We could predict good responders to vagus nerve stimulation: A surrogate marker by slow cortical potential shift

Abstract

論文題目We could predict good responders to vagus nerve stimulation: a surrogate marker by slow cortical potential shift (脳波の緩電位変化は迷走神経刺激療法の治療効果の代替マーカーとなる) (論文内容の要旨) Objective: Vagus nerve stimulation (VNS) is a palliative treatment option for patients with intractable epilepsy who are not good candidates for surgical resection. The stimulation of the vagus nerve is intermittent, and the usual stimulation condition is set to a signal on-time (VNS ON) of 30 s followed by an off-time (VNS OFF) of 3-5 min repeatedly. It has been reported that one third of patients have a >50% reduction in seizure frequency, another one third show a 30%-50% seizure reduction, and the remaining one third show no response. On the other hand, hyperpolarization of neurons, seen on electroencephalograms (EEGs) as positive slow cortical potential (SCP) shifts, represents activation of inhibitory postsynaptic potentials and inhibition of neuronal activity. Production of scalp-recorded positive SCP by a self-regulation training has been used for suppressing seizures, and some patients have even become seizure free. Slow hyperpolarization of cortical pyramidal neurons during the stimulation period in rat models was suggested as an underlying mechanism of action of VNS in suppressing seizures. The aim of this study was to investigate whether VNS induces a positive shift of SCPs in patients with >50% seizure reduction (responders) but not in non-responders. Methods: This retrospective study was approved by the ethics committees of the Kyoto University Hospital, Kindai University Hospital and Hiroshima University Hospital (IRB#E1736, #25-036 and #Epi1158 respectively). Routine clinical EEGs from 24 patients who were undergoing seizure treatment by VNS were analyzed. The patients were divided into 2 groups by hardware time constant (TC) of EEG: the TC 10-s group (10 patients) and TC 2-s group (14 patients). The SCPs at 5 electrodes (vertex and adjacent ones) were compared between the 2 states of VNS: during stimulation and between stimulations. A positive shift of the SCP was considered to be "present" when it was observed on the 5 electrodes during the stimulation period, and the Wilcoxon test value was <0.05. Seizure reduction was independently judged. Correlation between SCP (positivity or not) and seizure reduction (>50% or not) was estimated. Results: In the TC 10-s group, the correlation between SCP and seizure reduction was significant (p < 0.05) (i.e., both good results in 4 and both negative results in 5). In TC 2-s group, the correlation between SCP and seizure reduction was not significant (p = 0.209). Conclusions:This study compared scalp-recorded SCPs during VNS stimulation period with the inter-stimulation interval respectively from 5 electrodes in patients undergoing VNS therapy. The comparison showed that utilization of EEG with a long TC (10 s) revealed positive SCP shifts during VNS in good responders. A positive shift of SCP recorded by using a TC of 10 s could be a surrogate marker for VNS response.

Biomarkers of seizure response to vagus nerve stimulation: A scoping review

“…Finally, Bayasgalan et al investigated SCPs as markers of VNS response 38 . Positive SCPs seen on EEG represent inhibitory postsynaptic potentials and inhibition of neuronal activity, and their production has been associated with seizure suppression 38 . Using EEGs with a 10‐second time constant, they reported that positive‐polarity SCPs are associated with good VNS response.…”

Predictors of seizure reduction outcome after vagus nerve stimulation in drug-resistant epilepsy

“…But we still found that unilateral IEDs were perhaps predictors of good response to VNS, which agrees with Arcos et al [38], who considered that a temporal lobe discharge on the video-EEG was an indicator of an early response. Besides IEDs, the other EEG features, also reported as effective predictors for good response to VNS, included positive polarity of slow cortical potential (SCP) shifts on scalp EEG [39], the increase in P300 amplitude [40], lower global synchronization levels in delta and alpha frequency bands [41], ictal synchronization of brain activities measured with scalp EEG [42], and decreased connectivity with SEEG signals [43]. Conversely, Barbella et al [44] found no changes in epileptiform activity or in its localization in responders or non-responders, so more studies are needed that focus on the relation between EEG and the outcome of VNS in the future.…”

Neural Sources of Vagus Nerve Stimulation–Induced Slow Cortical Potentials

“…They all participated in our previous study and their clinical characteristics were described in detail. 9 At the last follow-up visit (mean 24.1, range 11.7-43.0 months), 12 patients became seizurefree. Patient demographics are briefly described in Table S1.…”

“…In a previous study, 9 we examined VNS-induced slow cortical potentials (SCPs) in patients with epilepsy and found an association between the presence of SCPs and seizure reduction, suggesting that alterations on electroencephalography (EEG) because of VNS reflect the efficacy of VNS against seizures. Because SCPs reflect repetitive firing of cortical neurons during VNS, SCPs from specific brain areas may be involved in the suppression of seizures.…”