Scientific Abstract Presentations: Migraine and Peripheral Nerve Session 3 Sunday, October 12 Sun, Oct 12 8:00-9:30 a.m. CDT

Surgical treatment of Rhinogenic Migraines: A Meta-Analysis of Patient-Reported Outcome Measures

Viren Patel, Quan Lu, Berk Ozman, R'ay Fodor, Ali Totonchi

Background: Headache is a common patient complaint, but poses a challenge for clinicians due to a wide range of etiologies and presentations. Due to overlap of symptomology, patients with migraines are often misdiagnosed as having rhinosinusitis and vice versa.1 Anatomic aberrancies of the nasal passages have long been implicated in the pathophysiology of headaches.2 Surgical approaches have been developed to address rhinogenic migraines, due to nasal contact points, but diagnosis, treatment and success of surgery is unclear due to wide range of available literature.

Methods: A systematic review was performed using PubMed database in December 2023 to identify studies that included patient-reported outcome measures (PROMs) following surgical treatment of rhinogenic migraines, usually with septoplasty or turbinate reduction. Due to heterogeneity of terminology used to characterize this condition in the literature, a broad search strategy was developed including terms "sinonasal, rhinogenic, rhinopathic, and "contact point." Inclusion criteria for the analysis was any study that reported PROMs and outcomes after surgical correction of rhinogenic migraines. Studies were excluded if patients with rhinosinusitis or other etiology of headache were indicated.

Results: From the search, 462 articles were identified, of which 46 were excluded for being written in Non-English language. The remaining titles and abstracts were reviewed and, ultimately, 14 were entered into the meta-analysis, comprising 591 patients. There were diverse terms to describe the condition including, "contact point headache" (n=6, 42%), "rhinogenic headache" (n=4, 29%), and "Rhinogenic contact point migraine" (n=2, 14%). The pooled mean difference in visual analog scale (VAS) score after surgery was 3.85 (95% CI: 3.80-3.90, p < 0.001). When comparing surgical and medical management, surgical patients had significantly greater improvement of VAS scores and significantly fewer headache days per month (p<0.05). VAS score improvement was similar for different indications including turbinate contact, septal spur and concha bullosa.

Conclusion: We present the first meta-analysis of studies describing surgical treatment of rhinogenic migraines. There is a large heterogeneity of terminology used to describe this condition and suggests that the migraine community should strive to used standard terminology and diagnostic standards. Overall, pooled analysis confirms significantly improved results for surgical management over medical treatment. Additionally, it seems that patients benefit from similar reduction in migraine symptoms, regardless of indication or severity of symptoms. Future studies should aim to better characterize patient complaints and predict which patients would benefit most from surgery.

1. Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C. Prevalence of Migraine in Patients With a History of Self-reported or Physician-Diagnosed "Sinus" Headache. Arch Intern Med. 2004;164(16):1769. doi:10.1001/archinte.164.16.1769
2. Stammberger H, Wolf G. Headaches and sinus disease: the endoscopic approach. Ann Otol Rhinol Laryngol Suppl. 1988;134:3-23. doi:10.1177/00034894880970s501

Introduction: Neurogenic thoracic outlet syndrome (nTOS) is characterized by the compression of neurovascular structures in the neck and shoulder region, leading to pain and paresthesia in the upper extremity. Diagnosis has traditionally been one of exclusion and heavily reliant on the clinical acumen of the physician. As MRI neurography (MRN)studies have become more readily available, it could help with the identification of patients with neurogenic TOS. This study evaluates MRN's reliability in aiding with the diagnosis of nTOS. Methods: We conducted a retrospective study of 32 patients who underwent TOS release surgery, with or without first rib resection, between 2021 and 2024. Patient records were reviewed for clinical presentation, demographics, TOS etiology, and diagnostic evaluation. We assessed MRN's ability to diagnose TOS compared to other methods. Results: All 32 patients underwent MRN prior to surgery. TOS was identified by MRN in 25 of 32 (78%) and by EMG in 20 of 32 (62%). All patients had at least one positive objective sign and subjective findings consistent with nTOS. The 7 patients with a negative MRN were negative by all other methods. After surgical decompression, 25 improved, 4 achieved complete or near-complete resolution, and 3 had persistent symptoms. Discussion: MRN proved to be a reliable method for preoperative TOS assessment, compared to other diagnostic tools. Its 78% detection rate supports its increasing use in TOS diagnosis. While its popularity increases, further studies are needed to establish it as a first-line diagnostic modality. The most common MRN findings were hyperintensity (80%), thickening (44%) and edema (16%). The most reported symptoms were paresthesia, burning sensation and pain. Additionally, 13 patients experienced symptom relief with injections. Conclusion: MRN is a valuable diagnostic tool for nTOS, aiding in preoperative assessment and diagnosis. While its use continues to grow, more studies are needed to establish it as a first-line modality.

BACKGROUND: Brachial plexus injuries (BPI) are severe and complex injuries that can lead to significant pain, functional impairment, and loss of sensation in the upper extremity, posing a substantial public health burden in the United States. BPI can affect both infants and adults through different mechanisms. Neonatal brachial plexus injuries (NBPI) often result from birth-related trauma, while adult BPI cases are primarily traumatic injuries caused by motor vehicle accidents or combat-related incidents. Despite advancements in surgical reconstruction, disparities in healthcare access persist, limiting treatment utilization, especially among racial and ethnic minority groups who have historically been underserved. This study aims to characterize the demographic distribution and utilization rates of surgical interventions among patients with BPIs. METHODS: A 10-year retrospective cohort study of 102 healthcare organizations (HCOs) in the TriNetX database was conducted. From January 2016 to February 2025, we identified all patients with BPIs using the International Classification of Diseases 10 (ICD 10) and Current Procedural Terminology (CPT) codes. The analyzed variables included age, gender, race, ethnicity, and the use of surgical treatments, defined as nerve transfers, tendon transfers, nerve grafts, free tissue muscle transfer, and neurolysis. Statistical analyses were conducted using TriNetX's Lucid Network. Continuous variables were compared with the Student's t-test, while categorical variables were analyzed using the Chi-squared test. A p-value of < 0.05 was deemed statistically significant. RESULTS: A total of 21,587 patients with BPIs were identified in the United States. The mean age was 44 ± 23 years (range: 0-90). Among these, 18,195 were adults (84.3%) and 3,360 were pediatric patients (15.6%). Male patients (60.6%) outnumbered female patients (37.1%). Within the cohort, 59.5% identified as White, 17.5% as Black or African American, 3.7% as Asian, 0.69% as Native Hawaiian, and 0.32% as American Indian. Additionally, 9.64% identified as Hispanic or Latino. The southern states had the highest proportion of BPI cases (36%). Among the identified cohort, 1,200 patients (5.6%) underwent surgical intervention. The most commonly performed procedures included neurolysis (41.6%), tendon transfers (38.5%), nerve grafts (28.2%), nerve transfers (11%), and free tissue muscle transfer (7.3%). Revision procedures were required in 179 cases (14.9%). Patients receiving surgical intervention were younger on average by 7.7 years (p < 0.0001). Demographic analysis indicated that male patients (p < 0.001) and Hispanic or Latino patients (p < 0.0001) were significantly overrepresented in the surgical group, while female patients (p < 0.0001), Asian patients (p = 0.0021), and American Indian patients (p < 0.0001) were statistically underrepresented. CONCLUSIONS: Surgical interventions have been shown to be an effective treatment modality for managing BPIs and may improve functional recovery and long-term outcomes despite its low utilization rate (5.6%). The significant demographic disparities in surgical utilization highlight unequal access to care. Future studies should aim to identify factors driving clinical variability, establish evidence-based protocols to standardize decision-making, optimize referral pathways, and address systemic disparities to ensure equitable access to care for all patients with BPI.

Introduction Adeno-associated viruses (AAVs) have become a widely used tool for gene therapy due to their low immunogenicity and inability to integrate into the host genome. Recent advancements have led to modified AAVs capable of efficiently targeting sensory neurons following systemic delivery. We hypothesized that localized intraneural injection of these vectors could achieve selective transduction of the injected nerves. To test this, we engineered an AAV vector to express cleaved caspase-3, a pro-apoptotic protein, with the goal of inducing targeted neuronal apoptosis and effectively eliminating specific nerves.

Methods A recombinant AAV9 vector was designed to express a modified form of cleaved caspase-3 under the control of the neuron-specific human synapsin 1 (hSyn1) promoter. This promoter ensures expression is restricted to neurons, triggering apoptosis upon activation. A control vector with identical regulatory elements was generated but expressed eGFP instead of caspase-3.

Experiments were performed on 6- to 10-week-old C57BL/6J mice following protocols approved by the Johns Hopkins University Animal Care and Use Committee. The common peroneal or sciatic nerve was injected with 10¹⁰ viral genomes (vg) of either the experimental or control vector using a 36-gauge needle.

At euthanasia, bilateral sciatic nerves, L3-L5 dorsal root ganglia (DRGs), and spinal cords were dissected, fixed in 4% paraformaldehyde for 24 hours, and cryoprotected in a 30% sucrose solution. Immunohistochemistry was performed using antibodies against cleaved caspase-3 (to confirm transgene expression), CD68 (a macrophage marker indicating inflammation and degeneration), and neurofilament (a neuronal marker). Samples transfected with the GFP-expressing vector were also analyzed for endogenous GFP fluorescence. ImageJ was used for quantitative image analysis, and statistical comparisons were conducted using Student's t-tests. Significance was defined as p<0.05.

Results Nine days after injection into the common peroneal nerve, numerous cell bodies in the ipsilateral L3 DRG exhibited cleaved caspase-3 expression, confirming successful transgene expression (p < 0.05). Three weeks post-injection into the sciatic nerve, a significant increase in CD68+ macrophages was observed in the ipsilateral sciatic nerve, consistent with Wallerian degeneration (p < 0.05). Additionally, nerve cross-sections revealed basement membrane gaps, likely corresponding to apoptotic neurons. Following direct injection into the common peroneal nerve, vector spread was limited, as evidenced by lack of expression in the tibial and sural nerves.

Conclusions Localized intraneural administration of viral vectors allows for selective transduction of targeted nerve fascicles. By driving the expression of cleaved caspase-3, these vectors can effectively induce neuronal apoptosis. This approach holds therapeutic potential for conditions where selective denervation is beneficial, including painful neuromas, osteoarthritis, and spasticity. Ongoing experiments are assessing the efficacy of this strategy in these models to further evaluate its therapeutic potential.

Magnetic Resonance Imaging Appearance of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces in Oncologic Amputees: A Retrospective Case Series

Amir-Ala Mahmoud BA, Amir-Ali Mahmoud MD, Sara M. Bahouth MD, Ged G.Wieschhoff MD, Marco Ferrone MD, Lydia A. Helliwell MD MMSc, Jacob Mandell MD

Background

Patients with extremity sarcomas undergo amputation when limb salvage surgery is not feasible. Targeted Muscle Reinnervation (TMR) or Regenerative Peripheral Nerve Interface (RPNI) procedures can mitigate the incidence of neuroma after amputation, however neuromas can still form. The purpose of this study is to describe the MRI characteristics of TMR/RPNI, assess how the neuromas that form after each procedure change over time, and differentiate the MRI appearance of neuroma formation from sarcoma recurrence.

Methods

All patients at our institution between 2013-2024 who underwent upper or lower extremity amputation (UEA/LEA) for sarcoma with TMR/RPNI, and with follow-up MRI surveillance imaging were included. The incidence, appearance (size, signal and enhancement characteristics, and morphology), and change over time were described by two radiologists. Statistics included the Chi-squared test and McNemar's test.

Results

26 patients (7 UEA, 19 LEA) underwent 62 TMRs and 46 RPNIs, with 7 receiving TMR-only, 7 RPNI-only, and 12 both TMR/RPNI, with an average follow-up length of 517 days (range 91-1705 days). Nodular, T2 hyperintense, enhancing foci developed at 44% of all nerve surgeries and in 73% of patients at initial follow-up MRI, with an average diameter of 0.8 cm (range 0.3-2.0 cm). The incidence of these nodular foci, presumed to represent neuromas, decreased over time across all patients (p <0.001) with no significant difference between nodule incidence in RPNI-only and TMR-only patients; however, TMR-only patients demonstrated a significant reduction in nodule size (p = 0.007). There were two cases of recurrence which demonstrated a progressive increase in irregularly-shaped nodule size. A third patient's persistent nodule was biopsied, with pathology of neuroma.

Conclusion

TMR and RPNI performed in the setting of amputation for sarcoma commonly demonstrate enhancing T2 hyperintense enhancing nodules at the first follow-up MRI which are presumed to represent neuromas. The incidence of these neuromas decreases over time, however only TMR results in a significant decrease in neuroma size. Any increase in size or presence of a nodule that is not in continuity with a peripheral nerve should raise concern for possible recurrence and should be biopsied. These findings are crucial for plastic surgeons that perform TMR/RPNI in the setting of sarcoma-related amputations. Understanding MRI characteristics of TMR/RPNI can aid in timely diagnosis and intervention, minimizing complications, delayed diagnoses, and unnecessary biopsies in this patient population.

Introduction

Migraine is a debilitating condition that significantly impacts quality of life and affects over 1 billion individuals worldwide (1). While pharmacological management remains first line for migraine treatment, many patients continue to experience refractory symptoms despite multiple medication trials (2). Migraine decompression surgery (MDS) has emerged as a potential intervention for select patients, targeting specific peripheral nerve trigger points to reduce headache frequency and severity (3). While prior research largely emphasizes symptom reduction, data on postoperative medication usage after MDS is limited (4). Examining the impact of migraine surgery on patients' usage of medication may offer valuable insights into the effectiveness of MDS and its potential to reduce medication burden. This retrospective case series assesses changes in the number of medications used by patients following MDS.

Methods:

CPT codes were used to identify MDS performed by a single surgeon from 2021-2025. Patient demographics, pre- and postoperative migraine medication usage, and improvements in migraine trigger site pain postoperatively were collected. SPSS was used for statistical analysis. Descriptive statistics were used to analyze overall results, with a paired T-test used to examine changes in overall medication usage.

Results:

Twenty-three patients with chronic migraines underwent MDS. All patients underwent diagnostic nerve block of trigger sites prior to surgery to identify the origin of pain. The average age at surgery was 44.7 years old (Range: 17-82 years, SD ± 17.7 years), with 19 patients being female and 4 patients being male. The majority of patients were white (82.6%) and non-Hispanic (91.3%). Prior to surgery, the average number of migraine medications trialed (whether failed or used at intake visit) was 13.26 (Range: 2-98, SD ± 19.0). The average number of migraine medications taken postoperatively was 5.48 (Range: 0-11, SD ± 2.92) for a mean difference of 3.91 fewer medications after surgery when excluding outliers (p<0.001). Nineteen patients (82.6%) reported resolution or >50% improvement in migraine symptoms at their most recent postoperative visit as a result of MDS.

Conclusion:

MDS is an effective treatment for chronic migraines and is associated with a significant reduction of migraine medication usage postoperatively. Future prospective studies on larger patient populations are needed to confirm these findings.

References

1. Amiri P, Kazeminasab S, Nejadghaderi SA, et al. Migraine: A Review on Its History, Global Epidemiology, Risk Factors, and Comorbidities. Front Neurol. 2022;12:800605. Published 2022 Feb 23. doi:10.3389/fneur.2021.800605

2. Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17(2):174-182. doi:10.1016/S1474-4422(17)30435-0

3. Guyuron B, Kriegler JS, Davis J, Amini SB. Comprehensive surgical treatment of migraine headaches. Plast Reconstr Surg. 2005;115(1):1-9.

4. Janis JE, Barker JC, Javadi C, Ducic I, Hagan R, Guyuron B. A review of current evidence in the surgical treatment of migraine headaches. Plast Reconstr Surg. 2014;134(4 Suppl 2):131S-141S. doi:10.1097/PRS.0000000000000661

PURPOSE: Preserving sensation after mastectomy is a key concern for women. This pilot study evaluates tactile sensory restoration across three breast reconstruction cohorts: non-neurotized, single-neurotized, and dual-neurotized reconstruction.

METHODS: Patients undergoing mastectomy with immediate alloplastic or deep inferior epigastric perforator (DIEP) flap reconstruction were prospectively enrolled and followed. In alloplastic reconstruction cases, no neurotization was performed, and this group served as the control. For DIEP reconstructions, patients underwent either single-nerve (pre-2024) or dual-nerve coaptation (post-2024) at the time of surgery.

Neurosensory testing using the pressure-specified sensory device was conducted across nine breast regions (outer superior (OS), outer medial (OM), outer inferior (OI), outer lateral (OL), inner superior (IS), inner medial (IM), inner inferior (II), inner lateral (IL), and nipple-areolar complex (NAC)) preoperatively and at multiple postoperative intervals. Sensory recovery was assessed relative to baseline, with all patients serving as their own controls. Average sensory scores were then compared among the three groups: (1) non-neurotized implant, (2) single-neurotized DIEP, and (3) dual-neurotized DIEP. Statistical analysis was performed using Student's t-tests with a Bonferroni correction to account for multiple comparisons.

RESULTS:
This study included 38 non-neurotized patients (64 breasts), 29 single-neurotized patients (50 breasts), and 16 dual-neurotized patients (30 breasts). Demographics, comorbidities, and adjunctive oncologic regimens were comparable between groups.

The dual-neurotized group had significantly better sensation than the non-neurotized group at all postoperative time points (p < 0.001). Specifically, at 3 months postoperatively, the dual-neurotized group showed significantly better sensation in the OS, IS, IM, II, and IL regions. By 6 and 9 months, sensory recovery was significantly superior in all nine regions.

The dual-neurotized group also had significantly greater sensory recovery than the single-neurotized group at 6 months (70.3% vs. 42.5%, p = 0.002) and 9 months postoperatively (74.8% vs. 47.0%, p = 0.015). At 6 months, sensory recovery was significantly greater in the OS, OI, and II regions compared to the single-neurotized group, and at 9 months, it was significantly greater in the OS, OI, OL, and IL regions.

CONCLUSION: This pilot study supports neurotization at the time of reconstruction, demonstrating superior tactile sensory recovery in dual-neurotized patients compared to both single-neurotized and non-neurotized patients.

PURPOSE: Preserving sensation after mastectomy is a key concern for women. This pilot study evaluates tactile sensory restoration across three breast reconstruction cohorts: non-neurotized, single-neurotized, and dual-neurotized reconstruction.

METHODS: Patients undergoing mastectomy with immediate alloplastic or deep inferior epigastric perforator (DIEP) flap reconstruction were prospectively enrolled and followed. In alloplastic reconstruction cases, no neurotization was performed, and this group served as the control. For DIEP reconstructions, patients underwent either single-nerve (pre-2024) or dual-nerve coaptation (post-2024) at the time of surgery.

Neurosensory testing using the pressure-specified sensory device was conducted across nine breast regions (outer superior (OS), outer medial (OM), outer inferior (OI), outer lateral (OL), inner superior (IS), inner medial (IM), inner inferior (II), inner lateral (IL), and nipple-areolar complex (NAC)) preoperatively and at multiple postoperative intervals. Sensory recovery was assessed relative to baseline, with all patients serving as their own controls. Average sensory scores were then compared among the three groups: (1) non-neurotized implant, (2) single-neurotized DIEP, and (3) dual-neurotized DIEP. Statistical analysis was performed using Student's t-tests with a Bonferroni correction to account for multiple comparisons.

RESULTS:
This study included 38 non-neurotized patients (64 breasts), 29 single-neurotized patients (50 breasts), and 16 dual-neurotized patients (30 breasts). Demographics, comorbidities, and adjunctive oncologic regimens were comparable between groups.

The dual-neurotized group had significantly better sensation than the non-neurotized group at all postoperative time points (p < 0.001). Specifically, at 3 months postoperatively, the dual-neurotized group showed significantly better sensation in the OS, IS, IM, II, and IL regions. By 6 and 9 months, sensory recovery was significantly superior in all nine regions.

The dual-neurotized group also had significantly greater sensory recovery than the single-neurotized group at 6 months (70.3% vs. 42.5%, p = 0.002) and 9 months postoperatively (74.8% vs. 47.0%, p = 0.015). At 6 months, sensory recovery was significantly greater in the OS, OI, and II regions compared to the single-neurotized group, and at 9 months, it was significantly greater in the OS, OI, OL, and IL regions.

CONCLUSION: This pilot study supports neurotization at the time of reconstruction, demonstrating superior tactile sensory recovery in dual-neurotized patients compared to both single-neurotized and non-neurotized patients.

Purpose Patients with neuropathic pain in the head and neck typically exhaust various conservative treatment options-including botulinum toxin injections, peripheral nerve blocks, and medications-that typically provide only temporary relief prior to undergoing nerve decompression. The extent to which surgery reduces the use of injectable treatments postoperatively is unclear. Therefore, this study aims to assess the postoperative reduction in the use of botulinum toxin and nerve blocks among patients who undergo nerve decompression surgery.

Methods A total of 50 patients who underwent nerve decompression surgery at Weill Cornell Medical Center (n=25) and Massachusetts General Hospital (n=25) between June 2023 and September 2024 were included in this study. Standardized surveys were administered prospectively at baseline (pre-operative), 3-month follow-up (post-operative), and 12-month follow-up. Patient data collection included demographic information and data regarding botulinum toxin and nerve blocks usage pre- and post-operatively.

Results The study population predominantly consisted of females (82%, n=41), with a mean age of 47.4 years (SD 15.4 years). The mean follow-up was 5.88 months (SD 4.2). Preoperatively, 78% (n=39) of patients received botulinum toxin injections, with a median of 7 injections per patient (IQR 15.75). Most patients (85%, n=33) received botulinum toxin injections in both the front and the back of their head. Symptom relief varied, with 51% (n=20) experiencing partial relief (<50%), 23% (n=9) reporting significant improvement (>50%), and only one patient achieving complete relief. The duration of botulinum toxin efficacy ranged from less than a week (23%, n=9) to more than 6 months (5%, n=2). Peripheral nerve blocks were administered in 86% (n=43) of patients prior to surgery, with a median of 5 injections (IQR 5.5). The most common injection site was the back of the head (65%, n=28). A subset of patients (21%, n=9) reported no symptom relief. The duration of relief ranged from less than an hour in 6 patients (15%) to more than a month but less than three months in 17% (n=7). Postoperatively, botulinum toxin use significantly declined from 78% to 30% (P<0.001). Additionally, among those who continued botulinum toxin treatment, nearly half (46%, n=6) reported improved efficacy. Similarly, nerve block administration decreased significantly, from 86% to 24% (n=12) (P<0.001), with 14% (n=1) noting improved efficacy following surgery.

Conclusion This study demonstrates that injectable treatments provide only limited and temporary relief preoperatively. Additionally, it shows that nerve decompression surgery significantly reduces the need for botulinum toxin injections and nerve blocks in patients with HDs caused by peripheral nerve compression. Limiting the need for repeated injectable treatment will improve patients' quality of life and reduce the financial burden on the healthcare system.

Trigeminal neuralgia is a chronic pain disorder of the face that affects the trigeminal nerve. The electric, shock-like facial pain can be either continuous or paroxysmal and is triggered by factors including light touch, talking, chewing, and drinking. Due to the presence of multiple branches, the trigeminal nerve is an anatomically complex structure. When considering surgical treatment options, it is important to consider possible anatomical variations of the nerve and its branches. However, few, if any, studies have analyzed variations in the supraorbital, supratrochlear, and infraorbital nerves with respect to patient outcomes regarding trigeminal neuralgia. This study aims to document variations in the supraorbital, supratrochlear, and infraorbital nerves in body donors and in patients with trigeminal neuralgia. The faces of four unembalmed body donors were dissected (6 hemi-faces total), and the supraorbital, supratrochlear, and infraorbital nerves were uncovered in each hemi-face. Images of each hemi-face were taken. The number of branches for each nerve was documented by two anatomists, one plastic surgeon, and one medical student independently and the final values for each nerve were averaged. The presence of a fibrous band associated with any of the nerves was also noted. Findings were compared to two patients who underwent surgical correction of trigeminal neuralgia. Across six hemi-faces, there was an average of 1.67 (Range: 1-2) main branches of the supraorbital nerve, 1 main branch of the supratrochlear nerve, and 3.98 (Range: 3-5) main branches of the infraorbital nerve. Regarding fibrous bands, one third of the hemi-faces had fibrous bands associated with either the supraorbital or supratrochlear notches. A similar fibrous band had to be cut to release the supraorbital nerve in one of the two patients who underwent surgical correction. Although the second patient did not have a fibrous band present, this patient had 3 main branches of the supraorbital nerve. This number of branches was not observed in the dissection of the hemi-faces. Both patients are now pain free one year and one month post operation, respectively. This study shows variation in the number of main branches of the supraorbital, supratrochlear, and infraorbital nerves. The comparison of our documented anatomical variations with the surgical decompression case indicates the presence of a fibrous band at the supraorbital notch may be an understudied cause of trigeminal neuralgia. Reconstructive surgeons should be aware of the variations of the trigeminal nerve and the presence of fibrous bands associated with the supratrochlear or supraorbital notches in order to provide optimal surgical outcomes in the treatment of trigeminal neuralgia.

Purpose: Osteomyelitis (OM) is a serious complication in amputees with osseointegrated implants (OI). This study characterizes OM in OI patients, focusing on risk factors, clinical presentation, infection progression, and diagnostic timelines.

Methods: A retrospective review of 127 OI patients (2017-2023) identified OM cases by positive intraoperative bone cultures or radiographic evidence (i.e., X-ray, CT, MRI). Demographic, clinical, and surgical characteristics were compared between OM and non-OM patients using statistical tests.

Results: OM occurred in 11 of 127 patients (8.7%) with no statistically significant differences between groups for any tested variable. Median follow-up was 2.6 years (IQR: 2.1) across all OI patients. OM patients were more often female (55% vs. 28%, p = 0.091) and had higher rates of tobacco use (45% vs. 34%, p = 0.5), alcohol use (55% vs. 40%, p = 0.4), and hypertension (36% vs. 27%, p = 0.5) but a lower median BMI (27.0 vs. 28.5, p = 0.3). They had a shorter median time from amputation to osseointegration (1 vs. 5 years, p = 0.2) and were more frequently amputated at the femur (64% vs. 59%, p > 0.9) and right limb (73% vs. 47%, p = 0.10). Trauma (64%) was the leading amputation cause, followed by infection (27%) and surgical complications (9%) in OM patients. Pain (91%) and functional limitation (91%) were the most common OM symptoms, followed by drainage (63%), erythema (18%), mechanical issues (36%), and sensory changes (36%). Among patients with drainage (64%), 45% had purulent, 9% serous, and 9% bloody discharge. Two (18%) OM cases were diagnosed incidentally via routine intraoperative cultures. Symptom onset to evaluation took 35 days (IQR: 92.5), and symptom onset to culture confirmation took 124 days (IQR: 232). Streptococci were the most common pathogens (64%), and 73% of infections were polymicrobial.

Conclusion: OM in OI patients is frequently polymicrobial and presents with pain and functional limitations. Diagnostic delays highlight the need for improved screening and treatment strategies. Further research should focus on optimizing infection control and implant retention strategies.

Purpose: Osteomyelitis (OM) is a serious complication in amputees with osseointegrated implants (OI). This study characterizes OM in OI patients, focusing on risk factors, clinical presentation, infection progression, and diagnostic timelines.

Methods: A retrospective review of 127 OI patients (2017-2023) identified OM cases by positive intraoperative bone cultures or radiographic evidence (i.e., X-ray, CT, MRI). Demographic, clinical, and surgical characteristics were compared between OM and non-OM patients using statistical tests.

Results: OM occurred in 11 of 127 patients (8.7%) with no statistically significant differences between groups for any tested variable. Median follow-up was 2.6 years (IQR: 2.1) across all OI patients. OM patients were more often female (55% vs. 28%, p = 0.091) and had higher rates of tobacco use (45% vs. 34%, p = 0.5), alcohol use (55% vs. 40%, p = 0.4), and hypertension (36% vs. 27%, p = 0.5) but a lower median BMI (27.0 vs. 28.5, p = 0.3). They had a shorter median time from amputation to osseointegration (1 vs. 5 years, p = 0.2) and were more frequently amputated at the femur (64% vs. 59%, p > 0.9) and right limb (73% vs. 47%, p = 0.10). Trauma (64%) was the leading amputation cause, followed by infection (27%) and surgical complications (9%) in OM patients. Pain (91%) and functional limitation (91%) were the most common OM symptoms, followed by drainage (63%), erythema (18%), mechanical issues (36%), and sensory changes (36%). Among patients with drainage (64%), 45% had purulent, 9% serous, and 9% bloody discharge. Two (18%) OM cases were diagnosed incidentally via routine intraoperative cultures. Symptom onset to evaluation took 35 days (IQR: 92.5), and symptom onset to culture confirmation took 124 days (IQR: 232). Streptococci were the most common pathogens (64%), and 73% of infections were polymicrobial.

Conclusion: OM in OI patients is frequently polymicrobial and presents with pain and functional limitations. Diagnostic delays highlight the need for improved screening and treatment strategies. Further research should focus on optimizing infection control and implant retention strategies.

Background: Peripheral nerve injuries (PNIs) are common, and the current standard of care relies on the slow and inefficient process of spontaneous regeneration. Electrical stimulation (ES) enhances motor and sensory regeneration; however, its effects on sympathetic regeneration is unknown.

Methods: To study acute ES effects, 1 hour, 20 Hz stimulation was applied to transected and repaired mouse sciatic nerves. ES was compared to a conditioning lesion (CL) and sham. Axonal regeneration was evaluated after 2 weeks via immunohistochemistry.

To study long-term ES effects, sweating recovery was tracked with a pilocarpine assay for 12 weeks after sciatic nerve transection, with and without ES. Reinnervation of the most distal sweat glands was assessed via immunohistochemistry, and neurons reinnervating the foot and tibialis anterior (TA) were fluorescently labeled. Purines in the gastrocnemius (GA) were quantified using high-performance liquid chromatography to evaluate skeletal muscle energy charge. In a separate 12-week cohort, compound muscle action potentials were measured from the GA.

Results: ES and CL do not enhance sympathetic regeneration but do enhance motor/sensory regeneration acutely. ES neither improves long-term sweating recovery nor reinnervation of the most distal sweat glands. ES improves motor reinnervation, but not sympathetic reinnervation, of the foot. Motor reinnervation of the TA is nearly complete by 12 weeks, but sympathetic reinnervation remains incomplete. Despite the return to baseline CMAP amplitudes 12 weeks after injury with or without ES, ES does not resolve injury-related mitochondrial metabolism deficits and muscle atrophy.

Conclusion: ES does not enhance sympathetic regeneration. Despite the return of motor reinnervation of more proximal muscles 12 weeks post-PNI, alterations in skeletal muscle energy charge and muscle bulk persist, likely due to decreased sympathetic reinnervation.

Background: Traumatic peripheral nerve injuries lead to motor deficits and irreversible muscle atrophy. While segmental nerve gaps are commonly repaired with autografts, their availability is limited, and harvesting them can cause donor site morbidity. Decellularized nerve allografts offer an alternative, but adequate vascularization is crucial for axonal regrowth, particularly in large-diameter or long-segment grafts. This study explores the use of tissue nanotransfection (TNT) to deliver vasculogenic genes to the recipient sciatic nerve before grafting with allografts, aiming to enhance revascularization and support axonal regeneration.

Methods: TNT was used to deliver a reprogramming vasculogenic gene cocktail-Etv2, Foxc2, and Fli1 (EFF)-to injured sciatic nerves. Ten-week-old C57BL/6 mice received decellularized allografts (1 cm) to the right sciatic nerve. Study groups included a control (sham surgery), allografts with sham TNT (mock plasmids), and allografts with EFF transfection. Functional recovery was assessed using the sciatic functional index (SFI), compound muscle action potential (CMAP), motor unit number estimation (MUNE), twitch and tetanic force, and grip strength, measured biweekly over 20 weeks. For histological analysis, allografts were harvested at two-week intervals and stained for endothelial cells, Schwann cells, and neurofilament.

Results: Vasculogenic transfection in allografts significantly increased grip strength, with statistical significance observed at week 12. Electromyography showed improved outcomes in the transfected allografts, with significant increases in twitch force at week 10 and tetanic force from week 8 through the study's conclusion at week 20. CMAP and MUNE remained comparable across all groups. Histologic analysis showed increased Cd31 cells in Eff treated grafts compared to other groups.

Conclusion: This study demonstrates that nanotransfection enhances vasculogenesis and functional muscle recovery in allografts in association with increased vasculogenesis. These findings suggest that TNT could be a promising strategy to improve outcomes in nerve allografting for large or complex nerve defects.

Introduction: Peripheral nerve injuries-in-continuity are challenging to manage in the acute setting due to difficulties with defining the zone of injury. Intraoperative nerve stimulation along the length of the injured nerve may help determine the extent of injury for acute resection and grafting. We present a novel in-vivo nerve stretch injury model that correlates intraoperative nerve stimulation findings with histological changes.

Methods: We created stretch injuries to the median nerves of 24–28-week-old Lewis rats by applying a vertical traction force of 4-5N using a digital force transducer and sling attachment. Electrical stimulation was performed at varying locations along the length of the nerve with bipolar electrodes was conducted before and after injury and evoked grip strength was measured. Animals were sacrificed at either 0-, 2-, and 8-weeks post-injury (n=5 per timepoint). Histological assessment of fibrosis and nerve microarchitecture was performed with Masson's Trichrome stain and immunohistochemical markers neurofilament-H and laminin to evaluate the zone of injury and compare histological findings with the motor responses elicited with intraoperative stimulation at varying points along the length of the injured nerve.

Results: Intraoperative stimulation at the site of traction injury, at time 0, elicited no motor response, which correlated with histological findings of axonal fragmentation, epineurial disruption, and loss of the characteristic undulations of the bands of Fontana. However, stimulation 1 cm distal to the injury site resulted in grip formation correlating with preserved native architecture. By 2 weeks, Wallerian degeneration was evident in the distal segment while the site of traction injury demonstrated pronounced axonal disorganization. At 8 weeks, a neuroma-in-continuity was present at the site of traction injury characterized by disorganized axonal growth and fibrosis. Despite applying the maximum stretch force to the nerves to avoid rupture, spontaneous regeneration and motor functional recovery was unexpectedly observed.

Conclusions: The location of the nerve distal to the site of stretch injury at which functional motor response was elicited with electrical stimulation correlates with the transition point between damaged and normal architecture. While spontaneous recovery occurred in our model due to the superlative regenerative capacities of rodents, our findings suggest that intraoperative stimulation may be useful in guiding the extent of resection needed when performing acute reconstruction of severe stretch injuries in which the surgeon is able to rule out the possibility of spontaneous recovery.

Purpose Regenerative Peripheral Nerve Interface (RPNI) surgery is a promising technique for treating post amputation and neuroma pain. Recent animal studies (1) have revealed potential sex-specific differences in pain mitigation after RPNI surgery, suggesting the influence of gender-based nociceptive pathways. These differences have not yet been examined in human studies. Identification of gender-based differences in pain outcomes following RPNI surgery allows a more individualized pain management. Methods: A retrospective institutional study was conducted using DataDirect, the University of Michigan Medicine's clinical database. We analyzed patients who underwent major upper or lower limb amputation between 2015 and 2024, with at least one year of post-operative clinical data. The cohort included male and female patients with and without RPNI surgery. Data collected included neuroma and phantom limb pain scores, length of hospital stay, along with analgesic and narcotic use. Narcotic use was standardized to milligrams morphine equivalents per day (MME/day), while overall analgesic use was quantified using the Medication Quantification Scale version III (MQSIII). Statistical analysis was performed using SPSS. Results 1,261 patients were identified: 844 males (184 RPNI patients, 660 controls) and 417 females (96 RPNI patients, 312 controls). Among the RPNI group, 22% of patients had phantom limb pain, compared to 49% in the control group. There was no significant difference between male and females in both groups. Additionally male RPNI group demonstrated significantly lower narcotic use compared to control. There was no significant difference between female and male narcotic use. Overall analgesic use did not vary significantly between groups. Both female and male RPNI groups demonstrated significantly shorter hospital stays compared to controls (p<0.01). Male control patients experienced shorter length of stay compared to female patients.
Conclusions RPNI surgery significantly reduced phantom limb pain and hospital length of stay for both male and female patients compared to controls, highlighting its efficacy in post-amputation pain management. These findings suggest that while RPNI is effective in mitigating post-amputation pain, further research is needed to explore potential gender-specific mechanisms influencing pain perception and medication use.

1. Amir Dehdashtian, Timek JH, Svientek SR, et al. Sexually Dimorphic Pattern of Pain Mitigation Following Prophylactic Regenerative Peripheral Nerve Interface (RPNI) in a Rat Neuroma Model. Neurosurgery. 2023;93(5):1192-1201. doi:https://doi.org/10.1227/neu.0000000000002548