Clinical utility of implantable neurostimulation devices as adjunctive treatment of uncontrolled seizures

Figures & data

Table 1 Randomized controlled trials for vagus nerve stimulation (VNS) in patients with refractory epilepsy

Study	Study type	Participants	Study protocol	Measure of effect (%)
The Vagus Nerve Stimulation Study Group, 1995^Citation14	Double-blind randomized controlled trial	114 patients ≥12 years old with refractory seizures	Patients were randomized to receive 14 weeks of high- or low-level VNS stimulation	High-level stimulation Responder rate =31 Decrease in seizure frequency =25 Seizure freedom =0 Low-level stimulation Responder rate =13 Decrease in seizure frequency =6 Seizure freedom =0
Handforth et al 1998^Citation15	Double-blind randomized controlled trial	192 patients aged 13–60 years old with refractory partial-onset seizures	Patients were randomized to receive a minimum of 3 months of high- or low-level VNS stimulation	High-level stimulation Responder rate = not reported Decrease in seizure frequency =28 Seizure freedom = not reported Low-level stimulation Responder rate = not reported Decrease in seizure frequency =15 Seizure freedom = not reported
Klinkenberg et al 2012^Citation28	Double-blind randomized controlled trial	41 patients aged 3–17 years old with refractory seizures	Patients were randomized to receive 20 weeks of high- or low-level VNS stimulation	High-level stimulation Responder rate =16 Decrease in seizure frequency =−23 (increase) Seizure freedom =0 Low-level stimulation Responder rate =21 Decrease in seizure frequency =9 Seizure freedom =0

Table 2 Randomized-controlled trials for deep brain stimulation (DBS) in patients with refractory epilepsy

Study	Study type	Target	Participants	Study protocol	Measure of effect (%)
Fisher et al 2010^Citation41	Double-blind randomized controlled trial	Anterior nucleus of the thalamus	110 patients aged 18–65 years with refractory partial-onset seizures	Patients were randomized to receive 3 months of 5 V or 0 V of stimulation, followed by an unblinded period of stimulation of up to 2 years	5 V stimulation Responder rate = not reported Decrease in seizure frequency =40 Seizure freedom =0 0 V stimulation (control) Responder rate = not reported Decrease in seizure frequency =16 Seizure freedom =1 Unblinded phase (at 2 years) Responder rate =54 Decrease in seizure frequency =56 Seizure freedom (.6 months) =13
Tellez-Zenteno et al 2006^Citation63	Double-blind multiple crossover randomized controlled trial	Axis of the left hippocampus	Four patients aged 24–37 years with refractory mesial temporal lobe epilepsy	Patients were randomized to receive one of three treatment pairs, containing two treatment periods of 1 month “ON” and 1 month “OFF”	Stimulator “ON” Responder rate =25 Decrease in seizure frequency =26 Stimulator “OFF” Responder rate =25 Decrease in seizure frequency =−49 (increase) Overall Seizure freedom (at 4 years) =25
Velasco et al 2007^Citation64	Double-blind randomized controlled trial	Hippocampal epileptic foci	Nine patients aged 14–43 years with refractory partial-onset complex seizures	Patients were randomized to either receive stimulation straight away after implantation, or a 1 month “OFF” period. This was followed by a follow-up period of 18 months	Normal MRI Responder rate =100 Decrease in seizure frequency = not reported Seizure freedom (at 18 months) =80 Hippocampal sclerosis Responder rate =100 Decrease in seizure frequency = not reported Seizure freedom =0
McLachlan et al 2010^Citation65	Double-blind crossover randomized controlled trial	Axis of both hippocampi	Two patients aged 45 and 54 years with refractory mesial temporal lobe epilepsy	Patients were randomized to receive a 3 month period where the stimulator was either “ON” or “OFF”	Responder rate =0 Decrease in seizure frequency =33 Seizure freedom =0
Wright et al 1984^Citation77	Double-blind multiple crossover randomized controlled trial	Cerebellum	12 patients aged 20–38 years with severe, refractory epilepsy of unknown cause	Patients were randomized to receive 2 months of continuous stimulation, 2 months of intermittent stimulation, and 2 months of no stimulation, in any order	Responder rate =0 Decrease in seizure frequency = not reported Seizure freedom =0 Eleven patients reported improvement
Velasco et al 2005^Citation78	Double-blind randomized controlled pilot study	Cerebellum	Five patients with refractory motor seizures	Patients were randomized to receive 3 months with the stimulator “ON” or “OFF”, after which, all were switched to “ON” for long-term follow-up	Follow-up (at 24 months) Decrease in seizure frequency → generalized tonic–clonic seizures =76 → tonic seizures =57 Seizure freedom =0

Abbreviation: MRI, magnetic resonance imaging.

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