Epileptic seizures can lead to changes in autonomic function affecting the sympathetic, parasympathetic, and enteric nervous systems. Changes in cardiac signals are potential biomarkers that may provide an extra-cerebral indicator of ictal onset in some patients. Heart rate can be measured easily when compared to other biomarkers that are commonly associated with seizures (e.g., long-term EEG), and therefore it has become an interesting parameter to explore for detecting seizures. Understanding the prevalence and magnitude of heart rate changes associated with seizures, as well as the timing of such changes relative to seizure onset, is fundamental to the development and use of cardiac based algorithms for seizure detection. We reviewed 34 articles that reported the prevalence of ictal tachycardia in patients with epilepsy. Scientific literature supports the occurrence of significant increases in heart rate associated with ictal events in a large proportion of patients with epilepsy (82%) using concurrent electroencephalogram (EEG) and electrocardiogram (ECG). The average percentage of seizures associated with significant heart rate changes was similar for generalized (64%) and partial onset seizures (71%). Intra-individual variability was noted in several articles, with the majority of studies reporting significant increase in heart rate during seizures originating from the temporal lobe. Accurate detection of seizures is likely to require an adjustable threshold given the variability in the magnitude of heart rate changes associated with seizures within and across patients.

SummaryObjective: Limited data are available regarding the evolution over time of the rate of sudden unexpected death in epilepsy patients (SUDEP) in drug-resistant epilepsy. The objective is to analyze a database of 40 443 patients with epilepsy implanted with vagus nerve stimulation (VNS) therapy in the United States (from 1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation follow-up period. Methods: Patient vital status was ascertained using the Centers for Disease Control and Prevention's National Death Index (NDI). An expert panel adjudicated classification of cause of deaths as SUDEP based on NDI data and available narrative descriptions of deaths. We tested the hypothesis that SUDEP rates decrease with time using the Mann-Kendall nonparametric trend test and by comparing SUDEP rates of the first 2 years of follow-up (years 1-2) to longer follow-up (years 3-10). Results: Our cohort included 277 661 person-years of follow-up and 3689 deaths, including 632 SUDEP. Primary analysis demonstrated a significant decrease in age-adjusted SUDEP rate during follow-up (S = À27 P = .008), with rates of 2.47/1000 for years 1-2 and 1.68/1000 for years 3-10 (rate ratio 0.68; 95% confidence interval [CI] 0.53-0.87; P = .002). Sensitivity analyses confirm these findings. Significance: Our data suggest that SUDEP risk significantly decreases during long-term follow-up of patients with refractory epilepsy receiving VNS Therapy. This finding might reflect several factors, including the natural long-term dynamic of SUDEP rate, attrition, and the impact of VNS Therapy. The role of each of these factors cannot be confirmed due to the limitations of the study. K E Y W O R D Sepilepsy, mortality, sudden unexpected death in epilepsy patients, vagus nerve stimulation --

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Major depressive disorder is a common global disease that causes a significant societal burden. Most interventional studies of depression provide a limited assessment of the interventions on mortality and suicide risks. This study utilizes data from an observational registry of patients with major depressive disorder to determine the impact of intervention (vagus nerve stimulation or standard pharmacological/non-pharmacological therapy) and a latent factor, patient trajectory toward response, on mortality, suicide and suicidal ideation. A total of 636 patients were available for an intent-to-treat analysis of all-cause mortality, suicide and suicidal ideation. Patients treated with vagus nerve stimulation in addition to standard therapies experienced lower, but not statistically significant, all-cause mortality (vagus nerve stimulation 4.93 per 1,000 person-years vs. 10.02 per 1,000 patient years for treatment as usual) and suicide rates (vagus nerve stimulation 0.88 per 1,000 person-years vs. 1.61 per 1,000 patient years for treatment as usual). Treatment with vagus nerve stimulation produced a statistically lower relative risk of suicidal ideation 0.80, 95% confidence interval (0.68,0.95). Further, patients that responded to either treatment saw a 51% reduction in relative risk of suicidal behavior; relative risk and 95% confidence interval of 0.49 (0.41,0.58). In summary, we find that treatment with adjunctive vagus nerve stimulation can potentially lower the risk of all-cause mortality, suicide and suicide attempts.

These findings suggest significant interictal cardiac electrical instability in this population of patients with drug-resistant epilepsy and suggest that VNS may be a novel approach to reducing risk.

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Objective: To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy ® plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models. Data sources and study selection: Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients. Data extraction: A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit. Response was based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions scale's Improvement subscale (CGI-I), as these were the two clinician-rated measures common across all or most studies. Remission was based on the MADRS. Results: Outcomes were compared from baseline up to 96 weeks of treatment with VNS + TAU (n = 1035) versus TAU (n = 425). The MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%, 18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24, 48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was associated with a greater likelihood of response (odds ratio [OR] = 3.19, 95% confidence interval [CI]: 2.12, 4.66) and remission (OR = 4.99, CI: 2.93, 7.76), compared with TAU. For patients who had responded to VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks (OR = 1.98, CI: 1.34, 3.01) and at 96 weeks (OR = 3.42, CI: 1.78, 7.31). Similar results were observed for CGI-I response. Conclusion: For patients with chronic TRD, VNS + TAU has greater response and remission rates that are more likely to persist than TAU. Keywords: Bayesian meta-analysis, remission rate, response rate, treatment-resistant depression, vagus nerve stimulation, VNS Therapy IntroductionDepression is a prevalent, disabling, and often chronic or recurrent psychiatric condition affecting about 350 million people worldwide.1 Among the general adult population in the US, the lifetime prevalence of major depressive disorder (MDD) is about 29.9% and the 12-month prevalence is about 8.6%.2 MDD imposes significant costs on patients, their families, caregivers, employers, and insurance payers, with an estimated Dovepress submit your manuscript | www.dovepress.com 54.191.190.102 on 11-May-2018 For personal use only. direct cost of more than US$80 billion per year to the US economy, which includes costs associated with health care, suicide mortality, and lost workplace productivity. 3,4 While several modal...

ObjectiveWe hypothesized that cardiac electrical instability and abnormal autonomic tone result from cumulative cardiac injury sustained in recurrent seizures. We tested this hypothesis by comparing T-wave alternans (TWA) and heart rate variability (HRV), both established markers of sudden cardiac death (SCD) risk, in patients with chronic as compared to newly diagnosed epilepsy.MethodsIn this prospective, observational cohort study, patients (newly diagnosed epilepsy, n = 6, age 41.8 ± 6.8 years; chronic epilepsy, n = 6, age 40.2 ± 5.6 years [p = 0.85]) were monitored either with Holter recorder alone or simultaneously with 14-day Zio XT extended continuous ECG patch monitor. TWA was assessed by Food and Drug Administration–cleared Modified Moving Average analysis; HRV was calculated by rMSSD.ResultsTWA levels in chronic epilepsy were significantly higher than in newly diagnosed epilepsy (62 ± 5.4 vs 35 ± 1.3 μV, p < 0.002); the latter did not differ from healthy control adults. In all patients with chronic epilepsy, TWA exceeded the established ≥47-μV TWA cutpoint and rMSSD HRV was inversely related to TWA levels. Patients with chronic epilepsy exhibited elevated TWA levels equivalently on Holter and ECG patch recordings (p = 0.38) with a high correlation (r2 = 0.99, p < 0.01) across 24 hours.ConclusionBased on the limited number of patients studied, it appears that chronic epilepsy, the common use of sodium channel antagonists, or other factors are associated with higher TWA levels and simultaneously with lower rMSSD HRV, which is suggestive of autonomic dysfunction or higher sympathetic tone. The ECG patch monitor used has equivalent accuracy to Holter monitoring for TWA and HRV and permits longer-term ECG sampling.