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.

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.

H3K27 trimethylation loss in malignant peripheral nerve sheath tumor: a systematic review and meta-analysis with diagnostic implications.

BACKGROUND: Multiple studies have reported the loss of trimethylation at lysine (K) 27 on histone 3 (H3K27me3) in high-grade malignant peripheral nerve sheath tumors (MPNSTs). However, the diagnostic potential of this finding in MPNSTs remains yet to be fully substantiated. Correspondingly, our aim was to pool systematically-identified metadata in the literature and substantiate the incidence of H3K27me3 loss in this setting. METHODS: Searches of 7 electronic databases from inception to May 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of loss was then pooled by random-effects meta-analysis of proportions. RESULTS: Nine pertinent studies described a total of 823 high-grade MPNST samples. When pooled, incidence (sensitivity) of complete H3K27me3 loss was estimated to be 53% (95% CI 42-64%). For MPNST subtypes, estimated incidences of complete loss in NF1 subtype was 52% (95% CI 41-62), in sporadic subtype was 53% (95% CI 36-70%), in the epithelioid subtype was 0% (95% CI 0-7%), and radiation-associated subtype was 98% (95% CI 86-100%). Finally, incidence of incomplete loss (specificity) in 1231 MPNST-mimic samples was estimated to be 96% (95% CI 90-99%). Certainty of these outcomes ranged from very low to high. CONCLUSIONS: The incidence of complete H3K27me3 loss is substantial in high-grade MPNSTs and is low in MPNST-mimics. Greater cohort study and biological investigation will validate the certainty of these findings as well as elucidate their true molecular and clinical significances.

The medial safe zone for treating intraneural ganglion cysts in the tarsal tunnel: a technical note.

INTRODUCTION: Intraneural ganglion cysts in the tarsal tunnel are rare but are being increasingly reported. The cysts involve the tibial or plantar nerves and are most commonly derived from a neighboring (degenerative) joint, (i.e., the tibiotalar or subtalar) via an articular branch arising from the medial aspect of the nerve. We describe a safe zone for approaching these cysts in the tarsal tunnel that allows for identification of the joint connection without injury to important distal branches. METHODS: We present a case of an intraneural ganglion cyst within the tarsal tunnel in a patient with symptoms consistent with tarsal tunnel syndrome. Using intraoperative photographs and artist rendering, we describe a technique to safely disconnect the abnormal joint connection while preserving the important distal branches of the tibial nerve. CONCLUSION: The safe zone for the tibial nerve in the tarsal tunnel can be exposed by mobilization and gentle retraction of the vascular bundle. In cases of intraneural ganglion cysts, all apparent connections between the nerve and degenerative joints within this safe zone can be resected without injury to important distal nerve branches.

Avoidance of scapular winging while approaching tumors of the middle scalene region.

BACKGROUND: Large tumors arising from the middle scalene region can displace the middle scalene muscle and distort regional anatomy, placing nerves at risk. Understanding the surgical anatomy of these nerves is key to approaching pathology of the middle scalene muscle and avoiding damage to the dorsal scapular, long thoracic, and spinal accessory nerves, each of which can cause scapular winging and associated morbidity if injured. METHODS: IRB approval was obtained for this study, allowing cases with relevant pathology to be reviewed and presented to highlight the relevant surgical technique. Anatomical depictions were created to correlate intraoperative images with known anatomical relationships. RESULTS: Key to this approach is consideration of the regional anatomy in a standard supraclavicular approach, the superficial plane, containing the anterior scalene muscle and brachial plexus, and the oblique plane containing the middle scalene muscle, long thoracic, spinal accessory, and dorsal scapular nerves. Identification and mobilization of each of these structures prior to lesion removal can not only provide likely boundaries of the tumor, but also allow for protection of the nerves to avoid injury that may lead to scapular winging with associated morbidity and functional impairment of the upper extremity. CONCLUSIONS: Lesions of the middle scalene region often split two important anatomical planes, the superficial and deep, creating an advantageous surgical corridor through an anterolateral approach. Through early identification of known anatomy, these two planes can be developed, and a safe approach to the lesion of the middle scalene region can be exploited.

Extensive perineural spread of an intrapelvic sciatic malignant peripheral nerve sheath tumor: a case report.

Perineural spread has been described in multiple neoplasms of neural and non-neural origin. The peripheral nervous system may represent a highway by which tumors can spread throughout the body. Malignant peripheral nerve sheath tumor (MPNST) is a neoplasm arising from peripheral nerves with high rates of local recurrence and distant metastases, leading to a poor 5-year overall survival. In many cases, the optimal treatment involves wide en bloc excision with negative margins as well as chemotherapy and radiation. Even in cases of negative surgical margins, recurrence rates are high, suggesting possible skip lesions or very distant infiltration along the involved nerve. We report a case of high-grade MPNST of the sciatic nerve with post-mortem dissection and histopathologic characterization of perineural spread of microscopic disease to sites significantly proximal and distal to areas with evidence of gross disease, which may help to explain the high rates of local and distal recurrence in MPNST.

Tumefactive appearance of peripheral nerve involvement in hematologic malignancies: a new imaging association.

OBJECTIVE: In neurolymphomatosis (NL), the affected nerves are typically described to be enlarged and hyperintense on T2W MR sequences and to avidly enhance on gadolinium-enhanced T1WI. This pattern is highly non-specific. We recently became aware of a "tumefactive pattern" of NL, neuroleukemiosis (NLK) and neuroplasmacytoma (NPLC), which we believe is exclusive to hematologic diseases affecting peripheral nerves. MATERIALS AND METHODS: We defined a "tumefactive" appearance as complex, fusiform, hyperintense on T2WI, circumferential tumor masses encasing the involved peripheral nerves. The nerves appear to be infiltrated by the tumor. Both structures show varying levels of homogenous enhancement. We reviewed our series of 52 cases of NL in search of this pattern; two extra outside cases of NL, three cases of NLK, and one case of NPLC were added to the series. RESULTS: We identified 20 tumefactive lesions in 18 patients (14 NL, three NLK, one NPLC). The brachial plexus (n = 7) was most commonly affected, followed by the sciatic nerve (n = 6) and lumbosacral plexus (n = 3). Four patients had involvement of other nerves. All were proven by biopsy: the diagnosis was high-grade lymphoma (n = 12), low-grade lymphoma (n = 3), acute leukemia (n = 2), and plasmacytoma (n = 1). CONCLUSIONS: We present a new imaging pattern of "tumefactive" neurolymphomatosis, neuroleukemiosis, or neuroplasmacytoma in a series of 18 cases. We believe this pattern is associated with hematologic diseases directly involving the peripheral nerves. Knowledge of this association can provide a clue to clinicians in establishing the correct diagnosis. Bearing in mind that tumefactive NL, NLK, and NPLC is a newly introduced imaging pattern, we still recommend to biopsy patients with suspicion of a malignancy.

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.

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.

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.

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.

CT and MR arthrograms demonstrate a consistent communication between the tibiofemoral and superior tibiofibular joints.

Communications between the tibiofemoral and superior tibiofibular joints (STFJ) have been thought to be infrequent. Previous anatomic studies have revealed these in only 10-64% of cases. In this study, the authors reviewed the results of direct knee arthrography performed in 17 consecutive patients from January 2010 to July 2011 with various knee or STFJ-related pathologies. In all 17 consecutive cases, the authors demonstrated evidence of knee and STFJ communications. The authors believe that high-resolution imaging arthrography, especially with physiological loading and delayed imaging, can demonstrate these communications more consistently than unenhanced anatomic studies.

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.

Curative Onyx embolization of tentorial dural arteriovenous fistulas.

OBJECT: The authors conducted a study to review their experience with tentorial dural arteriovenous fistulas (DAVFs) treated with transarterial endovascular embolization in which Onyx was used. METHODS: The authors reviewed prospectively collected data in 9 patients with tentorial DAVFs treated with Onyx embolization between 2008 and 2011. Information reviewed included clinical presentation, angiographic features, treatment, and clinical and radiologically documented outcome. Clinical follow-up was available in every patient. Radiological follow-up studies were available in 8 of 9 patients (mean follow-up 4.6 months). RESULTS: Six of 9 patients had complete angiographic obliteration (in 5 this was confirmed by a follow-up angiogram obtained 3-6 months later), and 2 patients had near-complete obliteration (faint filling of the venous drainage in the late venous phase). One patient had partial obliteration and required surgical disconnection. In all patients with complete obliteration, transarterial embolization was performed through the posterior branch of the middle meningeal artery. There were no procedural complications, and no morbidity or mortality resulted from Onyx embolization. CONCLUSIONS: Transarterial Onyx embolization is a valid, effective, and safe alternative to surgical disconnection in many patients with tentorial DAVFs. The presence of an adequate posterior branch of the middle meningeal artery is critical to achieve a microcatheter position distal enough to increase the likelihood of complete obliteration.

Orthostatic hypotension following resection of a dorsal medullary hemangioblastoma.

BACKGROUND: Orthostatic hypotension (OH) is an uncommon, but not rare manifestation of dorsal medullary lesions which has less commonly been described as arising de novo or significantly worsening following surgical resection of the lesion. METHODS: We present a case and review the English literature regarding dorsal medullary lesions and post-operative OH, focusing on the population of patients who develop new or significantly worsened OH after surgery with the hope that this information can be used to counsel patients. RESULTS: A 34-year old hypertensive woman was diagnosed with Von Hippel-Lindau syndrome during evaluation for headache. Magnetic resonance imaging of the brain and cervical spine revealed three posterior fossa hemangioblastomas and a resultant cervical syrinx. She was taken to surgery for resection of two of the posterior fossa hemangioblastomas, one of which was adherent to the obex. Post-operatively, the patient had significant OH requiring treatment. At the three month post-operative assessment, she was off all blood pressure medications. CONCLUSIONS: OH is an uncommon manifestation of dorsal medullary lesions and can rarely show significant worsening in severity following surgical resection of the lesion. Medical management in conjunction with physical rehabilitation may potentially result in recovery.

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.

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.