Monday, May 20, 2019

Vagus nerve stimulation in refractory and super-refractory status epilepticus

Maxine Dibué-Adjeia, Francesco Brigo, Takamichi Yamamoto, Kristl Vonck, Eugen Trinka.  Vagus nerve stimulation in refractory and super-refractory status epilepticus – A systematic review.  Brain Stimulation.  In press.  DOI:


•A systematic literature review of vagus nerve stimulation used as a last-resort treatment for refractory and super-refractory status epilepticus is performed.
•Cessation of RSE/SRSE occurred in 28 of the 38 cases reported in the literature, however data quality is low and the risk for reporting bias is high.
•VNS was implanted on average 18 days after the start of the SE episode.
•Cessation of the SE episode occurred on average 8 days after VNS implantation.


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 16–39%, 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.

We systematically searched EMBASE, CENTRAL,, and, 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.

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: 3–1680 days) and 8 days (range: 3–84 days) respectively. Positive outcomes occurred in 79% (31/38) of cases.

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.

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