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.

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.

A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma.

OBJECTIVE: Craniopharyngiomas are rare tumors with bimodal incidence in the pediatric and adult age groups. Treatment strategies range from aggressive resection to planned limited resection combined with adjuvant therapies. Currently there is no consensus for standard of care for pediatric craniopharyngioma. MATERIALS AND METHODS: We performed a systematic review of the published literature on pediatric craniopharyngioma. Patients were grouped based on extent of resection into gross total resection (GTR), subtotal resection (STR), and biopsy procedures. These groups were compared with respect to tumor control. Chi square was used to compare rates of recurrence. Kaplan-Meier was used to generate progression-free survival (PFS) estimates. Cox proportional hazard modeling was used to evaluate risk of progression. Each extent of resection group was also subdivided based on adjuvant therapy and compared. RESULTS: A total of 109 studies described extent of resection resulting in a cohort of 531 patients. Recurrence data were available for 377 patients. There was no difference in 1- or 5-year PFS between the groups who underwent GTR and STR combined with radiation (XRT; log-rank; p = 0.76; 1-year PFS 89 vs 84%; 5-year PFS 77 vs 73%, respectively). One-year PFS was 84% for STR+XRT compared to 76% for STR alone while 5-year PFS was 73% for STR+XRT compared to 43% for STR alone (log-rank; p = 0.003). CONCLUSION: Although there are limitations of a systematic review of retrospective data, our results suggest that STR+XRT of pediatric craniopharyngioma is associated with similar rates of tumor control as GTR.

Feasibility, safety, and indications for surgical biopsy of intrinsic brainstem tumors in children.

PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are rapidly progressive and aggressive tumors that usually arise in children. Their anatomic location makes gross total surgical resection impossible, and fewer than 10% of patients survive more than 2 years after diagnosis. Often, these lesions are treated based on imaging characteristics alone. However, despite aggressive chemotherapy and radiation treatments available, prognosis remains poor. There is therefore a need for new therapies directed by biologic profiling. This necessitates a tissue diagnosis and, therefore, surgical biopsy. We have reviewed the results of biopsy for DIPGs in children at a single institution and compared our results to those available in the literature to elucidate the utility of biopsy for DIPGs. METHODS: A historical cohort study was performed using medical records of patients under the age of 18 who underwent surgical biopsy of a DIPG at a single institution. RESULTS: Nine patients were included, four males and five females. Age at presentation ranged from 8 months to 10 years (average 5.7 years). Pathologic diagnoses included five high grade (WHO grade III or IV) gliomas and four low grade (WHO grade II) astrocytomas. There were no intraoperative complications, and only one patient developed a new postoperative neurologic deficit. CONCLUSIONS: Stereotactic biopsy of DIPGs is essential to obtain a pathologic diagnosis and is associated with low morbidity. This technique is important to elucidate biological characteristics of these tumors in order to direct multidisciplinary treatment plans possibly involving chemotherapy, radiation therapy, or other future clinical trial interventions for children with DIPGs.

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.

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.

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.

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.

Adjuvant enoxaparin therapy may decrease the incidence of postoperative thrombotic events though does not increase the incidence of postoperative intracranial hemorrhage in patients with meningiomas.

Patients with brain tumors including intracranial meningiomas are at increased risk for developing deep vein thrombosis (DVTs) and suffering thromboembolic events (VTEs). Many surgeons are concerned that early use of low dose enoxaparin may increase the risk of intracranial hemorrhage which outweighs the benefit of DVT/VTE reduction. We aimed to address concerns around the use of enoxaparin after meningioma resection in the development of postoperative intracranial hemorrhages and DVT/VTEs. This is a retrospective review of 86 patients with intracranial meningiomas who underwent craniectomy and surgical resection of the mass, treated by one attending surgeon at UCSF Medical Center between 2000 and 2005. Within 48 h after surgery patients treated 2003-2005 routinely received enoxaparin therapy unless there was documented intracranial hemorrhage, lumbar subarachnoid drain, enoxaparin hypersensitivity, or thrombocytopenia (n = 24). These were compared to a cohort treated 2000-2002 who did not receive the drug (n = 62). Exclusion criteria were prior VTEs or coagulopathies. The groups were similar in tumor and surgical characteristics. Enoxaparin therapy did not increase the incidence of intracranial hemorrhage following surgical meningioma resection and the incidence of DVTs/VTEs was 0% (n = 0) versus 4.8% (n = 3) in the non-enoxaparin group. Results did not reach statistical significance. In this retrospective study, postoperative administration of enoxaparin following meningioma resection does not increase the risk of intracranial hematoma though enoxaparin administration may slightly decrease the incidence of post-surgical thromboembolic events. Due to study design and power, we were not able to demonstrate DVT/VTE reduction with statistical significance.

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.

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.

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.

Subependymal spread of recurrent glioblastoma detected with the intraoperative use of 5-aminolevulinic acid: case report.

Recurrent glioblastoma (GBM) can occur locally or at distant sites within the brain. Though MRI is the standard imaging modality for primary and recurrent GBM, the full extent of diffuse lesions may not be appreciated on MRI alone. Glioblastomas with ependymal and/or subependymal spread are examples of diffuse infiltrative tumors that are incompletely seen on MRI. Some other adjuvant visualization technique such as intraoperative fluorescence-assisted 5-aminolevulinic acid (5-ALA) could be used to assist the surgeon in localizing the infiltrating tumor. The authors report on a 56-year-old man who presented 7 years after initial resection of an occipital lobe GBM with imaging consistent with distant discrete foci of tumor recurrence. Because these foci were distant from the original resection cavity, there was concern for diffuse, infiltrative tumor elsewhere throughout the brain versus a distant multicentric recurrence. Therefore, the patient was given 5-ALA prior to surgery to aid in tumor detection intraoperatively. Using fluorescent visualization of the resection cavity, it was confirmed that there was subependymal and ependymal spread of the recurrent tumor along the lateral ventricle connecting the recurrence to the previous tumor site. Magnetic resonance imaging may not completely detect the presence of diffuse tumor infiltrating the ependymal or subependymal spaces. Therefore, adjunct intraoperative use of fluorescence-assisted visualization with 5-ALA may be helpful in highlighting and detecting infiltrative tumor to accurately detect tumor burden and distinguish it from a separate multicentric recurrence.

A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas.

OBJECT: Ependymoma is the third most common primary brain tumor in children. Tumors are classified according to the WHO pathological grading system. Prior studies have shown high levels of variability in patient outcomes within and across pathological grades. The authors reviewed the results from the published literature on intracranial ependymomas in children to describe clinical outcomes as they relate to treatment modality, associated mortality, and associated progression-free survival (PFS). METHODS: A search of English language peer-reviewed articles describing patients 18 years of age or younger with intracranial ependymomas yielded data on 182 patients. These patients had undergone treatment for ependymoma with 1 of 5 modalities: 1) gross-total resection (GTR), 2) GTR as well as external beam radiation therapy (EBRT), 3) subtotal resection (STR), 4) STR as well as EBRT, or 5) radiosurgery. Mortality and outcome data were analyzed for time to tumor progression in patients treated with 1 of these 5 treatment modalities. RESULTS: Of these 182 patients, 69% had supratentorial ependymomas and 31% presented with infratentorial lesions. Regardless of tumor location or pathological grade, STR was associated with the highest rates of mortality. In contrast, GTR was associated with the lowest rates of mortality, the best overall survival, and the longest PFS. Children with WHO Grade II ependymomas had lower mortality rates when treated more aggressively with GTR. However, patients with WHO Grade III tumors had slightly better survival outcomes after a less aggressive surgical debulking (STR+EBRT) when compared with GTR. CONCLUSIONS: Mortality, PFS, and overall survival vary in pediatric patients with intracranial ependymomas. Pathological classification, tumor location, and method of treatment play a role in outcomes. In this study, GTR was associated with the best overall and PFS rates. Patients with WHO Grade II tumors had better overall survival after GTR+EBRT and better PFS after GTR alone. Patients with WHO Grade III tumors had better overall survival after STR+EBRT. Patients with infratentorial tumors had improved overall survival compared with those with supratentorial tumors. Progression-free survival was best in those patients with infratentorial tumors following STR+EBRT. Consideration of all of these factors is important when counseling families on treatment options.

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.

High-grade gliomas in children.

High-grade gliomas (HGGs) are malignant tumors and typically include glioblastoma multiforme and anaplastic astrocytoma subtypes. Brainstem gliomas and ependymomas are separate entities with respect to clinical presentation, treatment, prognosis, and outcome in comparison with supratentorial HGGs. In children, these tumors account for 3% to 7% of newly diagnosed brain tumors and 20% of all diagnoses of pediatric supratentorial brain tumors. These neoplasms are highly proliferative and mitotically active and of glial origin. This article reviews clinical, diagnostic, and pathologic features of HGG and current treatments and potential future therapies specific to pediatric patients with HGGs.

A meta-analysis of predictors of seizure freedom in the surgical management of focal cortical dysplasia.

OBJECT: Focal cortical dysplasia (FCD) is one of the most common causes of medically refractory epilepsy leading to surgery. However, seizure control outcomes reported in isolated surgical series are highly variable. As a result, it is not clear which variables are most crucial in predicting seizure freedom following surgery for FCD. The authors' aim was to determine the prognostic factors for seizure control in FCD by performing a meta-analysis of the published literature. METHODS: A MEDLINE search of the published literature yielded 37 studies that met inclusion and exclusion criteria. Seven potential prognostic variables were determined from these studies and were dichotomized for analysis. For each variable, individual studies were weighted by inverse variance and combined to generate an odds ratio favoring seizure freedom. The methods complied with a standardized meta-analysis reporting protocol. RESULTS: Two thousand fourteen patients were included in the analysis. The overall rate of seizure freedom (Engel Class I) among patients undergoing surgery for FCD in the cohort of studies was 55.8% ± 16.2%. Partial seizures, a temporal location, detection with MRI, and a Type II Palmini histological classification were associated with higher rates of postoperative seizure control. As a treatment-related factor, complete resection of the anatomical or electrographic abnormality was the most important predictor overall of seizure freedom. Neither age nor electroencephalographic localization of the ictal onset significantly affected seizure freedom after surgery. CONCLUSIONS: Using a large population cohort pooled from the published literature, an analysis identified important factors that are prognostic in patients with epilepsy due to FCD. The most important of these factors-diagnostic imaging and resection-provide modalities through which improvements in the impact of FCD can be effected.

Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review.

OBJECT: Craniopharyngiomas are benign tumors but their close anatomical relationship with critical neurological, endocrine, and vascular structures makes gross-total resection (GTR) with minimal morbidity difficult to achieve. Currently, there is controversy regarding the extent, timing, and modality of treatment for pediatric craniopharyngioma. METHODS: The authors performed a systematic review of the published literature on pediatric craniopharyngioma to determine patterns of clinical practice and the reported outcomes of standard treatment strategies. This yielded 109 studies, which contained data describing extent of resection for a total of 531 patients. Differences in outcome were examined based upon extent of resection and choice of radiation treatment. RESULTS: Gross-total resection was associated with increased rates of new endocrine dysfunction (OR 5.4, p < 0.001), panhypopituitarism (OR 7.8, p = 0.006), and new neurological deficits (OR 9.9, p = 0.03) compared with biopsy procedures. Subtotal resection (STR) was not associated with an increased rate of new neurological deficits. Gross-total was associated with increased rates of diabetes insipidus (OR 7.7, p = 0.05) compared with the combination of STR and radiotherapy (RT). The addition of RT to STR was associated with increased rates of panhypopituitarism (OR 9.9, p = 0.01) but otherwise similar rates of morbidities. CONCLUSIONS: Although subject to the limitations of a literature review, this report suggests that GTR is associated with increased rates of endocrinopathies compared with STR + RT, and this should be considered when planning goals of surgery.

Distinct patterns of human medulloblastoma dissemination in the developing chick embryo nervous system.

Medulloblastoma (MB) is the most common malignant primary brain tumor in children. Aggressive tumors that disseminate along the leptomeninges carry extremely poor prognoses. Mechanisms that predict dissemination are poorly understood. Our objective was to develop a reliable and reproducible model to study MB dissemination. We have created a chicken-human xenograft to study features of MB with leptomeningeal dissemination. Human MB cell lines (D283, Daoy), primary human MB cells (SF8113), and primary genetic mouse model (Math1cre:SmoM2 flox/flox) MB cells were either transfected to express green fluorescent protein (GFP) or were labeled with a membrane permeable green fluorescent probe. Cells were then injected as aggregates or implanted as pellets into the developing chicken brain immediately after neural tube closure at embryonic day 2 (E2). Most embryos were harvested three days after implantation (E5) though some were harvested up to E15. The developing brain was analyzed via whole mount fluorescent imaging and tissue section immunohistochemistry. Human and mouse MBs survived in the developing chicken central nervous system (CNS). They exhibited distinct patterns of incorporation and dissemination into the CNS that were consistent with observed phenotypes of the corresponding human patient or mouse host. Specifically, metastatic D283 cells disseminated along the leptomeninges whereas Daoy, primary mouse MB, and primary human MB cells did not. This work supports an avian-human xenograft as a successful model to study patterns of MB dissemination. Our model provides a basis for manipulating cell signaling mechanisms to understand critical targets involved in MB dissemination.

Stage-specific and opposing roles of BDNF, NT-3 and bFGF in differentiation of purified callosal projection neurons toward cellular repair of complex circuitry.

Cellular repair of neuronal circuitry affected by neurodegenerative disease or injury may be approached in the adult neocortex via transplantation of neural precursors ("neural stem cells") or via molecular manipulation and recruitment of new neurons from endogenous precursors in situ. A major challenge for potential future approaches to neuronal replacement will be to specifically direct and control progressive differentiation, axonal projection and connectivity of neural precursors along a specific neuronal lineage. This goal will require a progressively more detailed understanding of the molecular controls over morphologic differentiation of specific neuronal lineages, including neurite outgrowth and elongation, in order to accurately permit and direct proper neuronal integration and connectivity. Here, we investigate controls over the morphologic differentiation of a specific prototypical lineage of cortical neurons: callosal projection neurons (CPN). We highly enriched CPN to an essentially pure population, and cultured them at three distinct stages of development from embryonic and postnatal mouse cortex by retrograde fluorescence labelling, followed by fluorescence-activated cell sorting. We find that specific peptide growth factors exert direct stage-specific positive and negative effects over the morphologic differentiation and process outgrowth of CPN. These effects are distinct from the effects of these growth factors on CPN survival [Catapano et al. (2001)J. Neurosci., 21, 8863-8872]. These data may be critical for the future goal of directing lineage-specific neuronal differentiation of transplanted or endogenous precursors/"stem cells" toward cellular repair of complex cortical circuitry.