Systemic sclerosis-associated compressive cervical calcinosis: intersection of degenerative spine instability, lesional spinal cord compression, and traumatic spinal cord injury. Illustrative case.

BACKGROUND: Tumoral calcinosis, mass-like calcium deposition into the soft tissues, is an uncommon manifestation of the systemic sclerosis subtype of scleroderma. When this process affects the spinal epidural space, it can cause canal narrowing and place the spinal cord at significant risk of injury. OBSERVATIONS: Here a 62-year-old female with systemic sclerosis and no previous evidence of spinal cord compromise who developed acute spinal cord injury and quadriparesis after a mechanical fall is described. She was found to have a large dorsal epidural calcified mass compressing her cervical spinal cord. She underwent medical management for acute spinal cord compression as well as surgical management for acute spinal cord injury and degenerative spine disease. Her case illustrates a rare etiology of simultaneous degenerative spine instability and lesional spinal cord compression with acute spinal cord injury. LESSONS: Tumor calcinosis leading to acute spinal cord injury in the setting of systemic sclerosis is an uncommon but critical entity to recognize in patients with scleroderma and may require the physician to use a combination of medical and surgical management strategies from each of these categories of spine pathology.

Impact on neurosurgical management in a Level 1 trauma center post COVID-19 shelter-in-place restrictions.

The stringent restrictions from shelter-in-place (SIP) policies placed on hospital operations during the COVID-19 pandemic led to a sharp decrease in planned surgical procedures. This study quantifies the surgical rebound experienced across a neurosurgical service post SIP restrictions in order to guide future hospital programs with resource management. We conducted a retrospective review of all neurosurgical procedures at a public Level 1 trauma center between February 15th to August 30th for the years spanning 2018-2020. We categorized patient procedures into four comparative one-month periods: pre-SIP; SIP; post-SIP; and late recovery. Patient procedures were designated as either cranial; spinal; and other; as well as Elective or Add-on (Urgent/Emergent). Categorical variables were analyzed using χ2 tests and Fisher's exact tests. A total of 347 cases were reviewed across the four comparative periods and three years studied; with 174 and 152 spinal and cranial procedures; respectively. There was a proportional increase; relative to historical controls; in total spinal procedures (p-value < 0.001) and elective spinal procedures (p-value < 0.001) in the 2020 SIP to Post-SIP. The doubling of elective spinal cases in the Post-SIP period returned to historical baseline levels in three months after SIP restrictions were lifted. Total cranial procedures were proportionally increased during the SIP period relative to historical controls (p-value = 0.005). We provide a census on the post-pandemic neurosurgical operative demands at a major public Level 1 trauma hospital, which can potentially be applied for resource allocations in other disaster scenarios.

Impact on neurosurgical management in Level 1 trauma centers during COVID-19 shelter-in-place restrictions: The Santa Clara County experience.

Early COVID-19-targeted legislations reduced public activity and elective surgery such that local neurosurgical care greatly focused on emergent needs. This study examines neurosurgical trauma patients' dispositions through two neighboring trauma centers to inform resource allocation. We conducted a retrospective review of the trauma registries for two Level 1 Trauma Centers in Santa Clara County, one academic and one community center, between February 1st and April 15th, 2018-2020. Events before a quarantine, implemented on March 16th, 2020, and events from 2018 to 19 were used for reference. Encounters were characterized by injuries, services, procedures, and disposition. Categorical variables were analyzed by the χ2 test, proportions of variables by z-score test, and non-parametric variables by Fisher's exact test. A total of 1,336 traumas were identified, with 31% from the academic center and 69% from the community center. During the post-policy period, relative to matching periods in years prior, there was a decrease in number of TBI and spinal fractures (24% versus 41%, p < 0.001) and neurosurgical consults (27% versus 39%, p < 0.003), but not in number of neurosurgical admissions or procedures. There were no changes in frequency of neurosurgery consults among total traumas, patients triaged to critical care services, or patients discharged to temporary rehabilitation services. Neurosurgical services were similarly rendered between the academic and community hospitals. This study describes neurosurgical trauma management in a suburban healthcare network immediately following restrictive quarantine during a moderate COVID-19 outbreak. Our data shows that neurosurgery remains a resource-intensive subspeciality, even during restrictive periods when overall trauma volume is decreased.

Extraforaminal Vertebral Artery Anomalies and Their Associated Surgical Implications: An Epidemiologic and Anatomic Report on 1000 Patients.

OBJECTIVE: Extraforaminal vertebral anomalies involve entry at cervical transverse foramina other than at C6 and can appear with other anatomic variations along the V2 segment. Such unexpected vessel courses can have implications on surgical planning. We sought to evaluate the incidence of anomalous V2 segment entries, as well as their associations with vessel dominance, medialization, and C7 pedicle width. METHODS: We conducted a retrospective study on 1000 consecutive computed tomography angiograms, documenting level and laterality of vessel of entry, as well as vertebral dominance patterns. Patients with rostral C4 anomalies were assessed for medialization. The pedicle widths ipsilateral to caudal C7 anomalies were compared with those of contralateral and matched controls. RESULTS: A total of 157 patients were identified with extraforaminal entries, with 25 having bilateral findings. The most common alternative entry was at C5 (70.3%), followed by C4 (17.6%) and C7 (11.5%). Among patients with unilateral anomalies, there was an increased representation of contralateral vertebral dominance, relative to ipsilateral dominance (79.6% vs 20.4%, P < 0.0001). Among anomalous C4 entries, vertebral medialization was seen along the right (35%) and left sides (23.1%) spanning C6-T1. Among C7 anomalous entries there was no statistical difference in pedicle width. CONCLUSIONS: Extraforaminal anomalies may be more frequent than previously reported and are important considerations during subaxial cervical spine surgery planning. Particular attention should be paid to the contralateral dominance pattern within this subgroup. In patients with anomalous V2 segment entries, adherence to the standard, anatomic landmarks remains desirable.

Mortality prediction and long-term outcomes for civilian cerebral gunshot wounds: A decision-tree algorithm based on a single trauma center.

Gunshot wounds (GSW) are one of the most lethal forms of head trauma. The lack of clear guidelines for civilian GSW complicates surgical management. We aimed to develop a decision-tree algorithm for mortality prediction and report long-term outcomes on survivors based on 15-year data from our level 1 trauma center. We retrospectively reviewed 96 consecutive patients who presented with cerebral GSWs between 2003 and 2018. Clinical information from our trauma database, EMR, and relevant imaging scans was reviewed. A decision-tree model was constructed based on variables showing significant differences between survivors and non-survivors. After excluding patients who died at arrival, 54 patients with radiologically confirmed intracranial injury were included. Compared to survivors (51.9%), non-survivors (48.1%) were significantly more likely to have perforating (entry and exit wound), as opposed to penetrating (entry wound only), injuries. Bi-hemispheric and posterior fossa involvement, cerebral herniation, and intraventricular hemorrhage were more commonly present in non-survivors. Based on the decision-tree, Glasgow Coma Scale (GCS) > 8 and penetrating, uni-hemispheric injury predicted survival. Among patients with GCS ≤ 8 and normal pupillary response, lack of 1) posterior fossa involvement, 2) cerebral herniation, 3) bi-hemispheric injury, and 4) intraventricular hemorrhage, were associated with survival. Favorable long-term outcomes (mean follow-up 34.4 months) were possible for survivors who required neurosurgery and stable patients who were conservatively managed. We applied clinical and radiological characteristics that predicted survival to construct a decision-tree to facilitate surgical decision-making for GSW. Further validation of the algorithm in a large patient setting is recommended.

Elevated risk of venous thromboembolism among post-traumatic brain injury patients requiring pharmaceutical immobilization.

Traumatic brain injury (TBI) patients are known to have a high rate of venous thromboembolism (VTE), and additional neuromuscular blockade or barbiturate coma therapy has the theoretical risk of exacerbating baseline hemostasis and elevating the incidence of thromboembolic events. We conducted a single-institution retrospective review of patients surviving severe TBI, as determined by need for intracranial pressure (ICP) monitoring, who further required paralytics or barbiturate therapy to maintain ICP control. Patients were administered VTE prophylaxis as clinically appropriate. Predictors for VTE were subsequently determined with univariate and logistic multivariate regression analyses. The main cohort includes 144 patients, 34 of whom received pharmaceutical immobilization for ICP control. Mean ISS and GCS at intake were 31.9 and 5.2, respectively. Among those receiving vs not-receiving paralytics and/or barbiturate therapy, there was a statistical difference of 12/34 (35.3%) vs 18/110 (16.4%, p = 0.0280) in VTE events, at a mean time greater than two weeks from the time of trauma. Multivariate logistics regression indicated 3.2 times increased odds of developing a VTE (log odds = 1.17, p = 0.023). No pediatric patients were positive for an event (0/12 vs 7/22, p = 0.0356), and infections were only documented among those with VTE (0/22 vs 4/12, p = 0.0107). Overall, paralytics and barbiturate therapy were correlated with a higher incidence of VTE among TBI patients. Although the need for ICP control will outweigh an increase in thromboembolic risk, there is value for increased surveillance and screening during the prolonged inpatient stay of these patients.

Concussion and Mild-Traumatic Brain Injury in Rural Settings: Epidemiology and Specific Health Care Considerations.

Background Mild-traumatic brain injury (mTBI) and concussions cause significant morbidity. To date, synthesis of specific health care disparities and gaps in care for rural mTBI/concussion patients remains needed. Methods A comprehensive literature search was performed using PubMed database for English articles with keywords "rural" and ("concussion" or "mild traumatic brain injury") from 1991 to 2019. Eighteen articles focusing on rural epidemiology ( n = 5), management/cost ( n = 5), military ( n = 2), and concussion prevention/return to play ( n = 6) were included. Results mTBI/concussion incidence was higher in rural compared with urban areas. Compared with urban patients, rural patients were at increased risk for vehicular injuries, lifetime number of concussions, admissions for observation without neuroimaging, and injury-related costs. Rural patients were less likely to utilize ambulatory and mental health services following mTBI/concussion. Rural secondary schools had decreased access to certified personnel for concussion evaluation, and decreased use of standardized assessment instruments/neurocognitive testing. While school coaches were aware of return-to-play laws, mTBI/concussion education rates for athletes and parents were suboptimal in both settings. Rural veterans were at increased risk for postconcussive symptoms and posttraumatic stress. Telemedicine in rural/low-resource areas is an emerging tool for rapid evaluation, triage, and follow-up. Conclusions Rural patients are at unique risk for mTBI/concussions and health care costs. Barriers to care include lower socioeconomic status, longer distances to regional medical center, and decreased availability of neuroimaging and consultants. Due to socioeconomic and distance barriers, rural schools are less able to recruit personnel certified for concussion evaluation. Telemedicine is an emerging tool for remote triage and evaluation.

Pediatric Traumatic Brain Injury in the United States: Rural-Urban Disparities and Considerations.

INTRODUCTION: Traumatic brain injury (TBI) remains a primary cause of pediatric morbidity. The improved characterization of healthcare disparities for pediatric TBI in United States (U.S.) rural communities is needed to advance care. METHODS: The PubMed database was queried using keywords (("brain/head trauma" OR "brain/head injury") AND "rural/underserved" AND "pediatric/child"). All qualifying articles focusing on rural pediatric TBI, including the subtopics epidemiology (N = 3), intervention/healthcare cost (N = 6), and prevention (N = 1), were reviewed. RESULTS: Rural pediatric TBIs were more likely to have increased trauma and head injury severity, with higher-velocity mechanisms (e.g., motor vehicle collisions). Rural patients were at risk of delays in care due to protracted transport times, inclement weather, and mis-triage to non-trauma centers. They were also more likely than urban patients to be unnecessarily transferred to another hospital, incurring greater costs. In general, rural centers had decreased access to mental health and/or specialist care, while the average healthcare costs were greater. Prevention efforts, such as mandating bicycle helmet use through education by the police department, showed improved compliance in children aged 5-12 years. CONCLUSIONS: U.S. rural pediatric patients are at higher risk of dangerous injury mechanisms, trauma severity, and TBI severity compared to urban. The barriers to care include protracted transport times, transfer to less-resourced centers, increased healthcare costs, missing data, and decreased access to mental health and/or specialty care during hospitalization and follow-up. Preventative efforts can be successful and will require an improved multidisciplinary awareness and education.

Age and sex-mediated differences in six-month outcomes after mild traumatic brain injury in young adults: a TRACK-TBI study.

Introduction: Risk factors for young adults with mTBI are not well understood. Improved understanding of age and sex as risk factors for impaired six-month outcomes in young adults is needed. Methods: Young adult mTBI subjects aged 18-39 years (18-29y; 30-39y) with six-month outcomes were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study. Multivariable regressions were performed for outcomes with age, sex, and the interaction factor age-group*sex as variables of interest, controlling for demographic and injury variables. Mean-differences (B) and 95% CIs are reported. Results: One hundred mTBI subjects (18-29y, 70%; 30-39y, 30%; male, 71%; female, 29%) met inclusion criteria. On multivariable analysis, age-group*sex was associated with six-month post-traumatic stress disorder (PTSD; PTSD Checklist-Civilian version); compared with female 30-39y, female 18-29y (B= -19.55 [-26.54, -4.45]), male 18-29y (B= -19.70 [-30.07, -9.33]), and male 30-39y (B= -15.49 [-26.54, -4.45]) were associated with decreased PTSD symptomatology. Female sex was associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended (GOSE): B= -0.6 [1.0, -0.1]). Comparatively, 30-39y scored higher on six-month nonverbal processing speed (Wechsler Adult Intelligence Scale-Processing Speed Index (WAIS-PSI); B= 11.88, 95% CI [1.66, 22.09]). Conclusions: Following mTBI, young adults aged 18-29y and 30-39y may have different risks for impairment. Sex may interact with age for PTSD symptomatology, with females 30-39y at highest risk. These results may be attributable to cortical maturation, biological response, social modifiers, and/or differential self-report. Confirmation in larger samples is needed; however, prevention and rehabilitation/counseling strategies after mTBI should likely be tailored for age and sex.

Preinjury employment status as a risk factor for symptomatology and disability in mild traumatic brain injury: A TRACK-TBI analysis.

BACKGROUND: Preinjury employment status may contribute to disparity, injury risk, and recovery patterns following mild traumatic brain injury (MTBI). OBJECTIVE: To characterize associations between preinjury unemployment, prior comorbidities, and outcomes following MTBI. METHODS: MTBI patients from TRACK-TBI Pilot with complete six-month outcomes were extracted. Preinjury unemployment, comorbidities, injury factors, and intracranial pathology were considered. Multivariable regression was performed for employment and outcomes, correcting for demographic and injury factors. Mean-differences (B) and 95% CIs are reported. Statistical significance was assessed at p < 0.05. RESULTS: 162 MTBI patients were aged 39.8±15.4-years and 24.6% -unemployed. Unemployed patients demonstrated increased psychiatric comorbidities (45.0% -vs.- 23.8%; p = 0.010), drug use (52.5% -vs.- 21.3%; p < 0.001), smoking (62.5% -vs.- 27.0%; p < 0.001), prior TBI (78.4% -vs.- 55.0%; p = 0.012), and lower education (15.0% -vs.- 45.1% college degree; p = 0.003). On multivariable analysis, unemployment associated with decreased six-month functional outcome (Glasgow Outcome Scale-Extended: B = - 0.50, 95% CI [- 0.88, - 0.11]), increased psychiatric disturbance (Brief Symptom Inventory-18: B = 6.22 [2.33, 10.10]), postconcussional symptoms (Rivermead Questionnaire: B = 4.91 [0.38, 9.44]), and post-traumatic stress disorder (PTSD Checklist-Civilian: B = 5.99 [0.76, 11.22]). No differences were observed for cognitive measures or satisfaction with life. CONCLUSIONS: Unemployed patients are at risk for preinjury psychosocial comorbidities, poorer six-month functional recovery and increased psychiatric/postconcussional/PTSD symptoms. Resource allocation and return precautions should be implemented to mitigate and/or prevent the decline of at-risk patients.

Prospective comparison of long-term pain relief rates after first-time microvascular decompression and stereotactic radiosurgery for trigeminal neuralgia.

OBJECTIVE Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD), stereotactic radiosurgery (SRS), and radiofrequency ablation (RFA). Although the efficacy of each procedure has been described, few studies have directly compared these treatment modalities on pain control for TN. Using a large prospective longitudinal database, the authors aimed to 1) directly compare long-term pain control rates for first-time surgical treatments for idiopathic TN, and 2) identify predictors of pain control. METHODS The authors reviewed a prospectively collected database for all patients who underwent treatment for TN between 1997 and 2014 at the University of California, San Francisco. Standardized collection of data on preoperative clinical characteristics, surgical procedure, and postoperative outcomes was performed. Data analyses were limited to those patients who received a first-time procedure for treatment of idiopathic TN with > 1 year of follow-up. RESULTS Of 764 surgical procedures performed at the University of California, San Francisco, for TN (364 SRS, 316 MVD, and 84 RFA), 340 patients underwent first-time treatment for idiopathic TN (164 MVD, 168 SRS, and 8 RFA) and had > 1 year of follow-up. The analysis was restricted to patients who underwent MVD or SRS. Patients who received MVD were younger than those who underwent SRS (median age 63 vs 72 years, respectively; p < 0.001). The mean follow-up was 59 ± 35 months for MVD and 59 ± 45 months for SRS. Approximately 38% of patients who underwent MVD or SRS had > 5 years of follow-up (60 of 164 and 64 of 168 patients, respectively). Immediate or short-term (< 3 months) postoperative pain-free rates (Barrow Neurological Institute Pain Intensity score of I) were 96% for MVD and 75% for SRS. Percentages of patients with Barrow Neurological Institute Pain Intensity score of I at 1, 5, and 10 years after MVD were 83%, 61%, and 44%, and the corresponding percentages after SRS were 71%, 47%, and 27%, respectively. The median time to pain recurrence was 94 months (25th-75th quartiles: 57-131 months) for MVD and 53 months (25th-75th quartiles: 37-69 months) for SRS (p = 0.006). A subset of patients who had MVD also underwent partial sensory rhizotomy, usually in the setting of insignificant vascular compression. Compared with MVD alone, those who underwent MVD plus partial sensory rhizotomy had shorter pain-free intervals (median 45 months vs no median reached; p = 0.022). Multivariable regression demonstrated that shorter preoperative symptom duration (HR 1.005, 95% CI 1.001-1.008; p = 0.006) was associated with favorable outcome for MVD and that post-SRS sensory changes (HR 0.392, 95% CI 0.213-0.723; p = 0.003) were associated with favorable outcome for SRS. CONCLUSIONS In this longitudinal study, patients who received MVD had longer pain-free intervals compared with those who underwent SRS. For patients who received SRS, postoperative sensory change was predictive of favorable outcome. However, surgical decision making depends upon many factors. This information can help physicians counsel patients with idiopathic TN on treatment selection.

Ethnicity, Race, and Postoperative Stroke Risk Among 53,593 Patients with Asymptomatic Carotid Stenosis Undergoing Revascularization.

BACKGROUND: The incidence of postoperative stroke after carotid endarterectomy is an uncommon event, and differences by racial and ethnic subgroups are not described fully in the literature. OBJECTIVE: To investigate the impact of race and ethnicity on postoperative stroke risk among patients with asymptomatic carotid stenosis undergoing carotid endarterectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was searched for patients between the dates 2008 and 2015 to identify patients undergoing carotid endarterectomy with no history of stroke. Four racial and ethnic subgroups were included: non-Hispanic white, Hispanic white, non-Hispanic back, and non-Hispanic Asian. In addition to a descriptive statistical analysis, univariate and multivariate regression models were created to adjust for cardiovascular and perioperative risk factors and corrected for multiple comparisons. RESULTS: Among the 53,593 patients identified meeting the inclusion criteria, 788 (1.45%) patients experienced a stroke within 30 days. The non-Hispanic white group compared with the minority subgroups had a lower risk of postoperative stroke (1.43% vs. 1.67%, P = 0.18). The greatest difference was between the non-Hispanic white and Hispanic white groups, but this was not significant on multivariable analysis (odds ratio 1.40, 95% confidence interval 0.97-2.02, P = 0.08) after adjustment for risk stroke factors. The strongest predictors of postoperative stroke were perioperative blood transfusion, dependent functional status, and longer operative time. CONCLUSIONS: There was no difference between the racial and ethnic groups and the proportion of postoperative stroke among patients undergoing revascularization for asymptomatic carotid stenosis.

Use of Subdural Evacuating Port System Following Open Craniotomy with Excision of Native Dura and Membranes for Management of Chronic Subdural Hematoma.

An 86-year-old woman was admitted to the intensive care unit with a chronic subdural hematoma (CSDH) and rapid onset of worsening neurological symptoms. She was taken to the operating room for a mini-craniotomy for evacuation of the CSDH including excision of the dura and CSDH membrane. Postoperatively, a subdural evacuation port system (SEPS) was integrated into the craniotomy site and left in place rather than a traditional subdural catheter drain to evacuate the subdural space postoperatively. The patient had a good recovery and improvement of symptoms after evacuation and remained clinically well after the SEPS was removed. We offer the technique of dura and CSDH membrane excision plus SEPS drain as an effective postoperative alternative to the standard craniotomy leaving the native dura intact with traditional subdural drain that overlies the cortical surface of the brain in treating patients with CSDH.

A Superior Cerebellar Convexity Two-Part Craniotomy to Access the Paramedian Supra and Infratentorial Space: Technical Note.

A craniotomy over the superior cerebellar convexity for approaches to this region typically involves a small infratentorial craniotomy and then drilling down of the bone to expose some portion of the transverse/sigmoid sinuses. The authors describe the anatomy of the region and the method for a two-part paramedian occipital and suboccipital craniotomy (supra and infratentorial) that may have time-saving, safety, and cosmetic advantages. For this technique, a supratentorial craniotomy is used to expose the transverse sinus from above, and subsequently, dissection across the sinus over the cerebellar convexity can be done under direct vision. The two bone pieces are joined on the inner table side while plates for fixation above the superior nuchal line can be counter-sunk to avoid post-operative pain from the prominence of screws. There is no need for cranioplasty materials since there is no burring down of bone for adequate exposure of the transverse sinus. The technique has been used by two senior surgeons over the years convincing them of the speed, safety, and utility of the technique. Here, the authors present a single example of the technique.

Visualization of nerve fibers and their relationship to peripheral nerve tumors by diffusion tensor imaging.

OBJECT The majority of growing and/or symptomatic peripheral nerve tumors are schwannomas and neurofibromas. They are almost always benign and can usually be resected while minimizing motor and sensory deficits if approached with the proper expertise and techniques. Intraoperative electrophysiological stimulation and recording techniques allow the surgeon to map the surface of the tumor in an effort to identify and thus avoid damaging functioning nerve fibers. Recently, MR diffusion tensor imaging (DTI) techniques have permitted the visualization of axons, because of their anisotropic properties, in peripheral nerves. The object of this study was to compare the distribution of nerve fibers as revealed by direct electrical stimulation with that seen on preoperative MR DTI. METHODS The authors conducted a retrospective chart review of patients with a peripheral nerve or nerve root tumor between March 2012 and January 2014. Diffusion tensor imaging and intraoperative data had been prospectively collected for patients with peripheral nerve tumors that were resected. Preoperative identification of the nerve fiber location in relation to the nerve tumor surface as seen on DTI studies was compared with the nerve fiber's intraoperative localization using electrophysiological stimulation and recordings. RESULTS In 23 patients eligible for study there was good correlation between nerve fiber location on DTI and its anatomical location seen intraoperatively. Diffusion tensor imaging demonstrated the relationship of nerve fibers relative to the tumor with 95.7% sensitivity, 66.7% specificity, 75% positive predictive value, and 93.8% negative predictive value. CONCLUSIONS Preoperative DTI techniques are useful in helping the peripheral nerve surgeon to both determine the risks involved in resecting a nerve tumor and plan the safest surgical approach.

Downregulation of MYCN through PI3K Inhibition in Mouse Models of Pediatric Neural Cancer.

The MYCN proto-oncogene is associated with poor outcome across a broad range of pediatric tumors. While amplification of MYCN drives subsets of high-risk neuroblastoma and medulloblastoma, dysregulation of MYCN in medulloblastoma (in the absence of amplification) also contributes to pathogenesis. Since PI3K stabilizes MYCN, we have used inhibitors of PI3K to drive degradation. In this study, we show PI3K inhibitors by themselves induce cell cycle arrest, with modest induction of apoptosis. In screening inhibitors of PI3K against MYCN, we identified PIK-75 and its derivative, PW-12, inhibitors of both PI3K and of protein kinases, to be highly effective in destabilizing MYCN. To determine the effects of PW-12 treatment in vivo, we analyzed a genetically engineered mouse model for MYCN-driven neuroblastoma and a model of MYCN-driven medulloblastoma. PW-12 showed significant activity in both models, inducing vascular collapse and regression of medulloblastoma with prominent apoptosis in both models. These results demonstrate that inhibitors of lipid and protein kinases can drive apoptosis in MYCN-driven cancers and support the importance of MYCN as a therapeutic target.

High-resolution ultrasonography and diffusion tensor tractography map normal nerve fascicles in relation to schwannoma tissue prior to resection.

The goals of the present study were to demonstrate the ability of high-resolution ultrasonography to delineate normal nerve fascicles within or around peripheral nerve sheath tumors (NSTs). A blinded examiner evaluated 2 patients with symptomatic upper limb NSTs with high-resolution ultrasonography performed in the perioperative suite using a portable ultrasonography system. Ultrasonographic examinations located the tumor mass and identified the normal nerve fascicles associated with the mass. The locations of normal nerve tissue were mapped and correlated with results of MR tractography, operative inspection, and intraoperative electrophysiological monitoring. The study demonstrated a close correlation between normal nerve fascicles identified by ultrasonography, MR tractography, and intraoperative electrophysiological mapping. In particular, ultrasonographic examinations accurately identified the surface regions of the tumor without overlying normal nerve tissue. These preliminary data suggest that preoperative ultrasonographic examinations may provide valuable information, supplementary to the information obtained from intraoperative electrophysiological monitoring. Identification of normal nerve tissue prior to surgery may provide additional information regarding the risk of iatrogenic nerve injury during percutaneous tumor biopsy or open resection of the tumor and may also aid in selecting the optimum surgical approach.

Dual reinnervation of biceps muscle after side-to-side anastomosis of an intact median nerve and a damaged musculocutaneous nerve.

Traumatic peripheral nerve injury can lead to significant long-term disability for previously healthy persons. Damaged nerve trunks have been traditionally repaired using cable grafts, but nerve transfer or neurotization procedures have become increasingly popular because the axonal regrowth distances are much shorter. These techniques sacrifice the existing nerve pathway, so muscle reinnervation depends entirely on the success of the repair. Providing a supplemental source of axons from an adjacent intact nerve by using side-to-side anastomosis might reinnervate the target muscle without compromising the function of the donor nerve. The authors report a case of biceps muscle reinnervation after side-to-side anastomosis of an intact median nerve to a damaged musculocutaneous nerve. The patient was a 34-year-old man who had sustained traumatic injury primarily to the right upper and middle trunks of the brachial plexus. At 9 months after the injury, because of persistent weakness, the severely damaged upper trunk of the brachial plexus was repaired with an end-to-end graft. When 8 months later biceps function had not recovered, the patient underwent side-to-side anastomosis of the intact median nerve to the adjacent distal musculocutaneous nerve via epineural windows. By 9 months after the second surgery, biceps muscle function had returned clinically and electrodiagnostically. Postoperative electromyographic and nerve conduction studies confirmed that the biceps muscle was being reinnervated partly by donor axons from the healthy median nerve and partly by the recovering musculocutaneous nerve. This case demonstrates that side-to-side anastomosis of an intact median to an injured musculocutaneous nerve can provide dual reinnervation of the biceps muscle while minimizing injury to both donor and recipient nerves.

Histologic grade and extent of resection are associated with survival in pediatric spinal cord ependymomas.

PURPOSE: Prognostic factors affecting outcomes in pediatric spinal cord ependymomas are limited. We sought to investigate potential associations between extent of resection and histologic grade on progression-free survival (PFS) and overall survival (OS). METHODS: A comprehensive literature search was performed to identify pediatric patients who underwent surgical resection for spinal cord ependymomas. Only manuscripts with clearly defined age, tumor grade, extent of resection, and clinical follow-up were included. RESULTS: A total of 80 patients were identified with a histologic distribution as follows: 36 % myxopapillary (grade I), 54 % classical (grade II), and 10 % anaplastic (grade III). There was no association between tumor grade and PFS. The only factor associated with improved PFS was gross total resection (GTR), which remained significant in a multivariate model (hazard ratio (HR) = 0.248, p = 0.022). Moreover, older age (HR = 0.818, p = 0.026), GTR (HR = 0.042, p = 0.013), and anaplastic grade (HR = 19.847, p = 0.008) demonstrated a significant association with OS in a multivariate model. CONCLUSIONS: Among pediatric patients with spinal cord ependymomas, PFS did not differ across histologic grades but was prolonged among patients who underwent GTR. Age, extent of resection, and tumor grade were all significantly associated with survival.