Deep Dive into Denervation: Institutional Experience with Selective Denervation in Nonflaccid Facial Palsy.

Background: Selective denervation of facial nerve branches ("Modified Selective Neurectomy") improves smile dynamics in patients with nonflaccid facial palsy, but functional morbidity such as oral incompetence has been reported. A comprehensive outcomes assessment of selective denervation will help clinicians educate patients regarding risks and benefits, and improve decision making as they incorporate this procedure into treatment algorithms. Methods: Retrospective review identified selective denervation cases performed by the senior author between February 2019 and February 2020. Pre- and postoperative outcomes were assessed using chart review, the facial clinimetric evaluation (FaCE), the electronic clinician-graded facial function tool (eFACE), and an automated computer-aided facial assessment tool (Emotrics). Results: Twenty consecutive selective denervation procedures were performed in 19 patients. Review of patient-reported outcome measures demonstrated mixed results. Favorably, patients reported smile improvement (13/17, 76.5%) and improvements in facial tightness/discomfort (8/17, 47.1%). Seven patients (41.2%) had worse drooling and five patients (29.4%) had increased difficulty chewing after surgery. Clinician-graded evaluation revealed statistically significant improvements in nasolabial fold depth at rest, oral commissure (OC) position at rest, and OC movement with smile. Total, static, and dynamic eFACE scores all demonstrated significant improvements. Computer-aided facial assessment revealed a significant increase in dental display, and an increase in OC excursion that trended toward significance. Conclusions: Selective denervation improves patient-reported, clinician-graded, and automated smile metrics, but some patients experience exacerbations in oral incompetence and articulation difficulties, and must be counseled regarding these possibilities.

Safety and Dose Study of Targeted Lung Denervation in Moderate/Severe COPD Patients.

RATIONALE: Targeted lung denervation (TLD) is a novel bronchoscopic treatment for the disruption of parasympathetic innervation of the lungs. OBJECTIVES: To assess safety, feasibility, and dosing of TLD in patients with moderate to severe COPD using a novel device design. METHODS: Thirty patients with COPD (forced expiratory volume in 1 s 30-60%) were 1:1 randomized in a double-blinded fashion to receive TLD with either 29 or 32 W. Primary endpoint was the rate of TLD-associated adverse airway effects that required treatment through 3 months. Assessments of lung function, quality of life, dyspnea, and exercise capacity were performed at baseline and 1-year follow-up. An additional 16 patients were enrolled in an open-label confirmation phase study to confirm safety improvements after procedural enhancements following gastrointestinal adverse events during the randomized part of the trial. RESULTS: Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group, p = 0.6. Five patients early in the randomized phase experienced serious gastric events. The study was stopped and procedural changes made that reduced both gastrointestinal and airway events in the subsequent phase of the randomized trial and follow-up confirmation study. Improvements in lung function and quality of life were observed compared to baseline values for both doses but were not statistically different. CONCLUSIONS: The results demonstrate acceptable safety and feasibility of TLD in patients with COPD, with improvements in adverse event rates after procedural enhancements.

Catheter Ablation of Bradyarrhythmia: From the Beginning to the Future.

Enhanced parasympathetic tone may cause sinus bradycardia or pauses, transient or permanent atrioventricular block, with resultant vasovagal syncope. A substantial portion of these patients may be highly symptomatic and refractory to the conventional therapies and may require cardiac pacemaker implantation. Cardioneuroablation is a little known technique for management of patients with excessive vagal activation based on radiofrequency catheter ablation of main parasympathetic autonomic ganglia around the heart. Due to complicated inclusion criteria, ganglia detection methods, and ablation endpoints, routine usage of the procedure cannot be recommended at this time. In this comprehensive review, we aimed to discuss all aspects of cardioneuroablation procedure in bradyarrhythmias.

Parasympathectomy increases resting salivary secretion in normal and irradiated submandibular glands of rats.

Fluid and ion secretion from the submandibular gland (SMG) is mainly regulated by parasympathetic nerves. This study evaluated the effect of parasympathectomy on salivary secretion from normal and irradiated rat SMGs from 1 to 24 wk after denervation. Although stimulated salivary secretion was significantly lower in denervated SMGs compared with contralateral self-controls, the resting salivary flow rates were markedly higher in the denervated SMGs at 1, 12, and 24 wk after denervation. The levels of muscarinic acetylcholine M1 and M3 receptors, as well as of aquaporin 5, were up-regulated. Notably, although irradiated SMGs showed significantly lower resting and stimulated salivary secretion rates than non-irradiated SMGs, the resting salivary secretion rates of the irradiated and denervated SMGs were markedly higher than seen in the irradiated self-control SMGs at 1, 12, and 24 wk after parasympathectomy, and were even higher than seen in the non-irradiated sham-operated rats. The expression of M1 and M3 receptors was similarly elevated. Taken together, our results suggest that parasympathetic denervation increases resting salivary secretion of both normal and irradiated SMGs. This approach might provide a potential modality for relieving radiation-induced xerostomia, which is a common complication following treatment of head and neck cancer.

Transoral submandibular ganglion neurectomy: an anatomical feasibility study.

BACKGROUND: The management of sialorrhea can be difficult for both the patient and the clinician. Current management includes behavioral modification, anticholinergics, botulinum injections, and a variety of surgical options, which all have demonstrated some efficacy. As minimally invasive procedures flourish, we explore the feasibility of highly selective transoral submandibular neurectomy (TOSN) for the management of sialorrhea. METHODS: Ten human cadaver dissections of the floor of mouth were performed bilaterally, for a total of 20 separate cases. An intraoral technique for highly selective, submandibular ganglion neurectomy is demonstrated. RESULTS: A transoral submandibular ganglion neurectomy was performed in 10 cadavers (20 neurectomies) easily and reliably, without injury to the submandibular duct or the main trunk of the lingual nerve. CONCLUSION: Transoral submandibular neurectomy is an attractive addition to the armamentarium of surgical options for the treatment of medically intractable sialorrhea. Further study in selected patients would need to be performed to demonstrate clinical feasibility.

Endoscopic microdebrider-assisted inferior turbinoplasty with and without posterior nasal neurectomy.

OBJECTIVE: Endoscopic microdebrider-assisted inferior turbinoplasty (EMAIT) has been recognized as an efficient surgical technique in the management of hypertrophied inferior turbinate. In an attempt to further increase surgical successful outcomes, posterior nasal neurectomy (PNN) was developed. The aim of this retrospective case-control study was to assess the position of PNN in the surgery of hypertrophied turbinate. METHODS: Seventy patients were assigned to the two treatment groups: Group A (EMAIT) and Group B (EMAIT and PNN). Subjective outcomes were represented by symptom score and quality of life scores (Rhinoconjunctivitis Quality of Life Questionnaire - RQLQ). Objective outcomes were nasal resistance, saccharin transit time and acoustic rhinometry parameters. RESULTS: The survey demonstrated that symptoms and objective parameters improved postoperatively in both groups, with no statistical significant differences in objective and subjective outcomes between the surgical groups. CONCLUSION: The addition of PNN appears to offer no additional benefit in the subjective and objective outcome related with surgery of hypertrophied inferior turbinate. However, longer follow-up studies and larger number of patients are required in order to validate our results.

[Surgical correction of overactive bladder resistant to standard therapy].

Surgical treatment was given to 45 patients with overactive bladder: transurethral detrusorotomy was made in 21 patients (group 1), bladder hydrodilation (BH) was made in 24 patients (group 2). Detrusorotomy was performed by transurethral median cut of the bladder posterior wall by needle electrode leading to destroyment of intramural sympathic and parasympathic nervous fibres. Hydrodilation of the bladder was made under intravesical pressure equal to systolic arterial pressure with 2 min exposure. On day thirty after the operation regress of the lower urinary tract symptoms was registered in 20 (95.2%) patients of group 1 and 11 (45.8%) patients of group 2. Urge to voiding (UV) disappeared in 90.5% patients of group 1 and in 45.8% of group 2 (p < 0.05), the number of patients with miction pain reduced 6-fold and 1.9-fold, with UV--8.5 and 1.2-fold, respectively (p < 0.05). The number of diurnal mictions in group 1 decreased 3.2-fold vs 1.9-fold in group 2. The bladder size in urgency in group 1 patients increased 2.5-fold, the pressure fell also 2.5-fold. In group 2 these parameters changed only 1.2 times (p < 0.05). Cystometry recorded recurrent detrusor overactivity in 13 (54.2%) patients after hydrodilation and only in 3 (14.3%)--after cut of the bladder wall (p < 0.05). Thus, transurethral detrusorotomy in overactive bladder resistant to conventional treatment is much more effective than hydrodilation. The operation is low invasive and is well tolerated. Simple performance and good short-time results are advantages of this technique.

Targeted G-protein inhibition as a novel approach to decrease vagal atrial fibrillation by selective parasympathetic attenuation.

AIMS: The parasympathetic nervous system is thought to play a key role in atrial fibrillation (AF). Since parasympathetic signalling is primarily mediated by the heterotrimeric G-protein, Galpha(i)betagamma, we hypothesized that targeted inhibition of Galpha(i) interactions in the posterior left atrium (PLA) would modify the substrate for vagal AF. METHODS AND RESULTS: Cell-penetrating(cp)-Galpha(i)1/2 and cp-Galpha(i)3 C-terminal peptides were assessed for their ability to attenuate cholinergic-parasympathetic signalling in isolated feline atrial myocytes and in canine left atrium (LA). Confocal fluorescence microscopy indicated that cp-Galpha(i)1/2 and/or cp-Galpha(i)3 peptides moderated carbachol attenuation of cellular Ca(2+) transients in isolated atrial myocytes. High-density epicardial mapping of dog PLA, left atrial pulmonary veins (PVs), and left atrial appendage (LAA) indicated that the delivery of cp-Galpha(i)1/2 peptide or cp-Galpha(i)3 peptide into the PLA prolonged effective refractory periods at baseline and during vagal stimulation in the PLA and to varying extents also in the LAA and PV regions. After delivery of cp-Galpha(i) peptides into the PLA, AF inducibility during vagal stimulation was significantly diminished. CONCLUSION: These results demonstrate the feasibility of using specific G(i)-protein inhibition to achieve selective parasympathetic denervation in the PLA, with a resulting change in vagal responsiveness across the entire LA.

The otic ganglion in rats and its parotid connection: cholinergic pathways, reflex secretion and a secretory role for the facial nerve.

Otic ganglionectomy in rats was found to have affected the parotid gland more profoundly than section of the auriculotemporal nerve as assessed by reduction in gland weight (by 33 versus 20%) and total acetylcholine synthesizing capacity (by 88 versus 76%) 1 week postoperatively and, when assessed on the day of surgery under adrenoceptor blockade, by reflex secretion (by 99 versus 88%). The facial nerve contributed to the acetylcholine synthesizing capacity of the gland. Section of the nerve only, at the level of the stylomastoid foramen, reduced the acetylcholine synthesis by 15% and, combined with otic ganglionectomy, by 98% or, combined with section of the auriculotemporal nerve, by 82%. The facial nerve was secretory to the gland, and the response was of a cholinergic nature. The nerve conveyed reflex secretion of saliva and caused secretion of saliva upon stimulation. Most of the facial secretory nerve fibres originated from the otic ganglion, since after otic ganglionectomy (and allowing for nerve degeneration) the secretory response to facial nerve stimulation was markedly reduced (from 23 to 4 microl (5 min)(-1)). The persisting secretory response after otic ganglionectomy, exaggerated due to sensitization, and the residual acetylcholine synthesizing capacity (mainly depending on the facial nerve) showed that a minor proportion of pre- and postganglionic nerve fibres relay outside the otic ganglion. The great auricular nerve, which like the facial nerve penetrates the gland, caused no secretion of saliva upon stimulation. Avulsion of the auriculotemporal nerve was more effective than otic ganglionectomy in reducing the acetylcholine synthesizing capacity (by 94 versus 88%) and as effective as otic ganglionectomy in abolishing reflex secretion (by 99%). When aiming at parasympathetic denervation, avulsion may be the preferable choice, since it is technically easier to perform than otic ganglionectomy.

Recovery of respiratory function following C2 hemi and carotid body denervation in adult rats: influence of peripheral adenosine receptors.

The efficacy of the methylxanthine, theophylline, as a respiratory stimulant has been demonstrated previously in an animal model of spinal cord injury. In this model, an upper cervical (C2) spinal cord hemi paralyzes the ipsilateral hemidiaphragm. Theophylline restores respiratory-related activity in the paralyzed hemidiaphragm via activation of a latent respiratory motor pathway. Antagonism of central adenosine A1 receptors mediates this action. Theophylline also enhances respiratory frequency, f, defined as breaths per minute. Thus, long-term use may result in respiratory muscle or motoneuron fatigue particularly after spinal cord injury. We assessed the effects of an adenosine A1 receptor agonist, N6-p-sulfophenyladenosine (p-SPA) on theophylline's action in our model under standardized recording conditions. Four groups of rats, classified as hemisected/nonhemisected with the carotid bodies denervated (H-CBD or NH-CBD), and hemisected/nonhemisected with the carotid bodies intact (H-CBI or NH-CBI ) were used in the study. Eight days after recovery from carotid denervation, a left C2 hemi was performed in H-CBD rats. C2 hemi was also performed in H-CBI animals, and 24 h later, electrophysiologic experiments on respiratory activity were conducted in both groups of animals. Two groups using nonhemisected controls were also employed as described above. In H-CBD rats, theophylline significantly (P < 0.05) enhanced f and induced respiratory-related activity in the previously quiescent left phrenic nerve. In NH-CBD rats, theophylline significantly enhanced f. In both H-CBD and NH-CBD rats, p-SPA (0.25 mg/kg) did not significantly change theophylline-induced effects. In H-CBI rats, theophylline significantly (P < 0.05) enhanced f and induced activity in the previously quiescent left phrenic nerve. In H-CBI rats, p-SPA reduced the values to pre-theophylline discharge levels. Recovered activity was not obliterated with the agonist. In NH-CBI rats, p-SPA reduced theophylline-induced effects to pre-drug discharge levels. Adenosine A1 and A2A receptor immunoreactivity was detected in the carotid bodies. The significance of our findings is that theophylline-induced effects can be normalized to pre-drug levels by the selective activation of peripheral adenosine A1 receptors. The therapeutic benefits of theophylline, i.e., recovered respiratory function after paralysis, however, persists. The potential therapeutic impact is that respiratory muscle fatigue associated with long-term theophylline use may be minimized by a novel therapeutic approach.

Preservation of the anterior fat pad paradoxically decreases the incidence of postoperative atrial fibrillation in humans.

OBJECTIVES: The goal of this study was to determine if parasympathetic nerves in the anterior fat pad (FP) can be stimulated at the time of coronary artery bypass surgery (CABG), and if dissection of this FP decreases the incidence of postoperative atrial fibrillation (AF). BACKGROUND: The human anterior epicardial FP contains parasympathetic ganglia and is often dissected during CABG. Changes in parasympathetic tone influence the incidence of AF. METHODS: Fifty-five patients undergoing CABG were randomized to anterior FP preservation (group A) or dissection (group B). Nerve stimulation was applied to the FP before and after surgery. Sinus cycle length (CL) was measured during stimulation. The incidence of postoperative AF was recorded. RESULTS: Of the 55 patients enrolled, 26 patients were randomized to group A, and 29 patients were randomized to group B. In all of the 55 patients, the FP was identified before initiating cardiopulmonary bypass by CL prolongation with stimulation (865.5 +/- 147.9 ms vs. 957.9 +/- 155.1 ms, baseline vs. stimulation, p < 0.001). In group A, stimulation at the conclusion of surgery increased sinus CL (801.8 +/- 166.4 ms vs. 890.9 +/- 178.2 ms, baseline vs. stimulation, p < 0.001). In group B, repeat stimulation failed to increase sinus CL (853.6 +/- 201.6 ms vs. 841.4 +/- 198.4 ms, baseline vs. stimulation, p = NS). The incidence of postoperative AF in group A (7%) was significantly less than that in group B (37%) (p < 0.01). CONCLUSIONS: This is the first study demonstrating that direct stimulation of the human anterior epicardial FP slows sinus CL. This parasympathetic effect is eliminated with FP dissection. Preservation of the human anterior epicardial FP during CABG decreases incidence of postoperative AF.

Parasympathetic nerve fibers invade the upper dermis following sensory denervation of the rat lower lip skin.

The sympathetic division of the autonomic nervous system is known to play a role in the genesis of neuropathic pain. In the skin of the rat lower lip (hairy skin), sympathetic and parasympathetic fibers normally innervate the same blood vessels in the lower dermis but do not occur in the upper dermis. However, we have shown that sympathetic fiber migration into the upper dermis occurs following mental nerve lesions (Ruocco et al. [2000] J. Comp. Neurol. 422:287-296). As sensory denervation has a dramatic effect on sympathetic fiber innervation patterns in the rat lower lip skin, we decided to investigate the possible changes in the other autonomic fiber type in the skin-the parasympathetic fiber. Sensory denervation of the rat lower lip was achieved by bilateral transection of the mental nerve, and animals were allowed to recover for 1-8 weeks. Lower lip tissue was processed for double-labeling light microscopic immunocytochemistry (ICC), using antibodies against substance P (SP), which labels a subpopulation of peptidergic sensory fibers, and against the vesicular acetycholine transporter (VAChT), as a marker for parasympathetic fibers. In sham-operated rats, SP-immunoreactive (IR) sensory fibers were found in the epidermis and upper and lower dermal regions, whereas VAChT-IR fibers were confined to the lower dermis. Mental nerve lesions induced the gradual disappearance of SP-IR fibers from all skin layers accompanied by the progressive migration of VAChT-IR fibers into the upper dermis. Cholinergic fiber migration was evident by the second week post surgery, and the ectopic innervation of the upper dermis by these fibers persisted even at the last time point studied (8 weeks) when SP-IR fibers have completely regrown. VAChT-IR fibers were observed in the upper dermis, well above the opening of the sebaceous glands into the hair follicles. These results show that considerable changes occur in the innervation patterns of parasympathetic fibers following mental nerve lesions.

Selective denervation: reinnervation for the control of adductor spasmodic dysphonia.

OBJECTIVES: The objective of this study was to evaluate the efficacy of a new surgical procedure for adductor spasmodic dysphonia (AddSD). This surgery involves the bilateral selective division of the adductor branches of the recurrent laryngeal nerves with immediate reinnervation of the distal nerve trunks with branches of the ansa cervicalis (selective denervation-reinnervation). METHODS: Our first six patients to undergo this procedure were enrolled in the study. All patients suffered from AddSD and had previously received botulinum toxin A (Botox, Allergen, Markham, ON) therapy. Patients were recorded preoperatively and all underwent the same surgical procedure performed by the same lead surgeon. All patients were surveyed postoperatively and then re-recorded. Expert and untrained judges undertook perceptual evaluation of voice quality. Voice samples were also objectively evaluated for aphonic voice breaks. RESULTS: No major surgical complications were noted. Patient satisfaction was excellent, and five of the six patients no longer require botulinum toxin therapy. In five of the six patients, the majority of untrained and expert listeners perceived the postoperative voice to be superior. Objectively, the rate of aphonic voice breaks was also reduced in five of the six patients.

The effect of parasympathetic postganglionic denervation on parotid salivary protein secretion in anaesthetized sheep.

Effects of unilateral parasympathetic denervation of ovine parotid glands were examined in anaesthetized sheep 21-28 days after nerve section. Parasympathetic denervation reduced the mass of the ipsilateral gland while increasing that of the contralateral gland to the extent that total gland mass was greater than in sheep with normally innervated glands. The spontaneous secretion (8.8 +/- 1.1 microl min(-1) g gland(-1)) was significantly less from denervated than from innervated glands of normal control animals (26.0 +/- 2.7 microl min(-1) g gland(-1); P< 0.01) and contained more protein. Rates of flow, and the outputs of sodium and potassium, in response to sympathetic stimulation, were similar from normally innervated and chronically denervated glands, when allowance was made for the discrepancy in weights, whereas the output of protein was significantly enhanced following parasympathetic denervation (innervated--31.4 +/- 7.3 microg g gland(-1), denervated--83.4 +/- 26.6 microg g gland(-1); P< 0.05). Intra-arterial infusions of acetylcholine (130 pmol min(-1) kg(-1)) elicited a flow of parotid saliva, the protein content of which was significantly enhanced by prior parasympathetic denervation. Intra-arterial infusions of vasoactive intestinal peptide (VIP; 2.5 pmol min(-1) kg(-1)) produced a small but statistically significant (P< 0.05) increase in the flow of parotid saliva from the contralateral, innervated but not from denervated glands. It also caused a small increase in protein output, which was significantly enhanced by prior denervation. VIP had no synergistic effect on the parotid responses to acetylcholine. The results show that the parasympathetic innervation to the parotid gland of the sheep exerts important trophic effects on the gland. Interaction of adrenergic and cholinergic receptors makes an important contribution to stimulation of the secretion of protein and prior denervation potentiates the protein responses to both acetylcholine and VIP.