Identification of compounds that cause axonal dieback without cytotoxicity in dorsal root ganglia explants and intervertebral disc cells with potential to treat pain via denervation.

Low back pain, knee osteoarthritis, and cancer patients suffer from chronic pain. Aberrant nerve growth into intervertebral disc, knee, and tumors, are common pathologies that lead to these chronic pain conditions. Axonal dieback induced by capsaicin (Caps) denervation has been FDA-approved to treat painful neuropathies and knee osteoarthritis but with short-term efficacy and discomfort. Herein, we propose to evaluate pyridoxine (Pyr), vincristine sulfate (Vcr) and ionomycin (Imy) as axonal dieback compounds for denervation with potential to alleviate pain. Previous literature suggests Pyr, Vcr, and Imy can cause undesired axonal degeneration, but no previous work has evaluated axonal dieback and cytotoxicity on adult rat dorsal root ganglia (DRG) explants. Thus, we performed axonal dieback screening using adult rat DRG explants in vitro with Caps as a positive control and assessed cytotoxicity. Imy inhibited axonal outgrowth and slowed axonal dieback, while Pyr and Vcr at high concentrations produced significant reduction in axon length and robust axonal dieback within three days. DRGs treated with Caps, Vcr, or Imy had increased DRG cytotoxicity compared to matched controls, but overall cytotoxicity was minimal and at least 88% lower compared to lysed DRGs. Pyr did not lead to any DRG cytotoxicity. Further, neither Pyr nor Vcr triggered intervertebral disc cell death or affected cellular metabolic activity after three days of incubation in vitro. Overall, our findings suggest Pyr and Vcr are not toxic to DRGs and intervertebral disc cells, and there is potential for repurposing these compounds for axonal dieback compounds to cause local denervation and alleviate pain.

Long-term effect of posterior nasal neurectomy for perennial allergic rhinitis.

BACKGROUND: Surgical treatment is recommended for patients with severe allergic rhinitis (AR) refractory to medical treatment. Endoscopic posterior nasal neurectomy (PNN) is primarily performed to improve rhinorrhea in severe perennial AR, however studies on its long-term prognosis are lacking. AIMS/OBJECTIVES: This study aimed to investigate the long-term prognosis of PNN. MATERIALS AND METHODS: A questionnaire survey was administered to 17 patients (12 men and 5 women) at least 1 year after PNN. Nasal symptoms and medications, as well as patient satisfaction with surgery at the time of survey, were scored. Furthermore, scores were compared between patients with postoperative periods of >5 years and <5 years. RESULTS: Nasal symptoms and medication scores significantly improved after surgery. There was no significant difference between patients with a postoperative period of >5 years and <5 years in both preoperative and postoperative nasal symptoms and medication scores. No correlation was found between patient satisfaction with surgery and postoperative period. CONCLUSIONS AND SIGNIFICANCE: PNN improved nasal symptoms and medication scores in patients with severe perennial AR. Furthermore, the study results suggest that the long-term effect of PNN for perennial AR lasts for >5 years. J. Med. Invest. 71 : 62-65, February, 2024.

Redundant nerve roots on magnetic resonance imaging can predict ongoing denervation in patients with lumbar spinal stenosis.

INTRODUCTION/AIMS: Redundant nerve roots (RNRs) are abnormally elongated and tortuous nerve roots that develop secondary to degenerative spinal stenosis. RNRs have been associated with poorer clinical outcomes after decompression surgery; however, studies on their clinical characteristics are limited. This study aimed to investigate the association between RNRs and denervation potentials, that is, abnormal spontaneous activity (ASA), on electromyography. METHODS: We retrospectively reviewed data of patients who underwent an electrodiagnostic study of the lower extremities between January 2020 and March 2023. Of these, patients with lumbar central spinal stenosis, as seen on magnetic resonance imaging, were included. We analyzed clinical and imaging data, including presence of ASA, and compared them according to the presence of RNRs. Multivariable logistic regression analysis was employed to identify factors associated with development of ASA. RESULTS: Among the 2003 patients screened, 193 were included in the study. RNRs were associated with advanced age (p < .001), longer symptom duration (p = .009), smaller cross-sectional area of the dural sac at the stenotic level (p < .001), and higher frequency of ASA (p < .001). Higher probability of ASA was correlated with greater RNR severity (p < .001). In the multivariable logistic regression analysis, ASA occurrence was associated with smaller cross-sectional area, multiple stenotic sites, and severe-grade RNRs. DISCUSSION: The presence of RNRs, particularly severe-grade RNRs, was identified as a significant risk factor for the development of ASA on electromyography. This finding may aid physicians in estimating the prognosis of patients with central spinal stenosis.

Lingual Denervation Improves the Efficacy of Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinomas by Downregulating TGFß Signaling.

PURPOSE: Intratumoral nerve infiltration relates to tumor progression and poor survival in oral squamous cell carcinoma (OSCC). How neural involvement regulates antitumor immunity has not been well characterized. This study aims to investigate molecular mechanisms of regulating tumor aggressiveness and impairing antitumor immunity by nerve-derived factors. EXPERIMENTAL DESIGN: We performed the surgical lingual denervation in an immunocompetent mouse OSCC model to investigate its effect on tumor growth and the efficacy of anti-PD-1 immunotherapy. A trigeminal ganglion neuron and OSCC cell coculture system was established to investigate the proliferation, migration, and invasion of tumor cells and the PD-L1 expression. Both the neuron-tumor cell coculture in vitro model and the OSCC animal model were explored. RESULTS: Lingual denervation slowed down tumor growth and improved the efficacy of anti-PD-1 treatment in the OSCC model. Coculturing with neurons not only enhanced the proliferation, migration, and invasion but also upregulated TGFß-SMAD2 signaling and PD-L1 expression of tumor cells. Treatment with the TGFß signaling inhibitor galunisertib reversed nerve-derived tumor aggressiveness and downregulated PD-L1 on tumor cells. Similarly, lingual denervation in vivo decreased TGFß and PD-L1 expression and increased CD8+ T-cell infiltration and the expression of IFNγ and TNFα within tumor. CONCLUSIONS: Neural involvement enhanced tumor aggressiveness through upregulating TGFß signaling and PD-L1 expression in OSCC, while denervation of OSCC inhibited tumor growth, downregulated TGFß signaling, enhanced activities of CD8+ T cells, and improved the efficacy of anti-PD-1 immunotherapy. This study will encourage further research focusing on denervation as a potential adjuvant therapeutic approach in OSCC. SIGNIFICANCE: This study revealed the specific mechanisms for nerve-derived cancer progression and impaired antitumor immunity in OSCC, providing a novel insight into the cancer-neuron-immune network as well as pointing the way for new strategies targeting nerve-cancer cross-talk as a potential adjuvant therapeutic approach for OSCC.

Cadaveric study of flexor digitorum profundus and superficialis and flexor pollicis longus innervation patterns for application in selective neurectomy.

PURPOSE: Spasticity management in finger flexors (flexor digitorum profundus and superficialis and flexor pollicis longus) is a challenge. Recent studies demonstrated the short- and long-term efficacy of selective and hyperselective neurectomy for the spastic upper limb. However, hyperselective neurectomy of flexor digitorum profundus and flexor digitorum superficialis branches was incomplete, without impairing their muscular body and function. This cadaveric study describes a novel medial approach in the forearm, to reach all the muscular branches: flexor digitorum superficialis and profundus and flexor pollicis longus. MATERIAL AND METHODS: Fourteen cadaveric fresh frozen upper limbs were used. The feasibility of the medial surgical approach was studied, as well as the number, length and point of emergence of the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis. RESULTS: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerves to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, in all cases. A Martin Gruber communicating branch was found in 7 cases out of 14. CONCLUSION: The medial approach to the forearm gave access to all the muscular branches from the median and ulnar nerve to the flexor pollicis longus, flexor digitorum superficialis and flexor digitorum profundus, without extensive transmuscular dissection of the pronator teres or flexor digitorum superficialis muscles. This approach opens the way for selective neurectomy of the flexor pollicis longus, flexor digitorum profundus and flexor digitorum superficialis muscles. LEVEL OF EVIDENCE: IV.

The Role of Sensory Nerves in Dental Pulp Homeostasis: Histological Changes and Cellular Consequences after Sensory Denervation.

Homeostatic maintenance is essential for pulp function. Disrupting pulp homeostasis may lead to pulp degeneration, such as fibrosis and calcifications. Sensory nerves constitute a crucial component of the dental pulp. However, the precise involvement of sensory nerves in pulp homeostasis remains uncertain. In this study, we observed the short-term and long-term histological changes in the dental pulp after inferior alveolar nerve transection. Additionally, we cultured primary dental pulp cells (DPCs) from the innervated and denervated groups and compared indicators of cellular senescence and cellular function. The results revealed that pulp fibrosis occurred at 2 w after the operation. Furthermore, the pulp area, as well as the height and width of the pulp cavity, showed accelerated reductions after sensory denervation. Notably, the pulp area at 16 w after the operation was comparable to that of 56 w old rats. Sensory denervation induced excessive extracellular matrix (ECM) deposition and increased predisposition to mineralization. Furthermore, sensory denervation promoted the senescence of DPCs. Denervated DPCs exhibited decelerated cell proliferation, arrest in the G2/M phase of the cell cycle, imbalance in the synthesis and degradation of ECM, and enhanced mineralization. These findings indicate that sensory nerves play an essential role in pulp homeostasis maintenance and dental pulp cell fate decisions, which may provide novel insights into the prevention of pulp degeneration.

[The principle and practice of vidian neurectomy].

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.

Standing left recurrent laryngeal neurectomy for prospective evaluation of laryngeal hemiplegia evaluated by a high-speed treadmill test.

OBJECTIVE: To describe left recurrent laryngeal neurectomy (LRLn) performed under standing sedation and evaluate the effect of LRLn on upper respiratory tract function using a high-speed treadmill test (HST). We hypothesized that (1) unilateral LRLn could be performed in standing horses, resulting in ipsilateral arytenoid cartilage collapse (ACC); and (2) HST after LRLn would be associated with alterations in upper respiratory function consistent with dynamic ACC. ANIMALS: 6 Thoroughbred horses. METHODS: The horses were trained and underwent a baseline HST up to 14 m/s at 5% incline until fatigue. Evaluation included; airflow, pharyngeal and tracheal pressures, and dynamic upper respiratory tract endoscopy. Trans-laryngeal impedance (TLI) and left-to-right quotient angle ratio (LRQ) were calculated after testing. The following day, standing LRLn was performed in the mid-cervical region. A HST was repeated within 4 days after surgery. RESULTS: Standing LRLn was performed without complication resulting in Havemayer grade 4 ACC at rest (complete paralysis) and Rakestraw grade C or D ACC (collapse up to or beyond rima glottis midline) during exercise. Increasing treadmill speed from 11 to 14 m/s increased TLI (P < .001) and reduced LRQ (P < .001). Neurectomy resulted in an increase in TLI (P = .021) and a reduction in LRQ (P < .001). CLINICAL RELEVANCE: Standing LRLn induces laryngeal hemiplegia that can be evaluated using a HST closely after neurectomy. Standing LRLn may be useful for future prospective evaluations of surgical interventions for laryngeal hemiplegia.

Combined Hyperselective Neurectomy and Fractional Lengthening Technique for Triceps Spasticity.

Triceps spasticity can occur in patients with upper motor neuron syndrome. It is often undetected when there is predominant elbow flexion spasticity and/or contracture. This condition can become apparent after surgery for elbow flexor spasticity, leading to impaired active elbow. Although triceps muscle-tendon lengthening procedures can be performed, these techniques do not directly address the issue of spasticity which is neurally mediated. This article presents a surgical technique for addressing triceps spasticity with a combined approach of hyperselective neurectomy of the medial head of the triceps and muscle-tendon lengthening of the long and lateral heads.

Pre-Operative Factors May Predict Outcome in Selective Neurectomy for Synkinesis.

Background: While there has been great interest in offering selective neurectomy (SN) to patients with nonflaccid facial palsy (NFFP), postoperative outcomes are inconsistent. Objective: To assess overall SN outcome in NFFP patients and to examine correlation between preoperative factors and SN outcome. Methods: SN cases were retrospectively identified between 2019 and 2021. Patient factors and facial function 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). Correlations between preoperative factors and patients outcome were established. Results: Fifty-eight SN cases were performed; 88% were females, and median age was 53 years (range 11-81). Outcome assessment was 8 months on average (1-24 months). Postoperatively, multiple eFACE and Emotrics parameters improved significantly, including ocular, perioral, and synkinesis metrics. In preoperative factors assessment, age >50, facial palsy (FP) duration >2 years, poor preoperative facial function, and nontrauma etiology all correlated with greater improvements compared with younger patients, those with shorter duration facial palsy, trauma etiology, and better preoperative facial function. Conclusions: SN can significantly improve facial function; we have identified several preoperative factors that correlated to outcome.

Endoscopic vidian and vidian-branch neurectomy for refractory allergic rhinitis: A systematic review.

BACKGROUND: Endoscopic vidian neurectomy is expected to provide good therapeutic relief in patients with allergic rhinitis (AR) being refractory to medication therapy or conservative surgery. However, the evidence bases for its benefit remain debatable. In this study, we conducted a systematic review and meta-analysis to clarify the therapeutic role of various forms of vidian neurectomy in refractory AR. METHOD: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct a systematic review of primary studies that reported original patient data for endoscopic vidian neurectomy (EVN) and vidian-branch neurectomy, which includes selective vidian neurectomy (SVN) and posterior nasal neurectomy (PNN). The primary outcome was patient-reported outcome measures (PROMs), including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and Visual Analog Scale (VAS), to assess an improvement in nasal symptom severity and quality of patient's life. The incidence of surgical complications and other objective outcomes were considered secondary outcomes. RESULTS: This review included 24 clinical studies involving 1677 patients with refractory AR, of which 510 patients in six studies had combined chronic rhinosinusitis with nasal polyps (CRSwNP) and 95 patients in one study had combined asthma. Postoperative PROMs were significantly better than preoperatively in almost all patients who underwent vidianp (RQLQ: standardized mean difference [SMD] = 2.66, 95% confidence interval [CI] = 2.40-2.92, p < 0.001; VAS: SMD = 5.15, 95% CI = 4.29-6.02, p < 0.001) or vidian-branch neurectomy (RQLQ in PNN: SMD = 3.29, 95% CI = 2.45-4.13, p < 0.001; VAS in PNN: SMD = 4.38, 95% CI = 3.41-5.34, p < 0.001), and were generally better than in the conservative treatment group. Dividing with 18 months as the cutoff point, a subgroup analysis of the follow-up period was conducted, and the results showed that both long-term and short-term postoperative patients had considerably reduced symptoms compared to the preoperative period. The two surgical procedures, SVN and PNN, attributed to vidian-branch neurectomy have extremely few complications. However, EVN is more likely to cause dry eyes and palatal numbness, with no other serious complications. In patients with AR and CRSwNP, vidian or selective vidian neurectomy combined with functional endoscopic sinus surgery (FESS) is more effective than conventional FESS (RQLQ: SMD = 2.17, 95% CI = 1.66-2.69, p < 0.001; VAS: SMD = 6.42, 95% CI = 4.78-8.06, p < 0.001). For patients who have both AR and asthma, SVN with pharyngeal branch excision is a potential treatment option. CONCLUSION: EVN and vidian-branch neurectomy (including SVN and PNN) are effective treatments, but the former has a higher risk of complications. Additionally, vidian-branch neurectomy with FESS is beneficial for patients with mixed CRSwNP. SVN is a potential approach for patients with coexisting AR and asthma.

Understanding the Relationship Between Facial Nerve Branch Sacrifice and Selective Neurectomy Outcome.

Introduction: While there is great interest in selective neurectomy (SN) for patients with synkinesis, outcomes can be inconsistent. Objective: To examine the relationships between intraoperative facial nerve branch transection and both postoperative outcome and functional deficits. Methods: SN cases, with minimal follow-up of 4 months, were retrospectively identified between 2019 and 2021; outcome was assessed using FaCE instrument, eFACE and Emotrics. Correlations between intraoperative facial nerve branch preservation or transection, and functional outcome and new functional deficits were examined. Results: Fifty-six cases were performed: 88% were females, and median age was 53 years (range 11-81). Mean follow-up was 19.5 months (range 4-42). Oral commissure excursion improved in patients where all smile branches were preserved, no vertical vector smile branches were transected, and more than three smile antagonist branches were transected. A linear trend between smile antagonist branch sacrifice and favorable smile outcome was found. Lower lip movement was improved in patients in whom more than half of the identified lower lip branches were transected. Thirty percent of patients experienced untoward postoperative functional deficits, from which 47% recovered with interventions. Conclusions: Several correlations between SN intra-operative decisions and outcome were identified; new or worsening functional deficit rate can be high. However, chemodenervation or fillers can help diminish these deficits.

Favorable Outcome Perception in Facial Selective Neurectomy.

OBJECTIVE: Facial selective neurectomy (SN) improves facial function by denervation of muscles antagonistic to the smile in nonflaccid facial paralysis (NFFP) patients. This study aims to assess whether and which objective facial function metrics affect favorable SN outcome in NFFP patients, as perceived by facial nerve (FN) practitioners. STUDY DESIGN: Retrospective cohort study. SETTING: NFFP patients who underwent SN at the facial nerve center. METHODS: Standardized preoperative and postoperative facial photographs of patients undergoing SN were analyzed using clinician-graded measures (eFACE) and automated facial measurement (Emotrics). Favorable outcome was ranked subjectively by 3 independent FN practitioners. Correlations between objective metrics and favorable subjective outcome were examined. RESULTS: Fifty-eight SN cases were included. Oral commissure excursion with smile, interlabial distance, and lower lip movement were all considered statistically significantly important for favorable outcome perception. Each +1 mm of smile excursion increases the odds of a favorable outcome by 75.4% (odds ratio [OR]: 1.754). Each +1 mm of interlabial distance asymmetry decreases the odds of a favorable outcome by 24.7% (OR: 0.753). Each +1-point change in lower lip movement eFACE score increases the odds of a favorable outcome by 2.7% (OR: 1.027). CONCLUSION: Several smile metrics contribute to favorable SN outcome perception among FN practitioners. Smile excursion, interlabial distance, and lower lip movement were significant predictors of success. These observations may be extrapolated to other facial reanimation interventions and serve surgeons and patients during counseling and expectation management, and during surgery.

Early in vivo detection of denervation-induced atrophy by luminescence transient nanothermometry.

Denervation induces skeletal muscle atrophy due to the loss of control and feedback with the nervous system. Unfortunately, muscle atrophy only becomes evident days after the denervation event when it could be irreversible. Alternative diagnosis tools for early detection of denervation-induced muscle atrophy are, thus, required. In this work, we demonstrate how the combination of transient thermometry, a technique already used for early diagnosis of tumors, and infrared-emitting nanothermometers makes possible the in vivo detection of the onset of muscle atrophy at short (<1 day) times after a denervation event. The physiological reasons behind these experimental results have been explored by performing three dimensional numerical simulations based on the Pennes' bioheat equation. It is concluded that the alterations in muscle thermal dynamics at the onset of muscle atrophy are consequence of the skin perfusion increment caused by the alteration of peripheral nervous autonomous system. This work demonstrates the potential of infrared luminescence thermometry for early detection of diseases of the nervous system opening the venue toward the development of new diagnosis tools.

Stathmin-2 loss leads to neurofilament-dependent axonal collapse driving motor and sensory denervation.

The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Using a combination of approaches, including transient antisense oligonucleotide-mediated suppression, sustained shRNA-induced depletion in aging mice, and germline deletion, we show that stathmin-2 has an important role in the establishment and maintenance of neurofilament-dependent axoplasmic organization that is critical for preserving the caliber and conduction velocity of myelinated large-diameter axons. Persistent stathmin-2 loss in adult mice results in pathologies found in ALS, including reduced interneurofilament spacing, axonal caliber collapse that drives tearing within outer myelin layers, diminished conduction velocity, progressive motor and sensory deficits, and muscle denervation. These findings reinforce restoration of stathmin-2 as an attractive therapeutic approach for ALS and other TDP-43-dependent neurodegenerative diseases.

Pulsed radiofrequency or surgery for anterior cutaneous nerve entrapment syndrome: Long-term results of a randomized controlled trial.

PURPOSE: Patients with anterior cutaneous nerve entrapment syndrome (ACNES) often require a step-up treatment strategy including abdominal wall injections, pulsed radiofrequency (PRF) or a neurectomy. Long-term success rates of PRF and surgery are largely unknown. The aim of the current study was to report on the long-term efficacy of PRF and neurectomy in ACNES patients who earlier participated in the randomized controlled PULSE trial. METHODS: Patients who completed the PULSE trial were contacted about pain status and additional treatments in the following years. Treatment success was based on numerical rating scale (NRS) following IMMPACT recommendations and Patient Global Impression of Change (PGIC) scores. RESULTS: A total of 44 of the original 60 patients were eligible for analysis (73.3%). Median follow-up was 71.5 months. One patient (4.3%) was still free of pain after a single PRF session, and five additional patients (21.7%) were free of pain by repetitive PRF treatments. By contrast, 13 patients (61.9%) in the neurectomy group were still free of pain without additional treatments. All pain recurrences and therefore primary re-interventions occurred in the first 2 years after the initial treatment. CONCLUSION: Approximately one in five ACNES patients undergoing PRF treatment reports long-term success obviating the need of surgical intervention. Surgery for ACNES is long-term effective in approximately two of three operated patients. Recurrent ACNES beyond 2 years after either intervention is rare.

Dietary leucine supplementation restores T-cell mitochondrial respiration and regulates T-lineage differentiation in denervation-induced sarcopenic mice.

With the aim of offsetting immune dysfunction preceded by sarcopenia, the feasibility and efficiency of nutritional leucine supplementation were evaluated using a murine denervation-induced sarcopenia model. Sciatic nerve axotomy caused significant loss of skeletal muscle of the hind limbs and accelerated mitochondrial stress along with suppressed ATP production in spleen-derived T cells. Dietary leucine intake not only ameliorated muscle mass anabolism in a sarcopenic state, but also restored mitochondrial respiratory function, as indicated by elevated levels of basal respiration, maximal respiration, spare respiratory capacity, and ATP production, in T cells, which in turn led to downregulated expression of mTOR and downstream signals, as indicated by the findings of comprehensive transcriptome analysis. Consequentially, this finally resulted in amelioration of the sarcopenia-induced relative Th1/Th17-dominant proinflammatory microenvironment. These results highlight the importance of leucine-promoted metabolic cues in directing T cell fate in a sarcopenic microenvironment. The present study provides insights that particularly help rationalize the design and optimization of leucine supplementation for chronic sarcopenic patients with autoimmune diseases.

Endovascular Denervation for the Improvement of Limb Ischemia in Patients with Peripheral Artery Disease: A Randomized Clinical Trial.

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.

Development of an acute ovine model of polycystic ovaries to assess the effect of ovarian denervation.

Introduction: Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype. Methods: Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary. Results: Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle. Discussion: Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and survival.