Scientific Abstract Presentations: Migraine - Peripheral Nerve Session 1 Friday, September 27 Fri, Sep 27 2:00-3:30 p.m. PDT

Introduction: Surgical treatment of occipital headaches involves the decompression of peripheral occipital nerves. While the literature extensively describes the longitudinal midline incision approach, our group employs the transverse approach. (1-4) The aesthetic outcomes of both incision techniques remain unexplored.

Methods: Patients undergoing surgical decompression for occipital headaches were instructed to provide images of their exposed occipital scalp scar. Evaluation was conducted using the Stony Brook Scar Evaluation Scale (SBSES) and the Scar Cosmesis Assessment and Rating (SCAR) scale by three independent plastic surgeons. SBSES scores range from 0-5 (higher indicating better outcomes), while SCAR scores range from 0-15 (higher indicating worse outcomes). Comparisons were made between transverse and longitudinal scars, with factors influencing scores identified.

Results: Forty patients (average age: 47; 73% female) participated, with 28% having longitudinal midline scars and 72% having transverse scars. Patients with transverse scars exhibited higher SBSES scores (4.2 vs. 3.6; p=0.044) and lower SCAR scores (3.0 vs. 4.6; p=0.016). Longitudinal scar patients displayed more suture marks (SBSES: p=0.018; SCAR p= 0.003) and wider scar spread (SBSES: p= 0.013; SCAR: p= 0.038) compared to transverse scar patients. On regression analysis, higher BMI was associated with worse SCAR scores (p=0.015) and nearing significance in SBSES scores (p=0.057).

Conclusion: Our study reveals superior aesthetic outcomes with the transverse incision approach for occipital nerve decompression surgery compared to the longitudinal midline technique. Transverse scars exhibited higher SBSES scores and lower SCAR scores, indicating better cosmesis. Notably, longitudinal scars were associated with more prominent suture marks and wider scar spread.

1.Gfrerer, L., W.G. Austen, Jr., and J.E. Janis, Migraine Surgery. Plast Reconstr Surg Glob Open, 2019. 7(7): p. e2291. 2.Lee, M., et al., The role of the third occipital nerve in surgical treatment of occipital migraine headaches. J Plast Reconstr Aesthet Surg, 2013. 66(10): p. 1335-9. 3. Ducic, I., E.C. Hartmann, and E.E. Larson, Indications and outcomes for surgical treatment of patients with chronic migraine headaches caused by occipital neuralgia. Plast Reconstr Surg, 2009. 123(5): p. 1453-1461. 4. Afifi, A.M., et al., Alternative Approach for Occipital Headache Surgery: The Use of a Transverse Incision and "W" Flaps. Plast Reconstr Surg Glob Open, 2019. 7(4): p. e2176.

Background: Even though surgical treatment for headaches and migraines has proven to be a safe and effective therapy, headache surgery remains a controversial topic. The debate regarding the effectiveness of headache surgery is partly fueled by the fact that the ideal candidate for successful headache surgery is not entirely elucidated. The objective of this study was to assess the diagnosis and referral trends of headache surgery patients to attempt to characterize the ideal surgical candidate.

Methods: We retrospectively analyzed patients who underwent headache surgery between August 1, 2012 and May 17, 2017. Patients were administered three questionnaires pre- and post-operatively: the Headache Impact Test, the Migraine Disability Assessment Test, and the Migraine-Specific Quality-of-Life Questionnaire. Improvement in at least two of three of these questionnaires was considered a successful outcome. Diagnoses were collected as they were described in patients' charts. Referral sources were also collected. Patients were assigned into one of two cohorts based on if their surgery improved their symptoms or not. Univariate analysis was conducted for categorical variables using the Chi-square test of independence.

Results: Forty-one patients were eligible for analysis. Thirty-two (78.0%) patients reported successful outcomes at a mean postoperative follow-up time of 8.0 months (range, 6.0 to 15.0 months). Both successful and unsuccessful patient cohorts had a median number of two descriptive diagnoses. A diagnosis of "migraine" was the most frequent diagnosis for improved patients (n=9). "Chronic migraine" and "Chronic migraine without aura" were the most frequent diagnoses for patients without improvement (n=3, each). Most patients were referred to plastic surgery by a neurologist (n=20, 48.8%) however this was closely followed by self-referrals (n=15, 36.6%). There were no significant differences in the frequency of a descriptive diagnosis or referral source between both cohorts.

Conclusions: Our results suggest there are no significant differences regarding number of diagnoses, type of diagnoses, or referral source between successful and unsuccessful headache surgery patients, unfortunately providing no further clarity in identifying successful headache surgery candidates. However, our study demonstrates the importance of accessibility of headache surgery. Interestingly, while many patients were referred by neurologists, a considerable number of patients were self-referred. As a result, plastic surgeons should be aware of this as they organize their headache surgery practices. Evaluating patients only after a referral from a neurologist may pose as an unnecessary barrier to treating patients who suffer from what is often a debilitating condition. Future research with respect to access to headache surgery would be beneficial for increasing delivery of care to patients and collaboration with neurology and primary care colleagues.

Introduction: Surgical approaches to peripheral nerve defects have been the subject of significant research in recent years. A direct result of this trend is rapidly increasing rates of acellular nerve allograft use despite limited high-quality, comparative evidence of efficacy.1,2 Simultaneously, non-research payments to clinicians by the nerve allograft industry exceeds $10,000,000 over the last decade. In this study, the authors hypothesized that nerve allograft-related academic influence would correlate with industry funding.

Methods: PubMed studies and citations on nerve allografts in fourteen high impact plastic and reconstructive surgery journals were reviewed. An adjacency matrix containing all authors was used to generate a co-authorship network, and degree centrality - a quantitative measure of influence within a network - was calculated for each one.3 Using national provider identifier (NPI) numbers, Open Payments (OP) data on non-research associated funding from 2013-2022 for all authors was summated. Finally, Spearman's rank correlation and simple linear regression were used to analyze the relationship between centrality and payments received.

Results: 185 studies were included, with 581 unique authors (nodes) and 2,406 co-authorships (ties) between them. Mean centrality for all authors was 8.3 (SD = 7.8). Among authors with exceptional network influence (centrality > 10, 75th percentile; n = 113), 56 were clinicians with valid NPIs and therefore eligible for inclusion in the OP database. 44 (79%) of these authors received at least one payment from the nerve allograft industry. A total of $2,360,653 was distributed to these authors, 83% of which ($1,952,496) went to the top 25 of them. Spearman's rank correlation revealed a moderate (0.4 < ρ < 0.6) positive correlation between centrality and payments received (ρ = 0.52, p < 0.001). Simple linear regression demonstrated an estimated 18% increase in total pay per additional unit of centrality (p < 0.001; 95% CI 8%, 25%).

Conclusions: This research underscores a significant connection between academic influence and financial support from the nerve allograft industry. Such results warrant discussion concerning conflicts of interest in clinical research and best practices for mitigating potential bias related to commercially backed medical products. However, it remains unclear if academic influence is a target of industry, or if industry support sustains academic success.

References 1. Safa, Bauback MD; Momeni, Arash MD. "Reconsidering the Standard of Care for Peripheral Nerve Reconstruction." Plastic & Reconstructive Surgery-Global Open. 2023;11(11):e5320. doi:10.1097/GOX.0000000000005320 2. Frostadottir D, Chemnitz A, Johansson Ot LJ, Holst J, Dahlin LB. "Evaluation of Processed Nerve Allograft in Peripheral Nerve Surgery: A Systematic Review and Critical Appraisal." Plast Reconstr Surg Glob Open. 2023;11(6):e5088. doi:10.1097/GOX.0000000000005088 3. Fonseca Bde P, Sampaio RB, Fonseca MV, Zicker F. Co-authorship network analysis in health research: method and potential use. Health Res Policy Syst. 2016;14(1):34. Published 2016 Apr 30. doi:10.1186/s12961-016-0104-5

Background Nurtec, a versatile migraine medication, has gained popularity. However, awareness of migraine surgery remains uncertain.

Methods Following a descriptive approach, this cross-sectional study utilized Google Trends data as of December 1, 2023, to analyze internet search patterns. Approval from Vanderbilt University's institutional review board and adherence to STROBE guidelines were confirmed. Monthly Relative Search Volume (RSV) data for "migraine surgery," "Nurtec," and "Rimegepant" were collected from January 1, 2004, to November 11, 2023, within the United States. Statistical analysis involved determining mean monthly RSV values and percent changes for critical periods.

Results For "Nurtec," a significant surge in RSV occurred from March 2020 to April 2020 (344%). Additional peaks were observed from June 2020 to July 2020 (66%), October 2020 to December 2020 (169%), May 2021 to June 2021 (33%), and May 2023 to June 2023 (14%). "Migraine surgery" exhibited a notable 400% increase in RSV from March 2005 to May 2005. However, post-2006, RSV for "migraine surgery" consistently remained low without noticeable peaks.

Conclusion The analysis of RSV trends for "Nurtec" and "migraine surgery" from 2004 to 2023 reveals the impact of pivotal events and marketing strategies on public interest. The distinct peaks in "Nurtec" RSV align with FDA approvals and marketing campaigns, highlighting the medication's accessibility. Conversely, the consistently low RSV for "migraine surgery" indicates limited awareness, emphasizing the need for enhanced promotion and education regarding surgical interventions.

Purpose Dexmedetomidine (Precedex) is an alpha-2 adrenoreceptor agonist that prolongs anesthesia and duration of nerve block when administered intravenously with local anesthesia. In facial plastic surgery, Precedex has demonstrated intraoperative and postoperative benefits for rhytidectomy and palatoplasty patients. With perineural administration of Precedex as a nerve block adjunct, preliminary studies report conflicting data suggesting that Precedex can either protect or exacerbate lidocaine-induced nerve injection injury. Thus, this study aimed to better characterize the safety profile of Precedex and its potential for peripheral nerve injury using a nerve injection model.

Methods Lewis rats received a 50uL intrafasicular injection into the sciatic nerve using one of the following agents: (1) normal saline (negative control), (2) bupivacaine (positive control), (3) Precedex, (4) combination of bupivacaine+Precedex (combo group). Bupivacaine was used as a positive control instead of lidocaine given its role as the preferred local anesthetic used in nerve blocks. Sciatic nerve injections were proximal to the trifurcation, and injection sites were marked 1mm proximally and distally with 10-0 nylon suture. At a 2-week endpoint, sciatic nerves were harvested for light microscopy and quantitative histomorphometry. Outcomes included percent area injured, myelin g-ratio, and percent nerve. Injured area was determined qualitatively based on disruption of normal nerve architecture. Myelin g-ratio is the ratio of the inner-to-outer diameter of a myelinated axon.

Results Sciatic nerves had minimal damage after intrafasicular saline injection (negative control), as expected, with an average percent area injured of 2%. Percent area injured was 24% for bupivacaine (positive control), 17% for Precedex, and 19% for combo. There were significant differences in percent area injured between saline and each of the three anesthetic agent groups: saline vs bupivacaine (2±5 vs 24±18, p=0.004), saline vs Precedex (2±5 vs 17±9, p=0.01), and saline vs combo (2±5 vs 19±9, p=0.003). There were no significant differences in percent area injured with any direct comparison of the three anesthetic agent groups: bupivacaine vs Precedex (24±18 vs 17±9, p=0.3), bupivacaine vs combo (24±18 vs 19±9, p=0.5), and Precedex vs combo (17±9 vs 19±9, p=0.7).

The Precedex group had a significantly higher percentage of nerve tissue in the uninjured nerve areas compared to the bupivacaine group (61±3 vs 55±5, p=0.008), whereas bupivacaine vs combo and Precedex vs combo did not show significant differences. Percentage of nerve tissue in uninjured areas was significantly higher compared to that in injured areas within each group: bupivacaine (55±5 vs 12±7), Precedex (61±3 vs 5±7), combo (57±6 vs 13±7); all p<.001. There were no significant differences in myelin g-ratio between any groups for both uninjured and injured nerve.

Conclusion Our findings demonstrate both the local anesthetic bupivacaine and dexmedetomidine (Precedex) cause nerve damage when administered individually through intrafasicular nerve injections. In addition, a combined injection of both agents also causes nerve damage, but Precedex does not appear to exacerbate nerve injury when administered in combination with bupivacaine. Awareness of the potential for neurotoxicity is important for physicians administering these agents, especially when working with sedated patients. Physicians may find these results useful when counseling patients.

Purpose Brachial plexus birth injury (BPBI) may cause long-term functional disabilities in the affected upper extremity. Predicting which patients are likely to undergo nerve grafting and/or transfer can enhance medical decision-making by facilitating close follow-up, therapy, and when appropriate, surgical intervention. Here, we sought to develop a machine-learning model to predict the risk of requiring a nerve reconstruction in patients with BPBI and identify risk factors for progression to surgery.

Methods A single-institution retrospective study was performed on patients (aged 1 year or younger) with BPBI from January 2014 to September 2023. Variables with redundant features (Pearson coefficient > 0.6) or those missing over 80% of values were excluded. Term Frequency-Inverse Document Frequency (TF-IDF) was used to extract data from the initial clinical note evaluating brachial plexopathy. The primary outcome was any nerve procedure. Following an initial logistic regression, two random forest models were developed as a part of this study. The first was a model utilizing structured data only, including clinical and demographic features. A second model employed a combination of structured data and unstructured clinical notes. We compared the performance of both models to assess the optimal approach to predicting surgical intervention risk.

Results 355 patients were included in model development, with 57.2% females, median diagnosis age of 36 days (IQR [0-109 days]) and median BMI of 15.0 (IQR [13.5-17.1]). Other features included area deprivation index (Mean [SD] = 61.6 [22.6]), Elixhauser score (Mean [SD] = 0.1[0.3]), and race (27.0% White, 40.6% Black). A logistic regression model using these variables showed a significant association between higher BMI and nerve reconstruction (p=0.04, OR=1.49, 95% CI=[1.01, 2.20]). Utilizing these seven features in the random forest model for structured data achieved an AUC of 0.77 (SE±0.07) and accuracy of 0.83 (SE±0.04). The variables with the greatest impact on model predictions were BMI and age of evaluation. The model utilizing both structured features and unstructured notes achieved an AUC of 0.94 (SE±0.06) and accuracy of 0.94 (SE±0.02). The most important words as identified by Gini Importance were "concerns" and "weakness".

Conclusions Two machine learning models were developed to predict the need for nerve reconstruction in BPBI. In the first model using structured variables, BMI was the most important predictor, consistent with the rationale that larger babies have more significant traction and avulsion injuries at birth. Age of evaluation was the second most important factor, indicating that a delay in referral for BPBI evaluation may put a child at greater risk for requiring nerve reconstruction. The second "multimodal" model was trained on both structured data and unstructured clinic notes. The multimodal model demonstrated superior performance compared to the structured-variable-only model, with improved predictive capability as early as the first encounter. Therefore, a multimodal machine learning approach that merges structured clinical features with unstructured notes can serve as a valuable adjunct to clinical decision-making, aiding in early identification of patients that may benefit most from timely surgical intervention.

Introduction: Conventional methods of nerve repair, such as neurorraphy, nerve transfer, and nerve grafting, may not be feasible options if the distal nerve stump is not preserved after peripheral nerve injury. Direct muscle neurotization involves inserting a proximal nerve stump directly into the muscle, which becomes particularly relevant when other options have been exhausted. The increased sensitivity for acetylcholine in denervated muscles enables the inserted nerve to spread out nerve fibers throughout the muscle and reinnervate the neuromuscular junctions. Despite promising outcomes reported in literature, direct muscle neurotization remains not widely used in clinical practice. Previous studies described great variations in their nerve insertion technique. Hence, this study aims to investigate whether differences in reinnervation outcomes can be observed based on different nerve insertion techniques in a platysma flap in rats. Material & Methods: This study included 42 male Sprague Dawley rats, weighing between 240-380g. In all rats a 1.5 x 1.5 cm large platysma flap, innervated by the cervical branch of the facial nerve, was elevated without interfering with its vascular supply. In the positive control group the healthy platysma was harvested immediately. In all other groups the platysma was denervated by cutting and coagulating the cervical branch. In the four experimental groups a nerve transfer was performed by inserting the marginal mandibular nerve of the facial nerve into the muscle directly. Depending on the experimental group, the nerve was inserted either close or far away from the orginal nerve insertion and either spread into fascicles or kept intact. No re-innervation procedure was performed in the negative control group. Rats were sacrificed at 8 and 12 weeks postoperatively. During the terminal surgery, electrophysiology testing was performed measuring the compound muscle action potential (CMAP) and single fiber electromyography (SFEMG). The muscle flap was harvested, weighted and stained for immunohistochemistry and immunofluorescene. The distal end of the marginal mandibular nerve was epoxy embedded and stained with toluidine blue for histomorphometric analysis. Results: Successful reinnervation of the platysma muscle flap was achieved in all experimental groups. Full denervation of the platysma flap was confirmed by sacrificing two rats of the negative control group 14 days postoperatively. SFEMG indicated that the re-innervation of the platysma flap ranged from a minimum of 44% to a maximum of 92%. The highest observed CMAP amplitude was 1.12mV in the experimental group that underwent neurotization with the marginal mandibular nerve being separated into fascicles and sutured far away from the original nerve entry point. Comparison of the SFEMG showed no profound differences between the experimental groups and the healthy control group. However, substantial differences were observed when comparing the CMAP of the healthy platysma flap to the experiemental groups. SFEMG and histology showed different patterns of reinnervation depending on the nerve repair technique. Conclusion: In conclusion, our study demonstrated the influence of different nerve insertion techniques on neuromuscular reinnervation following direct muscle neurotization. Successful reinnervation of the platysma flap was achieved in all experimental groups, highlighting the efficacy of direct muscle neurotization for muscle reinnervation.

Introduction: Neuropathic pain following nerve injury is debilitating and negatively impacting the overall quality of life. (1) Targeted muscle reinnervation is an efficacious technique for management of neuropathic pain. (2) However, it has been identified that access to this technique is unequally available for many geographical locations. (3) Therefore, the aim of this study was to evaluate the association between area deprivation index (ADI) and pre-operative pain in patients undergoing TMR for treatment of neuropathic pain.

Methods: Patients who underwent TMR for neuropathic pain in the extremities, prospectively enrolled at our tertiary care clinic, were eligible for inclusion. A chart review was conducted on socioeconomic, surgery, and comorbidity parameters. Pre-operative pain scores on a 0-10 index, and the ADI, reflecting deprivation status on a 0-100 scale, were collected. (4)

Results: A total of 162 patients from 13 different states were included, of which 119 were amputees (73.5%). The median ADI was 25 (IQR: 16-41) and the median pre-operative pain score was 6 (IQR 5-8). A higher ADI was independently associated with higher pre-operative pain (ß=0.027, p=0.013, 95%CI [0.0049-0 .0404])). The time interval from nerve-injury-to-TNR was not associated with ADI (p=0.273).

Summary: - Patients undergoing TMR for treatment of neuropathic pain who are from more socially deprived settings have increased pain experience upon initial evaluation, despite having similar time from amputation to TMR. - These findings highlight the importance of identifying patients presenting from socially deprived settings as this may impact their physical and mental health along with their coping mechanisms, resulting in increased pain. - To reduce the gap between surgical care provided for amputee patients from more deprived areas and their potentially different needs, personalized care should be practiced in an attempt to understand individual needs based on differences in pre-operative pain and mental wellbeing.

References: 1. Atar MÖ, Kamacı GK, Özcan F, Demir Y, Aydemir K. The effect of neuropathic pain on quality of life, depression levels, and sleep quality in patients with combat-related extremity injuries. Journal of Trauma and Injury. 2022;35(3):202-208. 2. Eberlin KR, Ducic I. Surgical algorithm for neuroma management: A changing treatment paradigm. Plast Reconstr Surg Glob Open. 2018;6(10):1-8. 3. Valentine L, Alvarez AH, Weidman AA, et al. Disparities in Targeted Muscle Reinnervation in Major Upper Extremity Amputation. Plast Reconstr Surg Glob Open. 2023;11(4 Suppl):63-64. 4. Kind AJH, Buckingham W. Making Neighborhood Disadvantage Metrics Accessible: The Neighborhood Atlas. New England Journal of Medicine, 2018. 378: 2456-2458. DOI: 10.1056/NEJMp1802313. PMCID: PMC6051533. AND University of Wisconsin School of Medicine Public Health. 2021 Area Deprivation Index v4.0.1

Purpose: No imaging modality can reliably identify muscle denervation acutely after nerve injury and monitor for muscle reinnervation in the chronic period after injury or repair. We recently identified glutamate carboxypeptidase II (GCPII) expression as a novel biomarker for muscle denervation and demonstrated that an FDA approved PET imaging agent, 18F-DCFPyL, could detect changes in muscle GCPII expression. In this study we define how long 18F-DCFPyL remains elevated in denervated muscles after nerve injury and reinnervated muscles after nerve repair. Methods: A total of 20 male Lewis rats underwent right sciatic to femoral nerve transfer. This allowed for simultaneous monitoring of denervated sciatic nerve-innervated muscles and reinnervating femoral nerve-innervated muscles over time. The animals were divided into 5 postoperative timepoints: 2-, 4-, 8-, 12-, and 16-weeks (n=2-5 rats/group). At each timepoint, we performed ex vivo biodistribution studies after intravenous injection of 18F-DCFPyL. Muscle uptake was calculated using an automated gamma counter and expressed as percent injected dose per gram of wet tissue (%ID/g). We additionally performed near-infrared imaging (NIR) using a fluorescent GCPII ligand, YC27, at the 5 postoperative timepoints. Changes in muscle GCPII expression were evaluated using immunohistochemistry (n=10). Results: At 4-weeks post-surgery, the denervated gastrocnemius muscle had 1.88 times greater 18F-DCFPyL uptake compared to the unoperated gastrocnemius muscle (p=0.04). The reinnervated vastus medialis (VM) at 4-weeks post-surgery had 2.34 times greater 18F-DCFPyL uptake compared the unoperated side (p=0.03). There was a statistically significant decrease in the difference of 18F-DCFPyL uptake between the reinnervated VM and unoperated VM at 4- and 8-weeks (p=0.04), 4- and 12-weeks (p=0.02), and 4- and 16-weeks (p=0.03). Similar trends were seen on NIR imaging, with increased YC27 uptake in the denervated gastrocnemius muscle at all timepoints and decreasing uptake of the anterior thigh musculature over time. On histology, denervated gastrocnemius muscle demonstrated predominance of CD68+/GCPII+ cells in the first 4-weeks of the surgery with a shift to CD68-/GCPII+ cells at 8-, 12-, and 16-weeks.
Conclusion: GCPII expression remains elevated in denervated rodent muscles for at least 16 weeks after nerve injury. Reinnervation reduces GCPII expression in rodent muscles by 8-weeks after nerve repair. 18F-DCFPyL is a promising PET agent for non-invasive diagnosis and monitoring of nerve injuries.

Purpose: Objective assessment of facial movements remains pivotal for diagnosis, treatment planning, and monitoring rehabilitation progress for pediatric patients with facial palsy (FP). Traditional assessment methods primarily rely on clinical grading scales, which may not quantify the dynamic kinematics and three-dimensional (3D) characteristics of facial expressions. 3D video photography offers an accurate depiction of pediatric facial palsy, mirroring the eye's perception of depth and spatial relationships, thus enhancing the understanding of dynamic expressions and facial contours. The aims of this study were two-fold: 1) to utilize curvature analysis as a method for determining patient-specific depth and morphology in patients with facial palsy and 2) to quantify 3D morphologic dynamics of the nasolabial fold (NLF), cheek, and periorbital region during smiling, comparing the affected side to the unaffected side, and against normative data from control subjects.

Methods: Pediatric patients with FP and an age/sex-matched control group were selected. 3D video photography was used to capture facial movements from a neutral expression to a maximum smile. A custom MATLAB algorithm was implemented to assess the concavity and convexity of the facial surface, providing a detailed representation of the facial topography. In addition, a 40-vertex curve along the NLF-cheek-orbit facial contour was extracted from patient-specific 3D-face meshes for both the affected and unaffected sides of patients with FP and the right and left sides of control patients. This allowed for quantification of excursion and asymmetry for affected vs. unaffected sides in patients with FP and comparisons with the control group.

Results: 3D videos of 8 pediatric patients with FP and 8 control patients were collected and analyzed. The FP cohort's average age was 13.6 years, while the control group's average age was 13.3 years. FP etiology in the cohort was 37.5% congenital (n=3), 37.5% acquired (n=3), and 25% idiopathic (n=2). Differences in the curvature of the face are intensified during facial animation, especially in regions of interest including the nasolabial folds, cheek, and periorbital region. Visual analysis identified areas of concavity (blue) and convexity (red). Excursion and asymmetry were quantified on a per-patient basis along the NLF-cheek-orbit facial contour.

Conclusions: Curvature analysis offers new insights into the 3D morphological dynamics of facial concavity and convexity in pediatric FP, highlighting the degree of asymmetry between the affected and unaffected sides. The magnitude of asymmetry between the patient with FP's excursion compared to the control group's could allow surgical treatments to be tailored to an individual patient's dynamic anatomy by identifying and quantifying facial region-specific asymmetry.

Introduction: Tumors in the extremities may require amputation for oncologic cure, however, symptomatic neuroma following amputation is a primary cause of neuropathic pain. (1) It remains unknown to what extend time affects neuroma growth and whether morphology influences pain intensity. (2-3) Therefore, we aim to assess whether time influences radiographic neuroma size and shape, and their association with pain intensity in oncological amputees.

Methods: Oncological patients who underwent traditional extremity amputation without adjunctive nerve techniques such as Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) were included. MRIs were assessed post-amputation and prior to potential neuroma surgery. Pain of the residual limb, expressed on a Numeric Rating Scale (NRS, 0-10) within 3 months of the MRI assessment, and presence of neuropathic pain symptoms, were collected from chart review. Neuromas were classified as symptomatic neuromas or non-symptomatic neuromas based on description of pain with neuropathic symptoms. Two musculoskeletal radiologists independently assessed the MR images and described MRI features for each neuroma. Any discrepancy was solved by a third musculoskeletal radiologist serving as independent adjudicator. Neuroma size was expressed as the radiological Neuroma to Nerve Ratio (NNR).

Results: Sixty patients were included in this study, of which 27 (45.0%) were female and 49 (81.7%) were lower extremity amputees. A total of 78 neuromas were identified on MRI, of which 56 (71.8%) were symptomatic with a median pain score of 3.5 (IQR 2.0-5.0). The median radiographic NNR of all neuromas was 2.0 (IQR 1.5-2.9). NNR was not significantly different between symptomatic and asymptomatic neuromas (p=0.665), and varying pain intensity (p=0.471). A larger NNR was associated with longer time-to-neuroma excision interval (p=0.011, Spearman's ρ=0.285), and a smaller proximal nerve width (p<0.001, Spearman's ρ=-0.596). Symptomatic neuromas were associated with upper extremity amputation (p=0.001), T2 heterogeneity (p<0.001) and presence of distal heterotopic ossification of the adjacent residual bone (p=0.029). T2 heterogeneity (p=0.003), perineural edema (p=0.031), enlarged fascicles (p=0.042) and presence of distal heterotopic ossification of the adjacent bone (p=0.024) were associated with more painful neuromas.

Summary: - As assessed on MRI, smaller nerve caliber was associated with a larger NNR, and radiographic neuroma size increased with time. - Size (NNR) did not influence neuroma pain intensity. - MRI features associated with neuroma pain intensity were identified, and these findings may aid in physician awareness of neuromas in the oncological population and patient selection for surgical neuroma treatment.

References 1. Tofthagen C, McMillan SC. Pain, neuropathic symptoms, and physical and mental well-being in persons with cancer. Cancer Nurs. 2010 Nov ; 33(6): 436-444 2. Chung BM, Lee GY, Kim WT, Kim I, Lee Y, Park S Bin. MRI features of symptomatic amputation neuromas. Eur Radiol [Internet]. 2021 Oct 1;31(10):7684–95 3. Ahlawat S, Belzberg AJ, A. Montgomery E, Fayad LM. MRI features of peripheral traumatic neuromas. Eur Radiol [Internet]. 2016 Apr 1;26(4):1204–12

Background and Aim : Reconstruction of nerve injuries using nerve allograft still results in inferior regeneration and motor outcomes to the nerve autograft. Nerve regeneration after nerve injury is thought to be enhanced by modulating the local microenvironment of the nerve reconstruction site through the interaction of mesenchymal stem cells (MSCs) and surgical angiogenesis. Each treatment separately has resulted in improved nerve regeneration in rat nerve reconstruction models. The purpose of this study was to investigate the effect of MSCs and surgical angiogenesis, alone or in combination, on functional recovery in a larger animal model for clinically relevant translation.

Methods and Materials: Ninety New Zealand White rabbits were divided into five groups of 18 animals each. Unilateral 30-mm peroneal nerve defects were repaired with (i) autografts, (ii), decellularized allografts, (iii) decellularized allografts wrapped in a pedicled superficial inferior epigastric artery fascia flap (SIEF) to provide vascularization, (iv) decellularized allografts seeded with adipose-derived mesenchymal stem cells (MSCs), or (v) decellularized allografts seeded with MSCs and wrapped with a SIEF flap. Nerves harvested from Dutch Belted rabbits served as donors and were processed using a five-day decellularization protocol described by Hundepool et al (2017).1 Sixteen and 24 weeks after surgery, functional recovery of nerve regeneration was assessed using electrophysiology (compound muscle action potential, CMAP), muscle force measurement (isometric tetanic force, ITF), wet muscle weight, ankle contracture angle, and weight ratio pre-operative and at sacrifice. Ultrasonography of the tibialis anterior muscles was used to non-invasively measure the muscle cross-sectional area to evaluate muscle atrophy and reinnervation at baseline, and every four weeks until sacrifice.

Results: Autografts were found to be significantly superior compared to all groups at 16 weeks with respect to cross-sectional muscle area, electrophysiology, muscle force measurement, and wet muscle weight. Allografts vascularized with SIEFs were statistically comparable to autografts at 24 weeks with respect to cross-sectional muscle area (p=0.06), electrophysiology (p=0.07), muscle force measurement (p=0.24), and wet muscle weight (p=0.19). Autografts were significantly superior to all other groups at 24 weeks. No differences were found in the ankle contracture angle or the weight ratio pre-operative and at sacrifice between all groups for both time points. Normalization of all parameters was not observed at 24 weeks.

Conclusions: Surgical angiogenesis with an adipofascial SIEF flap to the nerve allograft successfully improved functional recovery in a long nerve gap model, comparable to the nerve autograft, while the addition of MSCs did not alter functional outcomes. This study suggests that surgical angiogenesis is more important in improving nerve regeneration compared to cellular modulation of the nerve micro-environment. Future studies are needed to investigate the limited impact of MSCs in a long nerve gap despite success in smaller animal models and evaluate later time points to adequately assess long-term outcomes.

Hundepool, C. A., Nijhuis, T. H., Kotsougiani, D., Friedrich, P. F., Bishop, A. T., & Shin, A. Y. (2017). Optimizing decellularization techniques to create a new nerve allograft: an in vitro study using rodent nerve segments. Neurosurgical focus, 42(3), E4.

Introduction

Nerve decompression surgery is an effective treatment for patients with headaches due to extracranial compression neuropathies. A proportion of headache patients who undergo this surgery have comorbid chronic pain disorders. We analyzed this subpopulation of patients and whether the presence of comorbid chronic pain disorders effect surgical outcomes.

Method

A prospective cohort study was conducted of 1223 headache patients who were screened for nerve decompression surgery between 2012 and 2023. Data included patient demographics, headache characteristics, the presence of comorbid chronic pain and associated diagnoses at the time of screening, site of nerve decompression surgery, and headache outcomes at 12 months postoperatively. Headaches were evaluated in terms of frequency (pain days per month), intensity (0-10), duration (hours) and Migraine Headache Index (MHI). Outcomes included percent reduction in MHI and reoperation. Surgical success was defined as a 50% or greater reduction in MHI. Univariable logistic regression analysis was performed.

Results

A total of 336 patients underwent nerve decompression surgery involving the greater occipital nerve (71.9%), lesser occipital nerve (43.8%), supraorbital/supratrochlear nerves (41.5%), zygomaticotemporal nerve (25.3%) and auriculotemporal nerve (10.1%). Comorbid chronic pain disorders were present in 47.9% of patients and associated diagnoses included musculoskeletal disorders (17.1%), fibromyalgia (10.6%), upper or lower extremity radiculopathy (9.6%), temporomandibular joint (TMJ) disorder (9.6%), thoracic outlet syndrome (4.2%), trigeminal neuralgia (4.1%), Ehlers-Danlos syndrome (1.9%) and small fiber neuropathy (1.4%). Patient demographics including age, BMI and gender were similar between patients with and without comorbid pain disorders (p>0.05). The mean preoperative headache pain frequency was 26.4 (±6.3) days per months, intensity 8.6 (±1.4), duration 19.5 (±9.4) hours and MHI score 134.4 (±95.1) and were similar between both groups (p>0.05). Patients with comorbid pain disorders had significantly longer symptom duration before surgical treatment (21.1±14.5 years versus 16.5±13.2 years, p<0.05), had significantly more associated sensory, motor and autonomic symptoms (6.1±3.0 versus 4.8±2.5, p<0.05), had significantly higher rates of psychiatric disorders including depression, anxiety and suicide attempts (68.5% versus 46.9%, p<0.01), consulted significantly more specialties prior to nerve decompression surgery (2.8±1.9 versus 2.2±1.5, p<0.05), had significantly more opioid use (35.5% versus 18.5%, p<0.05) and had significantly poorer mean percent nerve block response (71.1% versus 89.8%, p<0.05). Trigger sites addressed with nerve decompression surgery where similar between patients with and without comorbid chronic pain disorders (p>0.05). Postoperatively, patients with comorbid chronic pain disorders were significantly less likely to achieve at least a 50% reduction in MHI score as compared to patients without chronic comorbid pain disorders (75.1% versus 86.2%, p<0.05) and underwent significantly more reoperations (12.7% versus 3.7%, p<0.05).

Conclusion

Comorbid chronic pain disorders are commonly seen in headache patients screened for nerve decompression surgery. These patients may be at risk of poorer surgical outcomes. These findings may help guide evaluation for surgical candidacy as well as preoperative patient counseling.

Purpose Patients with headache disorders may present with compression of distal trigeminal nerve branches as well as other head and neck nerve branches such as the occipital nerves. In addition to these distal compression neuralgias, a coexisting diagnosis of trigeminal neuralgia of proximal origin may be present. This overlap in diagnoses complicates treatment. Therefore, this study aims to investigate the therapeutic effects of distal nerve decompression surgery in patients with coexisting trigeminal neuralgia from a proximal origin. Methods The charts of 1,112 patients who underwent screening for nerve decompression surgery were retrospectively reviewed. Patients with trigeminal neuralgia who underwent nerve decompression surgery were included. Data regarding preoperative and postoperative pain characteristics were collected. Results 17 (1.5%) patients met the inclusion criteria and underwent occipital decompression (n=15, 56%) (n=13 GON decompression, n=10 LON decompression), frontal decompression (n=5, 19%) (SON/STN decompression) and temporal decompression (n=6, 22%) (n=4 ZTN decompression, n=2 ATN decompression). The average time of postoperative follow-up was 17 (±12) months. Among the patients that underwent occipital decompression, 11 (73%) patients reported ≥80% pain relief, 1 (6.7%) patient reported ≥50% pain relief and 3 (20%) patients reported ≤20% pain relief. For frontal and or temporal decompression, only 2 (28%) patients achieved substantial pain relief (100% and 50%) while 5 (71%) patients experienced ≤20% pain relief. Conclusions Our results demonstrate that occipital nerve decompression is an effective treatment for alleviating occipital neuralgia in individuals with coexisting proximal trigeminal neuralgia. However, the outcomes of frontal and temporal decompression were less favorable.