Combat-related peripheral nerve injuries.

Active-duty service members (ADSM) and military Veterans represent a population with increased occupational risk for nerve injuries sustained both during training operations and wartime. Mechanisms of war-related nerve injuries have evolved over time, from the musket ball-related traumas described by S.W. Mitchell to complex blast injuries and toxic exposures sustained during Middle East conflicts in the 21st century. Commonly encountered nerve injury etiologies in this population currently include compression, direct trauma, nutritional deficits, traumatic limb amputation, toxic chemical exposures, or blast-related injuries. Expeditious identification and comprehensive, interdisciplinary treatment of combat-associated neuropathies, as well as prevention of these injuries whenever possible is critical to reduce chronic morbidity and disability for service members and to maintain a well-prepared military. However, diagnosis of a combat-associated nerve injury may be particularly challenging due to comorbid battlefield injuries or delayed presentation of neuropathy from military toxic exposures. Advances in imaging for nerve injury, including MRI and ultrasound, provide useful tools to compliment EMG in establishing a diagnosis of combat-associated nerve injury, particularly in the setting of anatomic disruption or edema. Surgical techniques can improve pain control or restoration of function. In all cases, comprehensive interdisciplinary rehabilitation provides the best framework for optimization of recovery. Further work is needed to prevent combat-associated nerve injuries and promote nerve recovery following injury.

G. Carl Huber (1865-1934): A Michigan Pioneer in Peripheral Nerve Injury and Regeneration.

The treatment of peripheral nerve injuries has seen tremendous innovations over the past century. Dr Gotthelf Carl Huber, an American immigrant and early experimental pioneer in the field of peripheral nerve injury, created a foundation of scientific knowledge for these advancements. At the beginning of his career, Huber published novel work in peripheral nerve injury, supporting the concept of Wallerian degeneration and demonstrating the use of nerve grafting for repair. As his scientific career evolved into other research areas at the University of Michigan, Huber's impact extended far beyond just the study of peripheral nerve injury. Because of the external forces of the First World War, Dr Huber's focus returned to translational projects concentrated on the treatment of neuromas and war time peripheral nerve injuries. Huber's scientific impact in the field of peripheral nerve injury and repair came as a result of his incredible work ethic, mentorship, and tremendous leadership qualities; through this, his work still influences clinical practice today, a century later.

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.

Survey of United States neurosurgeons on firearm injury prevention.

OBJECTIVE: Firearm-related injuries and deaths are an endemic problem in the US, posing a burden on the healthcare system with significant social and economic consequences. As front-line care providers for these patients, neurosurgeons are both knowledgeable about these injuries and credible messengers in the public discussion of ways to reduce firearm injuries. The purpose of this study was to explore US-based neurosurgeons' views and behaviors regarding firearms to understand and define a potential role for neurosurgical organizations in advocacy efforts to reduce firearm death and injuries. METHODS: The authors conducted an anonymous survey of US neurosurgeons using the American Association of Neurological Surgeons (AANS) member database from April to June 2023. The 22-question survey included questions related to firearm ownership, personal views on firearms, and support for both general and policy-specific advocacy efforts to reduce firearm deaths and injuries. RESULTS: The survey response rate was 20.7%, with 1568 of the 7587 members invited completing the survey. The survey completion rate was 93.4%, with 1465 of the 1568 surveys completed and included in this analysis. The majority of respondents were male (raw: 81.7%; weighted 81.1%), White (raw: 69.7%; weighted 70.2%), and older than 50 years (raw: 56.2%; weighted: 54%). Most respondents reported treating patients with firearm injuries (raw: 83.3%; weighted: 82%), 85.5% (weighted: 85.1%) had used a firearm, and 42.4% (weighted: 41.5%) reported owning a firearm. Overall, 78.8% (weighted: 78.7%) of respondents felt that organized neurosurgery should participate in advocacy efforts. When examining individual policies, those that restrict the acquisition of firearms garnered the support of at least 65% of respondents, while nonrestrictive policies were supported by more than 75% of respondents. Free-text responses provided insight into both motivations for and objections to organizational advocacy. CONCLUSIONS: The majority of US-based neurosurgeons support involvement in advocacy efforts to reduce firearm deaths and injuries. Themes expressed by members both supporting and objecting to advocacy provide insight into approaches that could ensure broad support. Neurosurgical organizations such as the AANS and Congress of Neurological Surgeons may use the results of this survey to make informed decisions regarding involvement in advocacy efforts on behalf of their membership to lessen the burden of firearm injury in the US.

Effects of age and time since injury on traumatic brain injury blood biomarkers: a TRACK-TBI study.

Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury. Our aims were to investigate age-related differences in diagnostic accuracy and 2-week evolution of four leading candidate blood-based traumatic brain injury biomarkers-plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, S100 calcium binding protein B and neuron-specific enolase-among participants in the 18-site prospective cohort study Transforming Research And Clinical Knowledge in Traumatic Brain Injury. Day-1 biomarker data were available for 2602 participants including 2151 patients with traumatic brain injury, 242 orthopedic trauma controls and 209 healthy controls. Participants were stratified into 3 age categories (young: 17-39 years, middle-aged: 40-64 years, older: 65-90 years). We investigated age-stratified biomarker levels and biomarker discriminative abilities across three diagnostic groups: head CT-positive/negative; traumatic brain injury/orthopedic controls; and traumatic brain injury/healthy controls. The difference in day-1 glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1 and neuron-specific enolase levels across most diagnostic groups was significantly smaller for older versus younger adults, resulting in a narrower range within which a traumatic brain injury diagnosis may be discriminated in older adults. Despite this, day-1 glial fibrillary acidic protein had good to excellent performance across all age-categories for discriminating all three diagnostic groups (area under the curve 0.84-0.96; lower limit of 95% confidence intervals all >0.78). Day-1 S100 calcium-binding protein B and ubiquitin carboxy-terminal hydrolase L1 showed good discrimination of CT-positive versus negative only among adults under age 40 years within 6 hours of injury. Longitudinal blood-based biomarker data were available for 522 hospitalized patients with traumatic brain injury and 24 hospitalized orthopaedic controls. Glial fibrillary acidic protein levels maintained good to excellent discrimination across diagnostic groups until day 3 post-injury irrespective of age, until day 5 post-injury among middle-aged or younger patients and until week 2 post-injury among young patients only. In conclusion, the blood-based glial fibrillary acidic protein assay tested here has good to excellent performance across all age-categories for discriminating key traumatic brain injury diagnostic groups to at least 3 days post-injury in this trauma centre cohort. The addition of a blood-based diagnostic to the evaluation of traumatic brain injury, including geriatric traumatic brain injury, has potential to streamline diagnosis.

Malignant Peripheral Nerve Sheath Tumors Without Muscle Weakness at Presentation: An Analysis of an Underappreciated Combination.

OBJECTIVE: Patients with malignant peripheral nerve sheath tumors (MPNSTs) of major motor nerves typically present with muscle weakness and pain. We aimed to analyze and characterize patients with MPNSTs of major motor nerves but without muscle weakness at initial presentation. METHODS: We performed a retrospective search of MPNSTs in a major nerve evaluated and/or treated at our institution from 1994 to 2019. Patients with no muscle weakness and available magnetic resonance imaging were analyzed. Clinical materials and magnetic resonance imaging and positron emission tomography scans were reviewed for features of malignancy. This group of patients was compared with patients who presented with MPNSTs and muscle weakness. RESULTS: Of 26 patients with MPNSTs who presented with no muscle weakness, 21 (81%) had a positive family history for malignancy. Only 16 (62%) magnetic resonance imaging scans were highly suspicious for malignancy. All 7 available positron emission tomography scans were highly suspicious for malignancy. Patients who presented with muscle weakness (n = 36) were more likely to have paresthesias and a history of neurofibromatosis 1 or radiation to the MPNST location (P < 0.05). CONCLUSIONS: MPNSTs of major motor nerves without muscle weakness represent an underappreciated subset of cases that have potential treatment and outcome implications. These patients presented with fewer symptoms and had fewer risk factors than patients with muscle weakness. Positron emission tomography should be considered as an additional method to try to anticipate the diagnosis of an MPNST.

High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study.

Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.

Treating Morton's neuroma by injection, neurolysis, or neurectomy: a systematic review and meta-analysis of pain and satisfaction outcomes.

BACKGROUND: Individual evidence suggests that multiple modalities can be used to treat entrapment pathology by Morton's neuroma, including injection, neurolysis, and neurectomy. However, their impacts on patient pain and satisfaction have yet to be fully defined or elucidated. Correspondingly, our aim was to pool systematically identified metadata and substantiate the impact of these different modalities in treating Morton's neuroma with respect to these outcomes. METHODS: Searches of 7 electronic databases from inception to October 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidences of outcomes were extracted and pooled by random-effects meta-analysis of proportions. RESULTS: A total of 35 articles satisfied all criteria, reporting a total of 2998 patients with Morton's neuroma managed by one of the three modalities. Incidence of complete pain relief after injection (43%; 95% CI, 23-64%) was significantly lower than neurolysis (68%; 95% CI, 51-84%) and neurectomy (74%; 95% CI, 66-82%) (P = 0.02). Incidence of complete satisfaction after injection (35%; 95% CI, 21-50%) was significantly lower than neurolysis (63%; 95% CI, 50-74%) and neurectomy (57%; 95% CI, 47-67%) (P < 0.01). The need to proceed to further surgery was significantly greater following injection (15%; 95% CI, 9-23%) versus neurolysis (2%; 95% CI, 0-4%) or neurectomy (5%; 95% CI, 3-7%) (P < 0.01). Incidence of procedural complications did not differ between modalities (P = 0.30). CONCLUSIONS: Although all interventions demonstrated favorable procedural complication incidences, surgical interventions by either neurolysis or neurectomy appear to trend towards greater incidences of complete pain relief and complete patient satisfaction outcomes compared to injection treatment. The optimal decision-making algorithm for treatment for Morton's neuroma should incorporate these findings to better form and meet the expectations of patients.

Morbidity and mortality in elderly patients undergoing evacuation of acute traumatic subdural hematoma.

OBJECTIVE: Acute traumatic subdural hematoma (atSDH) can be a life-threatening neurosurgical emergency that necessitates immediate evacuation. The elderly population can be particularly vulnerable to tearing bridging veins. The aim of this study was to evaluate inpatient morbidity and mortality, as well as predictors of inpatient mortality, in a national trauma database. METHODS: The authors queried the 2016-2017 National Trauma Data Bank registry for patients aged 65 years and older who had undergone evacuation of atSDH. Patients were categorized into three age groups: 65-74, 75-84, and 85+ years. A multivariable logistic regression model was fitted for inpatient mortality adjusting for age group, sex, race, presenting Glasgow Coma Scale (GCS) category (3-8, 9-12, and 13-15), Injury Severity Score, presence of coagulopathy, presence of additional hemorrhages (epidural hematoma [EDH], intraparenchymal hematoma [IPH], and subarachnoid hemorrhage [SAH]), presence of midline shift > 5 mm, and pupillary reactivity (both, one, or none). RESULTS: A total of 2508 patients (35% females) were analyzed. Age distribution was as follows: 990 patients at 65-74 years, 1096 at 75-84, and 422 at 85+. Midline shift > 5 mm was present in 72% of cases. With regard to additional hemorrhages, SAH was present in 21%, IPH in 10%, and EDH in 2%. Bilaterally reactive pupils were noted in 90% of patients. A major complication was observed in 14.4% of patients, and the overall mortality rate was 18.3%. In the multivariable analysis, the presenting GCS category was found to be the strongest predictor of postoperative inpatient mortality (3-8 vs 13-15: OR 3.63, 95% CI 2.68-4.92, p < 0.001; 9-12 vs 13-15: OR 2.64, 95% CI 1.79-3.90, p < 0.001; 30% of overall variation), followed by the presence of SAH (OR 2.86, 95% CI 2.21-3.70, p < 0.001; 25% of overall variation) and the presence of midline shift > 5 mm (OR 2.40, 95% CI 1.74-3.32, p < 0.001; 11% of overall variation). Model discrimination was excellent (c-index 0.81). Broken down by age decile group, mortality increased from 8.0% to 15.4% for GCS 13-15 to around 36% for GCS 9-12 to almost as high as 60% for GCS 3-8, particularly in those aged 85 years and older. CONCLUSIONS: The present results from a national trauma database will, the authors hope, assist surgeons in preoperative discussions with patients and their families with regard to expected postoperative outcomes following surgical evacuation of an atSDH.

Point-of-Care Platform Blood Biomarker Testing of Glial Fibrillary Acidic Protein versus S100 Calcium-Binding Protein B for Prediction of Traumatic Brain Injuries: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study.

Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13-15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3-15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3-15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472-3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26-397) or orthopedic trauma controls (n = 122; median = 13 pg/mL, IQR: 7-20), p < 0.001. Serum S100B levels were likewise higher in CT+ TBI subjects (median = 0.17 µg/L, IQR: 0.09-0.38) than in CT- TBI subjects (median = 0.10 µg/L, IQR: 0.06-0.18), p < 0.001. Receiver operating characteristic curves were generated for prediction of intracranial injury on admission CT scan; area under the curve (AUC) for GFAP was significantly higher than for S100B in the same cohort (GFAP AUC - 0.85, 95% confidence interval [CI] 0.83-0.87; S100B AUC - 0.67, 95% CI 0.64-0.70; p < 0.001). GFAP, measured on a point-of-care platform prototype assay, has high discriminative ability to predict intracranial abnormalities on CT scan in patients with TBI across the full injury spectrum of GCS 3-15 through 24 h post-injury. GFAP substantially outperforms S100B.

Plasma extracellular vesicles as a source of biomarkers in traumatic brain injury.

OBJECTIVE: The objective of this study was to isolate extracellular vesicles (EVs) from plasma in a cohort of patients with traumatic brain injury (TBI) and analyze their contents for novel biomarkers that could prove useful for rapid diagnosis and classification of brain injury during initial evaluation. METHODS: Plasma EVs were isolated by serial ultracentrifugation from patients with TBI (n = 15) and healthy controls (n = 5). Samples were obtained from the TRACK-TBI biorepository (2010-present). Size and concentration were determined by nanoparticle tracking. Glial fibrillary acidic protein (GFAP) concentration was determined in EV protein. EV RNA was isolated and deep sequencing of short noncoding RNA was performed. RESULTS: Plasma EVs are physically similar but contained approximately 10 times more GFAP in TBI patients with altered consciousness than patients and controls with normal consciousness. Eleven highly differentially expressed microRNAs (miRNAs) were identified between these groups. Genes targeted by these miRNAs are highly associated with biologically relevant cellular pathways, including organismal injury, cellular development, and organismal development. Multiple additional coding and noncoding RNA species with potential biomarker utility were identified. CONCLUSIONS: Isolating plasma EVs in patients with TBI is feasible. Increased GFAP concentration-a validated plasma TBI marker-in EVs from TBI patients with altered consciousness, along with differential expression of multiple miRNAs targeting TBI-relevant pathways, suggests that EVs may be a useful source of TBI biomarkers. Additional evaluation in larger patient cohorts is indicated.

Personal and Familial Malignancy History in Patients with Malignant Peripheral Nerve Sheath Tumors with a Focus on Sporadic Tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, in patients with neurofibromatosis 1, and in patients with prior radiation therapy. The incidence of unrelated prior malignancies and family history of malignancy in patients with MPNSTs has not been previously described. METHODS: A retrospective search for cases of MPNSTs at our institution for the years 1994-2019 was performed. The electronic medical record was reviewed for documentation of personal and family history of malignancies. RESULTS: The study included 331 patients. Of patients, 301 had documentation of their personal history of prior unrelated malignancies; 70 (23.3%) of these patients had a personal history of an unrelated previous malignancy. Of patients, 285 had information in the chart regarding family history of cancer; 210 (73.7%) of these patients had a family history of malignancy. Of patients, 145 had sporadic MPNSTs, 118 had neurofibromatosis 1-associated MPNSTs, 31 had radiation-induced MPNSTs, and 37 were missing this information. Among the sporadic cases, 29 had a personal history of an unrelated prior malignancy, and 10 developed an unrelated malignancy following diagnosis of MPNST. A family history of malignancy was present in 109 patients. There was a trend toward longer time to recurrence, time to metastasis, and overall survival in patients with sporadic MPNSTs and negative personal and family histories compared with patients with positive personal or family histories or both. CONCLUSIONS: Patients with sporadic MPNSTs had a high incidence of personal and family history of malignancy. The genetics associated with sporadic MPNSTs include RAS and p53 mutations, which are found in multiple oncologic processes and tumor-forming syndromes. This suggests an underlying genetic predisposition to formation of malignancies, including MPNSTs.

Teriparatide treatment increases Hounsfield units in the lumbar spine out of proportion to DEXA changes.

OBJECTIVE: The authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA). METHODS: A retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment. RESULTS: Fifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1-4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2-46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from -2.4 ± 1.5 to -1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from -2.5 ± 1.1 to -2.3 ± 1.0 (p value = 0.31). CONCLUSIONS: Teriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons' subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors' knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

Interfascicular Resection of Benign Peripheral Nerve Sheath Tumors.

BACKGROUND: Interfascicular resection is a surgical technique used to safely treat benign peripheral nerve sheath tumors through careful dissection of functional neural elements off the tumor surface1,2. DESCRIPTION: Proper operative technique is essential to improving symptoms, preserving neurologic function, and minimizing the chance for recurrence. Accurate tumor localization, ideal patient positioning, and placement of a longitudinal incision permit adequate exposure. Prior to tumor resection, normal nerve should be identified proximally and distally and controlled with vessel loops. This allows functional fascicles streaming around the tumor in the pseudocapsule to be visualized during resection. A fascicle-free window is identified on the tumor surface through visual inspection and intraoperative neurophysiology monitoring if desired. The pseudocapsule layers are divided with a sharp instrument until a smooth and shiny true capsule layer is found. This plane should have minimal resistance and is developed circumferentially until the tumor can be enucleated in toto. At the poles of the tumor, a single nonfunctional nerve fascicle that courses into the tumor is typically found. If there is >1 fascicle running into the tumor, further pseudocapsule layers should be undermined to sweep fascicles off the true capsule surface. The entering-exiting fascicle can be tested for function and is cut sharply. The specimen should be sent to pathology for permanent sectioning. The sides of the pseudocapsule are spread in opposite directions to evaluate for residual tumor, and any remaining tumor is removed if it can be done safely. Meticulous hemostasis is achieved, and the surgical site is closed in anatomical layers. ALTERNATIVES: Pain is the most common presenting symptom, and neuroleptic medications should be used in escalating dosage prior to surgical intervention. Nonoperative medical therapy does not typically result in symptom freedom, and patients often opt for resection. For tumors that are suspected of being malignant, an image-guided percutaneous or open biopsy and staging (positron emission tomography and/or computed tomography scans of the chest, abdomen, and pelvis) are recommended prior to treatment planning. For symptomatic benign extremity lesions, surgical resection is the treatment of choice, and adjuvant therapies like radiation and/or chemotherapy are not recommended. For malignant lesions, more aggressive surgery (wide resection or amputation) and preoperative, intraoperative, or postoperative radiation with or without chemotherapy are often utilized. RATIONALE: The treatment approach depends on a variety of presenting features such as onset, progression, symptom severity, tumor size, location, imaging features, presence of a syndrome, and patient age. There is little benefit from the resection of an incidentally found, small, nongrowing lesion. The most common reasons for removal of extremity lesions are a painful mass and/or radiating "nerve" pain. There is a high likelihood of relieving the symptoms and minimizing the risk of recurrence, and a relatively low risk of causing neurologic injury. The procedure provides a definitive diagnosis. For patients with severe pain, progressive weakness, rapid tumor growth, or concerning imaging characteristics, biopsy should be considered to determine malignant potential.

Synovial Sarcoma of the Nerve-Clinical and Pathological Features: Case Series and Systematic Review.

BACKGROUND: Synovial sarcoma of the nerve is a rare entity with several cases and case series reported in the literature. Despite an improved understanding of the biology, the clinical course is difficult to predict. OBJECTIVE: To compile a series of patients with synovial sarcoma of the peripheral nerve (SSPN) and assess clinical and pathological factors and their contribution to survival and recurrence. METHODS: Cases from 2 institutions collected in patients undergoing surgical intervention for SSPN. Systematic review including PubMed and Scopus databases were searched for related articles published from 1970 to December 2018. Eligibility criteria: (1) case reports or case series reporting on SSPN, (2) clinical course and/or pathological features of the tumor reported, and (3) articles published in English. RESULTS: From patients treated at our institutions (13) the average follow-up period was 3.2 yr. Tumor recurrence was seen in 4 cases and death in 3. Systematic review of the literature yielded 44 additional cases with an average follow-up period of 3.6 yr. From pooled data, there were 10 recurrences and 7 deaths (20% and 14%, respectively). Adjuvant treatment used in 62.5% of cases. Immunohistochemical markers used in diagnosis varied widely; the most common are the following: Epithelial membrane antigen (EMA), cytokeratin, vimentin, cluster of differentiation (CD34), and transducin-like enhancer of split 1 (TLE1). Statistical analysis illustrated tumor size and use of chemotherapy to be negative predictors of survival. No other factors, clinically or from pathologist review, were correlated with recurrence or survival. CONCLUSION: By combining cases from our institution with historical data and performing statistical analysis we show correlation between tumor size and death.

Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study.

BACKGROUND: After traumatic brain injury (TBI), plasma concentration of glial fibrillary acidic protein (GFAP) correlates with intracranial injury visible on CT scan. Some patients with suspected TBI with normal CT findings show pathology on MRI. We assessed the discriminative ability of GFAP to identify MRI abnormalities in patients with normal CT findings. METHODS: TRACK-TBI is a prospective cohort study that enrolled patients with TBI who had a clinically indicated head CT scan within 24 h of injury at 18 level 1 trauma centres in the USA. For this analysis, we included patients with normal CT findings (Glasgow Coma Scale score 13-15) who consented to venepuncture within 24 h post injury and who had an MRI scan 7-18 days post injury. We compared MRI findings in these patients with those of orthopaedic trauma controls and healthy controls recruited from the study sites. Plasma GFAP concentrations (pg/mL) were measured using a prototype assay on a point-of-care platform. We used receiver operating characteristic (ROC) analysis to evaluate the discriminative ability of GFAP for positive MRI scans in patients with negative CT scans over 24 h (time between injury and venepuncture). The primary outcome was the area under the ROC curve (AUC) for GFAP in patients with CT-negative and MRI-positive findings versus patients with CT-negative and MRI-negative findings within 24 h of injury. The Dunn Kruskal-Wallis test was used to compare GFAP concentrations between MRI lesion types with Benjamini-Hochberg correction for multiple comparisons. This study is registered with ClinicalTrials.gov, number NCT02119182. FINDINGS: Between Feb 26, 2014, and June 15, 2018, we recruited 450 patients with normal head CT scans (of whom 330 had negative MRI scans and 120 had positive MRI scans), 122 orthopaedic trauma controls, and 209 healthy controls. AUC for GFAP in patients with CT-negative and MRI-positive findings versus patients with CT-negative and MRI-negative findings was 0·777 (95% CI 0·726-0·829) over 24 h. Median plasma GFAP concentration was highest in patients with CT-negative and MRI-positive findings (414·4 pg/mL, 25-75th percentile 139·3-813·4), followed by patients with CT-negative and MRI-negative findings (74·0 pg/mL, 17·5-214·4), orthopaedic trauma controls (13·1 pg/mL, 6·9-20·0), and healthy controls (8·0 pg/mL, 3·0-14·0; all comparisons between patients with CT-negative MRI-positive findings and other groups p<0·0001). INTERPRETATION: Analysis of blood GFAP concentrations using prototype assays on a point-of-care platform within 24 h of injury might improve detection of TBI and identify patients who might need subsequent MRI and follow-up. FUNDING: National Institute of Neurological Disorders and Stroke and US Department of Defense.