Vagus nerve stimulation for trigeminal autonomic cephalalgias: Evidence, challenges and future directions.

A SENSORY CORTICAL REPRESENTATION OF THE VAGUS NERVE: WITH A NOTE ON THE EFFECTS OF LOW BLOOD PRESSURE ON THE CORTICAL ELECTROGRAM

Vagus nerve stimulation and late-onset bradycardia and asystole: Case report

To the Editor: We enjoyed the recent article entitled “Right-sided vagus nerve stimulation as a treatment for refractory epilepsy in humans” by McGregor et al. (1). We agree that right vagus nerve stimulation may be used in humans with epilepsy, as prior reports of cardiac effects after right-sided vagus nerve stimulation were based on experiments in dogs (2). Although complications with vagus nerve stimulation are low, as found in our report of 74 children undergoing this procedure (3), as surgeons, the option of left versus right side for vagus nerve stimulation is appealing, especially in cases of concomitant left-sided ventriculoperitoneal shunts, so that additional hardware (i.e., vagus nerve stimulator) is moved farther away from the shunt system, thus decreasing the risk of infection of the shunt. Our experience also has shown that another cardiovascular nerve (the carotid sinus nerve) can be stimulated on both left and right sides in a dog model with equal effect on causing cessation of cortically induced seizures (4). Furthermore, we found no significant cardiovascular effects when this nerve (carotid sinus nerve) was stimulated with parameters comparable to those used for vagus nerve stimulation in humans (4). Interestingly, both of these nerves synapse proximally in the cardiorespiratory part of the nucleus tractus solitarius. After right-sided vagus nerve stimulation, we have been unable to alter the cardiorespiratory system in a porcine model (5). These data imply, whether with vagus or carotid sinus nerve stimulation, that nerve stimulation responses (e.g., right-sided cardiorespiratory responses) may be species specific. We also agree with the authors' statement that the right vagus nerve may be desired for stimulation when a left-sided vagus nerve has been used and removed after infection. Indeed, we have shown in a single case that a left-sided vagus nerve that was often stimulated and removed at autopsy had severe demyelination (6).

Cardiac Autonomic Nerve Stimulation in the Treatment of Heart Failure

Case report: Vagal nerve stimulation and late onset asystole

Vagal nerve stimulation for treatment of children with epilepsy

Rapid Remission of Conditioned Fear Expression with Extinction Training Paired with Vagus Nerve Stimulation

Transcutaneous vagus nerve stimulation (tVNS) protocol for the treatment of major depressive disorder: A case study assessing the auricular branch of the vagus nerve.

Neuromodulation May Offer New Option for Patients With Psychiatric Disorders

Vagal and recurrent laryngeal nerves neuromonitoring during thyroidectomy and parathyroidectomy: A prospective study

Minimal access coronary artery bypass grafting without cardiopulmonary bypass has been used with increasing frequency. However, some surgeons are still unwilling to perform MIDCAB because the anastomosis is technically demanding. The aim of this study was to assess whether autonomic activation via right vagal nerve stimulation will be an effective support technique on heart rate during MIDCAB in dogs. Preliminary study. Cardiothoracic Surgery Unit, University Clinic. The right cervical vagal nerve was stimulated in five dogs. In one dog, right thoracotomy was performed to isolate the vagal nerve. Bipolar hook electrodes were attached to the vagal nerve. The vagal nerve was stimulated (3-5 mA, 40 Hz) for a few seconds while suturing the coronary artery. Experiments were conducted in two groups. In Group I, two dogs received vagal stimulation via the right neck, and one dog received vagal stimulation via the right thoracic cavity approach. In Group H, all vagal stimulations were performed via the neck during intravenous infusion of diltiazem (10 mg/hrs) or verapamil (5 mg/hrs). In Group I, when the cervical nerve stimulation started the heart rate decreased from 190 to 45 beats/min in one dog, and from 180 to 42 beats/min in another dog. During thoracic nerve stimulation, the heart rate decreased from 205 to 70 beats/min. In Group II, vagal stimulation of one dog (10 mg/hr diltiazem) caused ventricular arrest, and in the other dogs (5 mg/hr verapamil) vagal stimulation caused marked bradycardia with atrioventricular block. After the cessation of nerve stimulation, the heart rate returned to normal sinus rhythm immediately in each dog. Based on our findings, this type of autonomic stimulation (especially with i.v. administration of diltiazem or verapamil) can be an effective technique in reducing heart beats, thus obtaining relatively quiet surgical field for coronary anastomosis in CABG without cardiopulmonary bypass.

Accumulating evidence suggests that the respiratory control system exhibits an impressive degree of plasticity, as do many other neural networks in the central nervous system (Eldridge & Millhorn, 1986; McCrimmon et al. 1995; Ling et al. 1997a; Powell et al. 1998; Mitchell et al. 2001). For example, episodic hypoxia induces a persistent augmentation of respiratory activity (Cao et al. 1992; Bach & Mitchell, 1996; Turner & Mitchell, 1997; Olson et al. 2001; McGuire et al. 2002), known as long-term facilitation (LTF). Episodic carotid sinus nerve (CNS) stimulation (CSNS) also elicits phrenic LTF in anaesthetized animals (Millhorn et al. 1980a; Hayashi et al. 1993; Ling et al. 1997b), which is not abolished by decerebration or spinal transection at the C7-T1 level (Eldridge & Millhorn, 1986). These results suggest that LTF is elicited by central mechanisms located in the brainstem and/or cervical spinal cord, and that the carotid body, respiratory mechanics, systemic hypoxia, forebrain and the lower spinal cord are not necessary for its expression (Eldridge & Millhorn, 1986). Both hypoxia- and CSNS-induced LTF are serotonin-dependent (Millhorn et al. 1980b; Bach & Mitchell, 1996). Recent evidence further suggests that spinal serotonin receptors (Baker-Herman & Mitchell, 2002) and the synapses transmitting bulbospinal, inspiratory drive to the phrenic motoneurons (Fuller et al. 2002) play key roles in phrenic LTF. In these experiments, respiratory LTF is always preceded by repeated inspiratory augmentation. This fact suggests that induction of respiratory LTF is somehow related to inspiratory augmentation, and more specifically, that phrenic LTF relies heavily on an activity-dependent Hebbian mechanism (coincident pre- and post-synaptic activity strengthens synapses) in the synapses on the phrenic motoneurons. However, as all LTF to date has been induced by episodic inspiratory-excitatory stimulation, it has been difficult to directly test these hypotheses by separating the LTF from inspiratory augmentation. In contrast, vagus nerve (VN) stimulation (VNS) suppresses inspiration during stimulation, and induces a reduction (< 1 min duration) in phrenic amplitude and frequency after stimulation (0.5 min duration; Eldridge & Millhorn, 1986). We speculate that a relatively longer post-stimulation inhibitory memory is possible if using episodic and longer VNS. VNS has also been used as a tool in brain research (e.g. evoked potentials recorded from the cerebral cortex, hippocampus, thalamus and cerebellum; Rutecki, 1990) and neurophysiological studies of several reflexes (e.g. cough, swallow and Hering-Breuer reflex or inspiratory off-switch mechanisms) because vagal afferents provide an easily accessible, peripheral route by which to modulate the central nervous system function. However, these investigators all used brief VNS and focused mainly on immediate or short-term (< several min) effects, during and/or after VNS. For many years, episodic VNS has been used clinically as a common treatment for patients with medically intractable epilepsy (Schachter, 2002). However, the precise underlying mechanisms and the consequence of long-term VNS remain unclear. The aims of the present study were to (1) examine the long-term effects of episodic phrenic-inhibitory VNS on phrenic nerve activity and compare them with those elicited by phrenic-excitatory CSNS and (2) explore the possibility of using VNS as a tool to suppress phrenic motor neurons during LTF elicitation. We hypothesized that episodic VNS would induce phrenic long-term depression, but that phrenic activity would eventually return to baseline in less than 60 min.

Background: Most Recurrent Laryngeal Nerve Palsies (RLNP) occurs with visually intact nerves, indicating neurapraxia. However the mechanism of RLNP neurapraxia in intact nerves is not well understood. During thyroid surgery, Recurrent Laryngeal Nerve (RLN) palsy has occasionally been observed immediately following anteromedial rotation of the thyroid lobe (AMRT), upon identification but prior to dissection of the RLN. We postulated that traction placed on RLN during AMRT may lead to neurapraxia. This study aimed to describe these cases, and to measure Electromyographic (EMG) changes in the vocal cord adductors (VCA) with Vagus Nerve (VN) stimulation, before and after AMRT, and to correlate the EMG findings to prediction of RLN palsy. Methods: Firstly, the cases of RLN palsy following AMRT are described. Secondly, in a prospective study, the EMG amplitudes of 138 VCA muscles following VN stimulation were measured using the Intraoperative Nerve Integrity Monitor (IONM) during thyroidectomy in 90 patients. The EMG amplitudes of VCA with VN stimulation were measured before and after AMRT. All data was collected during a 16-month period, between 2012 and 2013. Standard statistical methods were used to analyse the data. Results: A retrospective series of 7 cases is described where EMG activity with VN stimulation was lost following AMRT upon identification but prior to dissection of the RLN. In the prospective study of 90 patients, anteromedial rotation of the thyroid caused a significant increase in EMG amplitude on the right side (p=0.02) but not on the left (p=0.44). Multivariate analysis identified only extralaryngeal branching of the RLN to be associated with the EMG change. Conclusion: The increase in EMG amplitude of the VCA with right VN stimulation is likely to represent hyper excitability of the RLN after AMRT. Further studies are required to explore the underlying mechanism of this finding, and correlate it to the development of nerve palsy.

The use of surgically implanted electronic devices for vagus nerve stimulation (VNS) is expanding in contemporary allopathic medical practice as a treatment option for selected clinical conditions, such as epilepsy, depression, tremor, and pain conditions, that are unresponsive to standard pharmacologic interventions. Although VNS device surgeries are considered minimally invasive, they are costly and have surgical and device-related risks; they can also cause serious adverse effects from excessive vagus nerve stimulation. For millennia, acupuncturists have treated those same clinical conditions by piquering acupoints that are located proximate to the sternocleidomastoid muscle site where the VNS device is implanted on the vagus nerve. The hypothesis of this study is that these acupuncture points produce clinical benefits through stimulation of the vagus nerve and/or its branches in the head and neck region. By using reference anatomic and acupuncture texts, classical and extraordinary acupoints in the head and neck region were identified that are anatomically proximate to vagus nerve pathways there, where the VNS electrode is surgically implanted. The clinical indications of these acupuncture points, as described in the acupuncture reference texts, were examined for similarities to those of VNS. This analysis demonstrated marked correspondences of the indications for those lateral head and neck acupoints to the clinical effects (beneficial and adverse) documented for the VNS device in the medical literature. This clinical correspondence, in conjunction with the anatomic proximity of the acupoints to the vagus nerve in the lateral neck, strongly suggests that vagus nerve (and hence the autonomic nervous system) stimulation is fundamental in producing the clinical effects of the acupoints. By having anatomic access to the vagus nerve and parasympathetic chain that permits electrical stimulation of those nerves in clinical practice, acupuncture may offer a less costly and safer alternative to implanted VNS devices for treating medically refractory epilepsy, tremor, depression, and pain conditions.

Over the past two decades, the number of somatic treatments for psychiatric disorders has expanded, leading to new insights into the complex relationship between chemical and electric transmission of signals in the brain. In this article, the authors discuss the different device-based treatments currently available in psychiatry. They review clinical indications; putative mechanism of action; efficacy and adverse effects; the results and limitations of salient clinical trials; and active areas of research into the neurobiology of device-based stimuli.