Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation

Galli, Renato; Limbruno, Ugo; Pizzanelli, Chiara; Giorgi, Filippo Sean; Lutzemberger, L.; Strata, G; Pataleo, L.; Mariani, Mario; Iudice, Alfonso; Murri, Luigi

doi:10.1016/s1566-0702(03)00081-x

Cited by 47 publications

(47 citation statements)

References 29 publications

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“…A few previous studies analyzed the effects of left vagus nerve stimulation (VNS) on cardiac autonomic function in patients with epilepsy [17] . Furthermore, a recent study assessed the effect of left VNS on proinflammatory and anti-inflammatory markers in patients with refractory depression [18] .…”

mentioning

confidence: 99%

Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy

Barone

Colicchio

Policicchio

et al. 2007

Neuroimmunomodulation

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Objective: Recent data suggest that vagus nerve stimulation (VNS) can inhibit cytokine release by inflammatory cells. Accordingly, an association between impaired cardiac parasympathetic function, as assessed by heart rate variability (HRV), and increased markers of inflammation has recently been reported. In this study we assessed the effect of direct left VNS on inflammatory markers and HRV in patients with refractory epilepsy. Methods: A 24-hour electrocardiogram Holter recording was performed both at baseline and after 3 months of left VNS in 8 patients (age 32 ± 24 years, 2 men) who underwent implantation of a VNS device because of refractory epilepsy. Tumor necrosis factor-α, interleukin-6 and C-reactive protein serum levels were measured, as markers of inflammation, at the same times. Results: No significant changes were found after 3 months of left VNS, compared to baseline, both for HRV variables and inflammatory markers. Also, no consistent correlation could be demonstrated between HRV parameters and inflammatory markers in these patients. Conclusions: Our data in epileptic patients without cardiovascular disease failed to show a significant effect of left VNS on cardiac autonomic function and on systemic inflammation at short-term follow-up.

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confidence: 99%

Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy

Barone

Colicchio

Policicchio

et al. 2007

Neuroimmunomodulation

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Section: Discussionmentioning

confidence: 99%

“…After one year of VNS, reductions of 34% to 45% in seizure frequency have been reported with 20% of patients experiencing a >75% reduction. Although the overall safety profile of VNS seems to be favorable, cardiac adverse effects (e.g., bradycardia and asystole during intraoperative lead test) have been reported in a small number of patients (Asconape et al, 1999;Galli et al, 2003;Ali et al, 2004).Brain-type natriuretic peptide (BNP) is a potent natriuretic, diuretic, and vasodilatative compound first discovered in the human brain, e.g., hypothalamus, hippocampus, and cerebral cortex, but mainly synthesized in the myocardium (Minamino et al, 1988;Takahashi et al, 1992). In patients with heart disease, both BNP and aminoterminal fragments of BNP (NT-proBNP) are used to detect left-ventricular dysfunction.…”

mentioning

confidence: 99%

Brain‐type Natriuretic Peptide Release and Seizure Activity during Vagal Nerve Stimulation

Rauchenzauner¹,

Haberlandt²,

Högler³

et al. 2007

Epilepsia

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Summary:Vagus nerve stimulation (VNS) has emerged as an effective adjunctive therapy for medically refractory epilepsy when surgery is inadvisable. N-terminal brain-type natriuretic peptide (NT-proBNP) is a potent natriuretic, diuretic, and vasodilatative compound first discovered in the human brain but mainly synthesized in the myocardium. The monitoring of VNS effectiveness in reducing seizure frequency or the detection of possible cardiac adverse effects would be helped by a reliable biochemical marker, which has not been available thus far. We report a four-year-old boy with drug-resistant idiopathic generalized epilepsy whose NT-proBNP levels increased during VNS and seizures. Key Words: VNS-BNP-Seizure-Epilepsy.Vagus nerve stimulation (VNS) has emerged as an effective adjunctive therapy for medically refractory epilepsy when surgery is inadvisable. VNS provides a programmed, regular electric stimulus from a pulse generator implanted in the chest through a coiled tunneled lead to electrodes attached to the left cervical vagal nerve (Morris and Mueller, 1999). After one year of VNS, reductions of 34% to 45% in seizure frequency have been reported with 20% of patients experiencing a >75% reduction. Although the overall safety profile of VNS seems to be favorable, cardiac adverse effects (e.g., bradycardia and asystole during intraoperative lead test) have been reported in a small number of patients (Asconape et al., 1999;Galli et al., 2003;Ali et al., 2004).Brain-type natriuretic peptide (BNP) is a potent natriuretic, diuretic, and vasodilatative compound first discovered in the human brain, e.g., hypothalamus, hippocampus, and cerebral cortex, but mainly synthesized in the myocardium (Minamino et al., 1988;Takahashi et al., 1992). In patients with heart disease, both BNP and aminoterminal fragments of BNP (NT-proBNP) are used to detect left-ventricular dysfunction. Furthermore, elevated NT-proBNP levels are associated with major cardiovascular events and provide prognostic information of mortality (Kistorp et al., 2005). Recently, elevated NT-proBNP concentrations in childhood epilepsy and febrile convulsions (Rauchenzauner, 2006) This case report discusses a possible role of NT-proBNP in monitoring VNS effectiveness in seizure control or in the detection of adverse cardiac effects. CASE REPORTA four-year-old boy was referred for severe, drugresistant idiopathic generalized epilepsy with tonic-clonic seizures, which he had developed at the age of two years. His EEG showed generalized spike-wave discharges. Cerebral magnetic resonance imaging (MRI) was normal. A comprehensive clinical and cardiologic evaluation (including standard ECG, 24-h-ECG, blood pressure measurement, and echocardiography), biochemical analysis, and screening for metabolic disorders revealed no pathological finding. At the age of three years, after several combinations of antiepileptic drugs had failed to improve his condition, a VNS device was implanted (Cyberonics, Inc, Houston, Texas, U.S.A.) according to standard methodology. The VN...

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“…Stemper et al 13 found an increase in both low-frequency and high-frequency power of the RR intervals during a 60-second on phase. Galli et al 14 did not find important cardiac effects of VNS stimulation, although HRV analysis revealed subtle changes in cardiac sympathovagal balance: a reduction in vagal tone, marked by a reduction in high-frequency power, was noted after long-term vagal nerve stimulation, mainly during sleep. Ronkainen et al 15 found a clear impairment of HRV in individuals with chronic refractory epilepsy but no change after treatment with VNS.…”

Section: Vnsmentioning

confidence: 94%

Autonomic effects of refractory epilepsy on heart rate variability in children: influence of intermittent vagus nerve stimulation

Jansen

Vandeput

Milosevic

et al. 2011

Developmental Medicine &Amp; Child Neurology

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HFnu High-frequency normalized units HRV Heart rate variability LFnu Low-frequency normalized units SWS Slow-wave sleep VNS Vagus nerve stimulation AIM Vagus nerve stimulation (VNS) is a therapeutic option for individuals with refractory epilepsy.Individuals with refractory epilepsy are prone to dysfunction of the autonomic nervous system. Reduced heart rate variability is a marker of dysfunction of the autonomic nervous system. Our goal was to study heart rate variability in children with refractory epilepsy and the influence of VNS on this parameter. METHODSIn 17 children (13 male; four female; mean age 7y 6mo; age range 3-16y) with refractory epilepsy, electroencephalographic and electrocardiographic data were obtained before and after implantation of VNS during stage 2 and slow-wave sleep. Time and frequency domain parameters were calculated and the results were compared with an age-and sex-matched group of individuals without refractory epilepsy. RESULTSOur results show that autonomic cardiac control is affected in individuals with refractory epilepsy. There is a striking reduction in vagal tone during slow-wave sleep and modulation capacity is smaller than in individuals without refractory epilepsy. Implantation of VNS induces a shift in sympathovagal balance towards sympathetic predominance and an improvement in autonomic modulation.INTERPRETATION Heart rate variability is affected in children with refractory epilepsy, and changes after implantation of VNS. The observed changes could be of importance in the cardiac complications of individuals with epilepsy and should be explored in more detail.In individuals with refractory epilepsy, vagus nerve stimulation (VNS) is an alternative therapeutic option. The working mechanism is still incompletely understood. In VNS therapy, the left vagal nerve is stimulated at the level of the neck by an electrode connected to a subcutaneous device. The left nerve is chosen to minimize the effect on heart rhythm because most of the cardiovagal fibers course through the right vagus nerve.The vagus nerve consists of 20% of efferent and 80% of afferent fibers. The efferent fibers originate from two separate nuclei in the brainstem, the dorsal motor nucleus and the nucleus ambiguus. They supply parasympathetic fibers to all the internal organs except the suprarenal glands. The afferent fibers originate in the end organs and project to the nucleus tractus solitarius. From the nucleus tractus solitarius, axons project throughout the brain. These afferent axons and synapses are thought to be responsible for the therapeutic effect of VNS.Heart rate variability (HRV) is defined as the fluctuation in length in consecutive RR intervals. This variability is mediated by sympathetic and parasympathetic efferent activity to the heart and can provide information on the functional state of the autonomic nervous system. The vagal influences on the heart are most pronounced during sleep. In early sleep stages there is still a relatively large influence of the sympathetic branch on HRV. In ty...

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Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation

Cited by 47 publications

References 29 publications

Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy

Effect of Vagal Nerve Stimulation on Systemic Inflammation and Cardiac Autonomic Function in Patients with Refractory Epilepsy

Brain‐type Natriuretic Peptide Release and Seizure Activity during Vagal Nerve Stimulation

Autonomic effects of refractory epilepsy on heart rate variability in children: influence of intermittent vagus nerve stimulation

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