A, Garcia Navarrete E, Chelvarajah R, Torres C, Navas M, Vico L, et al. Deep brain stimulation of the centromedian thalamic nucleus for the treatment of generalized and frontal epilepsies. Epilepsia 2013;54:1823-33.  Back to cited text no. 103
    
104.
Velasco AL, Velasco F, Velasco M, Trejo D, Castro G, Carrillo-Ruiz JD. Electrical stimulation of the hippocampal epileptic foci for seizure control: A double-blind, long-term follow-up study. Epilepsia 2007;48:1895-903.  Back to cited text no. 104
    
105.
Cukiert A, Cukiert CM, Burattini JA, Mariani PP, Bezerra DF. Seizure outcome after hippocampal deep brain stimulation in patients with refractory temporal lobe epilepsy: A prospective, controlled, randomized, double-blind study. Epilepsia 2017;58:1728-33.  Back to cited text no. 105
    
106.
Velasco F, Carrillo-Ruiz JD, Brito F, Velasco M, Velasco AL, Marquez I, et al. Double-blind, randomized controlled pilot study of bilateral cerebellar stimulation for treatment of intractable motor seizures. Epilepsia 2005;46:1071-81.  Back to cited text no. 106
    
107.
Voges J, Waerzeggers Y, Maarouf M, Lehrke R, Koulousakis A, Lenartz D, et al. Deep-brain stimulation: Long-term analysis of complications caused by hardware and surgery--experiences from a single centre. J Neurol Neurosurg Psychiatry 2006;77:868-72.  Back to cited text no. 107
    
108.
Kossoff EH, Ritzl EK, Politsky JM, Murro AM, Smith JR, Duckrow RB, et al. Effect of an external responsive neurostimulator on seizures and electrographic discharges during subdural electrode monitoring. Epilepsia 2004;45:1560-7.  Back to cited text no. 108
    
109.
Jarosiewicz B, Morrell M. The RNS System: Brain-responsive neurostimulation for the treatment of epilepsy. Expert Rev Med Devices 2020:1-10. doi: 10.1080/17434440.2019.1683445.  Back to cited text no. 109
    
110.
Thomas GP, Jobst BC. Critical review of the responsive neurostimulator system for epilepsy. Med Devices (Auckl) 2015;8:405-11.  Back to cited text no. 110
    
111.
Morrell MJ, Group RNSSiES. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 2011;77:1295-304.  Back to cited text no. 111
    
112.
Heck CN, King-Stephens D, Massey AD, Nair DR, Jobst BC, Barkley GL, et al. Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial. Epilepsia 2014;55:432-41.  Back to cited text no. 112
    
113.
Jobst BC, Kapur R, Barkley GL, Bazil CW, Berg MJ, Bergey GK, et al. Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas. Epilepsia 2017;58:1005-14.  Back to cited text no. 113
    
114.
Geller EB, Skarpaas TL, Gross RE, Goodman RR, Barkley GL, Bazil CW, et al. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy. Epilepsia 2017;58:994-1004.  Back to cited text no. 114
    
115.
Nair DR, Laxer KD, Weber PB, Murro AM, Park YD, Barkley GL, et al. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Neurology 2020;95:e1244-56.  Back to cited text no. 115
    
116.
Kokoszka MA, Panov F, La Vega-Talbott M, McGoldrick PE, Wolf SM, Ghatan S. Treatment of medically refractory seizures with responsive neurostimulation: 2 pediatric cases. J Neurosurg Pediatr 2018;21:421-7.  Back to cited text no. 116
    
117.
Bercu MM, Friedman D, Silverberg A, Drees C, Geller EB, Dugan PC, et al. Responsive neurostimulation for refractory epilepsy in the pediatric population: A single-center experience. Epilepsy Behav 2020;112:107389. doi: 10.1016/j.yebeh. 2020.107389.  Back to cited text no. 117
    
118.
Loring DW, Kapur R, Meador KJ, Morrell MJ. Differential neuropsychological outcomes following targeted responsive neurostimulation for partial-onset epilepsy. Epilepsia 2015;56:1836-44.  Back to cited text no. 118
    
119.
Giles TX, Bennett J, Stone CE, Gendreau JL, Abraham M, Mammis A. Characterizing complications of intracranial responsive neurostimulation devices for epilepsy through a retrospective analysis of the federal MAUDE database. Neuromodulation 2020. doi: 10.1111/ner. 13259.  Back to cited text no. 119
    
120.
DeGiorgio CM, Soss J, Cook IA, Markovic D, Gornbein J, Murray D, et al. Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology 2013;80:786-91.  Back to cited text no. 120
    
121.
Gil-Lopez F, Boget T, Manzanares I, Donaire A, Conde-Blanco E, Bailles E, et al. External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial. Brain Stimul 2020;13:1245-53.  Back to cited text no. 121
    
122.
Fregni F, Otachi PT, Do Valle A, Boggio PS, Thut G, Rigonatti SP, et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy. Ann Neurol 2006;60:447-55.  Back to cited text no. 122
    
123.
Stagg CJ, Best JG, Stephenson MC, O’Shea J, Wylezinska M, Kincses ZT, et al. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J Neurosci 2009;29:5202-6.  Back to cited text no. 123
    
124.
Tekturk P, Erdogan ET, Kurt A, Vanli-Yavuz EN, Ekizoglu E, Kocagoncu E, et al. The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Clin Neurol Neurosurg 2016;149:27-32.  Back to cited text no. 124
    
125.
San-Juan D, Espinoza Lopez DA, Vazquez Gregorio R, Trenado C, Fernandez-Gonzalez Aragon M, Morales-Quezada L, et al. Transcranial direct current stimulation in mesial temporal lobe epilepsy and hippocampal sclerosis. Brain Stimul 2017;10:28-35.  Back to cited text no. 125
    
126.
Dewan MC, Rattani A, Fieggen G, Arraez MA, Servadei F, Boop FA, et al. Global neurosurgery: The current capacity and deficit in the provision of essential neurosurgical care. Executive Summary of the Global Neurosurgery Initiative at the Program in Global Surgery and Social Change. J Neurosurg 2018:1-10. doi: 10.3171/2017.11.JNS171500.  Back to cited text no. 126
    
127.
Dorfer C, Rydenhag B, Baltuch G, Buch V, Blount J, Bollo R, et al. How technology is driving the landscape of epilepsy surgery. Epilepsia 2020;61:841-55.  Back to cited text no. 127
    


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