The role of vagus nerve stimulation in genetic etiologies of drug-resistant epilepsy: a meta-analysis

Abstract

OBJECTIVE Drug-resistant epilepsy (DRE) affects many children. Vagus nerve stimulation (VNS) may improve seizure control; however, its role in children with genetic etiologies of epilepsy is not well described. The authors systematically reviewed the literature to examine the effectiveness of VNS in this cohort. METHODS In January 2021, the authors performed a systematic review of the PubMed/MEDLINE, SCOPUS/Embase, Cochrane, and Web of Science databases to investigate the impact of VNS on seizure outcomes in children with genetic etiologies of epilepsy. Primary outcomes included seizure freedom rate, ≥ 90% seizure reduction rate, and ≥ 50% seizure reduction rate. Secondary outcomes were seizure severity and quality of life (QOL), including cognitive, functional, and behavioral outcomes. A random-effects meta-analysis was performed. RESULTS The authors identified 125 articles, of which 47 with 216 nonduplicate patients were analyzed. Common diagnoses were Dravet syndrome (DS) (92/216 patients [42.6%]) and tuberous sclerosis complex (TSC) (63/216 [29.2%]). Seizure freedom was not reported in any patient with DS; the pooled proportion (95% CI) of patients with ≥ 50% seizure reduction was 41% (21%–58%). Secondary cognitive outcomes of VNS were variable in DS patients, but these patients demonstrated benefits in seizure duration and status epilepticus. In TSC patients, the pooled (95% CI) seizure freedom rate was 40% (12%–71%), ≥ 90% seizure reduction rate was 31% (8%–56%), and ≥ 50% reduction rate was 68% (48%–91%). Regarding the secondary outcomes of VNS in TSC patients, several studies reported decreased seizure severity and improved QOL outcomes. There was limited evidence regarding the use of VNS to treat patients with other genetic etiologies of epilepsy, such as mitochondrial disease, Rett syndrome, Doose syndrome, Landau-Kleffner syndrome, Aicardi syndrome, Angelman syndrome, ring chromosome 20 syndrome, and lissencephaly; variable responses were reported in a limited number of cases. CONCLUSIONS The authors conducted a systematic review of VNS outcomes in children with genetic etiologies of DRE. Among the most studied conditions, patients with TSC had substantial seizure reduction and improvements in QOL, whereas those with DS had less robust seizure reduction. Increased testing, diagnosis, and long-term follow-up studies are necessary to better characterize VNS response in these children.

Vagus nerve stimulation in children with drug-resistant epilepsy of monogenic etiology

“…These findings suggest that VNS is to some extent effective for patients with DS, and should be considered as a treatment option. The meta-analysis also showed that the response rate among TSC patients was 68%; in one study of 20 patients with TSC, 40% achieved seizure freedom ( 11 ). These results suggest that VNS is a potential treatment option for TSC patients who cannot undergo or have a poor outcome after resection.…”

“…A meta-analysis has evaluated the efficacy of VNS in this population. A meta-analysis of 216 patients including 92 with DS and 63 with TSC showed that 41% of the DS group responded to VNS treatment ( 11 ). Our study included four patients with DS; among them, three (75%) were responders.…”

“…A retrospective study on the efficacy of VNS in seven children with Rett syndrome with a median age of seizure onset of 34 months (range: 2–64 months) and median age at stimulator implantation of 9 years (range: 1–14 years) found that at the 12-month follow-up, 86% of patients had a reduction in seizure frequency of ≥50% ( 15 ). A meta-analysis of 11 patients with Rett syndrome also showed that 82% of patients had a ≥50% reduction in seizure frequency ( 11 ). MECP2 duplication syndrome is characterized by cognitive impairment, seizures, autism, sleep disturbances and lower-respiratory-tract infections.…”

Long-term follow-up of vagus nerve stimulation in drug-resistant KCNT1-related epilepsy: a case presentation

“…VNS is a safe and effective neuromodulatory therapy for pediatric drug-resistant epilepsy, with a responder rate (> 50% seizure reduction) of around 35% to 50% after 2 years of follow up and higher rate after 5-year or longer follow-up [22,23]. In children, the responder rate is higher than that in adults with drug-resistant epilepsy with any etiology [24]. The precise mechanism of VNS treatment remains unknown, although several hypotheses have been offered by previous studies [25].…”

“…Patients with genetic aetiology of drug-resistant epilepsy can also achieve significant outcomes after VNS. In tuberous sclerosis complex (TSC) patients, about 40% patients could acquire seizure freedom and the responder rate was 68% [24]. In contrast to TSC patients, the responder rate of Dravet syndrome with SCN1A mutation was only 41% and none were seizure free [12].…”