23 Neuromodulation in Epilepsy

10.1055/b-0039-171742

23 Neuromodulation in Epilepsy

Kevin Mansfield, Joseph S. Neimat

Abstract

Targeted neuromodulation can be used to reduce seizure frequency in patients with medically intractable epilepsy who are not candidates for surgical resection. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), and Responsive Neurostimulation (RNS) can be used for different types of epilepsy and in varied patient populations. The indications differ slightly, and each requires unique surgical approaches. All require the placement of a pulse generator in an accessible location, and precise placement of electrodes at a target point in the nervous system. The procedures are well tolerated, and have risks comparable to other similar operations. In this chapter, we review the indications and anticipated benefit for each mode of neuromodulation.

23.1 Patient Selection

Epilepsy affects an estimated 1% of the world’s population. ¹ ^, ² In 20–30% of those individuals medication is not effective. ¹ ^, ³ ^, ⁴ Whereas resection or ablation of a seizure focus can produce great improvements in seizure control in well-selected patients, a substantial population of refractory patients is not appropriate for surgical resection. Those not eligible for resection or ablation may be considered for targeted neuromodulation.

Current stimulation works by using electrical waveforms to inhibit pathologic signal transmission through the central nervous system. Vagus Nerve Stimulation (VNS) and Deep Brain Stimulation (DBS) decrease the excitability of seizure circuitry. Both are open-looped systems. Responsive Neuromodulation (RNS) detects a seizure and instantaneously blocks propagation with a high frequency stimulus burst. This is a closed loop system. Both types can reduce seizure frequency, but will rarely produce seizure freedom. ⁵ ^, ⁶ ^, ⁷ Partial, focal and multifocal and generalized epilepsy syndromes have been studied, with variable results (▶ Table 23.1). ⁸ ^, ⁹ ^, ¹⁰ ^, ¹¹

**Table 23.1** Epilepsy studies and results
Therapy	% Seizure Reduction (during blinded phase)	% Responders (Achieving > 50% reduction by 1 year)	Notable Side Effects
VNS ¹² ^, ¹³	28	27	66.3% experienced voice alteration
DBS ⁶	40.4	43	Incidence of depression (14%) and memory impairment (11%) in active group.
RNS ¹⁴	37.9	46	2.1% experienced significant hemorrhage without permanent deficit. Death from SUDEP in 3 subjects with stimulation enabled
Note: Cohorts in the DBS and RNS studies included some patients that had failed VNS.

An algorithm for selecting the appropriate neuromodulation therapy is provided (▶ Fig. 23.1). Patients with a clear seizure focus in a non-eloquent area that can be safely resected or ablated should undergo surgical resection. Resection can provide a 50–70% chance of seizure free outcome. If the focus or foci can be identified but cannot be resected, then RNS may be better than the less specific VNS and DBS therapies. The inability to resect may be because either the focus is in eloquent cortex or arises from both hippocampi. If greater than two foci are present or if the foci cannot be identified, then VNS and DBS are the best options. Although slight differences in VNS and DBS therapeutic efficacy exist, they are comparable. The merits and challenges of each mode should be discussed with each patient and family in the selection process. Table 23.2 compares the practical requirements of each form of neuromodulation.

**Fig. 23.1** Algorithm for determining surgical therapy for epilepsy: *ANT = Anterior Nucleus of thalamus. Other targets may be suitable depending on the seizure type/onset; TLE = Temporal Lobe Epilepsy

**Table 23.2** Patient selection
Modality	Preoperative Planning	Surgical Stress	Inpatient Required	Time to Initiation
VNS	Standard workup only	Minimal	No	Same-day
DBS	Additional imaging, surgical planning*	Moderate; awake surgery sometimes required. Often staged over 1–2 weeks	Cranial portion only; generator placement is outpatient	2–4 weeks after generator placement
RNS	Possible additional imaging, surgical planning*	High, must tolerate craniotomy; performed asleep	Yes	1–2 months after placement
^* Image acquisition for frame targeting and trajectory planning; some platforms require planning 1 week prior to implantation.

23.1.1 Preoperative Preparation

Patients with medically-refractory epilepsy should be evaluated for the option of surgical resection. The elements of the workup depend upon the patient’s seizure pattern, and their tolerance for the testing. The goal is to identify the seizure foci, characterize the epilepsy type and clarify the risks of neurologic injury from the surgery. Neuropsychiatric evaluation should be included, to aid in localization and surgical risk assessment, and because depression and other psychiatric disorders may be exacerbated by the intervention. Even if a patient is not a candidate for resection or ablation, this data can guide the selection of the appropriate neuromodulation therapy.

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