The Importance of Stimulation Cycle in Vagus Nerve Stimulation for Drug-Resistant Epilepsies-Our Experience and Literature Review

C l i n M e d International Library Citation: Montano N, Fuggetta F, Papacci F, Bonaventura RD, Meglio M, et al. (2014) The Importance of Stimulation Cycle in Vagus Nerve Stimulation for Drug-Resistant EpilepsiesOur Experience and Literature Review. Int J Neurol Neurother 1:013. doi. org/10.23937/2378-3001/1/1/1013 Received: October 09, 2014: Accepted: December 15, 2014: Published: December 17, 2014 Copyright: © 2014 Montano N. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Montano et al. Int J Neurol Neurother 2014, 1:1


Introduction
Vagus nerve stimulation (VNS) is an adjunctive treatment for drug-resistant epileptic patients excluded from ablative surgery.The results reported in the literature are highly variable due to a widening of indications in the last years [1][2][3][4], the lack of defined prognostic factors [5] and the absence of full understanding of mechanism of action [6,7].Recently we published on this topic and showed that the lesional etiology and an implant age less than 18 years were associated with an higher probability to be a responder after VNS [8].Nevertheless the role of patient's stimulation cycle was not evaluation have previously been reported [13].Mean follow-up (FU) was 80.42 ± 54.01 months.The stimulation frequency was 30 Hz and the pulse width 500 µsec.Stimulation cycles used were the following: slow (30''on-5'off), intermediate (30''on-3'off), fast (7''on-20''off).
Each cycle was 1 year in duration.Our protocol was to start with the slow cycle, to switch to the fast cycle and then to the intermediate one.Ethical approval of this protocol was previously obtained by the institutional review board [13].We recorded the stimulation cycle at the latest available FU for each patient.
When considering the subgroup of patients who reached a 75% of reduction of seizures number (n=12) nobody was using the fast cycle.

Discussion
Our results indicate that in patients "responders" to VNS the slow and intermediate cycles maintain the benefit of stimulation.We investigated this parameter only in the responder patients to avoid the interference of other possible confounding variables that influence the prognosis of these patients.We think that this observation is interesting because the stimulation cycle affects the duration of generator that is directly correlated to the cost of this therapy.When examining the literature we found that the latest published metaanalysis didn't take into account the role of this parameter [5] and that the evidence to support the use of a determined cycle to reduce seizure occurrence was found insufficient in a recent evidencebased guideline update [12].Furthermore the role of stimulation cycle in VNS therapy was fully investigated only marginally [2,[9][10][11].Moreover these studies had a FU generally short (mean FU ranges from 3 to 15.8 months) (Table 2).While Labar [2] found that stimulation parameters did not affect seizure rates in their groups, Shermann and colleagues [9], evaluating two stimulation cycles (fast and slow cycles), evidenced as patients with stimulation-on period of 30 sec (slow cycle) had a significantly better seizure outcome than patients with stimulation-on periods of 7 sec (fast cycle).Moreover it has been showed that in the first 3 months of therapy, initial settings of 30 seconds on/3 minutes off are well tolerated, and produced the most 75% responders [11] and that patients in the settings of 30 sec on and 5 min off improve in their response over 1 year period [10].In our study the mean FU was 80.42 ± 54.01 months and we found that in patients with a FU more than 3 years, all but one case were using the slow or intermediate cycle.

Conclusions
Our study has some limitations due to the limited number of patients and the retrospective nature of data.However based on our observations and the reported literature, in managing patients after VNS implantation, we suggest to start with the slow cycle and, if there is no response, to switch to intermediate one.At that stage the probability for the patient of being a responder with the fast cycle is very low.Obviously further studies that should be multicentric and randomized are needed.In the first 3 months of therapy, initial setting of 30 seconds on/3 minutes off is well tolerated, and produce the most 75% responders

12 -
66 sec off/7-60 sec on 1.8 min off/7-60 sec on 3 min off/7-60 sec on 5 min off/7-60 sec on 30Hz  12    Patients with 30 sec on and 5 min off continue to respond or improve in their response over 1 year period.Some patients may benefit from reductions in off time (increases duty cycle)

Table 1 :
Clinical records and stimulation parameters of 21 "responders" to vagal nerve stimulation.

Table 2 :
Literature review of studies comparing stimulation cycles in vagus nerve stimulation for drug-resistant epilepsies.