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      Additional Effect of High-output Current and/or High-duty Cycle in Vagus Nerve Stimulation for Adolescent/Adult Intractable Epilepsy

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          Abstract

          A vagus nerve stimulation (VNS) device delivers electrical pulses to the vagus nerve at a rhythm defined by the duty cycle. The standard therapeutic range is advocated for an output current of 1.5-2.25 mA and a duty cycle of 10%. As the optimal settings vary from patient to patient, some patients may benefit from additional seizure reduction when stimulated beyond the standard range. A total of 74 patients (15 children aged <12 years and 59 adolescents/adults) who underwent VNS implantation between 2011 and 2020 and who were followed up for at least 2 years were included in this retrospective study. Stimulation parameters exceeding 2.25 mA of output current, 25% of duty cycle, and 0.5625 (2.25 mA × 25%) of current × duty cycle were defined as high stimulation. The proportion achieved an additional seizure reduction of 20%, and the 50% seizure reduction rate at the last follow-up was compared between adolescents/adults and children. Approximately 40% of patients in adolescents/adults treated with high stimulation experienced an additional acute effect, resulting in a 50% or greater reduction in seizures in almost all patients. Moreover, in adolescents/adults, 22.2%-41.9% of the patients were treated with high stimulation, and the responder rate was 69.5%. Conversely, the responder rate in children was 26.7%, significantly worse than that in adolescents/adults, despite higher stimulation. VNS with high-stimulation settings is effective for adolescent and adult patients with intractable epilepsy. Even high stimulation may not be effective in extremely refractory pediatric epilepsy with a high seizure frequency.

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          Most cited references28

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          ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

          The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
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            Enhanced recognition memory following vagus nerve stimulation in human subjects.

            Neuromodulators associated with arousal modulate learning and memory, but most of these substances do not freely enter the brain from the periphery. In rodents, these neuromodulators act in part by initiating neural messages that travel via the vagus nerve to the brain, and electrical stimulation of the vagus enhances memory. We now extend that finding to human verbal learning. We examined word-recognition memory in patients enrolled in a clinical study evaluating the capacity of vagus nerve stimulation to control epilepsy. Stimulation administered after learning significantly enhanced retention. These findings confirm in humans the hypothesis that vagus nerve activation modulates memory formation similarly to arousal.
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              Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: A critical review.

              Three decades after its introduction as an adjuvant therapeutic option in the management of selective drug-resistant epilepsy cases (DRE), vagus nerve stimulation (VNS) retains growing interest. An implantable device was first approved for epilepsy in Europe in 1994 and in the United States (US) in 1997. Subsequent modifications improved the safety and the efficacy of the system. The most recent application of vagal neurostimulation is represented by transcutaneous devices that are claimed to have strong therapeutic potential. In this review, we sought to analyze the most meaningful available data describing the indications, safety and efficacy of the different approaches of VNS in clinical practice. Therefore, we identified studies reporting VNS efficacy and/or safety in epilepsy and its comorbidities from January 1990 to February 2020 from various databases including PubMed, Scopus, Cochrane, US government databases and VNS manufacturer published resources. In general, VNS efficacy becomes optimal around the sixth month of treatment and a 50-100 % seizure frequency reduction is achieved in approximately 45-65 % of the patients. However, some clinically relevant differences have been reported with specific factors such as epilepsy etiology or type, patient age as well as the delay of VNS therapy onset. VNS efficacy on seizure frequency has been demonstrated in both children and adults, in lesional and non-lesional cases, in focal and generalized epilepsies, on both seizures and epilepsy comorbidities. Regarding the latter, VNS can lead to an improvement of about 25-35 % in depression scores, 35 % in anxiety scores and 25 % in mood assessment scores. If non-invasive devices are undeniably safer, their efficacy is limited due to the scarcity of large cohort studies and the disparity of methodological approaches (study design and stimulation parameters). Overall, we believe that there is a progress margin for improving the safety of implantable devices and, above all, the effectiveness of the various VNS approaches.
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                Author and article information

                Journal
                Neurol Med Chir (Tokyo)
                Neurol Med Chir (Tokyo)
                Neurologia medico-chirurgica
                The Japan Neurosurgical Society
                0470-8105
                1349-8029
                13 April 2023
                July 2023
                : 63
                : 7
                : 273-282
                Affiliations
                [1 ]Department of Neurosurgery, Nara Medical University, Kashihara, Nara, Japan
                [2 ]Epilepsy Center, National Hospital Organization Nara Medical Center, Nara, Nara, Japan
                [3 ]Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan
                Author notes

                Corresponding author: Kentaro Tamura, MD, PhD

                Department of Neurosurgery, Nara Medical University, 840 Shijyo-cho, Kashihara, Nara 634-8521, Japan.

                e-mail: ktamura@ 123456naramed-u.ac.jp

                Article
                10.2176/jns-nmc.2022-0280
                10406457
                37045770
                abf0fb05-ab8e-41db-a316-e3900900e213
                © 2023 The Japan Neurosurgical Society

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives International License.

                History
                : 31 August 2022
                : 20 February 2023
                Categories
                Special Topic

                drug-resistant epilepsy,vagus nerve stimulation,high-output current,high-duty cycle

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