2:00 PM
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ORAL PENTOXIFYLLINE REDUCES ATROGIN-1 AND MURF-1 UPREGULATION IN DENERVATION-INDUCED SKELETAL MUSCLE ATROPHY
Purpose: Denervation induces muscle atrophy by accelerating myofibrillar protein catabolism, via protein degradation pathways such as the ubiquitin-proteasome system, mediated by two E3 ubiquitin ligases: muscle atrophy F-box (MAFbx/atrogin-1) and muscle RING-finger protein-1 (MuRF-1). Both ligases act as early markers, reaching peak expression by day 3 post-injury, coinciding with the period of most rapid muscle loss following denervation. (1) Functional recovery relies on muscle integrity during re-innervation, necessitating increased efforts to minimize the amount of muscle degeneration following denervation. Pentoxifylline (PTX), a methylxanthine derivative that non-selectively inhibits PDE, has been shown to suppress the production of proinflammatory cytokines such as TNF-alpha, which mediate proteasome-dependent muscle catabolism through the transcription factor NF-κB. Although previous studies have demonstrated the ability of methylxanthines to reduce Atrogin-1 and MuRF-1 expression in burn-induced muscle injury, cancer cachexia, and sepsis, there is currently no evidence on the role of PTX in decreasing denervation-induced muscle loss. (2) This study aims to assess whether oral PTX administration can mitigate early-stage denervation-induced muscle atrophy in a rat sciatic nerve denervation model.
Materials and methods: Ten male Lewis rats, aged 8-10 weeks, underwent complete transection of the sciatic nerve. To prevent spontaneous reinnervation of the denervated muscle groups, the proximal end of the divided sciatic nerve was transposed to the anterior thigh and coapted to the distal end of the divided femoral nerve. The rats were then randomly assigned to two groups: one receiving PTX and the other receiving no treatment (n=5 rats/group). PTX was administered at a dose of 100mg/kg via oral gavage once daily for three days. After this period, the lateral gastrocnemius (LG) muscle was harvested and homogenized in a lysate buffer, and the resulting supernatant was utilized for assessing Atrogin-1 and MuRF-1 levels using ELISA. Statistical analysis of results was performed on R version 4.2.3. Group averages, presented as median [IQR], were compared using the Wilcoxon Rank-Sum test.
Results: At three days post-denervation, PTX-treated LG muscle samples exhibited a significant reduction in Atrogin-1 levels (Median PTX: 1.55 pg/1ug protein, IQR: [0.29]; Median No treatment: 2.73 pg/1ug protein, IQR: [1.05], p=0.01), indicating a reduction of approximately 43.1% when compared to the untreated group. PTX-treated LG muscle samples also demonstrated a significant reduction in MuRF-1 levels (Median PTX: 3.91 pg/1ug protein, IQR: [1.09]; Median No treatment: 5.00 pg/1ug protein, IQR: [0.16], p=0.01), indicating a 20.2% decrease compared to the untreated group.
Conclusion: The use of oral PTX shows promise in alleviating initial denervation-induced muscle atrophy. Further research is required to investigate the potential role of PTX in enhancing functional recovery in the context of chronic denervation injury.
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2:05 PM
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The Use of Grayscale Muscle Ultrasound to Indicate Muscle Recovery after Peripheral Nerve Reconstruction
Background and Aim: Currently, few, if any, non-invasive quantitative outcomes measures are clinically utilized to longitudinally evaluate peripheral nerve regeneration after major mixed motor/sensory nerve reconstruction. Neuromuscular disease has been shown to result in atrophy, fibrosis, and fatty infiltration of the muscle, all of which can be visualized on ultrasound as decreased muscle thickness or area, altered muscle texture, and increased muscle echointensity. Changes in echointensity, measured in grayscale value, can be assessed visually and quantified by computer analysis of the echogenicity from the region of interest within the muscle. This study aimed to assess the validity of grayscale muscle ultrasound analysis for the longitudinal evaluation of functional muscle reinnervation in a rabbit peroneal nerve defect model. Additionally, it aimed to evaluate its accuracy by correlating grayscale muscle ultrasound to previously validated functional motor recovery outcomes.
Methods and Materials: Eighteen New Zealand White rabbits underwent a 30-mm peroneal nerve reconstruction with autografts or decellularized allograft. Nerves harvested from Dutch Belted rabbits served as donors. Standardized ultrasound measurements of the bilateral tibialis anterior muscles were performed prior to surgery and at 4, 8, 12, 16, 20 and 24 weeks postoperatively, and included cross-sectional muscle area, mean gray value (MGV), and mean gray value normalized for area (MGVA). The MGV was divided by cross-sectional area to quantify the normalized MGVA, to correct for weight gain of the rabbit during the survival period. At 24 weeks, functional motor recovery was evaluated using isometric tetanic force (ITF) and compound muscle action potential (CMAP). Outcomes were compared between operated (left) and unoperated (right, control) sides within groups and as a ratio (L/R) across groups. MGVA data was compared with ITF and CMAP measurements by calculating the Spearman correlation coefficient.
Results:
The cross-sectional muscle area (L/R) of autografts was superior to allografts at 4, 12, 16, 20 and 24 weeks (p<0.03 for all comparisons). MGVs of the operated side were significantly higher for autografts at 4, 8 and 12 weeks, and for allografts at 12, 16, 20, and 24 weeks (p<0.01 for all comparisons), compared to their unoperated sides (control). Similar patterns were seen in both groups for MGVA (operated versus control side). Comparison of the MGVA L/R ratio between groups reflected faster denervation and reinnervation of autografts, illustrated by a peak at 8 weeks for autografts, with allografts showing a higher peak at 12 weeks. MGVA (L/R) demonstrated a strong correlation with ITF (L/R) for autografts (ρ = -0.7) and allografts (ρ = -0.87), but inconsistent with CMAPs (L/R).
Conclusions:
Quantitative muscle ultrasound, measuring muscle area and echointensity, demonstrated to be a valid, accurate, and non-invasive tool for evaluating motor recovery in a rabbit peroneal nerve reconstruction model. Clinical translation of grayscale ultrasound holds great promise as an outcome measure and provides valuable insights into muscle health and structural changes following nerve reconstruction, aiding early detection of complications, guiding rehabilitation programs, setting realistic patient recovery expectations, and bridging the gap between basic science research and clinical applications.
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2:10 PM
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Do Female and Male Chests Feel the Same? A Comprehensive Quantitative Sensory Analysis
Introduction
There is an increasing interest in chest sensory function in the field of plastic surgery due to a heightened awareness regarding sensory loss following surgery, including breast reconstruction, gender-affirming mastectomy, as well as gynecomastia surgery. While baseline quantitative sensory and pain thresholds have been established in various anatomic areas, there is little knowledge on baseline chest sensation in females and males as well as possible gender differences. Therefore, this study aimed to conduct a comprehensive quantitative sensory analysis to determine if female and male chests feel the same.
Methods
This cross-sectional study evaluated a total of 120 chests in 60 subjects (30 females and 30 males). Quantitative sensory testing (QST) was performed on quadrants of the nipple areola complex (NAC) and surrounding chest skin. QST included mechanical detection using Semmes-Weinstein monofilaments, two-point discrimination, vibration detection, pin prick, cold detection, warm detection and heat pain using a thermal sensory device, and pressure pain detection using an algometer. Sensory testing followed the QST protocol by the German Research Network on Neuropathic Pain (DFNS).
Results
The mean age of the study population was 28.1 years (±4.5) and BMI 26.9 kg/m2 (±5.5 kg/m2). Demographics were similar between females and males (p>0.05). Males were more sensitive than females to mechanical detection at both the NAC (3.34±0.32 versus 3.95±0.46, p<0.0001) and chest (2.91±0.11 versus 3.64±0.54, p<0.0001), vibration detection at the NAC (8.0±0.0 versus 7.48±0.42, p<0.0001) and chest (8.0±0.0 versus 7.08±0.34, p<0.0001), two-point discrimination at the NAC (62% versus 42%, p<0.05) and chest (2.7cm±3.0cm versus 5.5cm±1.3cm cm, p<0.0001) and pin prick at the NAC (8.0±0.0 versus 27.8±21.5, p<0.0001) and chest (8.0±0.0 versus 23.6±17.0, p<0.0001). Males could also feel cold sooner than females at the NAC (27.3°C±1.6°C versus 24.7°C±5.0°C, p<0.001) and chest (26.3°C±1.2°C versus 23.8°C±1.2°C, p<0.001), as well as warmth at the NAC (35.8°C±1.4°C versus 39.6±3.6°C, p<0.0001) and chest (36.6°C±1.2°C versus 38.9°C±3.2°C, p<0.0001). In contrast, heat pain was felt sooner in females as compared to males at both the NAC (43.0°C±3.3°C versus 44.2°C±2.7°C, p<0.05) and chest (43.4°C±2.4°C versus 45.4°C±2.4°C, p<0.001). Pressure pain was also felt sooner in females as compared to males at both the NAC (86.1kPa±73.5kPa versus 217.7kPa±72.1kPa, p<0.0001) and chest (102.6kPa±65.1kPa versus 267.5kPa±89.5kPa, p<0.0001).
Conclusion
The quantitative sensory functions of female and male chests are significantly different. While males were significantly more sensitive to mechanical detection, two-point discrimination, vibration, pin prick and temperature detection, females had significantly lower sensory thresholds to heat and pressure pain detection. This knowledge helps to better understand baseline sensory functions at the chest and the presence of gender differences in this anatomic area.
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2:15 PM
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Fat versus Muscle Flap-Comparison of techniques to protect the Greater Occipital Nerve after decompression
Background: Traditionally, Greater Occipital Nerve (GON) neurolysis is followed by elevation of a subcutaneous fat flap that is wrapped around the nerve for cushioning and protection from scar tissue that will form after surgery. However, this technique places the nerve in a more superficial and exposed position, and allows for potential interaction of axons with the dermis. More recently, techniques to bury the nerve under trapezius and semispinalis muscle have been employed in order to position and cushion the nerve deep in the soft tissues. In this article, both techniques are discussed and postoperative results are analyzed and compared.
Methods: We retrospectively identified patients that underwent screening for occipital nerve decompression surgery between 2010 and 2023 at three centers. All adult patients that had primary GON decompression surgery were included. Pain frequency (pain days per month), -intensity (scale of 0-10) and duration (in hours) was collected preoperatively and at 3 months and 12 months follow-up in a prospective fashion. Manual chart review was performed to collect data regarding type of flap used, complications and reoperations. Patients who underwent GON decompression followed by fat flap were compared to those who underwent decompression followed by muscle flap.
Results: Among the patients who were screened (n=1713), 317 (19%) patients underwent GON decompression surgery. The procedure was performed using a fat flap in 203 (64%) patients and using a muscle flap in 114 (36%) patients. The mean follow-up was 9 (±4.1) months. When comparing postoperative pain characteristics between the fat and the muscle flap group after the last intervention, the median pain days per month decreased by 15 (0-27) versus 16 (8-25) days (p=0.191), the median pain duration was reduced by 10 (0-24) versus 12 (3-22) hours (p=0.225) and the mean pain intensity decreased by 4 (±4) versus 5 (±2) points (p=0.419), respectively. The reoperation rate was significantly higher in the fat flap group as compared to the muscle flap group (n=24, 12% vs n=5, 4.4%, p=0.045). The reasons for reoperation included recurrent pain (n=17, 71% fat flap; n=3, 60% muscle flap) and persistent pain (n=7, 29% fat flap; n=2, 40% muscle flap). Postoperative complications were similar between groups and included wound infections (2.2%), seroma (1.6%) and wound dehiscence (1.0%) (p=0.674).
Conclusion
In comparing fat flap versus muscle flap techniques for GON decompression, both methods effectively reduced pain with no significant difference in pain characteristics. However, the muscle flap approach resulted in a lower reoperation rate, suggesting this option may provide better long-term pain relief.
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2:20 PM
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Predictive Value of Pre-operative Pain Sketches in Lower Extremity Amputees Undergoing Secondary Targeted Muscle Reinnervation for Treatment of Neuropathic Pain
Introduction: Targeted Muscle Reinnervation (TMR) is an effective surgical treatment for neuropathic pain in amputees. (1) Qualitative descriptions of pain could enhance the understanding of symptomatic improvement following surgery. (2) Pain sketches can be used to depict this, and have been used in various neuropathic pain conditions, including amputees who underwent prophylactic TMR at time of amputation. (3-4) Our aim is to assess whether pre-operative pain sketches, drawn by lower extremity (LE) amputees, can predict surgical outcomes following Secondary TMR surgery in amputees with preexisting neuropathic pain.
Methods: Eligible patients were LE amputees who underwent Secondary TMR surgery between 2017 and 2023. Pain sketches and pain scores were prospectively collected both before and after surgery. Pain progression, as categorized by pre-operative pain sketches, was analyzed and assessed for improvement, defined as reaching the Minimal Clinically Important Difference (MCID). (5) The transition to different pain sketches and the occurrence of phantom drawings were evaluated for their association with improvement.
Results: Fifty-eight patients were included, of which 18 (31.1%) depicted diffuse pain (DP), 26 (44.8%) depicted focal pain (FP) and 18 (24.1%) depicted radiating pain (RP) in their pre-operative sketch. FP sketches were associated with the lowest pre- (p=0.002) and post-operative (p=0.045) pain scores and most frequently progressed to sketches indicating "no pain" (p=0.007). RP sketches were associated with the least pain improvement, the lowest likelihood of achieving the MCID, and were more prevalent in patients with diabetes or depression (p<0.050). RP sketches were associated with phantom drawings (p<0.001); no other sketch types progressed into RP sketches at the final follow-up.
Summary:
- In LE amputees who underwent Secondary TMR, pre-operative pain sketches may predict pain progression.
- FP sketches were associated with the most improvement. These may specifically reflect pain related to symptomatic neuromas, which could be more responsive to surgical intervention than pain that is more diffuse or even centralized.
- RP sketches were associated with worse outcomes, which may indicate the activation of different central neuronal pathways, distinct from those involved in neuroma pain or phantom limb pain alone.
References
1. Mioton LM, Dumanian GA, Shah N, et al. Targeted Muscle Reinnervation Improves Residual Limb Pain, Phantom Limb Pain, and Limb Function: A Prospective Study of 33 Major Limb Amputees. Clin Orthop Relat Res. 2020;478(9):2161-2167.
2. Hill EJR, Patterson JMM, Yee A, Crock LW, Mackinnon SE. What is Operative? Conceptualizing Neuralgia: Neuroma, Compression Neuropathy, Painful Hyperalgesia, and Phantom Nerve Pain. J Hand Surg Glob Online. 2023;5(1):126-132.
3. Gfrerer L, Hansdorfer MA, Ortiz R, et al. Patient Pain Sketches Can Predict Surgical Outcomes in Trigger-Site Deactivation Surgery for Headaches. Plast Reconstr Surg. 2020;146(4):863-871
4. Gomez-Eslava B, Raasveld F V, Hoftiezer YA, et al. Pain Sketches Demonstrate Patterns of Pain Distribution and Pain Progression following Primary Targeted Muscle Reinnervation in Amputees. Plast Reconstr Surg. Published online May 26, 2023:online ahead of print.
5. Farrar JT, Young JP, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149-158.
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2:25 PM
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Rapid, Detergent-Free Method for Creation of Acellular Nerve Allografts
Introduction: Peripheral nerve injury remains an unsolved clinical challenge, with sensorimotor recovery especially poor for larger nerve gaps. To this date, autologous grafts (autografts) remain the gold standard for repairing transected nerves. Nerve allografts avoid several complications of autografts and have now been successfully applied in several clinical scenarios with promising efficacy. Despite this progress, there remains the potential for improvement. A potential shortcoming of several allograft protocols is the use of detergents, which ensure comprehensive breakdown and removal of cellular material, but also require long treatment times to remove residue and may destabilize graft durability. Detergent-free methods, on the other hand, may result in insufficient removal of cellular material, raising the likelihood of rejection by the host as well as physical and biological barriers to the pathfinding of regenerating axons.
Materials and Methods: We developed a new detergent-free approach for creating nerve allografts that avoids the above limitations. Rat sciatic nerves were subject to sequential cycles of sodium hydroxide treatment to disrupt cells and membranes; nucleases to destabilize nucleic acids; and agitation to clear debris. Preparation of acellular grafts was complete in less than 24 hours. Grafts were characterized using immunohistochemical approaches to evaluate clearance of cellular material and structural integrity; spectrophotometric methods to evaluate clearance of nucleic acids; and Schwann cell implantation into the graft to evaluate biocompatibility.
Results: Trichrome labeling and anti-laminin immunolabeling demonstrated preserved extracellular matrix and basal lamina structure. Spectrophotometry demonstrated nucleic acid reduction of over 90% compared to untreated controls. Schwann cells transfected with green fluorescent protein (GFP) were injected into the acellular grafts ex vivo, and repopulated the scaffold, demonstrating cyto-compatibility of the graft. Outcomes were superior or comparable to other published allograft fabrication approaches.
Conclusions: Our findings demonstrate the feasibility of generating biocompatible, detergent-free nerve allografts, with comparable cellular and nucleic acid clearance to other preparation methods as well as retained structural stability. Future directions will evaluate the use of these grafts in pre-clinical regenerative applications.
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2:30 PM
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Scientific Abstract Presentations: Migraine Session 2 - Discussion 1
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2:40 PM
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Treatment Strategy for Oral-Ocular Synkinesis after Facial Palsy: A Clinical Stratification using Palpebral Fissure Ratio
Abstract
Introduction: Oral-ocular synkinesis, a sequela following facial nerve palsy, significantly compromises the patients' quality of life.
Methods: This retrospective analysis considered 10 cases of oral-ocular synkinesis between April 2022 and March 2024. We favored hypoglossal-facial nerve side-to-side neurorrhaphy (cross-link) for cases with synkinesis and persistent incomplete paralysis within one year of onset [1]. For cases occurring one year or later from the onset, 10-15 units of botulinum toxin (BTX) were subcutaneously administrated into the affected orbicularis oculi muscle every three months, aiming at synkinesis alleviation. This BTX treatment was combined with mirror biofeedback (MBF) therapy (BTX+MBF) [2]. Persistent synkinesis cases underwent selective orbicularis oculi myo-neurectomy [3]. Synkinesis severity was classified into four categories based on the palpebral fissure ratio (PFR, %) at rest (rPFR) and during oral movement (mPFR). We analyzed the average PFR and patient-reported numerical rating scale (NRS) scores before and after treatment.
Results: Type I (blepharospasm): rPFR 100% and mPFR 100%. BTX administration alleviated muscle spasm, improving NRS score from 10 to 6 in one patient. Type II (moderate): rPFR 80-99% and mPFR 20-99%. BTX improved rPFR from 93.1% to 100.0%, mPFR from 69.5% to 100.7%, and NRS from 10 to 8.1 in five patients, including one who underwent cross-link surgery. Type III (severe): rPFR 0-79%, or mPFR 0-19%. BTX improved rPFR from 66.4% to 78.8%, mPFR from 19.8% to 69.3%, and NRS from 10 to 6.5 in two patients, with one cross-link surgery. Selective orbicularis oculi myo-neurectomy in another patient resulted in significant improvement. Type IV (fluctuating type): PFR fluctuates. BTX did not significantly improve this type; rPFR from 96.7% to 80.5%, mPFR from 75.1% to 52.3%, and NRS from 10 to 9.5 in two patients.
Discussion: Type I, II, and III responded to BTX administration. Type I showed alleviation of muscle spasm. Type II normalized completely, while type III required surgical intervention. Type IV (BTX non-responders) were indicated for supportive therapy rather than surgery.
Conclusion: Stratifying synkinesis severity using PFR proved valuable for determining treatment strategies and predicting outcomes.
References
[1] Yamamoto Y, et al. Surgical rehabilitation of reversible facial palsy: facial--hypoglossal network system based on neural signal augmentation/neural supercharge concept. J Plast Reconstr Aesthet Surg. 2007;60(3):223-31.
[2] Azuma T, et al. Mirror biofeedback rehabilitation after administration of single-dose botulinum toxin for treatment of facial synkinesis. Otolaryngol Head Neck Surg. 2012 Jan;146(1):40-5.
[3] Yoshioka N, et al. Selective orbicularis neuromyectomy for postparetic periocular synkinesis. J Plast Reconstr Aesthet Surg. 2015 Nov;68(11):1510-5.
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2:45 PM
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Neuroma to Nerve Ratio: Does Size Matter?
Introduction: Anatomic and morphological features of neuromas have been explored in imaging studies (1-2). However, there has been limited research into these features using ex-vivo, excised human neuroma specimens. Moreover, knowledge on how neuromas evolve over time and whether their size correlates with pain remains limited. Therefore, in this study, we aim to investigate the influence of time on neuroma growth and size and the clinical significance of neuroma their interactions.
Methods: Patients undergoing neuroma excision were prospectively included between January 2022 through September 2023. Neuroma specimens were obtained intra-operatively and standardized measurements of dimensions, expressed as the neuroma-nerve-ratio (NNR), were conducted with image analysis software ImageJ. Pain data (Numeric rating scale, 0-10) was prospectively collected during pre-operative evaluation, and patient factors were collected from chart review.
Additionally, we conducted preliminary experimental axonal staining of two neuroma specimens.
Results: Fifty terminal neuroma specimens from 31 patients were included in this study. Amputees compromised 92.3% of the population, of which 3 were upper (10.7%) and 25 were lower extremity (89.3%) amputees. The median neuroma diameter was 9.90mm (IQR 6.87-14.23mm) with a median proximal normal native nerve diameter of 3.68mm (IQR 2.11-7.61mm), resulting in a median NNR of 2.45 (IQR 1.68-3.11mm). The median time form injury until neuroma excision was 7.01 years (range 0.32 – 40.4 years). NNR was not associated with preoperative pain (p=0.079) or with nerve distribution (p=0.305). Time from injury to neuroma excision was significantly associated with a larger NNR (p=0.002), and with a smaller proximal nerve width (p=0.003). A smaller proximal nerve diameter was also associated with a larger NNR (p<0.001), Also, sensory nerves were associated with a larger NNR, compared to mixed nerves (Fig. 4). The preliminary experimental axonal staining of two neuroma specimens demonstrated that the composition of a neuroma of a sensory nerve (i.e. sural nerve) mainly consists of diffuse and disorganized sensory axons (neurofilament-positive), while a mixed nerve neuroma (i.e. sciatic) demonstrates disorganized sensory as well as motor axons (neurofilament and ChAT-positive).
Summary:
- In this study we observed that neuroma size, expressed as NNR, does not correlate with pain severity.
- NNR and the diameter of the proximal nerve demonstrated a negative correlation, indicating that larger nerve diameters tend to result in relatively smaller neuromas.
- The time-to-neuroma-excision was significantly associated with larger NNR, suggesting continued growth and development of neuromas over time.
- Preliminary axonal staining data suggests that motor axons constitute a significant portion of the volume of the neuromas of mixed nerves. Yet, regeneration and reinnervation following nerve injury occur in both efferent motor and afferent sensory axons.
- These findings may assist surgeons and researchers in better understanding of symptomatic neuroma development.
References:
1. Hwang CD, Hoftiezer YAJ, Raasveld FV et al. Biology and Pathophysiology of Symptomatic Neuromas. Pain. Published online 2023. doi:PAIN-D-22-01167R1
2. Chung BM, Lee GY, Kim WT, Kim I, Lee Y, Park S Bin. MRI features of symptomatic amputation neuromas. Eur Radiol. 2021;31(10):7684-7695. doi:10.1007/S00330-021-07954-2
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2:50 PM
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Peripheral Nerve Injury After Deoxycholic Acid (Kybella) Injection
PURPOSE:
Deoxycholic acid (Kybella) is a drug commonly injected in non-surgical aesthetic procedures to locally reduce subcutaneous fat. Kybella treatment has been reported to have adverse effects, one of which can cause marginal mandibular nerve injury with noticeable functional deficits when injected to target submental fat. As an adipocytolytic agent, Kybella may damage the lipid-rich myelin surrounding peripheral nerves. Given that limited basic science studies investigating this agent have been performed to date, this study seeks to characterize the nerve injury associated with Kybella.
METHODS:
Using a sciatic nerve injection model in rats, intrafascicular and extrafascicular injections of deoxycholic acid (Kybella) were compared to intrafascicular lidocaine (positive control) and intrafascicular saline (negative control) injections. All agents were administered in a 50 µL volume to the sciatic nerve proximal to its trifurcation. Injection sites were delineated with 10-0 nylon suture 1mm proximal and distal to the injection. Nerves were harvested at a 2-week endpoint for histomorphometric analysis and electron microscopy.
RESULTS:
Intrafascicular saline injection caused minimal injury to sciatic nerve. Comparing the area of healthy nerve with injured nerve fibers marked by scarring and fibrosis, the percent area of injured sciatic nerve was 78% in the intrafascicular Kybella group, 49% in the extrafascicular Kybella group, and 40% for the intrafascicular lidocaine group. There was a significant difference between the intrafascicular lidocaine and Kybella groups (p=0.003), as well as the intrafascicular and extrafascicular Kybella groups (p=0.045). The g-ratio assessing axonal myelination was not significantly different between the lidocaine (0.58), Kybella (0.58 and 0.56), and saline (0.56) injection groups.
CONCLUSION:
Initial results suggest deoxycholic acid (Kybella) is capable of extensive nerve injury. Although Kybella is a known adipocytolytic agent, its mechanism of damage does not seem to involve myelin. Physicians administering Kybella for non-surgical aesthetic treatment of excess fat should counsel patients appropriately based on these findings. Appropriate knowledge of surgical anatomy is recommended for those practitioners providing Kybella injections.
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2:55 PM
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Migraine Surgery: Is It A Headache to Fund?
Purpose
Migraine surgery has become a life-altering solution for patients who have struggled with migraines for years, sometimes decades. As life changing as the surgery can be, many insurances still consider surgery to be investigational and therefore do not provide coverage. Patients are then forced to seek other means to solve their financial dilemma. The objective of our study was to describe the prevalence of GoFundMe (GFM) campaigns as a way to gauge the financial burden faced by the patients undergoing migraine surgery.
Methods
On 18 December 2023, GoFundMe.com was queried for migraine surgery. Any campaigns in the U.S. fundraising for migraine surgery or related expenses were included. Campaigns that were duplicates, for charities or other surgeries were excluded. The primary outcome was campaigns' percentage of its goal met. Descriptive statistics were performed, and multivariate linear regression was used, adjusting for sex and race; significance was set at p<0.05.
Results
Overall, 998 campaigns were screened. Of the 43 campaigns included for analysis, patients were most commonly white (90.7%), female (83.7%), resided in the South (39.5%), and had surgeon out-of-network or no coverage (53.5%). Campaigns raised a median of $4,126 (IQR: 1,640-8,129), requested a median of $15,000 (IQR: 8,500-20,000), and met campaign goal by a median of 29.3% (IQR: 13-72). The majority of campaigns had a photo with the patient smiling (79.1%), and the most common ancillary expenses were lodging (30.2%) and pre/post operative appointments (30.2%). There were no differences observed in percentage of campaign goal met when analyzed by sex, race, transportation expenses, and patient smiling in campaign photo.
Conclusions
Our study showed that while migraine surgery is rising in popularity, patients are not using crowdfunding to fund this surgery that is usually not covered by insurance. In those that do utilize this resource, most of them are not able to raise enough to cover their surgeries, leaving patients stranded to figure out the surgery expenses on their own. Our study illuminates this problem so that plastic surgeons treating these patients are aware of the surgery's financial burden and can properly counsel their patients on potential financial resources. Furthermore, compared to other crowdfunding studies, our study showed a relatively lower fundraising success rate, mirroring the fact that migraine surgery itself has not been fully accepted in the medical field. Since only few centers are currently offering this life-changing surgery, our study supports the notion that patients must foot a high bill for travel expenses surrounding this surgery.
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3:00 PM
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Examining Socioeconomic Disparities in Brachial Plexus Birth Injuries: A Multicenter Public Health Analysis
Purpose:
The primary objective of this investigation is to analyze and compare the socioeconomic characteristics of infants diagnosed with brachial plexus birth injuries (BPBI) at two high-volume, distinct healthcare systems in the United States.
Methods:
All BPBI cases initially diagnosed between November 2021 and November 2023 at either institution, New York ("NY") or Los Angeles ("LA"), were included in the analysis. To stratify patients based on socioeconomic background, the Child Opportunity Index (COI) was utilized. COI scores and quintiles were assigned based on nationally normed ZIP code-level data, with a lower COI score signifying a lower childhood opportunity. For analysis, continuous variables underwent two-tailed, unpaired t-tests, while categorical variables were assessed using chi-squares. The significance level was set at p < 0.05.
Results:
When comparing the LA (n = 117) and NY (n = 107) cohorts, the overall COI of LA and NY averaged 37.1 (SD 27.3) and 17.3 (25.6), respectively (p <0.05). Similarly, when comparing the average child opportunity scores in the health and environment domain (31.5 SD 22.7 and 63.8 SD 12.5), social and economic domain (37.2 SD 26.5 and 14.7 SD 25.1), and education domain (41.3 SD 29.5 and 24.4 SD 27.3) when nationally-normed, there was a statistically significant difference between the mean scores of LA and NY, respectively. While there was a significantly higher number of patients from NY than LA falling into the categories of very low or low in the education domain, social and economic domain, and overall COI when normalized nationally or at the state level, the distributions of these categories in the LA cohort were more evenly spread across the cohort.
Conclusions:
Our findings challenge the previously held notion that BPBI infants primarily originate from lower socioeconomic backgrounds: at one location (LA), the child opportunity scores of BPBI infants were distributed among the COI quintiles.
While this study does not explain these trends, the results suggest the need to reconsider how we describe the associations with BPBIs.
This reevaluation may contribute to dispelling the theory that such injuries are confined to a specific socioeconomic group and our findings support the need for a widespread, multicenter national examination of BPBI socioeconomic factors.
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3:05 PM
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Molecular Alterations in Nociceptive and Mechanosensitive Traits of the Trapezius Fascia in Occipital Neuralgia Patients
Introduction
Headache surgery has now been well-established as a viable option for those suffering from chronic head pain or occipital neuralgia refractory to conventional treatment modalities. The surgery involves decompression or neurectomy of the affected nerves, namely the major or minor occipital nerves. While occipital neuralgia surgery shows promising reduction in painful perception, the causal neurobiological mechanisms of occipital neuralgia or potential nerve compression remain scarcely explored. In this study, we analyzed fascial tissue in patients undergoing neurolysis or neurectomy of the major or minor occipital nerves using specific molecular markers for nociception or mechanosensitive perception.
Methods
Eleven patients (mean age 43; 54% female) with occipital neuralgia were enrolled in the study. Tissue samples (major and minor occipital nerves, trapezius fascia, and periosteum) were harvested during decompression and neurectomy procedures. Additionally, uninjured trapezius fascia samples from patients with no history of chronic headaches (n=5) undergoing spinal closure procedures were harvested as a control. The specimens were processed for multicolor immunofluorescence staining using specific molecular markers (neurofilament, PGP9.5, TRPV1, CGRP, Piezo2, and S100). The images were acquired using a confocal microscope, and z-stacked images were compiled for 3D reconstruction. The neural and nociceptive entities within the fascia were analyzed using ImageJ.
Results
The major (n=4) and minor (n=7) occipital nerves across all patients showed signs of nerve compression based on the axonal architecture. Fascia tissue specimens demonstrated a vast neural network encompassing axons of different calibers (0.2-3 μm). Additionally, the fascia of headache patients showed high CGRP expression levels within the neural components compared to the control samples, indicating an adrenergic nociceptive nature of these axonal populations (Figure 1). Moreover, specific fluorescence staining of consecutive slices of the fascia samples (n=3) revealed mechanosensitive entities resembling Meissner corpuscles across the fascia samples.
Conclusion
The findings of this study suggest that pathological fascia tissue contributes to the nociceptive perception in occipital neuralgia patients. Moreover, the nociceptive and mechanosensitive neural network within the fascia tissue may shed light on the intrinsic neurobiological pathomechanism responsible for occipital neuralgia.
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3:10 PM
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Unveiling the Diagnostic Potential of MRI Neurography in Diverse Peripheral Nerve Disorders
Introduction
Peripheral nerve compression disorders can pose diagnostic challenges when standard diagnostic modalities fail to show an abnormal finding, despite the patient having clinically relevant symptoms on exam. This can make it difficult to determine when to refer the patient for surgery or committing to surgical intervention. This study explores MRI Neurography's diagnostic utility in various disorders.
Purpose:
Our aim is to demonstrate the effectiveness of MRIN in guiding surgical decisions, particularly when integrated into an algorithmic approach.
Methods:
We retrospectively analyzed patients (n=56) with neurogenic thoracic outlet syndrome (nTOS) (7), piriformis syndrome (17), meralgia paresthetica (13), occipital nerve compression (9), and chronic inguinal pain (10) from January 2021 to December 2022 who underwent MRIN as component of the diagnostic work-up to help guide surgical interventions based on the findings. High-resolution imaging identified nerve compression and anatomical abnormalities. Outcomes were assessed for symptomatic relief and surgical success.
Results:
In the cases of nTOS (n=7), EMG was normal/inconclusive in all, MRIN located compressive structures allowing for accurate diagnosis and brachial plexus decompression and/or neurolysis +/- first rib resection, scalenectomy, pectoralis minor release, targeted muscle reinnervation, relieving all patients of their symptoms. MRIN was positive for sciatic nerve impingement indicating piriformis syndrome in 15 cases. Piriformis tendon release, and neurolysis of gluteal and sciatic nerve led to pain resolution/improvement (83%). In meralgia paresthetica (n=13), MRIN positive for compression of the lateral cutaneous femoral nerve (n=7), 6 had symptoms resolution, 1 patient with a history of complex regional pain syndrome had persistent pain but still reported symptom improvement. One case of migraine where MRIN showed occipital nerve compression was treated with neuroma excision, neurolysis and TMR of left GON/LON/cervical nerve. MRIN done in 9 cases of chronic inguinal pain, revealed neuromas in inguinal nerves, and treatment with triple denervation surgery resulted in 7.5 points mean difference decrease in postoperative mean VAS score.
Conclusion:
MRIN is a powerful tool that is underused by physicians and can help confirm peripheral nerve compression disorders and surgical planning by visualizing nerves and identifying compression, enhancing outcomes.
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3:15 PM
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Scientific Abstract Presentations: Migraine Session 2 - Discussion 2
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