Economic Cost-Benefit Analysis of Nerve Implanted into Muscle versus Targeted Muscle Reinnervation versus Regenerative Peripheral Nerve Interface, for Treatment of the Painful Neuroma.

BACKGROUND: This study investigated the relative cost utility of three techniques for the management of symptomatic neuromas after neuroma excision: (1) implantation of nerve into muscle, (2) targeted muscle reinnervation (TMR), and (3) regenerative peripheral nerve interface (RPNI). METHODS: The costs associated with each procedure were determined using Common Procedural Terminology codes in combination with data from the Centers for Medicaid and Medicare Services Physician and Facility 2020 Fee Schedules. The relative utility of the three procedures investigated was determined using changes in Patient-Reported Outcomes Measurement Information System (PROMIS) and Numeric Rating Scale (NRS) pain scores as reported per procedure. The relative utility of each procedure was reported in terms of quality-adjusted life years (QALYs), as is standard in the literature. RESULTS: The least expensive option for the surgical treatment of painful neuromas was nerve implantation into an adjacent muscle. In contrast, for the treatment of four neuromas, as is common postamputation, TMR without a microscope was found to cost $50,061.55 per QALY gained, TMR with a microscope was found to cost $51,996.80 per QALY gained, and RPNI was found to cost $14,069.28 per QALY gained. While RPNI was more expensive than nerve implantation into muscle, it was still below the standard willingness-to-pay threshold of $50,000 per QALY, while TMR was not. CONCLUSION: Evaluation of costs and utilities associated with the various surgical options for the management of painful neuromas suggest that nerve implantation into muscle is the least expensive option with the best improvement in QALY, while demonstrating comparable outcomes to TMR and RPNI with regard to pain symptoms.

Cryoanalgesia: Review with Respect to Peripheral Nerve.

BACKGROUND: Cryoanalgesia is a tool being used by interventional radiology to treat chronic pain. Within a certain cold temperature range, peripheral nerve function is interrupted and recovers, without neuroma formation. Cryoanalgesia has most often been applied to the intercostal nerve. Cryoanalgesia has applications to peripheral nerve surgery, yet is poorly understood by reconstructive microsurgeons. METHODS: Histopathology of nerve injury was reviewed to understand cold applied to peripheral nerve. Literature review was performed utilizing the PubMed and MEDLINE databases to identify comparative studies of the efficacy of intraoperative cryoanalgesia versus thoracic epidural anesthesia following thoracotomy. Data were analyzed using Fisher's exact and analysis of variance tests. A similar approach was used for pudendal cryoanalgesia. RESULTS: Application of inclusion and exclusion criteria resulted in 16 comparative clinical studies of intercostal nerve for this review. For thoracotomy, nine studies compared cryoanalgesia with pharmaceutical analgesia, with seven demonstrating significant reduction in postoperative opioid use or postoperative acute pain scores. In these nine studies, there was no association between the number of nerves treated and the reduction in acute postoperative pain. One study compared cryoanalgesia with local anesthetic and demonstrated a significant reduction in acute pain with cryoanalgesia. Three studies compared cryoanalgesia with epidural analgesia and demonstrated no significant difference in postoperative pain or postoperative opioid use. Interventional radiology targets pudendal nerves using computed tomography imaging with positive outcomes for the patient with pain of pudendal nerve origin. CONCLUSION: Cryoanalgesia is a term used for the treatment of peripheral nerve problems that would benefit from a proverbial reset of peripheral nerve function. It does not ablate the nerve. Intraoperative cryoanalgesia to intercostal nerves is a safe and effective means of postoperative analgesia following thoracotomy. For pudendal nerve injury, where an intrapelvic surgical approach may be difficult, cryoanalgesia may provide sufficient clinical relief, thereby preserving pudendal nerve function.

Histologic evidence of brachial plexus compression sites at the thoracic inlet and variations in formation of the lower trunk in cadavers.

BACKGROUND: In thoracic "outlet" syndrome (TOS), pathologic evidence is well documented for vascular but not neurologic compression. We hypothesized that histologic evidence of compression would be identified at sites where the upper trunk was impacted by the anterior scalene muscle and the lower trunk by anatomic anomalies or the first rib. The purpose of this study was to investigate this hypothesis in human cadavers. MATERIALS AND METHODS: Twenty-five cadavers' brachial plexuses were dissected and excised. Histologic and descriptive analysis was directed at juncture 1, the upper trunk and anterior scalene muscle, and juncture 2, C8 and T1 nerve roots (lower trunk) with the posterior border of the first rib. Measurements were obtained at the juncture of the T1 nerve root with the C8 nerve root in relationship to the first rib. RESULTS: Histologic analysis demonstrated epineurial and perineurial fibrosis, myelin thinning, and Renaut bodies at junctures 1 and 2. Lower trunk formation occurred on or lateral to the first rib in 66% of specimens, with asymmetry in 32% of cadavers. A muscle of Albinus was present in 18% of cadavers. A large dorsal scapular artery coursed through 36% of plexuses with a high, arched subclavian artery. CONCLUSIONS: We report histologic changes consistent with chronic compression of the upper and lower plexus in the thoracic inlet at hypothesized sites of brachial plexus compression that may correlate with clinical neck/shoulder (upper trunk) and "ulnar nervelike" (C8-T1/lower trunk) symptoms. Anatomic anomalies identified should alert the surgeon to variations of lower trunk formation at compression sites.

A History of Anatomical Eponyms of the Ulnar Nerve.

The ulnar nerve has a long and often misunderstood history with eponym usage. We describe the history of eponym usage in the anatomy of the ulnar nerve-who, when, what, where, and how. The relevant anatomy is investigated from proximal to distal, from the Arcade of Struthers to Osborne's band, to forearm ulnar nerve to median nerve connections, to Guyon's canal. We hope to provide a historical perspective of interest, resolve any controversies in semantic definitions, and create a comprehensive library of eponymous terms related to ulnar nerve anatomy.

A Markov Analysis of Surgical versus Medical Management of Chronic Migraines.

BACKGROUND: Refractory chronic migraine is a common and debilitating neurologic condition, affecting over 8 million people in the United States. It is associated with billions of dollars in lost productivity annually. Novel medical (anti-calcitonin gene-related peptide antibodies) and surgical treatment modalities have emerged for chronic migraine in recent years. The current study investigated the cost-utility of surgical versus medical management of refractory chronic migraine. METHODS: A Markov cohort analysis using hybrid Monte Carlo patient simulation was performed to compare surgical decompression versus erenumab for the treatment of refractory chronic migraine in adults. Both societal and payer perspectives were considered. Primary model outcomes included incremental cost-effectiveness ratio, or cost per quality-adjusted life-year gained. RESULTS: Over a 5-year period, migraine surgery was associated with an increase of 0.2 quality-adjusted life-year per patient when compared to erenumab. In terms of costs, the results demonstrated a $19,337 decrease in direct medical costs and a $491 decrease in indirect costs (productivity lost) for the surgery cohort compared to erenumab. Because surgery improved quality of life and decreased costs compared to erenumab, even when considering revision surgery needs, surgery was the overall dominant treatment in terms of cost-effectiveness. Sensitivity analyses demonstrated that surgery was cost-effective compared to erenumab when patients required therapy for at least 1 year. CONCLUSIONS: Surgical deactivation of migraine trigger sites may pose a cost-effective approach to treating refractory chronic migraine in adults. This is especially the case when patients are anticipated to require therapy for more than 1 year.

Complex regional pain syndrome patient treated with a below knee amputation, implanting nerves directly into muscle: A case report.

Persistent, disabling lower extremity pain, outside the distribution of a single nerve, is termed chronic regional pain syndrome (CRPS), but, in reality, this chronic pain is often due to multiple peripheral nerve injuries. It is the purpose of this report to describe the first application of the "traditional," nerve implantation into muscle, usually used in the treatment of a painful neuroma, as a pre-emptive surgical technique in doing a below knee amputation (BKA). In 2011, a 51-year-old woman developed severe, disabling CRPS, after a series of operations to treat an enchondroma of the left fifth metatarsal. When appropriate peripheral nerve surgeries failed to relieve distal pain, a BKA was elected. The approach to the BKA included implantation of each transected peripheral nerve directly into an adjacent muscle. At 5.0 years after the patient's BKA, the woman reported full use of this extremity, using the prosthesis, and was free of phantom limb and residual limb pain. This anecdotal experience gives insight that long-term relief of lower extremity CRPS can be achieved by a traditional BKA utilizing the approach of implanting each transected nerve into an adjacent muscle.

Anococcygeal Nerve and Sitting Pain: Differential Diagnosis and Treatment Results.

BACKGROUND: The plastic surgeon is often asked to reconstruct the sacral area related to pilonidal cysts or a tumor, or after other surgery, such as coccygectomy. When sitting pain is not due to the pudendal or posterior femoral cutaneous nerve injury, the anococcygeal nerve (ACN) must be considered. Clinically, its anatomy is not well known. Rather than consider coccygectomy when the traditional nonoperative treatment of coccydynia fails, resection of the ACN might be considered. METHODS: A review of traditional anatomy textbooks was used to establish classical thoughts about the ACN. A retrospective cohort of patients with sitting pain related to the coccyx was examined, and those operated on, by resecting the ACN, were examined for clinicopathologic correlations. RESULTS: When the ACN is described in anatomy textbooks, it is with varying distributions of innervated skin territory and nerve root composition. Most include an origin from sacral 5 and coccygeal 1 ventral roots. Most agree that the ACN forms on the ventral side of the sacrum/coccyx, alongside the coccygeus muscle, to emerge laterally and travel dorsally to innervate skin over the coccyx and lower sacrum. A review of 13 patients with sitting pain due to the ACN, from 2015 to 2019, demonstrated a mean age of 54.6 years. Eleven were female. The etiologies of ACN injury were falls (9), exercise (3), and complication from surgery (1). Six of the 9 patients who had surgery were able to be followed up with a mean length of 36.3 months (range, 11-63 months). Overall, 3 had an excellent result, 2 had a good result, and 1 was not improved. The one with a failed result showed improvement with coccygectomy. CONCLUSIONS: The ACN must be included in the differential diagnosis of sitting pain. It is most often injured by a fall. The ACN can be evaluated with a diagnostic nerve block, can be identified at surgery, and can be resected, and its proximal end can be implanted into the coccygeus muscle. This surgery may prove an alternative to coccygectomy.

Approach to Diagnosis and Treatment of Dorsoradial Hand and Forearm Pain.

Dorsoradial forearm and hand pain was historically considered difficult to treat surgically due to a particular susceptibility of the radial sensory nerve (RSN) to injury and/or compression. A nerve block, if it were done at all, was directed at the region of the anatomic snuff box to block the RSN in an effort to provide diagnostic information as to the pain etiology. Even for patients with pain relief following a diagnostic block, resecting the RSN often proved unsuccessful in fully relieving pain. The solution to successful treatment of this refractory pain problem was the realization that the RSN is not the sole source of sensory innervation to the dorsoradial wrist. In fact, in 75% of people the lateral antebrachial cutaneous nerve (LABCN) dermatome overlaps the RSN with other nerves, such as the dorsal ulnar cutaneous nerve and even the posterior antebrachial cutaneous nerves, occasionally providing sensory innervation to the same area. With this more refined understanding of the cutaneous neuroanatomy of the wrist, the diagnostic nerve block algorithm was expanded to include selective blockage of more than just the RSN. In contemporary practice, identification of the exact nerves responsible for pain signal generation informs surgical decision-making for palliative neurolysis or neurectomy. This approach offers a systematic and repeatable method to inform the diagnosis and treatment of dorsoradial forearm and wrist pain.

Chronic Nerve Pain after Burn Injury: An Anatomical Approach and the Development and Validation of a Model to Predict a Patient's Risk.

BACKGROUND: A model that predicts a patient's risk of developing chronic, burn-related nerve pain may guide medical and/or surgical management. This study determined anatomy-specific variables and constructed a mathematical model to predict a patient's risk of developing burn-related nerve pain. METHODS: A retrospective analysis was conducted from 1862 adults admitted to a burn center from 2014 to 2019. One hundred thirteen patients developed burn-related nerve pain. Comparisons were made using 11 anatomy-specific locations between patients with and without burn-related nerve pain. The modified Delphi technique was used to select 14 potential risk variables. Multivariate regression techniques, Brier scores, area under the curve, Hosmer-Lemeshow goodness-of-fit, and stratified K-fold cross-validation was used for model development. Chronic pain was defined as pain lasting 6 or more months after release from the Burn Center. RESULTS: Prevalence rates of burn-related nerve pain were similar in the development (6.1 percent) and validation (5.4 percent) cohorts [Brier score = 0.15; stratified K-fold cross-validation (K = 10): area under the curve, 0.75; 95 percent CI, 0.68 to 0.81; Hosmer-Lemeshow goodness-of-fit, p = 0.73; n = 10 groups]. Eight variables were included in the final equation. Burn-related nerve pain risk score = -6.3 + 0.02 (age) + 1.77 (tobacco use) + 1.04 (substance abuse) + 0.67 (alcohol abuse) + 0.84 (upper arm burn) + 1.28 (thigh burn) + 0.21 (number of burn operations) + 0.01 (hospital length-of-stay). Burn-related nerve pain predicted probability = 1 - 1/[1 + exp(burn-related nerve pain risk score)] for 6-month burn-related nerve pain risk score. As the number of risk factors increased, the probability of pain increased. CONCLUSIONS: Risk factors were identified for developing burn-related nerve pain at 11 anatomical locations. This model accurately predicts a patient's risk of developing burn-related nerve pain at 6 months. Age, tobacco use, substance abuse, alcohol abuse, upper arm burns, thigh burns, the number of burn operations, and hospital length of stay represented the strongest predictors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Sensibility, Sensation, and Nerve Regeneration after Reconstructive Genital Surgery: Evolving Concepts in Neurobiology.

BACKGROUND: Sensory recovery following phalloplasty and vaginoplasty for gender dysphoria is essential to the overall success of gender-confirming surgery. Anecdotal evidence suggests that superior reinnervation results are seen in genitoplasty compared to other peripheral nerve repair scenarios. Despite these observed differences, the quality of available literature is poor. METHODS: The authors reviewed the body of English language literature regarding sensory outcomes following genitoplasty for gender confirmation. RESULTS: The available body of literature discussing the basic science and clinical science aspects of sensory recovery following gender-confirming genitoplasty is small. Available data show that sensory recovery following vaginoplasty produces high rates of reported orgasmic ability, largely through the neoclitoris, and a neovagina with vibratory and pressure sensation similar to that of the native vagina. Phalloplasty sensory outcomes are variable, with the largest series reporting return of sensation in the neophallus that is slightly less than what is measured in control men. Erogenous sensation, including the ability to orgasm, is present in nearly all patients after several months. CONCLUSIONS: Existing series indicate that genitoplasty patients experience faster and more complete recovery than any other peripheral nerve regeneration scenarios. However, there are many potential confounding factors in assessment and reporting, and more consistent and reproducible measure endpoints measures are needed. Further research is needed to better understand both the basic science and clinical science of peripheral nerve regeneration in genitoplasty, which may change fundamental aspects of current paradigms of peripheral nerve regeneration.

Midarch Foot Pain: Entrapment Neuropathy of the Distal Medial Plantar Nerve and Its Branches.

Medial forefoot pain, or midarch pain, is usually attributed to plantar fasciitis. The authors present their findings of a previously unreported nerve entrapment of the medial proper plantar digital nerve (MPPDN). Ten fresh-frozen cadaveric specimens were analyzed for anatomical variance in the nerve distribution of the MPPDN. In addition, clinical results from a retrospective review of nine patients who underwent surgical nerve decompression of the MPPDN are presented. Significant anatomical variance was found for the MPPDN in the cadaveric dissection of 10 fresh-frozen specimens. Nine patients with a clinical diagnosis of entrapment of the MPPDN all obtained excellent pain relief with surgical external neurolysis. Only one complication occurred: a hypertrophic scar formation that was successfully treated with intralesional steroid injections. The authors believe that this MPPDN entrapment is often overlooked or misdiagnosed as plantar fasciitis. Surgical peripheral nerve decompression of this nerve can provide positive outcomes for patients suffering from midarch foot pain caused by this pain generator.

The Effects of a Porcine Extracellular Matrix Nerve Wrap as an Adjunct to Primary Epineurial Repair.

PURPOSE: Outcomes after end-to-end epineural suture repair remain poor. Nerve wraps have been advocated to improve regeneration across repair sites by potentially reducing axonal escape and scar ingrowth; however, limited evidence currently exists to support their use. METHODS: Forty Lewis rats underwent median nerve division and immediate repair. Half were repaired with epineural suturing alone, and the others underwent epineural suture repair with the addition of a nerve wrap. Motor recovery was measured using weekly grip strength and nerve conduction testing for 15 weeks. Histomorphometric analyses were performed to assess intraneural collagen deposition, cellular infiltration, and axonal organization at the repair site, as well as axonal regeneration and neuromuscular junction reinnervation distal to the repair site. RESULTS: The wrapped group demonstrated significantly less intraneural collagen deposition at 5 weeks. Axonal histomorphometry, cellular infiltration, neuromuscular junction reinnervation, and functional recovery did not differ between groups. CONCLUSIONS: Nerve wraps reduced collagen deposition within the coaptation; however, no differences were observed in axonal regeneration, neuromuscular junction reinnervation, or functional recovery. CLINICAL RELEVANCE: These findings suggest that extracellular matrix nerve wraps can attenuate scar deposition at the repair site. Any benefits that may exist with regards to axonal regeneration and functional recovery were not detected in our model.

Nerve Pain after Burn Injury: A Proposed Etiology-Based Classification.

BACKGROUND: Understanding the mechanism of nerve injury may facilitate managing burn-related nerve pain. This proposed classification, based on cause of nerve injury, was developed to enhance the understanding and management of burn-related nerve pain. METHODS: This retrospective investigation included patients aged 15 years or older admitted to the burn center from 2014 to 2019. Burn-related nerve pain was patient-reported and clinically assessed as pain 6 months or more after burn injury, unrelated to preexisting illnesses/medications. The pain classification consisted of direct nerve injury, nerve compression, electrical injury, and nerve dysfunction secondary to systemic injury. The four categories were statistically analyzed between groups, using 52 variables. RESULTS: Of the 1880 consecutive burn patients, 113 developed burn-related nerve pain and were eligible for validation of the classification: direct nerve injury, n = 47; nerve compression, n = 12; electrical injury, n = 7; and nerve dysfunction secondary to systemic injury, n = 47. Factors, significantly increased, that distinguished one category from another were as follows: for direct nerve injury, continuous symptoms (p < 0.001), refractory nerve release response (p < 0.001), nerve repair (p < 0.001), and pruritus (p < 0.001); for nerve compression, Tinel signs (p < 0.001), shooting pain (p < 0.001), numbness (p = 0.003), intermittent symptoms (p < 0.001), increased percentage total body surface area burned (p = 0.019), surgical procedures (p < 0.001), and nerve release (p < 0.001); and for electrical injury, Tinel sign (p < 0.001), intermittent symptoms (p = 0.002), amputations (p = 0.002), fasciotomies (p < 0.001), and nerve release (p < 0.001). Nerve dysfunction secondary to systemic injury was distinguished by significantly less Tinel signs (p < 0.001), shooting pain (p < 0.001), numbness and tingling (p < 0.001), pruritus (p < 0.001), fascial excision (p = 0.004), skin grafts (p < 0.001), amputation (p = 0.004), nerve releases (p < 0.001), and third-degree burns (p = 0.002). CONCLUSION: A classification consisting of direct nerve injury, nerve compression, electrical injury, and nerve dysfunction secondary to systemic injury is presented that may guide patient management and research methods, with the goal of improving pain outcomes in burn-related nerve pain.