Core outcomes in nerve surgery: development of a core outcome set for brachial plexus and upper extremity nerve injuries.

OBJECTIVE: When considering traumatic brachial plexus and upper extremity nerve injuries, iatrogenic nerve injuries, and nontraumatic nerve injuries, brachial plexus and upper extremity nerve injuries are commonly encountered in clinical practice. Despite this, data synthesis and comparison of available studies are difficult. This is at least in part due to the lack of standardization in reporting and a lack of a core outcome set (COS). Thus, there is a need for a COS for adult brachial plexus and upper extremity nerve injuries (COS-BPUE). The objective of this study was to develop a COS-BPUE using a modified Delphi approach. METHODS: A 5-stage approach was used to develop the COS-BPUE: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-BPUE consisted of 36 data points/outcomes covering demographic, diagnostic, patient-reported outcome, motor/sensory outcome, and complication domains. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 24 months, with the consensus optimal time points for assessment being preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-BPUE should serve as a minimum set of data that should be collected in all future neurosurgical studies on adult brachial plexus and upper extremity nerve injuries. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Core outcomes in nerve surgery: development of a core outcome set for ulnar neuropathy at the elbow.

OBJECTIVE: Ulnar neuropathy at the elbow (UNE) is common, affecting 1%-6% of the population. Despite this, there remains a lack of consensus regarding optimal treatment. This is primarily due to the difficulty one encounters when trying to assess the literature. Outcomes are inconsistently reported, which makes comparing studies or developing meta-analyses difficult or even impossible. Thus, there is a need for a core outcome set (COS) for UNE (COS-UNE) to help address this problem. The objective of this study was to utilize a modified Delphi method to develop COS-UNE. METHODS: A 5-stage approach was utilized to develop COS-UNE: stage 1, consortium development; 2, literature review to identify potential outcome measures; 3, Delphi survey to develop consensus on outcomes for inclusion; 4, Delphi survey to develop definitions; and 5, consensus meeting to finalize the COS and definitions. The study followed the Core Outcome Set-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 21 participants, all neurological surgeons representing 11 countries. The final COS-UNE consisted of 22 data points/outcomes covering the domains of demographic characteristics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 6 months, with the consensus optimal timepoints for assessment identified as preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS: The authors identified consensus data points/outcomes and also provided definitions and specific scales to be utilized to help ensure that clinicians are consistent in their reporting across studies on UNE. This COS should serve as a minimum set of data to be collected in all future neurosurgical studies on UNE. The authors hope that clinicians evaluating ulnar neuropathy will incorporate this COS into routine practice and that future studies will consider this COS in the design phase.

What is new in intraneural perineurioma?

Since the initial description of intraneural (IN) perineurioma in 1964, advances in the understanding of the clinical presentation, diagnostic imaging, pathologic features, and genetic underpinnings have changed how this pathology is managed. IN perineuriomas are rare, benign peripheral nerve sheath tumors, most frequently coming to clinical attention when patients present with painless, progressive weakness or sensory loss in adolescence or young adulthood. The gold standard of diagnosis has traditionally been with targeted tissue biopsy demonstrating "pseudo-onion bulb" formation with positive epithelial membrane antigen (EMA) staining. However, modern magnetic resonance imaging is allowing some patients to forgo biopsy. Recent genetic studies of IN perineuriomas have demonstrated common TRAF7 point mutations and rare NF2 mutations, which may present targets for diagnosis or therapy in the future. Current advances have allowed for us to provide improved patient counseling with informed understanding for various clinical scenarios. With the workup and diagnosis now clearly defined, the next frontier is for improving the lives of patients with IN perineuriomas through the interaction between restoration of functional deficits and advances in our understanding of the genetics of this entity.

Causalgia: a military pain syndrome.

Causalgia, officially known as complex regional pain syndrome type II, is a pain syndrome characterized by severe burning pain, motor and sensory dysfunction, and changes in skin color and temperature sensation distal to an injured peripheral nerve. The pain syndrome primarily tends to affect combat soldiers after they sustain wartime injuries from blasts and gunshots. Here, the authors provide a historical narrative that showcases the critical contributions of military physicians to our understanding of causalgia and to the field of peripheral nerve neurosurgery as a whole.

Neurosurgery for the Neurologist: Peripheral Nerve Injury and Compression (What can be Fixed?).

This chapter will review the current management of patients with peripheral nerve injuries and nerve compression syndromes that result in favorable surgical outcomes when appropriately evaluated and referred in a timely fashion. Given the fact that neurologists frequently evaluate patients with these conditions and refer patients to neurosurgeons, it is important for them to be aware of the indications for, types and timing of surgical procedures, and expected outcomes with the various types of interventions.

The spectrum of brachial plexopathy from perineural spread of breast cancer.

OBJECTIVE: Perineural spread of breast cancer to the brachial plexus can lead to pain, sensory alterations, and upper-extremity weakness. Although rare, perineural spread is an often-misdiagnosed long-term complication following breast cancer diagnosis. The objective of this study was to critically review the clinical, radiological, and pathological findings of biopsy-proven perineural spread of breast cancer to the brachial plexus. METHODS: This is a retrospective study from a single institution in which a total of 19 patients with brachial plexus involvement from perineural spread of breast cancer who underwent fascicular biopsy between 1999 and 2021 were identified. Clinical, radiographic, and pathological data were retrospectively collected. Descriptive statistics were calculated for the cohort. RESULTS: The mean age of patients at the time of diagnosis of breast cancer perineural spread was 60.6 ± 11.5 years. The diagnosis of brachial plexopathy due to perineural spread was on average 12 years after the primary diagnosis of breast cancer. There was also a delay in diagnosis due to the rarity of this disease, with a mean time from initial symptom onset to diagnosis of perineural spread of 25 ± 30 months. All patients at the time of presentation had upper-extremity weakness and pain. Nearly all patients demonstrated T2 signal change and nodular so-called sugar-coating contrast enhancement on brachial plexus MRI. Similarly, all patients who underwent PET/MRI or PET/CT had increased FDG uptake in the involved brachial plexus. Breast cancer perineural spread has an overall poor prognosis, with 16 of 19 patients dying within 5.9 ± 3.0 years after diagnosis of perineural spread. CONCLUSIONS: Perineural spread should be considered in patients with a history of breast cancer, even 10 years after primary diagnosis, especially in patients who present with arm pain, weakness, and/or sensory changes. Further diagnostic workup with electrodiagnostic studies; brachial plexus MRI, PET/CT, or PET/MRI; and possibly nerve biopsy is warranted to ensure accurate diagnosis.

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/m2, 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.

Four-level Anterior Cervical Discectomy and Fusions: Results Following Multilevel Cervical Fusion With a Minimum 1-Year Follow-up.

STUDY DESIGN: A retrospective review of prospectively collected case series. OBJECTIVE: This is a retrospective review of prospectively collected data regarding the clinical outcomes, complications, and fusion rates of patients who underwent a 4-level (C3-C7) anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND: The use of multilevel ACDF for cervical spondylosis has been controversial. The literature regarding fusion rates and outcomes have been variable. This study intends to evaluate the outcomes following multilevel ACDF in a large cohort of patients. CLINICAL MATERIALS AND METHODS: Between 1994 and 2011, 60 patients underwent a 4-level ACDF by a single surgeon. All patients were followed for a minimum of 12 months, and outcome measures included neurological findings, presence or absence of radiographic fusion, and complication rates. All patients had radiographic documentation of spinal cord stenosis at 4 consecutive cervical levels as well as myelopathy and/or radiculopathy symptoms. RESULTS: Forty-eight patients underwent a single anterior procedure, only 5 patients underwent concurrent anterior and posterior fusion, and 7 patients required a second posterior surgery due to new-onset or residual symptoms or hardware complications after undergoing ACDF. Patients most commonly presented with paresthesias and were diagnosed with cervical stenosis. Overall, 18.3% reported early postoperative dysphagia; however, only 2 patients continued to have mild dysphagia symptoms on long-term follow-up. Other complications included hardware failure (11), residual neck pain (7), residual paresthesias (6), new-onset weakness (3), neck hematoma (1), cellulitis (1), and C5 radiculopathy (1). Overall, 88.3% of patients reported improvement in initial symptoms. Nurick scores were significantly lower following 4-level ACDF. The radiographic fusion rate for all levels was 95%. No patients required reoperation for pseudarthrosis. CONCLUSION: In appropriate patients, 4-level ACDF is a safe, efficacious method for treating multilevel cervical spinal cord compression, with acceptable complication rates and the ability to achieve neurological improvement and high fusion rates.

Sporadic Malignant Perineurioma: A Rare Diagnosis Among Malignant Peripheral Nerve Sheath Tumors.

BACKGROUND: Malignant perineurioma is a rare subset of malignant peripheral nerve sheath tumors (MPNSTs) with ultrastructural and immunohistochemical features of perineurial differentiation, distinguishing it from other MPNSTs, which typically demonstrate Schwannian features. The clinical course and prognosis of this rare tumor is not well defined. METHODS: The electronic medical records were searched for patients with a diagnosis of MPNST. Patients with a pathologic diagnosis of malignant perineurioma or MPNST with perineurial features were identified and further evaluated. RESULTS: Five patients with malignant perineurioma, or MPNST with perineurial features, were identified. Four patients (2 male and 2 female) were included with tumors associated with a common digital nerve, small muscular branch to the deltoid, sciatic nerve, and accessory nerve. One patient with the pathology diagnosis meeting inclusion criteria was excluded, as no clinical information was available for this patient. CONCLUSIONS: Patients in our series presented at varied stages of disease. Clinical courses after diagnosis of malignant perineurioma, where follow-up was available, were largely uncomplicated with regard to recurrence and metastatic disease. Careful follow-up is indicated, and further work is needed to characterize the clinical course of these rare tumors.

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.

Live-Streaming Surgery for Medical Student Education - Educational Solutions in Neurosurgery During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic significantly altered medical student education. The ability for students to be a part of the operating room team was highly restricted. Technology can be used to ensure ongoing surgical education during this time of limited in-person educational opportunities. DESIGN: We have developed an innovative solution of securely live-streaming surgery with real-time communication between the surgeon and students to allow for ongoing education during the pandemic. RESULTS: We successfully live-streamed multiple different types of neurosurgical operations utilizing multiple video sources. This method uses inexpensive, universal equipment that can be implemented at any institution to enable virtual education of medical students and other learners. CONCLUSIONS: This technology has facilitated education during this challenging time. This technological set-up for live-streaming surgery has the potential of improving medical and graduate medical education in the future.

Mercury vs. Water: An Analysis of Multi-Institutional Survey Data Assessing Intracranial Pressure Unit of Measure Awareness.

BACKGROUND: Intracranial pressure (ICP) reporting impacts neurosurgical care. Millimeters of mercury (mmHg) and centimeters of water (cmH2O) are both used to report ICP in clinical practice and the literature. In this study, we investigated ICP unit of measure awareness in the neurosurgical community. METHODS: A survey was conducted at four US academic neurosurgery departments asking the following questions: What is your threshold for a concerning ICP? How many minutes is that ICP sustained for you to be concerned? What unit are you implying when you state that ICP? What unit of measure is an ICP reported on the monitor when transduced? When setting an external ventricular drain Becker bag level, what unit of measure do you set it to? Do you ever manually check an ICP based on a column of cerebrospinal fluid? How many cmH2O is 20 mmHg? RESULTS: An ICP of 20 and sustained for five minutes were the two most common answers. Some 71% of residents and 34% of attendings reported using cmH2O as the unit of measure; 18% of residents and 24% of attendings implied different units when discussing ICP than the unit they thought was transduced; and 53% of residents and 34% of attendings did not know the transduced ICP unit of measure reported in their intensive care unit. CONCLUSIONS: Variability and discrepancies regarding the ICP unit of measure exist in academic neurosurgery departments. Clinicians should familiarize themselves with their hospital's practices. Institutions and all of medicine may consider standardizing the ICP unit of measure, using mmHg as a universal nomenclature.

Intrinsic Activity of C57BL/6 Substrains Associates with High-Fat Diet-Induced Mechanical Sensitivity in Mice.

Pain is significantly impacted by the increasing epidemic of obesity and the metabolic syndrome. Our understanding of how these features impact pain is only beginning to be developed. Herein, we have investigated how small genetic differences among C57BL/6 mice from 2 different commercial vendors lead to important differences in the development of high-fat diet-induced mechanical sensitivity. Two substrains of C57BL/6 mice from Jackson Laboratories (Bar Harbor, ME; C57BL/6J and C57BL/6NIH), as well as C57BL/6 from Charles Rivers Laboratories (Wilmington, MA; C57BL/6CR) were placed on high-fat diets and analyzed for changes in metabolic features influenced by high-fat diet and obesity, as well as measures of pain-related behaviors. All 3 substrains responded to the high-fat diet; however, C57BL/6CR mice had the highest weights, fat mass, and impaired glucose tolerance of the 3 substrains. In addition, the C57BL/6CR mice were the only strain to develop significant mechanical sensitivity over the course of 8 weeks. Importantly, the C57BL/6J mice were protected from mechanical sensitivity, which may be based on increased physical activity compared with the other 2 substrains. These findings suggest that activity may play a powerful role in protecting metabolic changes associated with a high-fat diet and that these may also be protective in pain-associated changes as a result of a high-fat diet. These findings also emphasize the importance of selection and transparency in choosing C57BL/6 substrains in pain-related research. PERSPECTIVE: Obesity and the metabolic syndrome play an important role in pain. This study identifies key differences in the response to a high-fat diet among substrains of C57BL/6 mice and differences in intrinsic physical activity that may influence pain sensitivity. The results emphasize physical activity as a powerful modulator of obesity-related pain sensitivity.

A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice.

Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice. High-fat-fed, exercised and ketogenic-fed mice had mildly elevated blood glucose; conversely, ketogenic diet-fed mice were unique in having reduced serum insulin levels. Ketogenic diet-fed mice never developed mechanical allodynia contrary to mice fed a high-fat diet. Ketogenic diet fed mice also had increased epidermal axon density compared all other groups. When a ketogenic diet was used as an intervention, a ketogenic diet was unable to reverse high-fat fed-induced metabolic changes but was able to significantly reverse a high-fat diet-induced mechanical allodynia. As an intervention, a ketogenic diet also increased epidermal axon density. In vitro studies revealed increased neurite outgrowth in sensory neurons from mice fed a ketogenic diet and in neurons from normal diet-fed mice given ketone bodies in the culture medium. These results suggest a ketogenic diet can prevent certain complications of prediabetes and provides significant benefits to peripheral axons and sensory dysfunction.

Safety, Efficacy, and Cost-Analysis of Percutaneous Endoscopic Gastrostomy and Ventriculoperitoneal Shunt Placement in a Simultaneous Surgery.

BACKGROUND: Limited historical data suggest that concomitant placement of both a ventriculoperitoneal (VP) shunt and percutaneous endoscopic gastrostomy (PEG) tube is associated with an increased risk of complications, including VP shunt infections. Here we compare the outcomes and cost difference between 2 groups of patients, one in which a VP shunt and PEG tube were placed in the same operation and the other in which separate operations were performed. METHODS: A total of 10 patients underwent simultaneous placement of a VP shunt and PEG tube. This group was compared with a group of 18 patients that underwent separate placements. Hospital billing charges were used to compare the total cost of the procedures in the 2 groups. RESULTS: Eight of the 10 patients presented with aneurysmal subarachnoid hemorrhage. The average length of stay was 25 ± 2 days for the simultaneous procedure group and 43 ± 7 days for the separate procedures group. The average duration of follow-up was 12 ± 3 months after simultaneous placement. No patient in the simultaneous surgery group had signs of infection or shunt malfunction at last follow-up. The overall complication rate was significantly lower in the simultaneous surgery group. A cost analysis demonstrated significant cost savings by completing both procedures in the same surgical procedure. CONCLUSIONS: Simultaneous placement of a PEG tube and VP shunt is safe, efficacious, and cost-effective. Thus, in patients requiring both a VP shunt and PEG tube, placement of both devices in a single surgical procedure should be considered.

Early ventral surgical treatment without traction of acute traumatic subaxial cervical spine injuries.

BACKGROUND: Spinal cord decompression after cervical spinal cord injury (SCI) is the standard of care. However, there is a lack of consensus regarding the optimal management of these injuries, including the role of traction and timing of surgery. Here, we report the safety/efficacy of ventral surgery without preoperative traction for intraoperative fracture reduction following acute cervical SCI. METHODS: We prospectively collected a series of patients who sustained acute traumatic subaxial cervical (C3-7) spine fractures between 2004 and 2016. Patients underwent anterior cervical decompression and fusion within 24 h of injury without the utilization of preoperative traction. RESULTS: Thirty-six patients (27 male, 9 female), averaging 35 years of age, sustained 25 motor-vehicle accidents, 4 sports-related injuries, and 7 falls. Fracture dislocations were seen in 26 patients, whereas burst fractures were seen in 10. The majority of injuries occurred at the C4-5 (13 patients) and C5-6 (13 patients) levels. Complete SCI occurred in 10 patients, and incomplete SCI in 26 patients. All patients underwent anterior surgery only; 16 required vertebrectomy in addition to anterior cervical discectomy and fusion. Intraoperative reduction was achieved in all patients using a Cobb elevator or distraction pins without the use of preanesthesia traction. There were no intraoperative complications. Postoperatively, there were one postoperative hematoma, two wound/hardware revisions, one subsequent posterior fusion, and one reoperation anteriorly after screw pullout. The average hospital length of stay was 10.6 days (range 1-39). CONCLUSION: Early direct surgical stabilization/fusion for acute SCI because of subaxial cervical spine fractures is both safe and effective in selected cases when performed anteriorly without preoperative traction in select cases.

Rats bred for low and high running capacity display alterations in peripheral tissues and nerves relevant to neuropathy and pain.

INTRODUCTION: Diet and activity are recognized as modulators of nervous system disease, including pain. Studies of exercise consistently reveal a benefit on pain. This study focused on female rats to understand differences related to metabolic status and peripheral nerve function in females. METHODS: Here, we investigated parameters of peripheral nerve function relevant to pain in rats selectively bred for high (high-capacity runners; HCR) or low endurance exercise capacity (low-capacity runners; LCR) resulting in divergent intrinsic aerobic capacities and susceptibility for metabolic conditions. RESULTS: LCR female rats have reduced mechanical sensitivity, higher intraepidermal nerve fiber density and TrkA-positive epidermal axons, increased numbers of Langerhans and mast cells in cutaneous tissues, and a higher fat content despite similar overall body weights compared to female HCR rats. Sensory and motor nerve conduction velocities, thermal sensitivity, and mRNA expression of selected genes relevant to peripheral sensation were not different. CONCLUSIONS: These results suggest that aerobic capacity and metabolic status influence sensory sensitivity and aspects of inflammation in peripheral tissues that could lead to poor responses to tissue damage and painful stimuli. The LCR and HCR rats should prove useful as models to assess how the metabolic status impacts pain.