ABSTRACT
In patients with end-stage renal disease (ESRD) undergoing haemodialysis, hypertension is of common detection and frequently inadequately controlled. Multiple pathophysiological mechanisms are involved in the development and progression of the ESRD-related high blood pressure state, which has been implicated in the increased cardiovascular risk reported in this hypertensive clinical phenotype. Renal sympathetic efferent and afferent nerves play a relevant role in the development and progression of elevated blood pressure values in patients with ESRD, often leading to resistant hypertension. Catheter-based bilateral renal nerves ablation has been shown to exert blood pressure lowering effects in resistant hypertensive patients with normal kidney function. Promising data on the procedure in ESRD patients with resistant hypertension have been reported in small scale pilot studies. Denervation of the native non-functioning kidney's neural excitatory influences on central sympathetic drive could reduce the elevated cardiovascular morbidity and mortality seen in ESRD patients. The present review article will focus on the promising results obtained with renal denervation in patients with ESRD, its mechanisms of action and future perspectives in these high risk patients.
Subject(s)
Hypertension , Kidney Failure, Chronic , Humans , Sympathetic Nervous System/surgery , Sympathectomy/adverse effects , Sympathectomy/methods , Kidney , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Hypertension/diagnosis , Hypertension/surgery , Blood Pressure/physiology , Denervation/adverse effectsABSTRACT
BACKGROUND: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials. METHODS: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used. RESULTS: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT (P=0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients (P=0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P=0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P<0.001) and -5.2 mm Hg (-7.1, -3.3; P<0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups. CONCLUSIONS: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260.
Subject(s)
Hypertension , Renal Artery , Female , Humans , Male , Antihypertensive Agents/therapeutic use , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Denervation/adverse effects , Denervation/methods , Hypertension/diagnosis , Hypertension/drug therapy , Kidney , Renal Artery/diagnostic imaging , Sympathectomy/methods , Treatment Outcome , Middle AgedABSTRACT
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.
Subject(s)
Luminescence , Thermometry , Humans , Muscular Atrophy/etiology , Muscular Atrophy/pathology , Thermometry/methods , Denervation/adverse effects , Early DiagnosisABSTRACT
Hypertension remains the leading treatable global cause of mortality due to high incidence and poor control rates despite of safe and effective drug therapy.Animal studies do not support functional nerve regrowth after RF-RDN and accordingly clinical evidence verify that RDN leads to durable BP reduction.Renal denervation is safe, as up to 36 months after the procedure, there are no statistically significant difference in procedure-related adverse events, deterioration of renal function and adverse cardiovascular outcomeRenal denervation is efficient in reducing BP in patients with no drug therapy, independently of the number of antihypertensive drugs and phenotype of patient. This sustained and safe reduction in BP observed up to 36 months after RDN could be associated with lower rates of renal and cardiovascular events.
Subject(s)
Hypertension , Kidney , Humans , Kidney/surgery , Hypertension/surgery , Hypertension/drug therapy , Denervation/adverse effects , Registries , Treatment Outcome , Sympathectomy/adverse effects , Blood Pressure , Antihypertensive Agents/therapeutic useABSTRACT
Early detection of skeletal muscle atrophy is important to prevent further muscle weakness. However, there are few non-invasive biomarkers for skeletal muscle atrophy. Recent studies have reported that the N-terminal fragment (N-titin) of titin, a giant sarcomeric protein, is detected in the urine of patients with muscle damage. In this study, we hypothesized that urinary N-titin would be a potential early biomarker of skeletal muscle atrophy in mice caused by sciatic nerve denervation. Male mice were randomly divided into control and denervation groups, and urinary N-titin levels were assessed daily for 9 days using an enzyme-linked immunosorbent assay system. Despite reduced titin protein levels in atrophic muscles 10 days after denervation, cleaved N-titin fragments were not increased in the urine of mice with denervation-induced muscle atrophy. Furthermore, we found no uptake of Evans blue dye from the extracellular space into the cytoplasm in atrophic muscles, suggesting that the sarcomeric membrane is intact in those muscles. The present results suggest that cleaved N-titin in the urine is not suitable as an early biomarker of skeletal muscle atrophy.
Subject(s)
Muscle Denervation , Muscle, Skeletal , Mice , Male , Animals , Connectin/metabolism , Muscle, Skeletal/metabolism , Muscular Atrophy/pathology , Biomarkers/metabolism , Denervation/adverse effects , Protein Kinases/metabolismABSTRACT
OBJECTIVE: Surgical denervation has been proposed as a treatment for pain in hand osteoarthritis (OA). This review aimed to summarise the available evidence and to propose a research agenda. METHODS: A systematic literature search was performed up to September 2022. Two investigators independently identified studies that reported on denervation for OA of the proximal interphalangeal, distal interphalangeal, metacarpophalangeal or carpometacarpal joints. Quality of studies was assessed and study characteristics, patient characteristics, details of the surgical technique and outcomes of the surgery were extracted. RESULTS: Of 169 references, 17 articles reporting on 384 denervations in 351 patients were selected. Sixteen case series reported positive outcomes with respect to pain, function and patient satisfaction. One non-randomised clinical trial reported no difference in outcome when comparing denervation of the first carpometacarpal (CMC I) joint to trapeziectomy. Adverse events were frequent, with sensory abnormalities occurring the most, followed by the need for revision surgery. All studies had significant risk of bias. CONCLUSION: Surgical denervation for pain in hand OA shows some promise, but the available evidence does not allow any conclusions of efficacy and higher-quality research is needed. Techniques should be harmonised and more data regarding how denervation compares to current usual care, other denervation methods or placebo in terms of outcomes and adverse events are needed.
Subject(s)
Carpometacarpal Joints , Osteoarthritis , Humans , Carpometacarpal Joints/surgery , Denervation/adverse effects , Denervation/methods , Osteoarthritis/complications , Osteoarthritis/surgery , Pain/etiology , Pain/surgery , Patient SatisfactionABSTRACT
Radiofrequency ablation of the medial branch is commonly used to treat chronic low back pain involving facet joints, which accounts for 12% to 37% of the total cases of chronic low back pain. An adverse effect of this procedure is the denervation of the multifidus muscle, which may lead to its atrophy which can affect the spine and possibly disc degeneration. This study aims to quantify changes in joint angles and loading caused by multifidus denervation after radiofrequency ablation. AnyBody model of the torso was used to evaluate intervertebral joints in flexion, lateral bending, and torsion. Force-dependent kinematics was used to calculate joint angles and forces. These dependent variables were investigated in intact multifidus, unilateral, and bilateral ablations of L3L4, L4L5, and L5S1 joints. The results showed pronounced angular joint changes, especially in bilateral ablations in flexion, when compared with other cases. The same changes' trend from intact to unilaterally then bilaterally ablated multifidus occurred in joint angles of lateral bending. Meanwhile, joint forces were not adversely affected. These results suggest that multifidus denervation after radiofrequency ablation affects spinal mechanics. Such changes may be associated with abnormal tissue deformations and stresses that can potentially alter their mechanobiology and homeostasis, thereby possibly affecting the health of the spine.
Subject(s)
Low Back Pain , Radiofrequency Ablation , Zygapophyseal Joint , Humans , Low Back Pain/etiology , Low Back Pain/surgery , Biomechanical Phenomena/physiology , Paraspinal Muscles , Zygapophyseal Joint/surgery , Zygapophyseal Joint/innervation , Zygapophyseal Joint/physiology , Radiofrequency Ablation/adverse effects , Denervation/adverse effects , Denervation/methods , Lumbar Vertebrae/surgery , Lumbar Vertebrae/physiologyABSTRACT
BACKGROUND: There is still controversy surrounding routine ilioinguinal neurectomy in open tension-free inguinal hernia repair. METHOD: PubMed, Cochrane Library and EMBASE databases were searched for randomized controlled trials of ilioinguinal neurectomy in open tension-free inguinal hernia repair. Revman 5.3 software was used for meta-analysis. RESULT: Meta-analysis revealed that the incidence of severe pain on the first postoperative day was lower in the ilioinguinal neurectomy group (ING) than in the ilioinguinal nerve preservation group (INPG) [P < 0.0001]. The incidence of no pain in the first month postoperatively [P = 0.0004], the incidence of no pain in the sixth months postoperatively [P < 0.00001], and the numbness incidence in the first month postoperatively [P = 0.001] in the ING was higher than that in the INPG. There was no significant difference in the incidence of severe pain in the first month postoperatively [P = 0.20], the numbness incidence in the sixth postoperative month [P = 0.05], the hypoesthesia incidence in the first [P = 0.15] and sixth [P = 0.85] postoperative months between the two groups. CONCLUSION: Ilioinguinal neurectomy in open tension-free inguinal hernia repair can better prevent postoperative pain.
Subject(s)
Hernia, Inguinal , Humans , Hernia, Inguinal/surgery , Hernia, Inguinal/complications , Hypesthesia/complications , Hypesthesia/surgery , Randomized Controlled Trials as Topic , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Pain, Postoperative/surgery , Denervation/adverse effects , Surgical Mesh/adverse effects , Herniorrhaphy/adverse effectsABSTRACT
PURPOSE: This study aims to determine the utility of selective partial neurectomy of the musculocutaneous nerve (MCN) in pediatric patients with bilateral spastic elbow. METHODS: A prospective, cross-sectional, case series study was performed in nine pediatric patients (four females and five males) with bilateral spastic elbow, all with a 11.4-year-old average age, where 18 selective partial neurectomies of the MCN were carried out. They were evaluated with goniometry of both spastic elbows at resting position and active amplitude, and staging spasticity employing the Modified Ashworth Scale (MAS) in the preoperative and postoperative period. The results are reported 1 year after surgery. RESULTS: The etiology of the spasticity was secondary to cerebral palsy in eight patients (88.8%) and in one patient (11.11%) secondary to traumatic brain injury. A clinical improvement was observed in goniometry comparing the preoperative and postoperative resting position, a mean preoperative of 44.38 degrees (SD ± 7.61) versus 98.05 degrees (SD ± 24.44), respectively, and preoperative active amplitude a mean of 86.55 degrees (SD ± 15.97) versus the mean postoperative of 47.33 (SD ± 17.86). A relevant decrease on the MAS after surgical intervention was observed, resulting from an average preoperative state according to MAS of 3.78 (SD ± 0.42) to a postoperative state according to MAS of 1.44 (SD ± 0.51), these changes being statistically significant (p ≤ 0.001). No postoperative complications were observed. CONCLUSIONS: Selective partial neurectomy of the MCN has shown good results in patients with bilateral spastic elbow in whom antispastic drugs and physical therapy have failed, and has prove permanent effects.
Subject(s)
Elbow , Musculocutaneous Nerve , Male , Female , Humans , Child , Elbow/surgery , Musculocutaneous Nerve/surgery , Muscle Spasticity/etiology , Muscle Spasticity/surgery , Prospective Studies , Cross-Sectional Studies , Denervation/adverse effectsABSTRACT
INTRODUCTION: Chronic inguinal pain or inguinodynia following hernioplasty is a relatively common complication that can be very incapacitating. Surgical treatment by triple neurectomy is a therapeutic option when previous treatments (oral/local therapy or neuromodulation) have failed. OBJECTIVE: Retrospective description of the surgical technique and results of laparoscopic and robot-assisted triple neurectomy for chronic inguinodynia. MATERIAL AND METHODS: We describe the inclusion/exclusion criteria as well as the surgical technique applied in 7 patients operated on at the University Health Care Complex of León (Urology Department) after failure of other treatment options. RESULTS: The patients presented chronic groin pain, reporting a preoperative pain VAS of 7.43 out of 10. After surgery, this score was reduced to 3.71 on the first postoperative day and to 4.2 points one year after surgery. Hospital discharge occurred 24 h after surgery with no relevant complications being reported. CONCLUSIONS: Laparoscopic or robot-assisted triple neurectomy is a safe, reproducible, and effective technique for the treatment of chronic groin pain refractory to other treatments.
Subject(s)
Hernia, Inguinal , Laparoscopy , Neuralgia , Robotics , Humans , Groin , Retrospective Studies , Hernia, Inguinal/complications , Neuralgia/etiology , Neuralgia/surgery , Pain, Postoperative/therapy , Denervation/adverse effects , Denervation/methods , Laparoscopy/methodsABSTRACT
Renal denervation is not a cure for hypertension. Although more recent sham-controlled trials were positive, a significant minority of patients in each trial were unresponsive. The optimal patient or patients need to be defined. Combined systolic/diastolic hypertension appears more responsive than isolated systolic hypertension. It remains uncertain whether patients with comorbidities associated with higher adrenergic tone should be targeted, including obesity, diabetes, sleep apnea, and chronic kidney disease. No biomarker can adequately predict response. A key to a successful response is the adequacy of denervation, which currently cannot be assessed in real time. It is uncertain what is the optimal denervation methodology: radiofrequency, ultrasound, or ethanol injection. Radiofrequency requires targeting the distal main renal artery plus major branches and accessory arteries. Although denervation appears to be safe, conclusive data on quality of life, improved target organ damage, and reduced cardiovascular events/mortality are required before denervation can be generally recommended.
Subject(s)
Denervation , Hypertension , Kidney , Humans , Hypertension/drug therapy , Kidney/blood supply , Kidney/innervation , Quality of Life , Treatment Outcome , Denervation/adverse effectsABSTRACT
BACKGROUND: Electrical stimulation of the left stellate ganglion (LSG) can evoke ventricular arrhythmias (VAs) that originate from the right ventricular outflow tract (RVOT). The involvement of pulmonary artery innervation is unclear. OBJECTIVES: This study investigated the effects of selective pulmonary artery denervation (PADN) on blood pressure (BP), sympathetic activity, ventricular effective refractory period (ERP), and the incidence of VAs induced by LSG stimulation in canines. METHODS: Radiofrequency ablation with basic anesthetic monitoring was used to induce PADN in canines. In Protocol 1 (n = 11), heart rate variability, serum norepinephrine and angiotensin-II levels, BP changes and ventricular ERP in response to LSG stimulation were measured before and after PADN. In Protocol 2 (n = 8), the incidence of VAs induced by LSG stimulation was calculated before and after PADN in a canine model of complete atrioventricular block. In addition, sympathetic nerves in the excised pulmonary arteries were immunohistochemically stained with tyrosine hydroxylase. RESULTS: The low-frequency components of heart rate variability, serum norepinephrine and angiotensin-II levels were remarkably decreased post-PADN. Systolic BP elevation and RVOT ERP shortening induced by LSG stimulation were mitigated by PADN. The number of RVOT-premature ventricular contractions as well as RVOT tachycardia episodes and duration induced by LSG stimulation were significantly reduced after PADN. In addition, a large number of tyrosine hydroxylase-immunoreactive nerve fibers were located in the anterior wall of the pulmonary artery. CONCLUSIONS: PADN ameliorated RVOT ERP shortening, and RVOT-VAs induced by LSG stimulation by inhibiting cardiac sympathetic nerve activity.
Subject(s)
Pulmonary Artery , Stellate Ganglion , Animals , Dogs , Tyrosine 3-Monooxygenase , Arrhythmias, Cardiac , Norepinephrine , Denervation/adverse effects , AngiotensinsABSTRACT
PURPOSE: Neuropathic pain is a complication after groin hernia surgery. Triple neurectomy of the iliohypogastric nerve, ilioinguinal nerve and genitofemoral nerve is an efficient treatment modality, with several surgical approaches. The minimally invasive endoscopic method to neurectomy was specifically investigated in this meta-analysis. Our aim is to determine the efficacy of this method in the treatment of chronic neuropathic pain posthernia repair surgery. METHODS: A systematic review was conducted using four databases to search for the keywords ("endoscopic retroperitoneal neurectomy" and "laparoscopic retroperitoneal neurectomy"). The NCBI National Library of Medicine, Cochrane Library, MEDLINE Complete and BioMed Central were last searched on 26 May 2022. Randomised control trials and retrospective or prospective papers involving endoscopic retroperitoneal neurectomy operations after inguinal hernia repair were included. All other surgeries, procedures and study designs were excluded. The internal quality of included studies was assessed using the Newcastle-Ottawa Scale. The percentage of patients who had reduction in pain ("positive treatment outcome") was used to assess the procedure's effectiveness in each analysis. RESULTS: Five comparable endoscopic retroperitoneal neurectomy studies with a total of 142 patients were analysed. Both the Wald test (Q (6) = 1.79, = .775) and the probability ratio test (Q (6) = 4.24, = .374) provide similar findings (0.000, 0.0% [0.0%; 78%]). The meta-analysis' key finding is that the intervention was up to 78% effective (95% confidence interval, 71%; 84%). CONCLUSION: Endoscopic retroperitoneal neurectomy can be an effective treatment option for postoperative neuropathic pain relief following surgical hernia repair. Although there is limited reported experience with this technique, it may provide a clinical benefit to the patient. We recommend further prospective data and long-term follow-up studies be conducted to confirm and expand on these outcomes.
Subject(s)
Chronic Pain , Hernia, Inguinal , Laparoscopy , Neuralgia , Humans , Chronic Pain/etiology , Chronic Pain/surgery , Denervation/adverse effects , Hernia, Inguinal/surgery , Hernia, Inguinal/complications , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Laparoscopy/methods , Neuralgia/etiology , Neuralgia/surgery , Pain, Postoperative/etiology , Retrospective StudiesABSTRACT
PURPOSE: Delayed facial palsy (DFP) is a rare postoperative complication after vestibular schwannoma (VS) surgery. The exact mechanism of DFP remains uncertain and the risk factors for DFP are still controversial. The authors aimed to investigate the characteristics, risk factors, and etiology of DFP after VS resection retrospectively. METHODS: Ninety-one consecutive surgeries with VS were analyzed. Patients with neurofibromatosis 2 in eight surgeries and postoperative facial palsy House-Brackmann (HB) grade more than 3 in two surgeries were excluded. Eighty-one surgeries were included in this research. Facial nerve function was evaluated using the HB grade. Delayed facial palsy was defined as deterioration in the facial function of at least 1 HB grade more than 1 day after undergoing VS resection. The characteristics of patients with VS and risk factors for DFP were analyzed. RESULTS: All surgeries were performed via a retrosigmoid approach. DFP was observed in nine patients. There were no statistically significant differences between the DFP group and non-DFP group in terms of the following characteristics: sex, age, side, size, Koos grading system, postoperative facial palsy, or extent of resection. Postoperative hematoma in the cerebellopontine angle (CPA) cistern was significantly higher in the DFP group than in the non-DFP group (p = 0.0023), and was significantly associated with DFP after VS surgery (odds ratio 18.40, p < 0.001). DFP improved in seven patients, but two patients did not improve. CONCLUSION: DFP occurred in 11.1% of patients after VS surgery. This study revealed that postoperative hematoma in the CPA cistern was significantly associated with DFP after VS surgery.
Subject(s)
Facial Paralysis , Neuroma, Acoustic , Humans , Facial Paralysis/epidemiology , Facial Paralysis/etiology , Neuroma, Acoustic/surgery , Neuroma, Acoustic/complications , Facial Nerve , Retrospective Studies , Treatment Outcome , Cohort Studies , Neurosurgical Procedures/adverse effects , Denervation/adverse effects , Disease Progression , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Factors , Hematoma/etiologyABSTRACT
BACKGROUND: Synkinesis is commonly encountered after flaccid facial paralysis and can have a detrimental impact on a patient's life. First-line treatment of synkinesis is chemodenervation with botulinum toxin (Botox) and neuromuscular retraining. Surgical options include selective myectomy, selective neurectomy (SN), cross-facial nerve grafting, nerve substitution, and free gracilis muscle transfer. Data on surgical management of synkinesis using SN is limited. EVIDENCE REVIEW: PubMed, Embase, Cochrane CENTRAL, Cochrane Neuromuscular Register, Clinicaltrials.gov, and World Health Organization International Clinical Trials Registry Platform were searched using a comprehensive keyword strategy in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All English-only texts published in the past 20 years were included. Two independent investigators reviewed 906 abstracts and 7 studies met inclusion criteria. Demographics, etiology of paralysis, time to surgery, and primary outcomes studied were collected. FINDINGS: A total of 250 patients were included across 7 studies. In 6 out of 7 studies, Botox was used prior to surgical intervention. Two studies showed significant reduction in Botox dosage postoperatively, while one study showed no difference. Other primary outcomes included the House-Brackmann Score, palpebral fissure width, electronic clinician-graded facial function scale (eFACE) score, Facial Clinimetric Evaluation (FaCE) scale, and Synkinesis Assessment Questionnaire (SAQ). Three studies showed significant improvement in the eFACE score, two studies showed significant improvement in the FaCE scale, while one study showed improvement in quality of life measured by the SAQ. CONCLUSION: SN can be considered as an adjunct to other management options including neuromuscular retraining, Botox, selective myectomy, and reanimation procedures. While there is great heterogeneity of study design in the studies included, many cohorts showed improvement in facial symmetry, facial function, and quality of life. There remains a great gap in knowledge in this subject matter and a need for large well-designed prospective studies comparing this technique to other management options.
Subject(s)
Botulinum Toxins, Type A , Facial Paralysis , Synkinesis , Humans , Facial Paralysis/surgery , Botulinum Toxins, Type A/therapeutic use , Synkinesis/etiology , Synkinesis/surgery , Prospective Studies , Quality of Life , Denervation/adverse effects , Denervation/methodsABSTRACT
Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in muscle growth is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation of muscle proteostasis. The myostatin (MSTN) pathway, a prominent muscle-specific regulator of proteostasis, is a putative signaling mechanism by which neonatal denervation could impair longitudinal muscle growth, and thus a potential target to prevent NBPI-induced contractures. Through a mouse model of NBPI, our present study revealed that pharmacologic inhibition of MSTN signaling induces hypertrophy, restores longitudinal growth, and prevents contractures in denervated muscles of female but not male mice, despite inducing hypertrophy of normally innervated muscles in both sexes. Additionally, the MSTN-dependent impairment of longitudinal muscle growth after NBPI in female mice is associated with perturbation of 20S proteasome activity, but not through alterations in canonical MSTN signaling pathways. These findings reveal a sex dimorphism in the regulation of neonatal longitudinal muscle growth and contractures, thereby providing insights into contracture pathophysiology, identifying a potential muscle-specific therapeutic target for contracture prevention, and underscoring the importance of sex as a biological variable in the pathophysiology of neuromuscular disorders.
Subject(s)
Contracture , Myostatin , Male , Animals , Female , Mice , Myostatin/genetics , Myostatin/metabolism , Contracture/etiology , Contracture/metabolism , Muscle, Skeletal/metabolism , Denervation/adverse effects , Hypertrophy , Atrophy/pathologyABSTRACT
INTRODUCTION: Total knee arthroplasty is a common operation performed to relieve pain and restore functional activity. While overall widely successful, a subset of patients has continued pain postoperatively with no identifiable cause. Neuroma formation has been identified as a possible contributor to this unexplained pain, often necessitating an additional procedure for neuroma removal. The purpose of our study was to evaluate if prophylactic neurectomy could reduce the occurrence of postoperative pain. METHODS: A total of 112 patients were compared, 44 control patients and 68 neurectomy patients. Demographic information, Numerical rating pain scale (NRS) and Knee Society Scores (KSS) were collected pre- and post-operatively. Patients were additional asked if they were overall satisfied with the operation. RESULTS: There were no differences between groups with respect to age (Median: 71 vs 69 years, p = 0.28), male sex (41% vs 44%, p = 0.85), or body mass index (Median: 32.2 vs 31.3, p = 0.80). When comparing the degree of change following surgery there were no statistically significant differences observed in NRS pain scores (Median change: -7 vs -6, p = 0.89) or KSS scores (Median change: +44 vs +40, p = 0.14). Similarly, there was no statistically significant difference in overall patient-reported satisfaction with the knee replacement (82.5% vs 86.6%, p = 0.59). CONCLUSION: We did not find a statistically significant difference in NRS, KSS, or overall patient satisfaction between the prophylactic neurectomy and control patient groups. Larger studies with evaluation of the nerve diameter will be needed to determine which patients are at risk for symptomatic neuroma development following total knee arthroplasty.
Subject(s)
Arthroplasty, Replacement, Knee , Neuroma , Aged , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Denervation/adverse effects , Humans , Male , Neuroma/complications , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Retrospective StudiesABSTRACT
Compression and irritation at the plantar aspect of the transverse intermetatarsal ligament may lead to a compressive neuropathy called Morton's neuroma. There are many treatment options for Morton's neuroma, with the most common surgical option being traction neurectomy. While there has been success in many surgical procedures, up to 35% of patients treated with traction neurectomy have recurrent pain and up to one-third of these patients have a recurrent stump neuroma. These neuromas are caused by abnormal axonal growth during regeneration, leading to an unorganized mass of fibrotic collagenous tissues, Schwann cells, and axons. More recent surgical treatments of neuromas have included nerve capping, which has been proposed to prevent painful neuroma formation by isolating the nerve end from external chemosignaling and reducing disorganized axonal outgrowth. An off-the-shelf, biocompatible porcine small intestine submucosa (pSIS) derived nerve cap with internal chambering has been investigated in a rodent study, which showed less pain sensitivity and less axonal swirling indicative of reduced likelihood of neuroma formation. Furthermore, a recent clinical study indicated that patients experienced a significant reduction in pain 3 months after Morton's neuroma excision followed by repair using a nerve cap. This article describes the surgical technique of the aforementioned clinical study to mitigate neuroma formation, where a Morton's neuroma is excised, and the remaining proximal nerve stump is inserted within a nerve cap and buried in the surrounding muscle.Level of Evidence: Level V: Expert opinion.