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## The clinical course and role of surgery in pediatric malignant peripheral nerve sheath tumors: a database study

### OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors found throughout the body, with their clinical course in children still not completely understood. Correspondingly, this study aimed to determine survival outcomes and specific clinical predictors of survival in this population from a large national database.

### METHODS

All patients with MPNSTs aged ≤ 18 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival was modeled using Kaplan-Meier and Cox regression analyses.

### RESULTS

A total of 251 pediatric patients with MPNSTs (132 [53%] females and 119 [47%] males) were identified; the mean age at diagnosis was 13.1 years (range 1–18 years). There were 84 (33%) MPNSTs located in the extremities, 127 (51%) were smaller than 1 cm, and 22 (9%) had metastasis at the time of diagnosis. In terms of treatment, surgery was pursued in 187 patients (74%), chemotherapy in 116 patients (46%), and radiation therapy in 129 patients (61%). The 5-year overall survival rate was estimated at 52% (95% CI 45%–59%), with a median survival of 64 months (range 36–136 months). Multivariate regression revealed that older age (HR 1.10, p < 0.01), metastases at the time of diagnosis (HR 2.14, p = 0.01), and undergoing biopsy only (HR 2.98, p < 0.01) significantly and independently predicted a shorter overall survival. Chemotherapy and radiation therapy were not statistically significant.

### CONCLUSIONS

In this study, the authors found that older patient age, tumor metastases at the time of diagnosis, and undergoing only biopsy significantly and independently predicted poorer outcomes. Only approximately half of patients survived to 5 years. These results have shown a clear survival benefit in pursuing maximal safe resection in pediatric patients with MPNSTs. As such, judicious workup with meticulous resection by an expert team should be considered the standard of care for these tumors in children.

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## Perineural spread of peripheral neurolymphomatosis to the cauda equina

### OBJECTIVE

Neurolymphomatosis (NL) is a rare manifestation of lymphoma confined to the peripheral nervous system that is poorly understood. It can be found in the cauda equina, but extraspinal disease can be underappreciated. The authors describe how extraspinal NL progresses to the cauda equina by perineural spread and the implications of this on timely and safe diagnostic options.

### METHODS

The authors used the Mayo Clinic medical records database to find cases of cauda equina NL with sufficient imaging to characterize the lumbosacral plexus diagnosed from tissue biopsy. Demographics (sex, age), clinical data (initial symptoms, cerebrospinal fluid, evidence of CNS involvement, biopsy location, primary or secondary disease), and imaging findings were reviewed.

### RESULTS

Ten patients met inclusion and exclusion criteria, and only 2 of 10 patients presented with cauda equina symptoms at the time of biopsy, with 1 patient undergoing a cauda equina biopsy. Eight patients were diagnosed with diffuse large B-cell lymphoma, 1 with low-grade B-cell lymphoma, and 1 with mantle cell lymphoma. Isolated spinal nerve involvement was identified in 5 of 10 cases, providing compelling evidence regarding the pathophysiology of NL. The conus medullaris was not radiologically involved in any case. Lumbosacral plexus MRI was able to identify extraspinal disease and offered diagnostically useful biopsy targets. FDG PET/CT was relatively insensitive for detecting disease in the cauda equina but was helpful in identifying extraspinal NL.

### CONCLUSIONS

The authors propose that perineural spread of extraspinal NL to infiltrate the cauda equina occurs in two phases. 1) There is proximal and distal spread along a peripheral nerve, with eventual spread to anatomically connected nerves via junction and branch points. 2) The tumor cells enter the spinal canal through corresponding neural foramina and propagate along the spinal nerves composing the cauda equina. To diffusely infiltrate the cauda equina, a third phase occurs in which tumor cells can spread circumdurally to the opposite side of the spinal canal and enter contralateral nerve roots extending proximally and distally. This spread of disease can lead to diffuse bilateral spinal nerve disease without diffuse leptomeningeal spread. Recognition of this phasic mechanism can lead to identification of safer extraspinal biopsy targets that could allow for greater functional recovery after appropriate treatment.

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## Do all outpatient spine surgeries cost the same? Comparison of economic outcomes data from a state-level database for outpatient lumbar decompression performed in an ambulatory surgery center or hospital outpatient setting

### OBJECTIVE

Spinal procedures are increasingly conducted as outpatient procedures, with a growing proportion conducted in ambulatory surgery centers (ASCs). To date, studies reporting outcomes and cost analyses for outpatient spinal procedures in the US have not distinguished the various outpatient settings from each other. In this study, the authors used a state-level administrative database to compare rates of overnight stays and nonroutine discharges as well as index admission charges and cumulative 7-, 30-, and 90-day charges for patients undergoing outpatient lumbar decompression in freestanding ASCs and hospital outpatient (HO) settings.

### METHODS

For this project, the authors used the Florida State Ambulatory Surgery Database (SASD), offered by the Healthcare Cost and Utilization Project (HCUP), for the years 2013 and 2014. Patients undergoing outpatient lumbar decompression for degenerative diseases were identified using CPT (Current Procedural Terminology) and ICD-9 codes. Outcomes of interest included rates of overnight stays, rate of nonroutine discharges, index admission charges, and subsequent admission cumulative charges at 7, 30, and 90 days. Multivariable analysis was performed to assess the impact of outpatient type on index admission charges. Marginal effect analysis was employed to study the difference in predicted dollar margins between ASCs and HOs for each insurance type.

### RESULTS

A total of 25,486 patients were identified; of these, 7067 patients (27.7%) underwent lumbar decompression in a freestanding ASC and 18,419 (72.3%) in an HO. No patient in the ASC group required an overnight stay compared to 9.2% (n = 1691) in the HO group (p < 0.001). No clinically significant difference in the rate of nonroutine discharge was observed between the two groups. The mean index admission charge for the ASC group was found to be significantly higher than that for the HO group ($35,017.28 ±$14,335.60 vs $33,881.50 ±$15,023.70; p < 0.001). Patients in ASCs were also found to have higher mean 7-day (p < 0.001), 30-day (p < 0.001), and 90-day (p = 0.001) readmission charges. ASC procedures were associated with increased charges compared to HO procedures for patients on Medicare or Medicaid (mean index admission charge increase $4049.27, 95% CI$2577.87–$5520.67, p < 0.001) and for patients on private insurance ($4775.72, 95% CI $4171.06–$5380.38, p < 0.001). For patients on self-pay or no charge, a lumbar decompression procedure at an ASC was associated with a decrease in index admission charge of −$10,995.38 (95% CI −$12124.76 to −\$9866.01, p < 0.001) compared to a lumbar decompression procedure at an HO.

### CONCLUSIONS

These “real-world” results from an all-payer statewide database indicate that for outpatient spine surgery, ASCs may be associated with higher index admission and subsequent 7-, 30-, and 90-day charges. Given that ASCs are touted to have lower overall costs for patients and better profit margins for physicians, these analyses warrant further investigation into whether this cost benefit is applicable to outpatient spine procedures.

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## Incidence and risk factors for prolonged postoperative opioid use following lumbar spine surgery: a cohort study

### OBJECTIVE

Sustained postoperative opioid use after elective surgery is a matter of growing concern. Herein, the authors investigated incidence and predictors of long-term opioid use among patients undergoing elective lumbar spine surgery, especially as a function of opioid prescribing practices at postoperative discharge (dose in morphine milligram equivalents [MMEs] and type of opioid).

### METHODS

The OptumLabs Data Warehouse (OLDW) was queried for postdischarge opioid prescriptions for patients undergoing elective lumbar decompression and discectomy (LDD) or posterior lumbar fusion (PLF) for degenerative spine disease. Only patients who received an opioid prescription at postoperative discharge and those who had a minimum of 180 days of insurance coverage prior to surgery and 180 days after surgery were included. Opioid-naive patients were defined as those who had no opioid fills in 180 days prior to surgery. The following patterns of long-term postoperative use were investigated: additional fills (at least one opioid fill 90–180 days after surgery), persistent fills (any span of opioid use starting in the 180 days after surgery and lasting at least 90 days), and Consortium to Study Opioid Risks and Trends (CONSORT) criteria for persistent use (episodes of opioid prescribing lasting longer than 90 days and 120 or more total days’ supply or 10 or more prescriptions in 180 days after the index fill). Multivariable logistic regression was performed to identify predictors of long-term use.

### RESULTS

A total of 25,587 patients were included, of whom 52.7% underwent PLF (n = 13,486) and 32.5% (n = 8312) were opioid-naive prior to surgery. The rates of additional fills, persistent fills, and CONSORT use were 47%, 30%, and 23%, respectively, after PLF and 35.4%, 19%, and 14.2%, respectively, after LDD. The rates among opioid-naive patients were 18.9%, 5.6%, and 2.5% respectively, after PLF and 13.3%, 2.0%, and 0.8%, respectively, after LDD. Using multivariable logistic regression, the following were identified to be significantly associated with higher risk of long-term opioid use following PLF: discharge opioid prescription ≥ 500 MMEs, prescription of a long-acting opioid, female sex, multilevel surgery, and comorbidities such as depression and drug abuse (all p < 0.05). Elderly (age ≥ 65 years) and opioid-naive patients were found to be at lower risk (all p < 0.05). Similar results were obtained on analysis for LDD with the following significant additional risk factors identified: discharge opioid prescription ≥ 400 MMEs, prescription of tramadol alone at discharge, and inpatient surgery (all p < 0.05).

### CONCLUSIONS

In an analysis of pharmacy claims from a national insurance database, the authors identified incidence and predictors of long-term opioid use after elective lumbar spine surgery.

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## A significant association between C5 nerve sheath tumors and new postoperative weakness

### OBJECTIVE

The objective of this study was to determine if patients with nerve sheath tumors affecting the C5 spinal nerve are at greater risk for postoperative weakness than those with similar tumors affecting other spinal nerves contributing to the brachial plexus.

### METHODS

A retrospective chart review (1998–2020)identified patients with pathologically confirmed schwannomas or neurofibromas from the C5 to T1 nerves. Patients with plexiform nerve sheath tumors, tumors involving more than 1 nerve, and malignant peripheral nerve sheath tumors were excluded. Collected variables included basic demographics, tumor dimensions, its location relative to the dura, involved nerve level, surgical approach, extent of resection, presenting symptoms, postoperative neurological deficits, and recurrence rate.

### RESULTS

Forty-six patients (23 men, 23 women) were identified for inclusion in the study with an average age of 47 ± 17 years, BMI of 28 ± 5 kg/m, and follow-up of 32 ± 45 months. Thirty-nine patients (85%) had schwannomas and 7 (15%) had neurofibromas. Tumors involved the C5 (n = 12), C6 (n = 11), C7 (n = 14), C8 (n = 6), and T1 (n = 3) nerves. Multivariable logistic regression analysis with an area under the curve of 0.85 demonstrated C5 tumor level as an independent predictor of new postoperative weakness (odds ratio 7.4, p = 0.028). Of those patients with new postoperative weakness, 75% improved and 50% experienced complete resolution of their motor deficits.

### CONCLUSIONS

Patients with C5 nerve sheath tumor resections are at higher odds of new postoperative weakness. This may be due to the predominant single innervation of shoulder muscle targets in contrast to other upper extremity muscles that receive input from 2 or more spinal nerves. These findings are important for clinical decision-making and preoperative patient counseling.

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## High-resolution MRI of a peroneal intraneural ganglion cyst arising from the knee joint: illustrative case

### BACKGROUND

The advancement of high-resolution imaging and increased clinical experience have led to an increased understanding of the formation and treatment of intraneural ganglion cysts. Nearly all intraneural ganglion cysts in the common peroneal nerve have been reported to arise from a joint connection to the superior tibiofibular joint. The authors have identified four cases of intraneural ganglion cysts arising from the knee joint itself; however, none of these reported cases were well described, documented, or illustrated with high-resolution imaging.

### OBSERVATIONS

Here the authors present the case of an intraneural ganglion cyst arising from the knee joint and causing intermittent weakness and pain. The articular branch to the knee joint was clearly demonstrated on high-resolution magnetic resonance imaging and confirmed at surgical exploration. The patient was treated with articular branch ligation and has had complete resolution of his symptoms without recurrence of the cyst on follow-up imaging.

### LESSONS

This case adds to the mounting evidence that intraneural cyst pathology is dependent on a connection to a synovial joint as stated in the unifying theory of intraneural cyst development.

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## Analysis of the effect of intraoperative neuromonitoring during resection of benign nerve sheath tumors on gross-total resection and neurological complications

### OBJECTIVE

The aim of this study was to examine the role of intraoperative neuromonitoring (IONM) during resection of benign peripheral nerve sheath tumors in achieving gross-total resection (GTR) and in reducing postoperative neurological complications.

### METHODS

Data from consecutive adult patients who underwent resection of a benign peripheral nerve sheath tumor at 7 participating institutions were combined. Propensity score matching was used to balance covariates. The primary outcomes of interest were the association between IONM and GTR and the association of IONM and the development of a permanent postoperative neurological complication. The secondary outcomes of interest were the association between IONM and GTR and the association between IONM and the development of a permanent postoperative neurological complication in the subgroup of patients with tumors involving a motor or mixed nerve. Univariate and multivariate logistic regression were then performed on the propensity score–matched samples to assess the ability of the independent variables to predict the outcomes of interest.

### RESULTS

A total of 337 patients who underwent resection of benign nerve sheath tumors were included. In multivariate analysis, the use of IONM (OR 0.460, 95% CI 0.199–0.978; p = 0.047) was a significant negative predictor of GTR, whereas none of the variables, including IONM, were associated with the occurrence of a permanent postoperative neurological complication. Within the subgroup of motor/mixed nerve tumors, in the multivariate analysis, IONM (OR 0.263, 95% CI 0.096–0.723; p = 0.010) was a significant negative predictor of a GTR, whereas IONM (OR 3.800, 95% CI 1.925–7.502; p < 0.001) was a significant positive predictor of a permanent postoperative motor deficit.

### CONCLUSIONS

Overall, 12% of the cohort had a permanent neurological complication, with new or worsened paresthesias most common, followed by pain and then weakness. The authors found that formal IONM was associated with a reduced likelihood of GTR and had no association with neurological complications. The authors believe that these data argue against IONM being considered standard of care but do not believe that these data should be used to universally argue against IONM during resection of benign nerve sheath tumors.

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## Meralgia paresthetica treated by injection, decompression, and neurectomy: a systematic review and meta-analysis of pain and operative outcomes

### OBJECTIVE

Meralgia paresthetica is caused by entrapment of the lateral femoral cutaneous nerve (LFCN) and often presents with pain. Multiple treatment options targeting the LFCN can be pursued to treat the pain should conservative measures fail, with the most common options being injection, neurolysis, and neurectomy. However, their efficacy in causing pain relief and their clinical outcomes have yet to be directly compared. The aim of this study was to interrogate the contemporary literature and quantitatively define how these options compare.

### METHODS

The electronic databases Ovid Embase, PubMed, SCOPUS, and the Cochrane Library were interrogated from inception to May 2020 following the PRISMA guidelines. Candidate articles were screened against prespecified criteria. Outcome data were abstracted and pooled by random-effects meta-analysis of proportions.

### RESULTS

There were 25 articles that satisfied all criteria, reporting outcomes for a total of 670 meralgia paresthetica patients, with 78 (12%) treated by injection, 496 (74%) by neurolysis, and 96 (14%) by neurectomy. The incidence of complete pain relief was 85% (95% CI 71%–96%) after neurectomy, 63% (95% CI 56%–71%) after neurolysis, and 22% (95% CI 13%–33%) after injection, which were all statistically different (p < 0.01). The incidence of revision procedures was 12% (95% CI 4%–22%) after neurolysis and 0% (95% CI 0%–2%) after neurectomy, which were significantly lower than 81% (95% CI 64%–94%) after injection (p < 0.01). The incidences of treatment complications were statistically comparable across all three treatments, ranging from 0% to 5% (p = 0.34).

### CONCLUSIONS

There are multiple treatment options to target pain in meralgia paresthetica. The incidence of complete pain relief appears to be the greatest among the 3 interventions after neurectomy, accompanied by the lowest incidence of revision procedures. These findings should help inform patient preference and expectations. Greater exploration of the anatomical rationale for incomplete pain relief after surgical intervention will assist in optimizing further surgical treatment for meralgia paresthetica.

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## Need for arthrodesis following facetectomy for spinal peripheral nerve sheath tumors: an institutional experience and review of the current literature

### OBJECTIVE

Spinal peripheral nerve sheath tumors (PNSTs) are a group of rare tumors originating from the nerve and its supporting structures. Standard surgical management typically entails laminectomy with or without facetectomy to gain adequate tumor exposure. Arthrodesis is occasionally performed to maintain spinal stability and mitigate the risk of postoperative deformity, pain, or neurological deficit. However, the factors associated with the need for instrumentation in addition to PNST resection in the same setting remain unclear.

### METHODS

An institutional tumor registry at a tertiary care center was queried for patients treated surgically for a primary diagnosis of spinal PNST between 2002 and 2016. An analysis focused on patients in whom a facetectomy was performed during the resection. The addition of arthrodesis at the index procedure comprised the primary outcome. The authors also recorded baseline demographics, tumor characteristics, and surgery-related variables. Logistic regression was used to identify factors associated with increased risk of fusion surgery.

### RESULTS

A total of 163 patients were identified, of which 56 (32 had facetectomy with fusion, 24 had facetectomy alone) were analyzed. The median age was 48 years, and 50% of the cohort was female. Age, sex, and race, as well as tumor histology and size, were evenly distributed between patients who received facetectomy alone and those who had facetectomy and fusion. On univariate analysis, total versus subtotal facetectomy (OR 9.0, 95% CI 2.01–64.2; p = 0.009) and cervicothoracic versus other spinal region (OR 9.0, 95% CI 1.51–172.9; p = 0.048) were significantly associated with increased odds of performing immediate fusion. On multivariable analysis, only the effect of total facetectomy remained statistically significant (OR 6.75, 95% CI 1.47–48.8; p = 0.025).

### CONCLUSIONS

The authors found that total facetectomy and cervicothoracic involvement may be highly associated with the need for concomitant arthrodesis at the time of index surgery. These findings may help surgeons to determine the best surgical planning for patients with PNST.

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## Strengthening the association of lipomatosis of nerve and nerve-territory overgrowth: a systematic review

### OBJECTIVE

Lipomatosis of nerve (LN) is a massive enlargement of a nerve due to abundant proliferation of adipose and fibrotic tissue within the epineurium—part of the spectrum of adipose lesions of nerves, including intra- and extraneural lipomas. LN has been frequently associated with soft-tissue and/or osseous overgrowth. Unfortunately, much confusion exists since many names have been used for LN (e.g., fibrolipomatous hamartoma, macrodystrophia lipomatosa, and so on). To better understand this condition and to evaluate its association with nerve-territory overgrowth, the authors attempted to compile the world’s literature on published LN cases.

### METHODS

PubMed and Google Scholar databases were searched to identify published articles on LN cases, using a variety of terms. Publications in all languages were assessed. All publications with cases determined likely to be LN were read. Cases that provided clear clinicopathological and/or radiological evidence of LN were labeled as “definite” and cases that demonstrated features of LN (e.g., nerve-territory overgrowth) but lacked definite proof of nerve involvement were labeled as “probable.”

### RESULTS

Initial screening revealed a total of 2465 papers. After exclusions, 281 publications reported cases with a definite diagnosis of LN and 120 articles reported cases with a probable diagnosis of LN. The authors identified 618 definite and 407 probable cases of LN. Sex distribution was balanced (51% female). Early diagnosis was common, with two-thirds of patients having symptoms in the 1st decade of life. The most commonly affected nerve was the median nerve (n = 391). Nerve-territory overgrowth was common (62% definite LN; 78% combined cases); overgrowth was exclusive to the territory of the affected nerve in all cases but 5.

### CONCLUSIONS

The authors present a comprehensive review and analysis of the literature of LN cases. One of the main findings was the nerve-territory overgrowth was associated with LN, especially when present earlier in life. The authors believe that all cases of LN associated with overgrowth can be explained on anatomical grounds, even in the few reported cases in which this is not immediately obvious.