Vagus nerve stimulation in refractory and super-refractory status epilepticus – A systematic review

Abstract

Rationale: Refractory status epilepticus (RSE) is the persistence of status epilepticus despite second-line treatment. Super-refractory SE (SRSE) is characterized by ongoing status despite 48 h of anaesthetic treatment. Due to the high case fatality in RSE of 16e39%, off label treatments without strong evidence of efficacy in RSE are often administered. In single case-reports and small case series totalling 28 patients, acute implantation of VNS in RSE was associated with 76% and 26% success rate in generalized and focal RSE respectively. We performed an updated systematic review of the literature on efficacy of VNS in RSE/ SRSE by including all reported patients. Methods: We systematically searched EMBASE, CENTRAL, Opengre.eu, and ClinicalTrials.gov, and PubMed databases to identify studies reporting the use of VNS for RSE and/or SRSE. We also searched conference abstracts from AES and ILAE meetings. Results: 45 patients were identified in total of which 38 were acute implantations of VNS in RSE/SRSE. Five cases had VNS implantation for epilepsia partialis continua, one for refractory electrical status epilepticus in sleep and one for acute encephalitis with refractory repetitive focal seizures. Acute VNS implantation was associated with cessation of RSE/SRSE in 74% (28/38) of acute cases. Cessation did not occur in 18% (7/38) of cases and four deaths were reported (11%); all of them due to the underlying disease and unlikely related to VNS implantation. Median duration of the RSE/SRSE episode pre and post VNS implantation was 18 days (range: 3e1680 days) and 8 days (range: 3e84 days) respectively. Positive outcomes occurred in 82% (31/38) of cases. Conclusion: VNS can interrupt RSE and SRSE in 74% of patients; data originate from reported studies classified as level IV and the risk for reporting bias is high. Further prospective studies are warranted to investigate acute VNS in RSE and SRSE.

The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization

“…About 50% to 60% of patients achieve 50% reduction in seizure frequency after 1 year of treatment (Englot et al, 2016;Kawai et al, 2017;Panebianco et al, 2015). A recent meta-analysis (Dibué-Adjei et al, 2019) suggested that acute VNS implantation could reverse refractory status epilepticus, with an overall response rate of 74%. However, mechanisms underlying the effects of VNS remain misunderstood (Vonck and Boon, 2015).…”

Probable Mechanism of Antiepileptic Effect of the Vagus Nerve Stimulation in the Context of the Recent Results in Sleep Research

“…Vagus nerve stimulation is widely used as a seizure-preventive action in many types of otherwise incurable epilepsy and is extensively studied for treating other conditions ranging from rheumatoid arthritis to depression (Vonck et al, 2001;Groves and Brown, 2005;Yuan and Silberstein, 2016;Dibue-Adjei et al, 2019;Noller et al, 2019). It is well-known that vagus nerve is engaged in the bidirectional information transfer between the internal organs and the brain, but how changes in activity going along visceral pathways may be related to paroxysmal events occurring in various brain areas remained unclear.…”

Health Technology Assessment Report on Vagus Nerve Stimulation in Drug-Resistant Epilepsy

“…De Benedictis et.al report a series of four patients with SE who saw an improvement in seizure after 5 weeks since stimulation onset, and a persistence of the effect after a mean follow-up of 3 years [ 82 ]. On the other hand, a review of 17 papers did not recommend the use of VNS for resistant status epilepticus (RSE); nevertheless, a more recent review by Dibué-Adjei concludes that VNS can interrupt RSE in 74% of patients, with a class IV evidence level [ 83 ]. VNS was considered as a promising tool in the prevention or reduction in sudden unexpected death in epilepsy (SUDEP) [ 84 , 85 , 86 ].…”