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

Workewych, Adriana M.; Arski, Olivia N; Mithani, Karim; Ibrahim, George M.

doi:10.1111/epi.16661

Cited by 35 publications

(35 citation statements)

References 70 publications

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“…Neuroimaging methods have further revealed acute and prolonged effects of VNS in thalamic and cortical nodes (15,(24)(25)(26)(27). Recent connectomic studies support these observations by demonstrating that the robustness of leftlateralized microstructure and connectivity within limbic, thalamocortical, and hemispheric association fibers reliably predict VNS therapeutic responsiveness (28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 94%

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy

Afra

Adamolekun

Aydemir

et al. 2021

Front. Med. Technol.

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The vagus nerve stimulation (VNS) Therapy® System is the first FDA-approved medical device therapy for the treatment of drug-resistant epilepsy. Over the past two decades, the technology has evolved through multiple iterations resulting in software-related updates and implantable lead and generator hardware improvements. Healthcare providers today commonly encounter a range of single- and dual-pin generators (models 100, 101, 102, 102R, 103, 104, 105, 106, 1000) and related programming systems (models 250, 3000), all of which have their own subtle, but practical differences. It can therefore be a daunting task to go through the manuals of these implant models for comparison, some of which are not readily available. In this review, we highlight the technological evolution of the VNS Therapy System with respect to device approval milestones and provide a comparison of conventional open-loop vs. the latest closed-loop generator models. Battery longevity projections and an in-depth examination of stimulation mode interactions are also presented to further differentiate amongst generator models.

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Section: Introductionmentioning

confidence: 94%

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy

Afra

Adamolekun

Aydemir

et al. 2021

Front. Med. Technol.

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“…Though our model demonstrated an ability to predict VNS response at a rate slightly better than chance, our analysis demonstrated that clinical variables alone are not sufficient to accurately predict VNS response in this patient population. More advanced data, like biomarkers 16 , are warranted for more accurate predictions of VNS response. This tool may be utilized as an adjunct during the initial outpatient evaluation of seizure control options for pediatric patients with ASM-resistant epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…The authors demonstrated that heart rate variability was an independent marker of VNS response and their results indicated that brain network connectivity analyses are a promising avenue for predicting seizure responsiveness to VNS. 16 Such connectonomic and biomarker analyses have an important role in understanding the mechanism of VNS and could aid patient selection at specialized epilepsy centers. The variables utilized in this study's clinical prediction tool are easily attainable by an outpatient care provider and demonstrates better predictive accuracy (65%) than chance alone.…”

Section: Clinical Predictive Modelmentioning

confidence: 99%

“…Workewych et al have suggested that brain connectivity is a promising avenue to predict outcomes following VNS. 16 However, these techniques are under development and most epilepsy centers do not have network-based connectomic biomarkers readily available during initial discussions of VNS therapy. We sought to evaluate whether a simple prediction model based on clinical factors alone could guide initial discussions about the individualized benefits of VNS therapy for a given patient with ASMresistant epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Development of a clinical model to predict vagus nerve stimulation response in pediatric patients with drug-resistant epilepsy

Muthiah

Mallela

Vodovotz

et al. 2022

Preprint

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Introduction Epilepsy impacts 470,000 children in the United States, and children with epilepsy are estimated to expend 6 times more on healthcare than those without epilepsy. For patients with antiseizure medication (ASM)-resistant epilepsy and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. We aimed to create a clinical prediction score which could be utilized in a routine outpatient clinical setting. Methods We performed an 11-year, single-center retrospective analysis of patients <21 years old with ASM-resistant epilepsy who underwent VNS. The primary outcome was >50% seizure frequency reduction after one year. Univariate and multivariate logistic regressions were performed to assess clinical factors associated with VNS response; 70% and 30% of the sample were used to train and validate the multivariate model, respectively. A prediction score was developed based on the multivariate regression. Sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated. Results This analysis included 365 patients. Multivariate logistic regression revealed that variables associated with VNS response were: <4 years of epilepsy duration before VNS (p=0.008) and focal motor seizures (p=0.037). The variables included in the clinical prediction score were: epilepsy duration before VNS, age at seizure onset, number of pre-VNS ASMs, if VNS was the patient's first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUC was 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. Conclusions We developed a clinical model to predict VNS response in one of the largest samples of pediatric VNS patients to date. While the presented clinical prediction model demonstrated an acceptable AUC in the training cohort, clinical variables alone likely do not accurately predict VNS response. This score may be useful upon further validation, though its predictive ability underscores the need for more robust biomarkers of treatment response.

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“…[5][6][7]9,13,14 The vagus nerve has direct afferent projections to the thalamus. 13 Response variation to VNS therapy in children is hypothesized to be attributable to the heterogeneity of seizure etiologies and the age-dependent varying effects of VNS on thalamocortical connectivity of the developing brain, known as the vagus afferent network. 13,15 A better understanding of the characteristics of good and poor responders to VNS therapy in the pediatric population is critical to improve patient selection and response prediction.…”

Section: Introductionmentioning

confidence: 99%

Patient Characteristics Associated with Seizure Freedom after Vagus Nerve Stimulation in Pediatric Intractable Epilepsy: An Analysis of “Super-Responders”

Tamura

Yau

et al. 2021

Journal of Pediatric Epilepsy

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Clinical responses to vagus nerve stimulation (VNS) therapy for intractable epilepsy can be unpredictable, and factors that predict response to therapy are elusive. Minority of children undergoing VNS achieve seizure freedom. The current study aimed to characterize this exceptional patient population, defined as “super-responders” (SRs). Retrospective data were collected from 150 children who underwent VNS at a single pediatric institution. The patients' mean age at VNS device implantation was 12.0 years (range, 3.09–17.9 years). Ten SRs (6.7%) were identified who achieved and maintained seizure freedom for longer than 1 year following implantation. The interval between epilepsy onset and VNS device implantation was significantly shorter in SRs than in the other children (mean epilepsy duration 5.72 vs. 8.44 years, respectively; p = 0.032). SRs also had a significantly shorter proportion of life with epilepsy compared with the other children (mean ratio of epilepsy duration to age at implantation 0.52 vs. 0.71, respectively; p = 0.023). SRs reported their seizure freedom relatively early (six patients within 6 months and all patients within 12 months after implantation) at relatively low device settings (mean output current 0.81 mA at their last follow-up). Compared with conventional models, responsive VNS models with autostimulation features did not increase the ratio of SRs. No other clinical or imaging characteristic difference between SRs and the other children was found in this cohort. The current study showed a significant association between shorter epilepsy duration and shorter proportion of life with epilepsy and seizure freedom after VNS.

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

Cited by 35 publications

References 70 publications

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy

Development of a clinical model to predict vagus nerve stimulation response in pediatric patients with drug-resistant epilepsy

Patient Characteristics Associated with Seizure Freedom after Vagus Nerve Stimulation in Pediatric Intractable Epilepsy: An Analysis of “Super-Responders”

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