Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters.

BACKGROUND: Noninvasive transcutaneous vagus nerve stimulation (tVNS) has promising therapeutic potential in a wide range of applications across somatic and psychiatric conditions. Compared with invasive vagus nerve stimulation, good safety and tolerability profiles also support the use of tVNS in pediatric patients. Potential neurodevelopment-specific needs, however, raise concerns regarding the age-appropriate adjustment of treatment protocols and applied stimulation parameters. OBJECTIVE: In this study, we aimed to review registered trials and published studies to synthesize existing tVNS treatment protocols and stimulation parameters applied in pediatric patients. MATERIALS AND METHODS: A systematic search of electronic data bases (PubMed, Scopus, MEDLINE, Cochrane Library, and PsycINFO) and ClinicalTrials was conducted. Information on patient and study-level characteristics (eg, clinical condition, sample size), the tVNS device (eg, brand name, manufacturer), stimulation settings (eg, pulse width, stimulation intensity), and stimulation protocol (eg, duration, dosage of stimulation) was extracted. RESULTS: We identified a total of 15 publications (four study protocols) and 15 registered trials applying tVNS in pediatric patients (<18 years of age). Most of these studies did not exclusively address pediatric patients. None of the studies elaborated on neurodevelopmental aspects or justified the applied protocol or stimulation parameters for use in pediatric patients. CONCLUSIONS: No dedicated pediatric tVNS devices exist. Neither stimulation parameters nor stimulation protocols for tVNS are properly justified in pediatric patients. Evidence on age-dependent stimulation effects of tVNS under a neurodevelopment framework is warranted. We discuss the potential implications of these findings with clinical relevance, address some of the challenges of tVNS research in pediatric populations, and point out key aspects in future device development and research in addition to clinical studies on pediatric populations.

Transcutaneous vagus nerve stimulation and the realm of its therapeutic hopes and physiologic enigmas.

Vagus nerve stimulation (VNS) is an established treatment option for patients with treatment resistant epilepsy and depression. However, the procedure is invasive and has side-effects. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive alternative. Particularly transcutaneous stimulation at the outer ear is gaining increasing interest. While the scope of therapeutic tVNS applications is expanding, there are still questions regarding the optimal stimulation parameters and site as well as the physiology and pathways of auricular tVNS. This Special Issue of Autonomic Neuroscience: Basic & Clinical provides an introduction and overview on basic aspects as well as special topics of tVNS.

Technical aspects and future approaches in transcutaneous vagus nerve stimulation (tVNS).

With the emergence of transcutaneous vagus nerve stimulation (tVNS) as a therapy option for a multitude of clinical indications, the development and improvement of the stimulators becomes an increasingly important point of focus. This paper aims to discuss electrotechnical and software-based improvements to the state-of-the-art stimulators, in order to reduce the experienced side effects of the subjects as well as to increase the efficacy of the stimulation. It was found that side effects such as erythema and pain at the stimulation site are caused by electrolysis at the site of stimulation, which can be reduced by maintaining a voltage below the decomposition voltage. This can be achieved by using electroactive materials and rare-earth fractal metal coatings on the electrode, or by stimulating at the chronaxie with a biphasic rectangular waveform and an in-built short circuit to avoid an after-potential. It is furthermore discussed how the currently most promising stimulation site, the cymba conchae, can technically be stimulated in a feasible and tolerable way for the subject. Utilizing the subjects individual pain threshold is also demonstrated as a good indicator for optimal stimulation, as stimulation just below the pain threshold activates Aα and Aß-fibers, while being unable to polarize the smaller diameter Aδ and C-fibers responsible for pain signaling. Finally, an outlook to individualized tVNS therapy is given, by using evolution algorithms that utilize device and subject data to optimize stimulation parameters.

Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol.

Stimulation of the vagus nerve, a parasympathetic nerve that controls the neuro-digestive, vascular, and immune systems, induces pain relief, particularly in clinical conditions such as headache and rheumatoid arthritis. Transmission through vagal afferents towards the nucleus of the solitary tract (NST), the central relay nucleus of the vagus nerve, has been proposed as the main physiological mechanism that reduces pain intensity after vagal stimulation. Chronic pain symptoms of fibromyalgia patients might benefit from stimulation of the vagus nerve via normalization of altered autonomic and immune systems causing their respective symptoms. However, multi-session non-invasive vagal stimulation effects on fibromyalgia have not been evaluated in randomized clinical trials. We propose a parallel group, sham-controlled, randomized study to modulate the sympathetic-vagal balance and pain intensity in fibromyalgia patients by application of non-invasive transcutaneous vagus nerve stimulation (tVNS) over the vagal auricular and cervical branches. We will recruit 136 fibromyalgia patients with chronic moderate to high pain intensity. The primary outcome measure will be pain intensity, and secondary measures will be fatigue, health-related quality of life, sleep disorders, and depression. Heart rate variability and pro-inflammatory cytokine levels will be obtained as secondary physiological measures. We hypothesize that multiple tVNS sessions (five per week, for 4 weeks) will reduce pain intensity and improve quality of life as a result of normalization of the vagal control of nociception and immune-autonomic functions. Since both vagal branches project to the NST, we do not predict significantly different results between the two stimulation protocols.

Coaxial waveguide MRI.

As ultrahigh-field MR imaging systems suffer from the standing wave problems of conventional coil designs, the use of antenna systems that generate travelling waves was suggested. As a modification to the original approach, we propose the use of a coaxial waveguide configuration with interrupted inner conductor. This concept can focus the radiofrequency energy to the desired imaging region in the human body and can operate at different Larmor frequencies without hardware modifications, as it is not limited by a lower cut-off frequency. We assessed the potential of the method with a hardware prototype setup that was loaded with a tissue equivalent phantom and operated with imaging areas of different size. Signal and flip angle distributions within the phantom were analyzed, and imaging at different Larmor frequencies was performed. Results were compared to a finite difference time domain simulation of the setup that additionally provides information on the spatial distribution of the specific absorption rate load. Furthermore, simulation results with a human model (virtual family) are presented. It was found that the proposed method can be used for MRI at multiple frequencies, achieving transmission efficiencies similar to other travelling wave approaches but still suffers from several limitations due to the used mode of wave propagation.

An invasive and a noninvasive approach for the automatic differentiation of obstructive and central hypopneas.

The automatic differentiation of obstructive and central respiratory events is a major challenge in the diagnosis of sleep-disordered breathing. Esophageal pressure (Pes) measurement is the gold-standard method to identify these events. This study presents a new classifier that automatically differentiates obstructive and central hypopneas with the Pes signal and a new approach for an automatic noninvasive classifier with nasal airflow. An overall of 28 patients underwent night polysomnography with Pes recording, and a total of 769 hypopneas were manually scored by human experts to create a gold-standard annotation set. Features were automatically extracted from the Pes signal to train and test the classifiers (discriminant analysis, support vector machines, and adaboost). After a significantly (p < 0.01) higher incidence of inspiratory flow limitation episodes in obstructive hypopneas was objectively, invasively assessed compared to central hypopneas, the feasibility of an automatic noninvasive classifier with features extracted from the airflow signal was demonstrated. The automatic invasive classifier achieved a mean sensitivity, specificity, and accuracy of 0.90 after a 100-fold cross validation. The automatic noninvasive feasibility study obtained similar hypopnea differentiation results as a manual noninvasive classification algorithm. Hence, both systems seem promising for the automatic differentiation of obstructive and central hypopneas.

Assessment of changes in upper airway obstruction by automatic identification of inspiratory flow limitation during sleep.

New techniques for automatic invasive and noninvasive identification of inspiratory flow limitation (IFL) are presented. Data were collected from 11 patients with full nocturnal polysomnography and gold-standard esophageal pressure (Pes) measurement. A total of 38,782 breaths were extracted and automatically analyzed. An exponential model is proposed to reproduce the relationship between Pes and airflow of an inspiration and achieve an objective assessment of changes in upper airway obstruction. The characterization performance of the model is appraised with three evaluation parameters: mean-squared error when estimating resistance at peak pressure, coefficient of determination, and assessment of IFL episodes. The model's results are compared to the two best-performing models in the literature. The obtained gold-standard IFL annotations were then employed to train, test, and validate a new noninvasive automatic IFL classification system. Discriminant analysis, support vector machines, and Adaboost algorithms were employed to objectively classify breaths noninvasively with features extracted from the time and frequency domains of the breaths' flow patterns. The results indicated that the exponential model characterizes IFL and subtle relative changes in upper airway obstruction with the highest accuracy and objectivity. The new noninvasive automatic classification system also succeeded in identifying IFL episodes, achieving a sensitivity of 0.87 and a specificity of 0.85.

[Identification of patients with atrial fibrillation using HRV parameters]. / Identifizieren von Patienten mit Vorhofflimmern anhand von HRV-Parametern.

Atrial fibrillation is the most common sustained cardiac rhythm disturbance. One of the most drastic complications is embolism, particularly stroke. Patients with atrial fibrillation have to be identified. This can lead to early therapy and thus avoiding strokes. The algorithm presented here detects atrial fibrillation securely and reliably. It is based on a single-channel ECG, which takes 60 min. First, the R-peaks are detected from the ECG and the RR interval is calculated. To be independent from pulse variations, the RR interval is normalized to 60 bpm. A parameter of heart rate variability is calculated in time domain (SDSD) and the so-called Poincaré plot is generated. The image analysis of the figures of the Poincaré plot is made automatically. The results from analysis in time domain, as well as image analysis, yield a risk level, which indicates the probability for the occurrence of atrial fibrillation. Even if there is no atrial fibrillation in the ECG while analyzing, it is possible to identify patients with atrial fibrillation. The sensitivity depends on the burden of atrial fibrillation. Even if a burden of 0% is assumed, the results still prove satisfactory (sensitivity of nearly 83%).

Algorithm for identifying patients with paroxysmal atrial fibrillation without appearance on the ECG.

Although atrial fibrillation is the most common sustained cardiac rhythm disturbance, it remains under-diagnosed. One of the most drastic complications is embolism, and strokes in particular. Patients having atrial fibrillation must be identified in order to reduce the number of strokes. The algorithm presented detects atrial fibrillation, even without it being indicated in the analyzed ECG. Based on parameters of heart rate variability, only a 60-minute single channel ECG is required. At first, all R peaks are detected and all RR intervals are calculated. After normalizing the RR intervals, the time domain parameter SDSD is calculated and the so-called Poincaré Plot is generated. The image and the time domain analysis assess a risk level, which determines whether the patient is suffering from atrial fibrillation. The resulting sensitivity calculated for ECG recordings from the MIT-BIH Atrial Fibrillation Database is 91.5% and the specificity determined for the ECG recordings from the MIT-BIH Normal Sinus Rhythm Database is 96.9%. The sensitivity depends on the atrial fibrillation burden. Even if a burden of 0 % is assumed, the results still prove satisfactory (sensitivity nearly 83%).

Screening device for identification of patients with paroxysmal atrial fibrillation to prevent ischemic strokes.

The most frequently occurring cardiac arrhythmia in the adulthood is atrial fibrillation. In Germany, the number of sick people is estimated at 800,000. Patients who suffer from atrial fibrillation often do not sense any symptoms of the illness. Through the uncontrolled blood flow in the atrium, a blood clot, which can lead to the blood circulation for an embolism or for a stroke, can form itself. These persons must be recognized, because of their increased stroke risk in order to be able to attend it. In this work, the chest strap CorBelt, developed by the company Corscience GmbH&Co.KG, is equipped with an algorithm for the recognition of atrial fibrillation with the aid of heart rate variability.

CAALYX: a new generation of location-based services in healthcare.

Recent advances in mobile positioning systems and telecommunications are providing the technology needed for the development of location-aware tele-care applications. This paper introduces CAALYX--Complete Ambient Assisted Living Experiment, an EU-funded project that aims at increasing older people's autonomy and self-confidence by developing a wearable light device capable of measuring specific vital signs of the elderly, detecting falls and location, and communicating automatically in real-time with his/her care provider in case of an emergency, wherever the older person happens to be, at home or outside.

The Karlsruhe TeleHomeCare concept.

Chronically ill and care-intensive patients are those who account for a large share of the cost and work that service providers invest in the health sector. With the introduction of DRGs (Diagnoses Related Groups), hospitals will work on shortening hospitalization periods, thereby increasing the demand for outpatient care capacities. To prevent a quality decline due to early hospital release, partners in research an industry have joined in an effort to develop a platform for patients to be treated at home with service quality equal to in-hospital standards.