Scientific Abstract Presentations: Migraine & Peripheral Nerve Session 1 Saturday, October 17 Sat, Oct 17 10:30 a.m.-12:30 p.m. CDT

Background New daily persistent headache (NDPH) is a primary headache disorder characterized by the abrupt onset of a continuous, unremitting headache and is frequently refractory to conventional medical therapies. Effective treatment options for medically refractory NDPH remain limited. Surgical deactivation of peripheral nerve and vascular compression sites has demonstrated efficacy in migraine but has not been systematically investigated in NDPH. Methods A retrospective analysis was performed of patients with neurologist-confirmed NDPH who underwent surgical decompression of peripheral nerve trigger sites. All procedures were performed by a single surgeon. Headache outcomes were assessed using headache intensity (0–10 numerical rating scale), headache frequency (days per month), headache duration, and the Migraine Headache Index (MHI). Results Fifty-one patients with NDPH underwent decompression of 214 trigger sites. Mean follow-up was 28.3 months. Surgical intervention resulted in significant improvements across all headache metrics. Mean MHI decreased from 234.5 preoperatively to 50.0 postoperatively (p < 0.001). Headache intensity, duration, and frequency were all significantly reduced (all p < 0.001). Complete resolution of headache burden, defined as ≥90% reduction in MHI, was achieved in 62.6% of patients. Postoperative opioid use decreased from 23.5% to 5.9%. Conclusion Peripheral nerve decompression combined with elimination of dynamic arterial compression is associated with substantial improvement in patients with treatment-refractory NDPH. These findings suggest a potential role for surgical intervention in the treatment of NDPH patients and warrant further prospective investigation.

Background: OnabotulinumtoxinA is an FDA-approved on label indication for prophylactic treatment for chronic migraine. Traditionally injected using a fixed-site injection paradigm derived from Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) studies does not account for peripheral nerve trigger sites implicated in headache pathogenesis. Targeted injections directed at these anatomical zones have shown promise but lack direct comparative evaluation against PREEMPT-trial patterns.

Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. EMBASE and PubMed databases were searched for studies reporting outcomes of onabotulinumtoxinA using either PREEMPT or anatomically targeted injection strategies in chronic migraine patients. Included studies reported headache days/month, migraine headache index (MHI), or symptom elimination rates. Independent t-tests compared changes in outcomes between groups.

Results: Fifteen studies met inclusion criteria: thirteen employing PREEMPT (n=1,339) and two using targeted injections (n=48). Both approaches significantly reduced monthly headache frequency: PREEMPT from 23.3 ± 6.7 to 11.9 ± 7.9 days (p<0.001) and targeted from 15.1 ± 11.2 to 4.1 ± 5.4 days (p<0.001). No significant difference was found between groups in magnitude of improvement (p=0.75). MHI also improved significantly in the targeted group. Reported complications were mild and transient in both cohorts, with fewer total adverse events observed in the targeted injection group.

Conclusions: Both PREEMPT and targeted onabotulinumtoxinA injections effectively reduce migraine burden. While efficacy is comparable, the targeted approach may confer benefits in individualized treatment, lower toxin use, and reduced complications. Further prospective trials are needed to optimize patient selection and protocol choice.

Introduction:

Double crush syndrome describes serial nerve compression along the same neural pathway, in which proximal impairment increases susceptibility to distal entrapment. In neurogenic thoracic outlet syndrome (nTOS), distal neuropathy may coexist at presentation or emerge after decompression. Recent reports suggest distal entrapment may occur in up to one-quarter of patients following nTOS surgery, yet its true frequency and postoperative diagnostic approach remain poorly defined. Persistent symptoms are often attributed to recurrent proximal pathology, potentially leading to unnecessary reoperation. We report the incidence, clinical presentation, evaluation strategy, and outcomes of delayed distal decompression in a consecutive nTOS cohort.

Methods

A retrospective review was performed of 97 consecutive nTOS decompressions from 2016 to 2025. Patients undergoing simultaneous thoracic outlet and distal nerve procedures, or those treated with distal decompression first due to combined symptoms at presentation, were excluded to isolate delayed distal pathology. Double crush was defined as new or progressive symptoms distal to the elbow following nTOS surgery prompting distal nerve decompression. Extracted variables included demographics, pre- and post-nTOS symptom distribution, distal provocative findings (Tinel), postoperative testing (EMG, MRI, MR neurography), time from nTOS surgery to distal surgery, and outcomes after distal decompression.

Results: Double crush occurred in 22/97 cases (22.7%), representing 21 unique patients. Mean age was 42.6 ± 19.3 years; 61.9% were female and mean BMI was 30.2. Mean symptom duration prior to nTOS surgery was 41.8 months, and mean follow-up was 19.7 months. After nTOS decompression, all patients developed pain distal to the elbow and 66.7% reported distal numbness. Preoperative distal Tinels were uncommon (cubital 23.8%, carpal 14.3%, radial 0%), whereas postoperative distal Tinels were frequent (cubital 71.4%, carpal 33.3%, radial 4.8%). Postoperative EMG was obtained in 71.4% and was positive in 57.1%. Mean time from nTOS surgery to distal decompression was 10.6 months. Distal procedures included cubital tunnel release (n=17), carpal tunnel release (n=12), and radial nerve release (n=2), with some patients undergoing multiple decompressions. Persistent pain after distal decompression occurred in 4/21 patients (19.0%) and persistent numbness in 5/21 (23.8%). Seventeen patients (81.0%) reported pain improvement. Extended opioid use was required in 2/21 patients (9.5%), one of whom had preoperative opioid use. One patient developed additional radial compression after prior cubital release requiring further decompression, and another required repeat thoracic outlet surgery for proximal pathology including phrenic nerve neuroma. No consistent secondary etiology was identified in the remaining cases.

Conclusions:

This study suggests that delayed distal double crush represents a clinically relevant contributor to persistent symptoms following nTOS decompression. Recognition of a postoperative shift toward distal symptom localization with corresponding distal examination findings may assist in identifying candidates for secondary decompression. A structured distal-focused evaluation may enhance decision-making in this setting. Future prospective studies are warranted to validate this diagnostic framework and further define optimal evaluation and treatment strategies for patients with persistent post-nTOS symptoms.

BACKGROUND: There is no consensus regarding optimal management or surgical technique for treating symptomatic neuroma, such as traction neurectomy, Targeted Muscle Reinnervation (TMR), Regenerative Peripheral Nerve Interface (RPNI), and Vascularized Denervated Muscle Targets (VDMT), based on inconsistent outcomes (1). The objective of this study was to investigate the outcomes of a novel, in-situ forming, sutureless hydrogel cap placed prophylactically (during primary treatment of a disrupted nerve), therapeutically (during symptomatic neuroma resection), and during salvage for a recalcitrant symptomatic neuroma (following prior neuroma surgical intervention).

METHODS: This multi-center, retrospective study included 68 patients (72 procedures) aged 55.1 ± 18.0 years old with 147 transected distal nerve stumps who received prophylactic (29 patients, 31 procedures, 81 nerves), or therapeutic or salvage (39 patients, 41 procedures, 66 nerves, Figure 1) treatment with the hydrogel cap (allay™ hydrogel cap, Tulavi Therapeutics) from 2024 through 2026. All symptomatic neuromas were identified pre-operatively using established diagnostic criteria (2). Follow-up was greater than 6 months for 21 of 68 patients (prophylactic: 8 patients, 17 nerves; therapeutic: 11 patients, 17 nerves; salvage: 2 patients, 6 nerves). Outcomes assessed included pre- and post-operative Visual Analogue Scale (VAS) scores, symptomatic neuroma formation, and device associated adverse events.

RESULTS No new or recurrent neuroma formation was identified in the 21 patients (22 procedures, 40 nerves, 38% female) at a minimum of 6 months follow up across prophylactic, therapeutic, or salvage procedures. Prophylactic patients (8 patients, 9 procedures, 17 nerves) had average follow-up of 13.5 ± 3.8 months and therapeutic and salvage patients (11 therapeutic patients,17 nerves; 2 salvage patients, 6 nerves) had average follow-up of 9.2 ± 3.1 months. Collected pre- (average 8) and post- (average 1) VAS scores demonstrated an average reduction of 7.0 ± 2.5 points (average follow up of 9.8 ± 3.3 months). No adverse events were observed in any patients (n=68) regardless of the follow-up interval (average 5.1 ± 4.7 months across all groups).

CONCLUSIONS Hydrogel nerve cap application in prophylactic, therapeutic, and salvage cases was highly effective in reducing symptomatic neuroma formation in all patients at greater than 6 months following treatment. Our outcomes support continued assessment and use of a novel hydrogel cap applied to transected nerves as prophylactic treatment for reducing symptomatic neuroma formation and as therapeutic treatment for symptomatic primary or recalcitrant neuromas based on substantial and consistent reduction in pre- and post-operative VAS pain scores and an absence of device associated adverse events following its use.

SOURCES 1. Starr BW, Chung KC. Traditional Neuroma Management. Hand Clin. 2021;37(3):335-344. doi: 10.1016/j.hcl.2021.04.002 2. Arnold DMJ, Wilkens SC, Coert JH, Chen NC, Ducic I, Eberlin KR. Diagnostic Criteria for Symptomatic Neuroma. Ann Plast Surg. 2019;82(4): 420-427. doi: 10.1097/SAP.0000000000001796

Background: Targeted botulinum toxin injections and peripheral nerve blocks are both used to identify surgical candidates for trigger point deactivation surgery for migraine headaches. However, their comparative predictive values have not been directly evaluated yet. The purpose of this study was to compare the positive predictive value (PPV) of diagnostic botulinum toxin (Botox) injections versus peripheral nerve blocks in predicting successful trigger point deactivation surgery to optimize patient selection and further refine diagnostic algorithms in migraine surgery.

Methods: A retrospective review was performed of patients undergoing trigger point deactivation surgery between December 2015 and January 2025 by a single surgeon. Inclusions required neurologist-diagnosed migraine headaches refractory to medical management and receipt of preoperative diagnostic Botox injection, peripheral nerve block or both, with injection sites corresponding to surgical trigger sites. Baseline migraine characteristics included frequency, intensity, duration and migraine headache index (MHI). Positive diagnostic response required ≥50% improvement of symptoms after injection. To compare tools while accounting for clustering of multiple surgeries within patients and multiple tools per surgery, mixed-effects logistic regression models were used. When multiple diagnostic tests were used for a single surgery, the last diagnostic test prior to surgery was used to assess PPV for each tool. A sensitivity analysis that uses any positive test as a rule was also performed.

Results: A total of 128 patients met inclusion criteria and demographic variables were comparable between groups. Botox injection demonstrated a PPV of 0.76 (16/21), while nerve blocks demonstrated a PPV of 0.81 (43/53). No significant differences were found between modalities after cluster adjustment (p=0.85). Sensitivity analysis yielded similar findings, with a PPV of 0.70 (19/27) for Botox injections comparing to a PPV of 0.81 (43/53) for nerve blocks. No significant differences were found between modalities for sensitivity analysis, p=0.34.

Conclusions: Both diagnostic Botox injections and peripheral nerve blocks demonstrate high and comparable positive predictive values (PPV) in successfully identifying trigger sites for patients undergoing trigger point deactivation surgery. These findings support the use of either modality and suggest that selection may be guided by clinical context, patient preference and resource availability to further optimize surgical candidacy and outcomes.

Background Peripheral nerve decompression surgery ("migraine surgery") offers long-term relief for patients with medically refractory chronic migraine. However, the size of the global population potentially eligible for this procedure remains largely unquantified. We estimated the annual number and rate of surgery-eligible patients across 204 countries using publicly available epidemiological data.

Methods This cross-sectional modeling study used Global Burden of Disease 2023 (GBD 2023) aggregate data. For each country, sex, age group, and incident headache cases were passed through four key transitions. These included patients diagnosed with migraine, chronic migraine, medically refractory migraines, and those evaluated to be potential migraine surgery patients. Three modeling scenarios (conservative, base-case, and liberal) were defined to capture uncertainty in clinical pathway estimates. Age- and sex-weighted standardized probabilities were applied to reflect the demographics of reported surgical cohorts. Additionally, disability-adjusted life years (DALYs) attributable to surgery-eligible patients and lost GDP related to illness were also estimated.

Results In 2023, the modeled global population across 204 countries included an estimated 820.0 million incident headache disorder cases, including 268.8 million incident migraine cases, 26.9 million chronic migraine cases, and 8.1 million medically refractory chronic migraine cases. Following age- and sex-weighting, there were 5.6 million incident migraine surgery–eligible patients worldwide, which corresponds to 76.2 eligible patients per 100,000 and 313,400 headache-related DALYs at an economic valuation of US$4.7 billion globally. The surgery-eligible population was predominantly female (83.3%), with nearly half (49.4%) of all candidates aged 20–39 years. Broadly, East Asia and the Pacific carried the largest regional share of surgery-eligible patients (1.51 million; 26.7%), followed by South Asia (1.26 million; 22.3%), with Europe and Central Asia (0.78 million; 13.8%) and Sub-Saharan Africa (0.73 million; 13.0%) contributing similar proportions. The largest absolute numbers of surgery-eligible patients were observed in India (1,093,322), China (812,538), and the United States of America (307,307). Per-capita rates were highest in Cyprus (99.8 per 100 000), the United States and Norway (each 97.2 per 100,000), the United Kingdom (95.8 per 100,000), and the Russian Federation (94.2 per 100,000).

Discussion This study provides the first global, country-level estimates of the population potentially eligible for migraine surgery, identifying millions of patients annually who may benefit from peripheral nerve decompression. The clear female predominance among early-to-middle adulthood highlights both the epidemiology of migraine and the demographics of reported surgical cohorts. These patterns carry important implications for surgical access, patient advocacy, and health equity.

Introduction Neurogenic thoracic outlet syndrome (NTOS) remains a diagnostic challenge due to overlapping compression sites and the lack of standardized criteria for surgical selection. Interscalene block and pectoralis minor botulinum toxin A (BTX-A) injection are frequently used independently to highlight symptoms; however, their combined diagnostic and presurgical value has not been well described. This study evaluates outcomes and safety associated with using both interventions to address the interscalene triangle and retropectoralis minor space. Methods A retrospective review was performed on patients who underwent diagnostic injection and subsequent surgical decompression for NTOS between 2021 and 2024 by a single surgeon. Three injection patterns were analyzed: combined interscalene block with 2 cc of 0.5% ropivacaine plus pectoralis minor BTX-A injection (100 units), scalene-only, and pectoralis-only. Outcomes included symptom improvement, persistent pain, paresthesias, reintervention, and complications. Results The overall mean age was 37.1 years, 43 for males and 24 for females respectively. A total of 35 patients were included, of whom 22 (32.4%) underwent diagnostic injections prior to surgery: 8 received both interscalene and pectoralis minor injections, 7 received scalene-only, and 7 received pectoralis-only. Among the injected patients, 21 of 22 (95.5%) reported postoperative symptomatic improvement. Persistent pain and paresthesias were each observed in 6 (27.3%) patients. Reintervention occurred in 3 (13.6%) overall-none in the dual-injection group, compared with 1 (14.3%) in scalene-only and 2 (28.6%) in pectoralis-only. No major complications or extended opioid use occurred. One case of Parsonage–Turner syndrome followed interscalene block and resolved with conservative management. Discussion The interscalene block with ropivacaine serves as a valuable diagnostic tool, temporarily alleviating compression of the brachial plexus by the anterior scalene muscle. A positive response (pain reduction) suggests anterior scalene involvement and predicts a higher likelihood of surgical success. The subsequent BTX-A injection into the pectoralis minor provides a minimally invasive "chemical tenotomy" therapeutic component, reducing muscle spasm and further decompressing the brachial plexus. Conclusion Diagnostic injections were overall highly effective, with more than 95% of patients reporting improvement and no major complications. Symptom relief following targeted injections likely reinforces diagnostic accuracy, serving as a functional complement to imaging findings. The absence of reinterventions in the dual-injection group suggests that combining interscalene and pectoralis minor injections streamlines the diagnostic process and may optimize presurgical management. By providing a broader functional assessment across potential compression sites, this combined approach appears to be a safe and clinically valuable adjunct in the multidisciplinary management of NTOS, however is imporant to consider no procedure is risk free and should be considered carefully.

Purpose: Peripheral nerve injuries often result in incomplete recovery and long-term complications despite adequate microsurgical repair. Perineural scar formation and neuroma development may impair regeneration, contribute to pain, and increase the risk of revision surgery, socioeconomic burden, and reduced quality of life. Nerve wrapping materials have been introduced to protect the coaptation site, reduce scar and adhesion formation, and support regeneration; however, comparative evidence across materials remains limited. We performed a systematic review and meta-analysis of animal studies to evaluate the effects of nerve wrapping after peripheral nerve coaptation.

Methods: A systematic review and meta-analysis of animal experimental studies was conducted in accordance with PRISMA guidelines. Studies evaluating application of wrapping materials around peripheral nerve coaptation sites were included. Outcomes related to perineural scar formation and functional recovery were extracted and compared. Meta-analysis was performed for the Sciatic Functional Index (SFI) when sufficient data were available.

Results: Twenty-eight studies evaluating 45 wrapping materials or material combinations met inclusion criteria. Among included studies, 23 (82.1%) demonstrated a significant positive effect of nerve wrapping in at least one quantitatively measured outcome related to perineural scar formation. Meta-analysis of SFI outcomes showed improved functional recovery in animals treated with nerve wrapping compared with controls, with significant effects at mid- to late postoperative time points.

Conclusions: Available animal data suggest that wrapping peripheral nerve coaptation sites may be a promising strategy to reduce adverse perineural healing and support postoperative functional regeneration. No consistent trend favoring a specific wrapping material type was identified, which may indicate that benefit is related to the wrapping technique itself rather than a single material class. The lack of direct comparative studies highlights the need for targeted experimental and translational research to define material-specific effects and optimize clinical application.

Purpose: Regenerative peripheral nerve interface (RPNI)-the implantation of transected nerve endings into muscle grafts-has shown promise in mitigating neuropathic sequelae following amputation. While peripheral vascular disease (PVD) is a leading cause of amputation, RPNI has not been studied in this group [1-4]. The objective of this study is to evaluate outcomes in patients with PVD treated with RPNI.

Methods and Materials:
A retrospective review identified patients who underwent major limb amputation with RPNI between 2019 to 2025. Demographic data, PVD status, post-operative neuropathic outcomes, and complications were compared between patients with and without PVD.

Results: Of 2,132 patients identified, 35 were treated with RPNI. Among PVD patients, 75% (9/12) reported phantom limb pain compared to 61% (14/23) without PVD (odds ratio [OR] 1.93, 95% CI 0.41–9.1, p = 0.48). Peripheral neuropathy occurred in 42% (5/12) of PVD patients and 35% (8/23) without PVD (OR 1.34, 95% CI 0.32–5.6, p = 0.73). Neuromas were noted in 17% (2/12) of PVD patients versus 26% (6/23) without PVD (OR 0.57, 95% CI 0.10–3.4, p = 0.69). Wound dehiscence was more common in the PVD group (25%, 3/12) versus 9% (2/23) without PVD (p = 0.31). Surgical site infection occurred in 25% (3/12) of PVD patients compared to 9% (2/23) without PVD (p = 0.31).

Conclusion: RPNI offers similar pain outcomes in PVD and non-PVD patients undergoing amputation, with no statistically significant rise in complications. RPNI shows promise for neuropathic pain prevention in high-risk patients and warrants further interdisciplinary study and collaboration.

References:
1. Chang BL, Mondshine J, Fleury CM, Attinger CE, Kleiber GM. Incidence and Nerve Distribution of Symptomatic Neuromas and Phantom Limb Pain after Below-Knee Amputation. Plast Reconstr Surg. 2022 Apr 1;149(4):976-985. doi: 10.1097/PRS.0000000000008953. PMID: 35188944.

2. Lin Z, Yu P, Chen Z, Li G. Regenerative peripheral nerve interface reduces the incidence of neuroma in the lower limbs after amputation: a retrospective study based on ultrasound. J Orthop Surg Res. 2023 Aug 24;18(1):619. doi: 10.1186/s13018-023-04116-6. PMID: 37620955; PMCID: PMC10463429.

3. Kubiak CA, Kemp SWP, Cederna PS, Kung TA. Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain. Plast Reconstr Surg. 2019 Sep;144(3):421e-430e. doi: 10.1097/PRS.0000000000005922. PMID: 31461024.

4. Molina CS, Faulk JB. Lower Extremity Amputation. [Updated 2022 Aug 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546594/

The clinical diagnosis of femoral nerve compression is a rare but disabling cause of anterior thigh pain and weakness. This condition has long been described in literature but is often under recognized. Etiologies vary from post-surgical injury or scarring, variant iliopsoas musculature, or dynamic constriction beneath the inguinal ligament or within the iliopsoas compartment. Because symptomology overlaps with hip and lumbar pathology, diagnosis is often delayed. This study looked at the clinical assessment of femoral nerve compression and outcomes following surgical nerve decompression. A retrospective chart review of the senior surgeon's records found 43 patients that underwent femoral nerve decompression between November 2021 and December 2024. Patient data was excluded if their final follow up was less than 3 months. Physical examination included muscle strength testing and pain assessment with palpation and both passive and active movement. MRI, MRI-Neurography, or electromyography evaluated for femoral neuropathy. Charts were reviewed for presentation and etiology, diagnostic criteria, and outcomes. Patients presented with anterior thigh pain, weakness, or paresthesia localized to the femoral distribution with an average symptom duration of 21 months. Etiologies included hip surgery (n=14), back surgery (n=1), hematoma or mass effect (n=2), trauma (n=3), or idiopathic (n=5). On physical exam, 14 patients had reproducible pain with palpation and 3 with active motion. In the diagnostic work-up, 15% had positive MRI findings, 79% had positive MRI-Neurography (MRN) findings, and 62% has positive EMG findings for femoral neuritis or neuropathy, respectively. Surgical decompression involved a limited incision below the inguinal ligament with release of constricting iliopsoas muscle fascia overlying the femoral nerve, extending into the pelvis and the anterior thigh. There were no operative complications. Most patients described their symptoms as much improved at final follow up (59%), with 23% reporting their symptoms had resolved, 14% reporting they were better but persistent, 5% as the same prior to surgery, with no patients reporting worsening of their preoperative symptoms. Post-operative complications were limited to wound erythema successfully treated with antibiotics in 3 patients with only 1 patient developing a seroma that was able to be drained in clinic. Average final follow-up after surgery was 11 months. Femoral nerve compression remains underrecognized but potentially reversible. Focused physical examination and utilizing imaging resources such as MRN and EMG can facilitate earlier detection with specificity. Targeted release of the femoral nerve offers reliable symptom relief and functional recovery. Future longitudinal studies will further define outcomes, prognostic factors, and long-term functionality.

Background: Fillet flaps are invaluable for complex oncologic reconstructions following high-level extremity amputations. While their oncologic safety is well documented, data on pain outcomes when used as recipients for targeted muscle reinnervation (TMR) remain limited. This study is the first to compare patient-reported pain outcomes between TMR in fillet flaps and conventional TMR or regenerative peripheral nerve interface (RPNI) procedures. Methods: We performed a retrospective cohort study of oncologic amputees treated between 2018 and 2024. Patients who underwent either conventional TMR/RPNI (n=100) or TMR in a free fillet flap (n=23) were included. Pain outcomes included Numerical Rating Scale (NRS) scores for residual limb pain (RLP) and phantom limb pain (PLP), as well as PROMIS scores for pain intensity, pain interference, and pain behavior. Opioid consumption was tracked using morphine milligram equivalents (MME) from national prescription data. Results: Forequarter amputations (n=8) and Hemipelvectomies (n=12) comprised 87% of the Fillet population (35% and 52%, respectively). Contrary to patients with conventional TMR/RPNI, fillet TMR patients did not report significant improvements in PLP, RLP, pain intensity, and pain interference over a 21-month follow-up period. However, both groups experienced a significant decline in postoperative opioid use over time. At their latest survey beyond nine months, phantom limb pain and pain interference remained significantly higher in the fillet group. Nonetheless, despite higher initial opioid requirements, final opioid use was comparable between groups. Conclusion: TMR performed in fillet flaps is associated with a meaningful reduction in long-term opioid use, comparable to that seen with conventional TMR/RPNI. However, patient-reported phantom pain and interference remain elevated in the fillet group, likely due to the more extensive nature of the index amputation.

Background: Targeted muscle reinnervation (TMR) is increasingly performed at the time of below-knee amputations (BKAs) to reduce neuroma formation and phantom limb pain. Although functional benefits are well established, its association with survival remains poorly defined. This study evaluates patient characteristics, perioperative variables, and mortality outcomes associated with TMR.

Methods: A retrospective review was conducted of all patients undergoing BKA at a single institution from 2013–2023. Patients were stratified into those who underwent primary or secondary TMR and those who did not receive TMR. Demographics, comorbidities, operative details, prior limb interventions, and mortality outcomes were compared. Mortality was obtained via a national database incorporating Social Security and public records. Multivariable logistic regression was performed to identify independent predictors of mortality.

Results: A total of 568 patients were identified, of whom 338 (59.5%) underwent TMR and 230 (40.5%) did not. Median age (59 years) sex distribution (67.4% male), and median BMI (28.7 kg/m2) were similar between groups. The TMR cohort demonstrated a higher comorbidity burden, including diabetes mellitus (81.7% vs 62.6%, p=0.001), peripheral vascular disease (84.6% vs 60.9%, p=0.001), and end-stage renal disease (26.9% vs 18.3%, p=0.017). TMR patients more frequently underwent prior angiography (54.2% vs 41.3%, p<0.001) and endovascular intervention (12.7% vs 6.5%, p=0.017). Despite greater comorbidity burden, TMR was associated with significantly lower overall mortality (28.7% vs 47.0%, p<0.001). One-year mortality was not significantly different between groups (9.5% vs 13.9%, p=0.100); however, divergence became evident over time, with lower mortality in the TMR cohort at 3 years (21.6% vs 30.0%, p=0.023), 4 years (24.9% vs 35.2%, p=0.008), and 5 years (27.8% vs 39.1%, p=0.005). On multivariable analysis, TMR remained independently associated with reduced mortality (OR 0.31, 95% CI 0.21–0.46, p<0.001). Diabetes (OR 1.78, p=0.017) and peripheral vascular disease (OR 2.66, p<0.001) were independent predictors of death.

Conclusions: TMR, whether performed primarily or secondarily in patients undergoing BKA, is associated with significantly improved long-term survival in highly comorbid patients. These survival benefits may be mediated by reductions in neuroma formation and limb pain, leading to improved postoperative ambulation and overall functional status. Future studies will explore the association between TMR and functional outcomes as a mediator of improved mortality.

Purpose: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) have been demonstrated to reduce the likelihood of neuroma formation and phantom limb pain following extremity amputation. Despite growing evidence supporting their efficacy, national adoption patterns and predictors of utilization remain poorly characterized. In this study, we sought to evaluate patient- and hospital-level factors associated with receipt of TMR and RPNI following extremity amputation using a nationally representative database.

Methods: We performed a retrospective cohort study using the National Inpatient Sample for the years 2017-2019 and 2022. Adult patients undergoing upper or lower extremity amputation were identified using ICD-10-PCS codes. TMR was defined by the presence of concurrent peripheral nerve reposition, supplement, or transfer codes, and RPNI by the presence of concurrent muscle transfer codes. Demographic variables included age, sex, race, primary payer, and income quartile. Hospital characteristics included bed size, teaching status, and geographic region. Clinical comorbidities were identified using ICD-10-CM diagnosis codes. Survey-weighted multivariable logistic regression models were constructed to identify factors associated with TMR and RPNI utilization, accounting for stratification and discharge-level weights.

Results: A weighted estimate of 829,945 adult amputations were identified. TMR was performed in 2,795 patients (0.34%) and RPNI was performed in 5,735 patients (0.69%). Compared with 2017, odds of receiving TMR were significantly higher in 2019 (OR 3.46, 95% CI 2.15-5.56, p < 0.001) and 2022 (OR 9.55, 6.16-14.83, p < 0.001). RPNI similarly increased in 2019 (OR 1.29, 1.07-1.56, p = 0.007) and 2022 (OR 1.23, 1.02-1.48, p = 0.031). Socioeconomic factors were independently associated with the receipt of both TMR and RPNI. Higher income quartile was associated with increased odds of TMR (OR 1.98, 1.58-2.49, p < 0.001) and RPNI (OR 1.29, 1.12-1.48, p < 0.001). Private insurance was associated with higher odds of TMR (OR 1.40, 1.05-1.86, p = 0.021). Hospital characteristics further influenced adoption. Treatment at large hospitals increased odds of TMR (OR 1.91, 1.46-2.49, p < 0.001) and RPNI (OR 1.32, 1.16-1.51, p < 0.001), and urban teaching centers were found to exhibit particularly strong associations with TMR (OR 4.29, 1.91-9.60, p < 0.001) and RPNI (OR 2.22, 1.67-2.96, p < 0.001). Regional variation was observed, with lower odds in the West for both TMR (OR 0.48, 0.31-0.73, p < 0.001) and RPNI (OR 0.79, 0.64-0.99, p = 0.041) relative to the Northeast. Overall, fewer than 1% of amputees nationally received either procedure.

Conclusions: Despite increasing adoption, TMR and RPNI remain markedly underutilized nationwide. Utilization is concentrated in large, urban teaching hospitals, consistent with early-stage dissemination within tertiary centers. Socioeconomic gradients, including higher utilization among privately insured and higher-income patients, suggest inequitable access. Broader adoption and equitable referral will be necessary to ensure that access to nerve management procedures reflects clinical need rather than institutional or socioeconomic factors.

Purpose: Up to 80% of patients suffer from neurogenic pain post-amputation, significantly limiting function and quality of life. Regenerative peripheral nerve interface (RPNI) – which implants free muscle grafts to nerve endings – has emerged as a promising strategy, but evidence is limited by small sample sizes and heterogeneous results. While targeted muscle reinnervation (TMR) is well studied, the current RPNI literature lacks evidence-based benchmarks for pain and complication outcomes. This is the first systematic review to evaluate the clinical efficacy and biological integration of RPNI and establish pooled benchmarks to guide its adoption in amputation care.

Methods: Following PRISMA guidelines, PubMed, Scopus, Embase, and CENTRAL databases were searched for human and animal studies on RPNI. Demographics and surgical details were extracted, along with pain outcomes and complications from human studies, and electromyography and histology from animal studies. Chi-square test and meta-analysis with a random-effects model were used for statistical analysis.

Results: Thirty-five studies were included. Of 495 patients (N = 21 studies), 43% received RPNI, 17% TMR+RPNI, and 32% controls receiving amputations alone. Patients (mean age: 45.9, 69.6% male) received below-knee (39.2%), above-knee (12.1%), and upper extremity (20.1%) amputations. On average, patients received 3.2 RPNIs from the gastrocnemius (15.6%), vastus lateralis (41.9%), and soleus muscles (15.6%). Rates of residual pain, phantom pain, complications, and reoperations in RPNI patients were 32.9%, 17.1%, 21.9%, and 7.2%, respectively, with an average follow-up time of 1 year. Compared to amputation alone, RPNI patients had lower residual pain (OR[95% CI], 0.33[0.13-0.82]; p=0.02), complications (0.55[0.36-0.84]; p=0.01), neuroma formation (p<0.001), and opioid use (p=0.02). Complications were similar between RPNI and TMR+RPNI (p=0.23).

In animal studies (323 rats), the common peroneal (33.3%), tibial (30.3%), or sciatic nerves (24.6%) were transected with RPNI created using the extensor digitorum longus (46.4%) or adductor magnus muscles (18.6%). RPNI cohorts had compound muscle action potential (CMAP) amplitudes of 7.1±1.2, with higher amplitudes than cohorts receiving nerve transection alone. No neuromas were found in any RPNI cohorts (N = 8 studies) as opposed to control cohorts. Autotomy behaviors (N=2) and cold and thermal allodynia (N=1) were significantly lower in the RPNI group. Robust vascularity (N=6) was found in 100% of RPNIs, and confirmation of neuromuscular junction formation (N = 5) was found with neurofilament-200, α-bungarotoxin, and cholinesterase staining.

Conclusion: This study provides pooled clinical evidence supporting RPNI as an effective adjunct for limb amputations. Patients receiving RPNI experienced significantly reduced neuromas, residual pain, and complications compared to amputation alone. In animal studies, the CMAP amplitude suggests successful motor axonal integration within the muscle graft, while robust vascularity indicates a favorable environment for graft viability. Given that RPNI demonstrated similar complication rates to TMR+RPNI, future prospective studies should compare outcomes between TMR, RPNI, and TMR+RPNI to develop evidence-based treatment algorithms that optimize pain and functional recovery in amputees.

Introduction Neuropathic pain frequently persists following peripheral nerve reconstruction. Gabapentin is commonly used in peri- and postoperative settings for pain control and has been associated with improved postoperative pain outcomes in burn and pediatric amputation populations, as well as higher rates of opioid cessation. However, concerns have been raised regarding the long-term neurocognitive effect of gabapentin use. Therefore, this study aims to assess whether postoperative gabapentin exposure is associated with long-term neurocognitive clinical deficits in patients following peripheral nerve surgery.

Methods We conducted a retrospective cohort study using the TriNetX Global Collaborative Network to identify patients who had undergone peripheral nerve surgery or reconstruction. Patients were stratified based on exposure to postoperative gabapentin within one year of the index procedure, defined as receipt of six prescriptions or more. Primary outcomes included dementia and mild cognitive impairment, with secondary neuropsychiatric outcomes and opioid utilization assessed during long-term follow-up. Propensity score matching was performed to balance baseline demographics, comorbidities, and prior exposure to medication such as opioids and antidepressants. Outcomes were compared using risk difference with corresponding confidence intervals.

Results Following propensity matching, 2,945 patients were identified as either patients exposed to postoperative gabapentin, or those who were not. Rates of dementia development in both the exposure and control groups were identical (1.7%v1.7%, p=0.84), while rates of mild cognitive impairment were similar (1.8% v 1.4%, p=0.26). Gabapentin exposure was associated with higher rates of altered mental status (2.5% v 1.5%, p=0.009) and depression (29.8% v 27.4%, p=0.038), while anxiety rates were similar. Postoperative opioid use was significantly lower in the gabapentin cohort (88.7% v 94.7%, p<0.001).

Conclusion In this large national database study, the use of gabapentin after peripheral nerve surgery was associated with a significantly decreased utilization of opioids. While gabapentin was associated with small but significantly increased rates of transient neurological complications such as altered mental status when it was used in this setting, it was not associated with a higher risk of developing dementia or mild cognitive decline. These findings provide reassurance regarding cognitive safety while supporting the role of gabapentin for postoperative pain management, while highlighting the need for further prospective investigations to define the long-term neuropsychiatric effects.

Background: Migraines affect approximately 14% of the global population (1). Despite preventive and abortive therapies, up to one-third of patients remain refractory (2). Migraine decompression surgery (MDS) is an option for medically refractory disease, but postoperative hypersensitivity reactions (HSR) and secondary trigger sites (STS) are common and may require further treatment (3,4). Mental health can influence pain and migraine chronicity, yet its association with post-MDS complications remains unclear (5). This study investigates whether preoperative anxiety and/or depression is associated with HSR and STS after MDS.

Methods: A retrospective cohort study of patients undergoing MDS by a single surgeon between May 2021 and January 2025 was performed. All patients had neurologist-confirmed, medication-refractory migraines with a positive diagnostic anesthetic injection at the primary trigger site and a minimum 3 months' follow-up. Primary exposure was preoperative anxiety and/or depression diagnosis. Outcomes were HSR (distressing sensory changes at the operative site requiring intervention), STS (new postoperative trigger site not present preoperatively), time-to-onset of each, and surgical success (>50% symptom improvement). Groups were compared with chi-square or Fisher's exact tests; surgical success used univariable odds ratios (p < 0.05).

Results: Twenty patients undergoing MDS were included, 14 with a mental health diagnosis. Baseline demographics, migraine frequency, and comorbidities were similar between groups (all p > 0.05). HSR occurred in 50% of both cohorts (p = 1.0), with similar time to HSR (38.7 vs 56.7 days, p = 0.364). STS developed in 36% of patients with a mental health diagnosis and 50% of those without (p = 0.921), with similar time to STS (230.4 vs 100.0 days, p = 0.489). Surgical success occurred in 93% of patients with a preoperative mental health diagnosis and 83% of patients without (OR 2.46, p = 0.52).

Conclusion: Preoperative anxiety and/or depression was not associated with postoperative HSR, STS, or surgical success after MDS. These findings suggest that preoperative mental health diagnoses alone should not preclude consideration of MDS, although larger prospective studies are needed to better define their impact on postoperative outcomes.

1. GBD 2023 Headache Collaborators. Global, regional, and national burden of headache disorders, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. Lancet Neurol. 2025 Dec;24(12):1005-1015. doi: 10.1016/S1474-4422(25)00402-8. PMID: 41240916; PMCID: PMC12612381.
2. Khansa I, Janis JE. Surgical treatment of migraine headaches. In: Janis JE, ed. Essentials of Plastic Surgery. 3rd ed. New York, NY: Thieme; 2023:315-328.
3. Faizo E et al. The Efficacy of Trigger Site Surgery in the Elimination of Chronic Migraine Headache: An Update in the Rate of Success and Failure. Cureus. 2024;16(2):e54504. Published 2024 Feb 20. doi:10.7759/cureus.54504.
4. Punjabi, Ayesha M.D.; Brown, Matthew M.D.; Guyuron, Bahman M.D.. Emergence of Secondary Trigger Sites after Primary Migraine Surgery. Plast Reconstr Surg 137(4):p 712e-716e, April 2016. | DOI: 10.1097/PRS.0000000000002011.
5. Castelnuovo G et al. Psychological Considerations in the Assessment and Treatment of Pain in Neurorehabilitation and Psychological Factors Predictive of Therapeutic Response: Evidence and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. Front Psychol. 2016;7:468. Published 2016 Apr 19. doi:10.3389/fpsyg.2016.00468.

Background Many patients with temporal or occipital migraines experience localized and throbbing pain, suggesting potential involvement of extracranial vessels. This study aimed to assess the presence or absence of vascular anomalies through proteomic analysis of biopsies.

Methods Intraoperatively, thirty-three biopsies were collected, including 19 from the superficial temporal artery and 14 from the occipital artery, and immediately processed for proteomic analysis. Based on differences noted in the preliminary results, patients were divided into two Groups: A (age ≤ 40 years) and B (age ≥ 41 years).

Results A total of 5339 proteins were identified. Comparison of temporal arteries between patients from Group A and patients from Group B revealed 394 significantly dysregulated proteins, with 204 upregulated in younger patients and 190 upregulated in older patients. Similarly, comparison of occipital arteries between younger and older patients revealed 325 significantly dysregulated proteins, with 91 upregulated in younger patients and 234 upregulated in older patients.

Conclusions The data collected, indicative of organic lesions, support the rationale for surgical therapy. Our results suggest differences between patients (showing an anti-inflammatory substrate or displaying a pro-inflammatory substrate), which need to be better investigated.

Background: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) are increasingly utilized to prevent neuroma formation following limb amputation, with prior studies demonstrating reductions in neuroma pain and phantom limb pain [1, 2]. However, long-term comparative recurrence data at the nerve level remain limited. This study evaluates long-term neuroma recurrence rates following TMR versus RPNI using a nerve-level analysis. Methods: A retrospective cohort study was conducted of 52 amputees undergoing TMR or RPNI, encompassing 132 treated nerves. Baseline demographics, amputation characteristics, and neuroma recurrence events were analyzed. The primary outcome was nerve-level neuroma recurrence. Secondary outcomes included patient-level recurrence and reoperation rates. Multivariable generalized estimating equations logistic regression was performed to assess independent predictors of recurrence. Results: The cohort had a mean age of 50.2 ± 17.9 years, and 67.3% were male. Traumatic injury accounted for 67.3% of amputations. A total of 97 nerves underwent TMR and 35 underwent RPNI. During a mean follow-up of 19.5 months, nerve-level neuroma recurrence occurred in 7.2% of TMR-treated nerves and 5.7% of RPNI-treated nerves. At the patient level, 3 patients developed neuromas from different nerves, while 9 developed recurrence from nerves that had previously received either TMR or RPNI. Multivariable analysis demonstrated no independent association between procedure type, traumatic etiology, or vascular comorbidities and neuroma recurrence. Conclusions: Both TMR and RPNI demonstrate low long-term neuroma recurrence rates based on nerve-level analysis. No significant difference in recurrence risk was observed between procedures after multivariable adjustment. These findings support the sustained effectiveness of both techniques in neuroma prevention following limb amputation, consistent with previously reported clinical outcomes. References: 1. Dumanian GA, Potter BK, Mioton LM, et al. Targeted Muscle Reinnervation Treats Neuroma and Phantom Pain in Major Limb Amputees: A Randomized Clinical Trial. Ann Surg. 2019;270(2):238-246. 2. Woo SL, Kung TA, Brown DL, Leonard JA, Kelly BM, Cederna PS. Regenerative Peripheral Nerve Interfaces for the Treatment of Postamputation Neuroma Pain: A Pilot Study. Plast Reconstr Surg Glob Open. 2016;4(12):e1038.

PURPOSE: Peripheral nerve injuries (PNIs) are a major source of lifelong disability and chronic pain, affecting approximately 67,800 individuals annually in the United States and occurring in up to 3% of extremity trauma cases. A key obstacle to improving outcomes is prompt identification and localization of PNIs to guide appropriate surgical reconstruction. However, current diagnostic modalities, such as electrodiagnostic studies and magnetic resonance imaging (MRI), provide incomplete and potentially misleading information, hindering optimal management. We recently identified the α7-Nicotinic Acetylcholine Receptor (α7-nAChR), a neuroinflammatory modulator expressed on macrophages and Schwann cells, as a promising biomarker of PNIs. In this study, we hypothesized that an FDA approved PET imaging agent [18F]ASEM, targeting α7-nAChR, could be used to identify and localize injured nerve segments after PNI in a rat sciatic nerve injury model.

METHODS: First, 27 male Lewis rats underwent right sciatic nerve transection without repair, followed by ex-vivo biodistribution studies one week after injury. Rats were intravenously injected with the [18F]ASEM radiotracer and harvested at 5, 15, 30, 90, 120, and 180 minute post-injection timepoints (n=4-5 rats/timepoint). Tissue collected from each rat included injured proximal and distal right sciatic nerve segments, uninjured left sciatic nerve, healthy and denervated muscles (bilateral gastrocnemius, bilateral biceps femoris), blood, brain, and kidney. Radiotracer uptake per sample was calculated using an automated gamma counter and expressed as percent injected dose per gram of wet tissue (%ID/g). Next, 10 male Lewis rats stratified into immediate repair (n=5) and unrepaired (n=5) groups underwent right sciatic nerve transection and ex-vivo biodistribution three weeks post-injury using the same methods described above. Finally, 2 additional Lewis rats underwent right sciatic transection (n=1 immediate repair; n=1 unrepaired) followed by dynamic PET/MRI of the lower extremities one week post-injury to assess in-vivo radiotracer distribution and time-activity patterns.

RESULTS: At 180 minutes after injection, [18F]ASEM uptake was statistically significantly higher in the distal injured sciatic nerve compared to healthy nerve, healthy muscle, and denervated muscle (p=0.006). These findings are consistent with expectations of Wallerian degeneration at an acute timepoint, where inflammation is expected to be greatest at the distal segment of injured nerve. At three weeks post-injury, radiotracer uptake remained significantly elevated in the unrepaired, injured nerve compared to the contralateral uninjured nerves (p<0.01). Importantly, uptake was attenuated in repaired relative to unrepaired nerves. This supports that α7-nAChR expression may reflect ongoing injury state and biological response to repair. Finally, dynamic PET/MRI demonstrated focal radiotracer accumulation at the site of unrepaired injury with high spatial resolution, supporting the feasibility of [18F]ASEM PET for in-vivo localization.

CONCLUSIONS: α7-nAChR-targeted PET imaging with [18F]ASEM enables noninvasive detection and localization of PNI in a rat model. Radiotracer uptake corresponds with the expected spatial and temporal profile of Wallerian degeneration and is modulated by surgical repair. These findings support further translation of α7-nAChR as an imaging biomarker of PNI to guide diagnosis, surgical planning, and monitoring in peripheral nerve reconstruction.

Purpose Clinical outcomes following microsurgical coaptation of peripheral nerves remain variable, limited by factors such as perineural scarring and incomplete axonal regeneration. This study evaluates the effects of MatriDerm® (MD), an FDA-approved synthetic collagen-elastin matrix clinically used for dermal wound coverage, on peripheral nerve regeneration in a rat sciatic nerve model. This material has previously been described to reduce scar tissue formation around intact peripheral nerves, but an investigation of the effect on peripheral nerve repair has not yet been performed.

Methods Forty female Lewis rats underwent right sciatic nerve transection and were randomized into four groups: direct epineural coaptation (EC), EC with additional MatriDerm® wrapping (EC-MD), autologous nerve graft interposition (AG), and AG with additional MatriDerm® wrapping (AG-MD). Over the 12-week postoperative period, functional recovery was evaluated weekly using the Visual Static Sciatic Index (VSSI). Body weight was analyzed as a potential correlate of pain and stress. After 12 weeks, the injured and healthy contralateral sciatic nerves, along with two target muscles, were harvested. Nerve specimens were analyzed histologically to quantify scar tissue formation and histomorphometry was performed to evaluate axonal regeneration. Muscle weight and histological sections of the muscle specimens were analyzed for signs of atrophy.

Results AG-MD animals exhibited significantly improved weight gain from postoperative week 3 onward (p < 0.05), whereas no difference was observed between EC groups. Functional recovery was enhanced in MatriDerm®-treated animals: the EC-MD group demonstrated significantly higher VSSI scores during the mid-recovery phase (p < 0.05 at week 3, 5, 6 and 8), indicating accelerated functional regeneration. In the autograft groups, MD-treated animals demonstrated superior functional recovery compared to the control group, with statistical significance at weeks 8 to 12 (p < 0.05). Histological analysis of scar tissue area in nerve cross-sections showed reduced epineural scarring in nerves treated with MatriDerm® in both injury models.

Conclusion MatriDerm® application appears to enhance peripheral nerve regeneration, resulting in earlier functional recovery in both repair types and improved postoperative weight gain in grafted animals. The effect of MD on limiting scar tissue formation was observed in both injury models. Owing to its clinical availability and ease of use, these findings support further translational evaluation of MatriDerm® as an adjunct in peripheral nerve repair.