Introducing the Index of Response to Stimulation (IRES): A Novel Metric for Assessing Vagus Nerve Stimulation Outcomes in Drug-Resistant Epilepsy
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Objective
2.2. Study Design
2.3. Participants
2.4. IRES Score Review
2.5. VNS Therapy Settings
2.6. Ethical Considerations
2.7. Results
2.7.1. Scoring Criteria
- 0 points means little or no change (0–25% improvement).
- 1 point means minimal to moderate improvement (25–50% improvement).
- 2 points are given to those with strong improvement, more than 50%.
- As each dimension is assessed within this range then the overall IRES score will be from 0 to 8 where 0 represents no observed improvement and 8 represents observed maximum improvement over all assessed aspects.
2.7.2. Interpretation of IRES Scores
- Scores between 0 and 2 indicate minimal or no improvement in the response to VNS therapy and, therefore, the treatment had little effect on the patient.
- Scores of 3–6 are indicative of partial response to treatment in some of the dimensions evaluated, with the improvement being moderate to modest. The range suggests that symptomatic improvement has taken place for the patient following therapy.
- Scores greater than 6 points manifest a highly significant response to treatment or remission, reflecting substantial therapeutic benefit that may be translated into improvement in the quality of life or control over symptoms.
2.7.3. IRES Score Assessment
- -
- SDD: shows a gradual increase in mean scores from 0.51 at 6 months to 0.96 at 18 months, indicating a moderate improvement in seizure duration over time.
- -
- SID: the mean scores go up from 0.22 at 6 months to 0.55 at 18 months, with a suggestion of slight to moderate reduction in seizure intensity across the study period.
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- IQoF: marked improvement, with the mean score increasing from 0.74 at 6 months to 1.17 at 18 months.
- -
- SFD: the mean scores rise from 0.41 at 6 months to 1.14 at 18 months.
3. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Component | 0 Points | 1 Point | 2 Points |
Seizure Duration Decrease | 0–25% improvement | 25–50% improvement | >50% improvement |
Seizure Intensity Decrease | 0–25% improvement | 25–50% improvement | >50% improvement |
Improvement in Quality of Life | No changes in daily life No observable improvement in the patient’s life after VNS | Feels a little better Reflects a slight but noticeable enhancement in day-to-day well-being | Good improvement Marked reductions in depressive symptoms and an overall betterment of mood and functionality |
Seizure Frequency Decrease | 0–25% improvement | 25–50% improvement | >50% improvement |
Total IRES Points: | 0–2 points | 3–6 points | >6 points |
Interpretation: | Minimal or no response | Partial or moderate improvement | Significant or complete response |
Category | IRES 6 Months Mean | IRES 12 Months Mean | IRES 18 Months Mean | 6–12 Months t-Value | 6–12 Months p-Value | 12–18 Months t-Value | 12–18 Months p-Value |
---|---|---|---|---|---|---|---|
19–29 | 2.08 | 3.33 | 3.92 | −5.23945 | <0.05 | −4.98573 | <0.05 |
30–40 | 1.80 | 3.17 | 3.83 | −7.69827 | <0.05 | −4.99831 | <0.05 |
>40 | 1.93 | 3.32 | 3.82 | −7.43701 | <0.05 | −4.52522 | <0.05 |
Sex F | 1.88 | 3.18 | 3.70 | −9.00464 | <0.05 | −5.87516 | <0.05 |
Sex M | 1.90 | 3.35 | 4.03 | −7.21193 | <0.05 | −4.7678 | <0.05 |
IRES Score | Pearson 6 Months | Significance p-Value 6 Months | Pearson 12 Months | Significance p-Value 12 Months | Pearson 18 Months | Significance p-Value 18 Months |
---|---|---|---|---|---|---|
ICV | 0.716 | <0.0001 | 0.863 | <0.0001 | 0.874 | <0.0001 |
SDC | 0.779 | <0.0001 | 0.754 | <0.0001 | 0.816 | <0.0001 |
SFD | 0.731 | <0.0001 | 0.819 | <0.0001 | 0.834 | <0.0001 |
SIC | 0.303 | <0.01 | 0.54 | <0.001 | 0.454 | <0.0001 |
Study Reference | Patient Cohort | Follow-Up Duration | Main Outcome Measures | Key Findings |
---|---|---|---|---|
Kawai et al., 2017 [1] | 385 patients | Up to 36 months | Seizure frequency reduction, quality of life (QoL) | Seizure control progressively improved during treatment, showing a significant median reduction of seizures at various time points. |
Colicchio et al., 2012 [2] | 53 patients | Mean 55.96 months | Seizure frequency, responder rate, response time (RT) | Lesion etiology and an age at implant of <18 years are found to have a better response. |
Liu et al., 2018 [3] | 32 patients | 1 year | Heart rhythm complexity HRV | VNS reversed the increased complexity in heart rhythm, which might be related to therapeutic effect. |
Wang et al., 2019 [4] | Meta-analysis | Varies | Seizure frequency reduction >50% | A significant predictor of VNS outcomes was duration of epilepsy. |
Elliott et al., 2011 [5] | 436 patients | Up to 11 years | Seizure frequency reduction, safety outcomes | Over 60% of these patients showed a decrease in seizure burden by at least 50%. |
Rong et al., 2014 [6] | 50 patients | 24 weeks | Seizure frequency reduction | The effectiveness and safety of ta-VNS was confirmed with 38% seizure reduction in seizure frequency in patients up to 24 weeks. |
Hajtovic et al., 2022 [7] | Meta-analysis on genetic etiologies | Varies | Seizure freedom rate, ≥ 50% seizure reduction | Patients with TSC had substantial seizure reduction; those with DS had less robust seizure reduction. |
Constantinescu et al., 2020 [8] | 5 patients | 3 months | HRV parameters | VNS did not alter cardiac autonomic function after 3 months of neurostimulation. |
Sen et al., 2021 [9] | International registry | 36–60 months | Seizure frequency, seizure severity, QoL | Aims to examine long-term safety and clinical outcomes of VNS in people with DRE. |
Liu et al., 2018 [10] | 63 patients | 1 year | Preoperative HRV, VNS outcomes | Preoperative HRV analyses can help predict VNS outcomes in patients with DRE. |
Bauer et al., 2016 [11] | Randomized trial | 20 weeks | Seizure frequency reduction | No superiority of 25 Hz tVNS over 1 Hz tVNS in reducing seizure frequency. |
Zhang et al., 2019 [12] | 110 patients | Post-operative period | Seizure frequency and severity, McHugh seizure outcome | Significant reduction in seizure frequency observed; VNS effect improves over time. |
Lagae et al., 2015 [13] | 70 patients | Varies | Responder rate, age at implantation effect | Younger age at VNS implantation might result in a better outcome. |
Benedetti-Isaac et al., 2012 [14] | 4 patients | Post-VNS implant | Seizure frequency reduction | VNS was an alternative for seizure frequency reduction in patients with previous corpus callosotomy. |
Nalbantoğlu et al., 2014 [15] | 35 patients | 26 ± 19.2 months | Seizure outcomes, responder rate | A total of 80% of the patients were responders, thus showing VNS as an alternative good treatment. |
Verrier et al., 2016 [16] | 28 patients | Pre- and post-implantation | T-wave alternans (TWA) levels, cardiac electrical stability | TWA level was decreased by VNS treatment in 70% of the patients. |
Shan et al., 2022 [17] | 45 patients | November 2016–August 2021 | Clinical outcome, safety | Confirmed efficacy and safety of VNS; no significant prognostic factors were identified. |
Bao et al., 2011 [18] | 45 cases | Over 1 year | Seizure frequency, treatment duration | Critical for improved prognosis was a longer duration of VNS therapy. |
Tanaka et al., 2017 [19] | Randomized, double-blind clinical trial | 20 weeks | Efficacy and safety of tVNS | tVNS was associated with high adherence to treatment and was well tolerated. The efficacy results justify further trials. |
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Urian, F.-I.; Toader, C.; Covache Busuioc, R.-A.; Corlatescu, A.-D.; Costin, H.P.; Iacob, G.; Ciurea, A.V. Introducing the Index of Response to Stimulation (IRES): A Novel Metric for Assessing Vagus Nerve Stimulation Outcomes in Drug-Resistant Epilepsy. Medicina 2025, 61, 75. https://doi.org/10.3390/medicina61010075
Urian F-I, Toader C, Covache Busuioc R-A, Corlatescu A-D, Costin HP, Iacob G, Ciurea AV. Introducing the Index of Response to Stimulation (IRES): A Novel Metric for Assessing Vagus Nerve Stimulation Outcomes in Drug-Resistant Epilepsy. Medicina. 2025; 61(1):75. https://doi.org/10.3390/medicina61010075
Chicago/Turabian StyleUrian, Flavius-Iuliu, Corneliu Toader, Razvan-Adrian Covache Busuioc, Antonio-Daniel Corlatescu, Horia Petre Costin, Gabriel Iacob, and Alexadru Vlad Ciurea. 2025. "Introducing the Index of Response to Stimulation (IRES): A Novel Metric for Assessing Vagus Nerve Stimulation Outcomes in Drug-Resistant Epilepsy" Medicina 61, no. 1: 75. https://doi.org/10.3390/medicina61010075
APA StyleUrian, F.-I., Toader, C., Covache Busuioc, R.-A., Corlatescu, A.-D., Costin, H. P., Iacob, G., & Ciurea, A. V. (2025). Introducing the Index of Response to Stimulation (IRES): A Novel Metric for Assessing Vagus Nerve Stimulation Outcomes in Drug-Resistant Epilepsy. Medicina, 61(1), 75. https://doi.org/10.3390/medicina61010075