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Chronic pain is a global health problem, having a tremendous effect on the quality-of-life (QoL) of patients. Monitoring the outcome of a specific therapy and the condition of the patient is of utter importance for effective pain management. A smartphone application was developed for comprehensive pain management in chronic pain patients. It allows patients to enter and keep track of their health related QoL, pain, and medication intake in an easy, fast, and regular daily routine. The app was built based on standardized questionnaires and the needs of pain specialists and patients assessed via a brief survey in a small target group. The survey showed an unmet need for applications in clinical practice, which enable comprehensive monitoring of QoL, pain, therapeutic progress, and thus allow for patient engagement and overall improved pain management. Beneficially, patients can share their reported outcome measures gathered via the app with their pain specialist via PDF exports for remote monitoring. The smartphone app has been realized and is currently evaluated in beta tests. The easy, comprehensible, and routine assessment of the patient’s condition, combined with a future integration into an online therapy management system, may further advance pain management in chronic pain patients.

Development of wearable point-of-care medical devices faces many challenges. Besides technological and clinical issues, demands on robustness, miniaturization, and user interface design are of paramount importance. However, a systematic assessment of these non-functional but essential requirements is often impossible within the first product cycle. Later, surveys on user satisfaction with existing devices and user demands can offer significant input for device re-development and improvement. In this paper, we present a survey on satisfaction with and demands for a wearable medical device for percutaneous auricular vagus nerve stimulation (pVNS). We analyzed 36 responses from patients treated with pVNS and five responses from experienced physicians in order to devise a future concept of pVNS. Main shortcomings of a current pVNS device were identified to be lacking water resistance and mechanical robustness, both impairing daily activities. Painful sensation during pVNS application, unwanted side effects like skin irritations and strongly varying perception of the stimulation were reported. Results urge for more patient self-governance and an (automatic) adjustment of the stimulation to the current physiological state of the patient. Attained results support a strategic approach for future developments of pVNS towards personalized health care.

An accurate detection of anatomical structures in electrical impedance tomography (EIT) is still at an early stage. Aorta detection in EIT is of special interest, since it would favor non-invasive assessment of hemodynamic processes in the body. Here, diverse EIT reconstruction parameters of the GREIT algorithm were systematically evaluated to detect the aorta after saline bolus injection in apnea. True aorta position and size were taken from computed tomography (CT). A comparison with CT showed that the smallest error for aorta displacement was attained for noise figure nf = 0.7, weighting radius rw = 0.15, and target size ts = 0.01. The spatial extension of the aorta was most precise for nf = 0.7, rw = 0.25, and ts = 0.07. Detection accuracy (F1-score) was highest with nf = 0.6, rw = 0.15, and ts = 0.04. This work provides algorithm-related evidence for potentially accurate aorta detection in EIT after injection of a saline bolus.

Autonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge. Thirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA). A repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F (2,116) = 27.97, p <.001, η p 2 >.14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p <.05, Cohen's d = 1.27). Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind. • pVNS inhibits pupil dilation in an anticholinergic challenge in alcohol withdrawal syndrome. • Novel neuromodulatory techniques may have the potential to mitigate symptoms of alcohol withdrawal syndrome. • pVNS decreased alcohol craving, though this effect could be confounded by treatment. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions., Methods: A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS-needle electrodes) and transcutaneous (tVNS-surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint., Results: A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of - 1.95 (95% confidence interval [CI]: - 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (- 5.40 [- 8.94; - 1.85] vs. - 1.00 [- 1.55; - 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with - 0.70 [- 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated., Conclusion: This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes., (© 2024. The Author(s).)

Background: Current guidelines recommend a personalized, multimodal, and interdisciplinary approach for the treatment of chronic pain. Already in the acute treatment of postoperative pain, it can be useful to minimize risk factors for chronification. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy for the treatment of chronic and acute pain., Aim of the Work: The aim of this systematic review is to evaluate the clinical efficacy of aVNS in chronic and acute pain as well as its effect on medication intake., Materials and Methods: A systematic literature search was carried out on the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence and evaluated via the Jadad scale as well as their scientific validity, and then analyzed in terms of indication, method, stimulation parameters, duration of treatment, efficacy, and safety., Results: Twenty studies on chronic pain indications, ten studies on acute postoperative pain, as well as seven studies on experimental acute pain were identified and analyzed. The search revealed a total of n = 1105 aVNS-treated patients. The best evidence on the efficacy of aVNS is available for the indications chronic low back pain, chronic cervical syndrome, chronic abdominal pain, and chronic migraine as well as acute postoperative pain in oocyte aspiration, laparoscopic nephrectomy, and open colorectal surgery. Additionally a significant reduction in analgesic or opiate intake was evident in most studies. In three randomized controlled trials in chronic pain patients, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated., Conclusion: This review indicates that aVNS can be a complementary and effective non-drug treatment for patients with chronic and acute postoperative pain. Future studies in these indications should focus on standardizing and optimizing treatment parameters, inclusion of quality-of-life outcome parameters, and longer follow-up periods to better understand the sustainable therapeutic effect of aVNS., (© 2023. The Author(s).)

Background: Chronic low back pain is a global health problem having a tremendous effect on the quality of life of patients., Objectives: An online therapy management system (TMS) is developed for comprehensive management of chronic low back pain patients., Methods: A smartphone and a web app are built based on the Keep-In-Touch Telehealth Platform. The smartphone app allows entering patient reported outcomes and connection to third party devices to monitor physiological data and parameters of therapy., Results: The TMS has been realized and a wearable auricular vagus nerve stimulation device has been integrated. The TMS is currently evaluated in a randomized clinical trial.

Objective. Recent research suggests that percutaneous auricular vagus nerve stimulation (pVNS) beneficially modulates the autonomic nervous system (ANS). Bursted pVNS seems to be efficient for nerve excitation. Bursted pVNS effects on cardiac autonomic modulation are not disclosed yet. Approach. For the first time, the present study evaluates the effect of pVNS on cardiac autonomic modulation in healthy subjects ( n  = 9) using two distinct bursted stimulation patterns (biphasic and triphasic stimulation) and heart rate variability analysis (HRV). Stimulation was delivered via four needle electrodes in vagally innervated regions of the right auricle. Each of the two bursted stimulation patterns was applied twice in randomized order over four consecutive stimulation sessions per subject. Main results. Bursted pVNS did not change heart rate, blood pressure, and inflammatory parameters in study subjects. pVNS significantly increased the standard deviation of heart inter-beat intervals, from 46.39 ± 10.4 ms to 63.46 ± 22.47 ms ( p  < 0.05), and the total power of HRV, from 1475.7 ± 616.13 ms 2 to 3190.5 ± 2037.0 ms 2 ( p  < 0.05). The high frequency ( HF ) power, the low frequency ( LF ) power, and the LF/HF ratio did not change during bursted pVNS. Both stimulation patterns did not show any significant differences in cardiac autonomic modulation. Stimulation intensity to reach a tingling sensation was significantly lower in triphasic compared to biphasic stimulation ( p < 0.05). Bursted stimulation was well tolerated. Significance. Bursted pVNS seems to affect cardiac autonomic modulation in healthy subjects, with no difference between biphasic and triphasic stimulation, the latter requiring lower stimulation intensities. These findings foster implementation of more efficient pVNS stimulation., (Creative Commons Attribution license.)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice., Competing Interests: EK and SK are employed by company SzeleSTIM GmbH. JS received honoraria from SzeleSTIM GmbH and owns patents in the field of the auricular vagus nerve stimulation. EK, SK, and JS are shareholders of SzeleSTIM GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TS declared a shared affiliation, with no collaboration, with one of the authors HJ, to the handling editor at the time of review., (Copyright © 2021 Farmer, Strzelczyk, Finisguerra, Gourine, Gharabaghi, Hasan, Burger, Jaramillo, Mertens, Majid, Verkuil, Badran, Ventura-Bort, Gaul, Beste, Warren, Quintana, Hämmerer, Freri, Frangos, Tobaldini, Kaniusas, Rosenow, Capone, Panetsos, Ackland, Kaithwas, O'Leary, Genheimer, Jacobs, Van Diest, Schoenen, Redgrave, Fang, Deuchars, Széles, Thayer, More, Vonck, Steenbergen, Vianna, McTeague, Ludwig, Veldhuizen, De Couck, Casazza, Keute, Bikson, Andreatta, D'Agostini, Weymar, Betts, Prigge, Kaess, Roden, Thai, Schuster, Montano, Hansen, Kroemer, Rong, Fischer, Howland, Sclocco, Sellaro, Garcia, Bauer, Gancheva, Stavrakis, Kampusch, Deuchars, Wehner, Laborde, Usichenko, Polak, Zaehle, Borges, Teckentrup, Jandackova, Napadow and Koenig.)

Objective: Excitation of myelinated nerve fibers is investigated by means of numerical simulations, for the application of percutaneous auricular vagus nerve stimulation (pVNS). High sensitivity to axon diameter is of interest regarding the goal of targeting thicker fibers., Methods: Excitation and blocking thresholds for different pulse types, phase durations, axon depths, axon-electrode distances, temperatures and axon diameters are investigated. The used model consists of a 50 mm long axon and a centrally located needle electrode in a layered medium representing the auricle. Neuronal excitation is simulated using the Frankenhaeuser-Huxley equations for all combinations of parameter values., Results and Conclusion: Multiple modes and locations of excitation along the axon were observed, depending on the pulse type and amplitude. When increasing the axon-electrode distance from 1 mm to 2 mm, sensitivity of thresholds to axon depth decreased with ca. 50%, while sensitivity to axon-electrode distance, axon diameter and phase duration each increased with ca. 15% to 20%, except from monophasic anodal pulses, showing a 45% decrease for axon-electrode distance. These trends for axon diameter and axon-electrode distance allow for more selective stimulation of thicker target fibers using monophasic anodal pulses at higher axon-electrode distances. Cathodal monophasic pulses did not perform well due to blocking of the thicker fibers, which was only rarely seen for other pulse types., Significance: Sensitivities of stimulation thresholds to these parameters by numerical simulation reveal how the stimulation parameters can be changed in order to increase therapeutic effect and comfort during pVNS by enabling more selective stimulation.

Objective: Percutaneous electrical stimulation of the auricular vagus nerve (pVNS) is an electroceutical technology. The selection of stimulation patterns is empirical, which may lead to under-stimulation or over-stimulation. The objective is to assess the efficiency of different stimulation patterns with respect to individual perception and to compare it with numerical data based on in-silico ear models., Methods: Monophasic (MS), biphasic (BS) and triphasic stimulation (TS) patterns were tested in volunteers. Different clinically-relevant perception levels were assessed. In-silico models of the human ear were created with embedded fibers and vessels to assess different excitation levels., Results: TS indicates experimental superiority over BS which is superior to MS while reaching different perception levels. TS requires about 57% and 35% of BS and MS magnitude, respectively, to reach the comfortable perception. Experimental thresholds decrease from non-bursted to bursted stimulation. Numerical results indicate a slight superiority of BS and TS over MS while reaching different excitation levels, whereas the burst length has no influence. TS yields the highest number of asynchronous action impulses per stimulation symbol for the used tripolar electrode set-up., Conclusion: The comparison of experimental and numerical data favors the novel TS pattern. The analysis separates excitatory pVNS effects in the auricular periphery, as accounted by in-silico data, from the combination of peripheral and central pVNS effects in the brain, as accounted by experimental data., Significance: The proposed approach moves from an empirical selection of stimulation patterns towards efficient and optimized pVNS settings.

Therapeutic applications of auricular vagus nerve stimulation (VNS) have drawn recent attention. Since the targeted stimulation process and parameters depend on the electrode-tissue interaction, the lack of structural anatomical information on innervation and vascularization of the auricle restrain the current optimization of stimulation paradigms. For the first time, we employed high-resolution episcopic imaging (HREM) to generate histologic volume data from donated human cadaver ears. Optimal parameters for specimen preparation were evaluated. Anatomical 3D vascular and nerve structures were reconstructed in one sample of an auricular cymba conchae (CC). The feasibility of HREM to visualize anatomical structures was assessed in that diameters, occupied areas, volumes, and mutual distances between auricular arteries, nerves, and veins were registered. The selected region of CC (3 × 5.5 mm) showed in its cross-sections 21.7 ± 2.7 (mean ± standard deviation) arteries and 14.66 ± 2.74 nerve fibers. Identified nerve diameters were 33.66 ± 21.71 μm, and arteries had diameters in the range of 71.58 ± 80.70 μm. The respective occupied area showed a share of, on average, 2.71% and 0.3% for arteries and nerves, respectively, and similar volume occupancy for arteries and nerves. Inter-centroid minimum distance between arteries and nerves was 274 ± 222 μm. The density of vessels and nerves around a point within CC on a given grid was assessed, showing that 50% of all vessels and nerves were found in a radial distance of 1.6-1.8 mm from any of these points, which is strategically relevant when using stimulation needles in the auricle for excitation of nerves. HREM seems suitable for anatomical studies of the human ear. A 3D model of CC was established in the micrometer scale, which forms the basis for future optimization of the auricular VNS. Obviously, the presented single cadaver study needs to be validated by additional anatomical data on the innervation and vascularization of the auricle., (Copyright © 2020 Dabiri, Kampusch, Geyer, Le, Weninger, Széles and Kaniusas.)

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging technology in the field of bioelectronic medicine with applications in therapy. Modulation of the afferent vagus nerve affects a large number of physiological processes and bodily states associated with information transfer between the brain and body. These include disease mitigating effects and sustainable therapeutic applications ranging from chronic pain diseases, neurodegenerative and metabolic ailments to inflammatory and cardiovascular diseases. Given the current evidence from experimental research in animal and clinical studies we discuss basic aVNS mechanisms and their potential clinical effects. Collectively, we provide a focused review on the physiological role of the vagus nerve and formulate a biology-driven rationale for aVNS. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the framework of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on physiological aspects - a discussion of engineering aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Electrical stimulation of the auricular vagus nerve (aVNS) is an emerging electroceutical technology in the field of bioelectronic medicine with applications in therapy. Artificial modulation of the afferent vagus nerve - a powerful entrance to the brain - affects a large number of physiological processes implicating interactions between the brain and body. Engineering aspects of aVNS determine its efficiency in application. The relevant safety and regulatory issues need to be appropriately addressed. In particular, in silico modeling acts as a tool for aVNS optimization. The evolution of personalized electroceuticals using novel architectures of the closed-loop aVNS paradigms with biofeedback can be expected to optimally meet therapy needs. For the first time, two international workshops on aVNS have been held in Warsaw and Vienna in 2017 within the scope of EU COST Action "European network for innovative uses of EMFs in biomedical applications (BM1309)." Both workshops focused critically on the driving physiological mechanisms of aVNS, its experimental and clinical studies in animals and humans, in silico aVNS studies, technological advancements, and regulatory barriers. The results of the workshops are covered in two reviews, covering physiological and engineering aspects. The present review summarizes on engineering aspects - a discussion of physiological aspects is provided by our accompanying article (Kaniusas et al., 2019). Both reviews build a reasonable bridge from the rationale of aVNS as a therapeutic tool to current research lines, all of them being highly relevant for the promising aVNS technology to reach the patient.

Analysis of heart rate variability (HRV) can be applied to assess the autonomic nervous system (ANS) sympathetic and parasympathetic activity. Since living systems are non-linear, evaluation of ANS activity is difficult by means of linear methods. We propose to apply the Higuchi fractal dimension (HFD) method for assessment of ANS activity. HFD measures complexity of the HRV signal. We analyzed 45 RR time series of 84 min duration each from nine healthy and five diabetic subjects with clinically confirmed long-term diabetes mellitus type II and with diabetic foot ulcer lasting more than 6 weeks. Based on HRV time series complexity analysis we have shown that HFD: (1) discriminates healthy subjects from patients with diabetes mellitus type II; (2) assesses the impact of percutaneous auricular vagus nerve stimulation (pVNS) on ANS activity in normal and diabetic conditions. Thus, HFD may be used during pVNS treatment, to provide stimulation feedback for on-line regulation of therapy in a fast and robust way.

Objective: Percutaneous stimulation of the auricular branch of the vagus nerve (pVNS) by miniaturized needle electrodes in the auricle gained importance as a treatment for acute and chronic pain. The objective is to establish a realistic numerical model of pVNS and investigate the effects of stimulation waveform, electrodes' depth, and electrodes' position on nerve excitation threshold and the percentage of stimulated nerves., Methods: Simulations were performed with Sim4Life. An electrostatic solver and neural tissue models were combined for electromagnetic and neural simulation. The numerical model consisted of a realistic high-resolution model of a human ear, blood vessels, nerves, and three needle electrodes., Results: A novel 3D ear model was established, including blood vessels and nerves. The electric field distribution was extracted and evaluated. Maximum sensitivity to needles' depth and displacement was evaluated to be 9.8 and 15.5% per 0.1 mm, respectively. Stimulation was most effective using biphasic compared to mono-phasic pulses., Conclusion: The established model allows easy and quantitative evaluation of various stimulation setups, enabling optimization of pVNS in experimental settings. Results suggest a high sensitivity of pVNS to the electrodes' position and depth, implying the need for precise electrode positioning. Validation of the model needs to be performed.

Electrical impedance tomography (EIT) is a promising imaging technique for bedside monitoring of lung function. It is easily applicable, cheap and requires no ionizing radiation, but clinical interpretation of EIT-images is still not standardized. One of the reasons for this is the ill-posed nature of EIT, allowing a range of possible images to be produced-rather than a single explicit solution. Thus, to further advance the EIT technology for clinical application, thorough examinations of EIT-image reconstruction settings-i.e., mathematical parameters and addition of a priori (e.g., anatomical) information-is essential. In the present work, regional ventilation distribution profiles derived from different EIT finite-element reconstruction models and settings (for GREIT and Gauss Newton) were compared to regional aeration profiles assessed by the gold-standard of 4-dimensional computed tomography (4DCT) by calculating the root mean squared error (RMSE). Specifically, non-individualized reconstruction models (based on circular and averaged thoracic contours) and individualized reconstruction models (based on true thoracic contours) were compared. Our results suggest that GREIT with noise figure of 0.15 and non-uniform background works best for the assessment of regional ventilation distribution by EIT, as verified versus 4DCT. Furthermore, the RMSE of anteroposterior ventilation profiles decreased from 2.53±0.62% to 1.67±0.49% while correlation increased from 0.77 to 0.89 after embedding anatomical information into the reconstruction models. In conclusion, the present work reveals that anatomically enhanced EIT-image reconstruction is superior to non-individualized reconstruction models, but further investigations in humans, so as to standardize reconstruction settings, is warranted.

Primary cervical dystonia is characterized by abnormal, involuntary, and sustained contractions of cervical muscles. Current ways of treatment focus on alleviating symptomatic muscle activity. Besides pharmacological treatment, in severe cases patients may receive neuromodulative intervention such as deep brain stimulation. However, these (highly invasive) methods have some major drawbacks. For the first time, percutaneous auricular vagus nerve stimulation (pVNS) was applied in a single case of primary cervical dystonia. Auricular vagus nerve stimulation was already shown to modulate the (autonomous) sympathovagal balance of the body and proved to be an effective treatment in acute and chronic pain, epilepsy, as well as major depression. pVNS effects on cervical dystonia may be hypothesized to rely upon: (i) the alteration of sensory input to the brain, which affects structures involved in the genesis of motoric and nonmotoric dystonic symptoms; and (ii) the alteration of the sympathovagal balance with a sustained impact on involuntary movement control, pain, quality of sleep, and general well-being. The presented data provide experimental evidence that pVNS may be a new alternative and minimally invasive treatment in primary cervical dystonia. One female patient (age 50 years) suffering from therapy refractory cervical dystonia was treated with pVNS over 20 months. Significant improvement in muscle pain, dystonic symptoms, and autonomic regulation as well as a subjective improvement in motility, sleep, and mood were achieved. A subjective improvement in pain recorded by visual analog scale ratings (0-10) was observed from 5.42 to 3.92 (medians). Muscle tone of the mainly affected left and right trapezius muscle in supine position was favorably reduced by about 96%. Significant reduction of muscle tone was also achieved in sitting and standing positions of the patient. Habituation to stimulation leading to reduced stimulation efficiency was observed and counteracted by varying stimulation patterns. Experimental evidence is provided for significantly varied sympathovagal modulation in response to pVNS during sleep, assessed via heart rate variability (HRV). Time domain measures like the root mean square of successive normal to normal heart beat intervals, representing parasympathetic (vagal) activity, increased from 37.8 to 67.6 ms (medians). Spectral domain measures of HRV also show a shift to a more pronounced parasympathetic activity., (Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)