Dataset Information

Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration.

ABSTRACT:

Background

Cervical vagus nerve stimulation (VNS) has been widely accepted as adjunctive therapy for drug-resistant epilepsy and major depression. Its effects on glycemic control in humans were however poorly understood. The aim of our study was to investigate the potential effects of VNS on fasting blood glucose (FBG) in patients with drug-resistant epilepsy.

Methods

Patients with drug-resistant epilepsy who had received VNS implants at the same hospital were retrospectively studied. Effects on FBG, weight, body mass index and blood pressure were evaluated at 4, 8 and 12 months of follow-up.

Results

32 subjects (11 females/21 males, 19 ± 9 years, body mass index 22.2 ± 4.0 kg/m²) completed 12-month follow-up. At the 4 months, there were no significant changes in FBG concentrations from baseline to follow-up in both Sham-VNS (4.89 ± 0.54 vs. 4.56 ± 0.54 mmol/L, N = 13, p = 0.101) and VNS (4.80 ± 0.54 vs. 4.50 ± 0.56 mmol/L, N = 19, p = 0.117) groups. However, after 8 (4.90 ± 0.42 mmol/L, N = 32, p = 0.001) and 12 (4.86 ± 0.40 mmol/L, N = 32, p = 0.002) months of VNS, FBG levels significantly increased compared to baseline values (4.52 ± 0.54 mmol/L, N = 32). Changes in FBG concentrations at both 8 (R² = 0.502, N = 32, p < 0.001) and 12 (R² = 0.572, N = 32, p < 0.001) months were negatively correlated with baseline FBG levels.

Conclusions

Our study suggests that chronic cervical VNS elevates FBG levels with commonly used stimulation parameters in patients with epilepsy. Trial registration VNSRE, NCT02378792. Registered 4 March 2015-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02378792.

SUBMITTER: Liu H

PROVIDER: S-EPMC7257242 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration.

Liu Hongyun H Zhan Ping P Meng Fangang F Wang Weidong W

Biomedical engineering online 20200529 1

<h4>Background</h4>Cervical vagus nerve stimulation (VNS) has been widely accepted as adjunctive therapy for drug-resistant epilepsy and major depression. Its effects on glycemic control in humans were however poorly understood. The aim of our study was to investigate the potential effects of VNS on fasting blood glucose (FBG) in patients with drug-resistant epilepsy.<h4>Methods</h4>Patients with drug-resistant epilepsy who had received VNS implants at the same hospital were retrospectively stud ...[more]

PMID: 32471438

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Project description:Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated "ON" and nonstimulated "OFF" periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during "ON" and "OFF" periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p < 0.05). No significant differences in MST were observed between R and NR patients. Conclusion: The correlation between VNS-induced interictal EEG time-series desynchronization and decrease in seizure frequency suggested that VNS therapeutic impact might be related to changes in interictal functional connectivity. Impact statement Electroencephalography (EEG) desynchronization has been proposed to be a mechanism for antiepileptic effect of vagus nerve stimulation (VNS). We measured interictal EEG time-series synchronization during stimulated (ON) and nonstimulated (OFF) periods in epileptic patients treated by VNS. Phase lag index differences between ON and OFF periods were measured in delta, theta, and beta bands only in responder patients. To our knowledge, our study is the first to statistically correlate interictal cortical desynchronization during ON periods with reduction in seizure frequency. Our result supports the hypothesis that the antiseizure effect of VNS is mediated by cortical desynchronization.

Project description:The locus coeruleus-norepinephrine system is thought to be involved in the clinical effects of vagus nerve stimulation. This system is known to prevent seizure development and induce long-term plastic changes, particularly with the release of norepinephrine in the hippocampus. However, the requisites to become responder to the therapy and the mechanisms of action are still under investigation. Using MRI, we assessed the structural and functional characteristics of the locus coeruleus and microstructural properties of locus coeruleus-hippocampus white matter tracts in patients with drug-resistant epilepsy responding or not to the therapy. Twenty-three drug-resistant epileptic patients with cervical vagus nerve stimulation were recruited for this pilot study, including 13 responders or partial responders and 10 non-responders. A dedicated structural MRI acquisition allowed in vivo localization of the locus coeruleus and computation of its contrast (an accepted marker of LC integrity). Locus coeruleus activity was estimated using functional MRI during an auditory oddball task. Finally, multi-shell diffusion MRI was used to estimate the structural properties of locus coeruleus-hippocampus tracts. These characteristics were compared between responders/partial responders and non-responders and their association with therapy duration was also explored. In patients with a better response to the therapy, trends toward a lower activity and a higher contrast were found in the left medial and right caudal portions of the locus coeruleus, respectively. An increased locus coeruleus contrast, bilaterally over its medial portions, correlated with duration of the treatment. Finally, a higher integrity of locus coeruleus-hippocampus connections was found in patients with a better response to the treatment. These new insights into the neurobiology of vagus nerve stimulation may provide novel markers of the response to the treatment and may reflect neuroplasticity effects occurring in the brain following the implantation.

Project description:BackgroundDrug-resistant epilepsy (DRE) affects approximately one-third of epilepsy patients who do not achieve adequate seizure control with medication. Vagus nerve stimulation (VNS) is an adjunctive therapy for DRE, but its long-term effects on cortical excitability remain unclear.ObjectivesThis study aims to elucidate the long-term effects of VNS on electroencephalography (EEG) aperiodic components in patients with DRE. Our objective is to identify biomarkers that can serve as indicators of therapeutic efficacy and provide mechanistic insights into the underlying neural processes.DesignThis longitudinal observational study focused on patients with DRE undergoing VNS therapy at Sanbo Brain Hospital. The reduction in seizure frequency rates was quantified over short-term (⩽1 year), medium-term (1-3 years), and long-term (⩾3 years) intervals to assess the therapeutic efficacy of VNS. Both the periodic and aperiodic components of EEG data were analyzed.MethodsAdvanced signal processing techniques were utilized to parameterize the periodic and aperiodic components of EEG data, focusing particularly on "offset" and "exponent." These measures were compared before and after VNS therapy. Correlation analyses were conducted to explore the relationship between these EEG parameters and clinical outcomes.ResultsIn all, 18 patients with DRE participated in this study. During the long-term follow-up period, the responder rate was 55.56%. Significant decreases were observed in aperiodic offset (p = 0.022) and exponent (p = 0.039) among responders. The impact of age on these results was not significant. Correlation analyses revealed a negative association between therapeutic efficacy and a decrease in offset (R = -0.546, p = 0.019) and exponent (R = -0.636, p = 0.019).ConclusionEEG aperiodic parameters, including offset and exponent, have the potential to serve as promising biomarkers for evaluating the efficacy of VNS. An understanding of the regulatory influence of VNS on cortical excitability through these aperiodic parameters could provide a basis for the development of more effective stimulation parameters and therapeutic strategies.

Project description:ObjectiveTo investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years.MethodsThe study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years.ResultsThe median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs.SignificanceBased on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs.Plain language summaryExecutive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.

Project description:The mechanisms of action of Vagus Nerve Stimulation (VNS) and the biological prerequisites to respond to the treatment are currently under investigation. It is hypothesized that thalamocortical tracts play a central role in the antiseizure effects of VNS by disrupting the genesis of pathological activity in the brain. This pilot study explored whether in vivo microstructural features of thalamocortical tracts may differentiate Drug-Resistant Epilepsy (DRE) patients responding and not responding to VNS treatment. Eighteen patients with DRE (37.11 ± 10.13 years, 10 females), including 11 responders or partial responders and 7 non-responders to VNS, were recruited for this high-gradient multi-shell diffusion Magnetic Resonance Imaging (MRI) study. Using Diffusion Tensor Imaging (DTI) and multi-compartment models - Neurite Orientation Dispersion and Density Imaging (NODDI) and Microstructure Fingerprinting (MF), we extracted microstructural features in 12 subsegments of thalamocortical tracts. These characteristics were compared between responders/partial responders and non-responders. Subsequently, a Support Vector Machine (SVM) classifier was built, incorporating microstructural features and 12 clinical covariates (including age, sex, duration of VNS therapy, number of antiseizure medications, benzodiazepine intake, epilepsy duration, epilepsy onset age, epilepsy type - focal or generalized, presence of an epileptic syndrome - no syndrome or Lennox-Gastaut syndrome, etiology of epilepsy - structural, genetic, viral, or unknown, history of brain surgery, and presence of a brain lesion detected on structural MRI images). Multiple diffusion metrics consistently demonstrated significantly higher white matter fiber integrity in patients with a better response to VNS (pFDR < 0.05) in different subsegments of thalamocortical tracts. The SVM model achieved a classification accuracy of 94.12%. The inclusion of clinical covariates did not improve the classification performance. The results suggest that the structural integrity of thalamocortical tracts may be linked to therapeutic effectiveness of VNS. This study reveals the great potential of diffusion MRI in improving our understanding of the biological factors associated with the response to VNS therapy.

Dataset Information

Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration.

Background

Methods

Results

Conclusions

Publications

Chronic vagus nerve stimulation for drug-resistant epilepsy may influence fasting blood glucose concentration.

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