Beyond seizure freedom: Dissecting long-term seizure control after surgical resection for drug-resistant epilepsy.

OBJECTIVE: This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy. METHODS: This retrospective database-driven cohort study included all patients with >9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (>6 months, >1 year, and longest duration), and (3) seizure freedom at last follow-up. RESULTS: We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as >1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively. SIGNIFICANCE: Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

Cognitive phenotypes in frontal lobe epilepsy.

OBJECTIVE: Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics. METHOD: One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes. RESULTS: Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region. SIGNIFICANCE: This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

The role of cancer stem cells in glioblastoma.

Recurrence in glioblastoma is nearly universal, and its prognosis remains dismal despite significant advances in treatment over the past decade. Glioblastoma demonstrates considerable intratumoral phenotypic and molecular heterogeneity and contains a population of cancer stem cells that contributes to tumor propagation, maintenance, and treatment resistance. Cancer stem cells are functionally defined by their ability to self-renew and to differentiate, and they constitute the diverse hierarchy of cells composing a tumor. When xenografted into an appropriate host, they are capable of tumorigenesis. Given the critical role of cancer stem cells in the pathogenesis of glioblastoma, research into their molecular and phenotypic characteristics is a therapeutic priority. In this review, the authors discuss the evolution of the cancer stem cell model of tumorigenesis and describe the specific role of cancer stem cells in the pathogenesis of glioblastoma and their molecular and microenvironmental characteristics. They also discuss recent clinical investigations into targeted therapies against cancer stem cells in the treatment of glioblastoma.

Preparing Residents to Navigate Neurosurgical Careers in the 21st Century: Implementation of a Yearlong Enhanced Didactics Curriculum.

BACKGROUND: Neurosurgery residency, known for its rigorous training, must adapt to evolving healthcare demands. Formal education should now encompass areas like quality improvement and patient safety, machine learning, career planning, research infrastructure, grant funding, and socioeconomics. We share our institution's experience with a yearlong enhanced didactics curriculum, complementing our traditional teaching. METHODS: Our resident and faculty team evaluated essential skills for trainee success and leadership, identified knowledge gaps, and addressed them with 31 lectures. We conducted pre- and 6-month surveys using a Likert scale (1=strongly disagree, 3=neutral, 5=strongly agree) to assess resident education. Survey results were analyzed using Student t-tests, with P<0.05 indicating statistical significance. RESULTS: Eleven out of 12 residents completed the pre- and 6-month surveys. The surveys revealed improved scores in areas such as research career preparation (3.0/5-4.33/5, P = 0.002), building research skills (3.18/5-4.33/5, P = 0.002), and comfort with quality and patient safety (4.09/5-4.75, P = 0.04). Residents found the lectures highly effective in supplementing their residency training (4.58/5). Qualitative feedback from faculty was highly positive as well. CONCLUSIONS: Organized neurosurgery excels in clinical and technical training for residents but lacks formalized training in crucial nonclinical areas, such as quality improvement and patient safety, machine learning/artificial intelligence, research infrastructure, and socioeconomics. Our formal curriculum focused on these topics, with positive resident engagement and feedback over the first six months. However, continuous longitudinal monitoring is needed to confirm the curriculum's efficacy. This program may guide other neurosurgery departments in enhancing resident education in these areas.

Using Resource Utilization in Spine Healthcare to Complement Patient-Reported Outcome Measurements in Assessing Surgical Success.

OBJECTIVE: Patient-reported outcome measures (PROMs) are utilized to assess surgical success but are limited by data collection, response bias, and subjectivity. The large volume of digital healthcare data offers a new method to utilize healthcare utilization as a longitudinal, individualized, and objective proxy for health needs among surgical patients. This study aimed to design and evaluate a novel resource utilization in spine healthcare (RUSH) clustering method that complements PROMs in evaluating post-operative patient outcomes. METHODS: This retrospective cross-sectional study conducted at a large, tertiary healthcare system included all adult patients undergoing cervical or lumbar surgery between 2014 to 2020 with at least 3 months follow-up. Post-operative healthcare utilization was analyzed using clinic visits, inpatient encounters, telephone encounters, MyChart messages, opioid use, physical therapy, injections, and imaging. Latent profile analysis determined RUSH clusters and changes in PROM Information System Physical Health (PROMIS-PH) scores pre- and 12-months post-operation. RESULTS: This study included 5,602 surgeries (mean age 61.3 ± 13.1, 49.9% female). Four RUSH groups were identified: low utilizers (21.5%), moderate utilizers without advanced imaging (34.7%), moderate utilizers with advanced imaging (10.7%), and high utilizers (33.1%,). Utilization patterns varied by surgery type, with lower-utilization patterns among non-fusion procedures and a consistent sub-population of high utilizers across all surgery types. High RUSH utilizers had the lowest pre-operative PROMIS-PH scores and the worst average postoperative change. CONCLUSIONS: RUSH clustering provides a novel, data-driven approach to measure surgical success, complementing traditional PROMs, and leveraging big data to monitor and respond to surgical outcomes.

The impact of skull thickness on pediatric stereoencephalography electrode implantation and technical considerations.

OBJECTIVE: One consideration in pediatric stereoencephalography (SEEG) is decreased skull thicknesses compared with adults, which may limit traditional bolt-based anchoring of electrodes. The authors aimed to investigate the safety profile, complication rates, and technical adaptations of placing SEEG electrodes in pediatric patients. METHODS: The authors retrospectively reviewed all patients aged 12 years or younger at the time of SEEG implantation at their institution. Postimplantation CT scans were used to measure skull thickness at the entry point of each SEEG lead. Postimplantation lead accuracy was also assessed. RESULTS: Fifty-three patients were reviewed. The median skull thickness was 4.1 (interquartile range [IQR] 3.15-5.2) mm. There were 5 total complications: 1 retained bolt fragment, 3 asymptomatic subdural hematomas, and 1 asymptomatic intracranial hemorrhage. Median radial error from the lead target was 3.5 (IQR 2.24-5.25) mm. Linear regression analysis revealed that increasing skull thickness decreased the deviation from the intended target, implying an improved accuracy to target at thicker skull entry points; this trended towards improved accuracy, but did not achieve statistical significance (p = 0.54). CONCLUSIONS: This study found a 1.9% hardware complication rate and a 9.4% asymptomatic hemorrhage rate. Suturing electrodes to the scalp may represent a reasonable option if there are concerns of young age or a thin skull. These data indicate that invasive SEEG evaluation is safe among patients 12 years old or younger.

Determinants of epileptogenic zone identification and seizure outcome in children with refractory epilepsy undergoing stereoelectroencephalography.

OBJECTIVE: The objective of this paper was to investigate the factors associated with successful epileptogenic zone (EZ) identification and postsurgical seizure freedom in pediatric patients with drug-resistant epilepsy who underwent first-time stereoelectroencephalography (SEEG). METHODS: The authors conducted a retrospective cohort study of all consecutive patients younger than 18 years of age at the time of recommendation for invasive evaluation with SEEG who were treated from July 2009 to June 2020. The authors excluded patients who had undergone failed prior resective epilepsy surgery or prior intracranial electrode evaluation for seizure localization. For their primary outcome, the authors evaluated the relationship between clinical and radiographic factors and successful identification of a putative EZ. For their secondary outcome, the authors investigated whether these factors had a significant relationship with seizure freedom (according to the Engel classification) at last follow-up. RESULTS: The authors included 101 patients in this study. SEEG was safe, with no major morbidity or mortality experienced. The population was complex, with an MRI lesion present in less than 40% of patients and patients as young as 2.9 years included. A proposed EZ was identified in 88 (87%) patients. Patients with an older onset of epilepsy (OR 1.20/year, p = 0.04) or epilepsy etiology suspected to be due to a developmental lesion (OR 8.38, p = 0.02) were more likely to have proposed EZ identification. Patients with a preimplantation bilateral seizure-onset hypothesis (OR 0.29, p = 0.047) and those who underwent longer periods of monitoring (OR 0.86/day, p = 0.006) were somewhat less likely to have proposed EZ identification. The presence of an MRI lesion was a positive factor on secondary analyses (OR 4.18, p = 0.049; 1-tailed test). Fifty percent of patients who underwent surgical treatment with resection or laser ablation achieved Engel class I outcomes, in contrast to 0% of patients who underwent neuromodulation. Patients with a preimplantation hypothesis in the frontal/parietal lobes had increased odds of seizure freedom compared with patients with a hypothesis in other locations (OR 3.64, p = 0.01). CONCLUSIONS: Pediatric SEEG is safe and often identifies a proposed resectable EZ. These results suggest that SEEG is effective in patients with frontal/parietal preimplantation hypothesis, with or without identified lesions on MRI.

A Pilot Remote Curriculum to Enhance Resident and Medical Student Understanding of Machine Learning in Healthcare.

BACKGROUND: Despite the expanding role of machine learning (ML) in health care and patient expectations for clinicians to understand ML-based tools, few for-credit curricula exist specifically for neurosurgical trainees to learn basic principles and implications of ML for medical research and clinical practice. We implemented a novel, remotely delivered curriculum designed to develop literacy in ML for neurosurgical trainees. METHODS: A 4-week pilot medical elective was designed specifically for trainees to build literacy in basic ML concepts. Qualitative feedback from interested and enrolled students was collected to assess students' and trainees' reactions, learning, and future application of course content. RESULTS: Despite 15 interested learners, only 3 medical students and 1 neurosurgical resident completed the course. Enrollment included students and trainees from 3 different institutions. All learners who completed the course found the lectures relevant to their future practice as clinicians and researchers and reported improved confidence in applying and understanding published literature applying ML techniques in health care. Barriers to ample enrollment and retention (e.g., balancing clinical responsibilities) were identified. CONCLUSIONS: This pilot elective demonstrated the interest, value, and feasibility of a remote elective to establish ML literacy; however, feedback to increase accessibility and flexibility of the course encouraged our team to implement changes. Future elective iterations will have a semiannual, 2-week format, splitting lectures more clearly between theory (the method and its value) and application (coding instructions) and will make lectures open-source prerequisites to allow tailoring of student learning to their planned application of these methods in their practice and research.

Maintaining Human Glioblastoma Cellular Diversity Ex vivo using Three-Dimensional Organoid Culture.

Glioblastoma (GBM) is the most commonly occurring primary malignant brain cancer with an extremely poor prognosis. Intra-tumoral cellular and molecular diversity, as well as complex interactions between tumor microenvironments, can make finding effective treatments a challenge. Traditional adherent or sphere culture methods can mask such complexities, whereas three-dimensional organoid culture can recapitulate regional microenvironmental gradients. Organoids are a method of three-dimensional GBM culture that better mimics patient tumor architecture, contains phenotypically diverse cell populations, and can be used for medium-throughput experiments. Although three-dimensional organoid culture is more laborious and time-consuming compared to traditional culture, it offers unique benefits and can serve to bridge the gap between current in vitro and in vivo systems. Organoids have established themselves as invaluable tools in the arsenal of cancer biologists to better understand tumor behavior and mechanisms of resistance, and their applications only continue to grow. Here, details are provided about methods for generating and maintaining GBM organoids. Instructions of how to perform organoid sample embedding and sectioning using both frozen and paraffin-embedding techniques, as well as recommendations for immunohistochemistry and immunofluorescence protocols on organoid sections, and measurement of total organoid cell viability, are all also described.

Three-dimensional organoid culture unveils resistance to clinical therapies in adult and pediatric glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain tumor with a dismal prognosis. The inherent cellular diversity and interactions within tumor microenvironments represent significant challenges to effective treatment. Traditional culture methods such as adherent or sphere cultures may mask such complexities whereas three-dimensional (3D) organoid culture systems derived from patient cancer stem cells (CSCs) can preserve cellular complexity and microenvironments. The objective of this study was to determine if GBM organoids may offer a platform, complimentary to traditional sphere culture methods, to recapitulate patterns of clinical drug resistance arising from 3D growth. METHODS: Adult and pediatric surgical specimens were collected and established as organoids. We created organoid microarrays and visualized bulk and spatial differences in cell proliferation using immunohistochemistry (IHC) staining, and cell cycle analysis by flow cytometry paired with 3D regional labeling. We tested the response of CSCs grown in each culture method to temozolomide, ibrutinib, lomustine, ruxolitinib, and radiotherapy. RESULTS: GBM organoids showed diverse and spatially distinct proliferative cell niches and include heterogeneous populations of CSCs/non-CSCs (marked by SOX2) and cycling/senescent cells. Organoid cultures display a comparatively blunted response to current standard-of-care therapy (combination temozolomide and radiotherapy) that reflects what is seen in practice. Treatment of organoids with clinically relevant drugs showed general therapeutic resistance with drug- and patient-specific antiproliferative, apoptotic, and senescent effects, differing from those of matched sphere cultures. CONCLUSIONS: Therapeutic resistance in organoids appears to be driven by altered biological mechanisms rather than physical limitations of therapeutic access. GBM organoids may therefore offer a key technological approach to discover and understand resistance mechanisms of human cancer cells.

The Clinical Utility of Surgical Histopathology in Predicting Seizure Outcomes in Patients with Rasmussen Encephalitis Undergoing Hemispherectomy.

OBJECTIVE: The objectives of this study were to determine the relationship between the severity of pathology and seizure outcomes in patients who underwent hemispherectomy for Rasmussen encephalitis (RE) and to investigate which clinical factors correlated with severity of pathology. METHODS: In this retrospective cohort study, we collected and reviewed pathology and clinical variables. We ascertained seizure outcomes using Engel's classification, and Pardo stages were used to grade pathology. RESULTS: We included 29 unique patients who underwent 34 hemispherectomy procedures for analysis. There was no statistically significant correlation between Pardo stage and seizure outcome (P = 1). Increasing duration of epilepsy (ß = 0.011, P = 0.02) and duration of hemiparesis (ß = 0.024, P = 0.01) were significantly associated with a more severe Pardo stage. In contrast, the presence of epilepsia partialis continua had a negative relationship with Pardo stage (ß = -0.49, P = 0.04). Twenty-six (89.75%) patients were Engel class I at the last follow-up, including all 5 patients who underwent redo hemispherectomy in our cohort. CONCLUSIONS: Consistent with the progressive nature of RE, more severe pathology was associated with a longer duration of epilepsy and longer duration of hemiparesis, while the presence of epilepsia partialis continua was associated with less severe pathology. Results from this series suggest the degree of cortical involvement with RE as assessed on surgical histopathology does not correlate with seizure outcome after hemispherectomy, which appears to be more dependent on surgical technique/complete disconnection.

Seizure Outcomes and Reoperation in Surgical Rasmussen Encephalitis Patients.

BACKGROUND: Rasmussen encephalitis (RE) is a rare inflammatory disease affecting one hemisphere, causing progressive neurological deficits and intractable seizures. OBJECTIVE: To report long-term seizure outcomes, reoperations, and functional outcomes in patients with RE who underwent hemispherectomy at our institution. METHODS: Retrospective review was performed for all patients with RE who had surgery between 1998 and 2020. We collected seizure history, postoperative outcomes, and functional data. Imaging was independently reviewed in a blinded fashion by 2 neurosurgeons and a neuroradiologist. RESULTS: We analyzed 30 patients with RE who underwent 35 hemispherectomies (5 reoperations). Using Kaplan-Meier analysis, seizure-freedom rate was 81.5%, 63.6%, and 55.6% at 1, 5, and 10 years after surgery, respectively. Patients with shorter duration of hemiparesis preoperatively were less likely to be seizure-free at follow-up (P = .011) and more likely to undergo reoperation (P = .004). Shorter duration of epilepsy (P = .026) and preoperative bilateral MRI abnormalities (P = .011) were associated with increased risk of reoperation. Complete disconnection of diseased hemisphere on postoperative MRI after the first operation improved seizure-freedom (P = .021) and resulted in fewer reoperations (P = .034), and reoperation resulted in seizure freedom in every case. CONCLUSION: Obtaining complete disconnection is critical for favorable seizure outcomes from hemispherectomy, and neurosurgeons should have a low threshold to reoperate in patients with RE with recurrent seizures. Rapid progression of motor deficits and bilateral MRI abnormalities may indicate a subpopulation of patients with RE with increased risk of needing reoperation. Overall, we believe that hemispherectomy is a curative surgery for the majority of patients with RE, with excellent long-term seizure outcome.

Use of a Standardized Perioperative Care Path for Adolescent Idiopathic Scoliosis Leads to Decreased Complications and Readmissions.

STUDY DESIGN: Retrospective review of patients ages 10-18 who underwent posterior fusion for adolescent idiopathic scoliosis (AIS) at a single institution from 2014 to 2019. OBJECTIVE: The aim was to evaluate a standardized Care Path to determine its effects on perioperative outcomes in patients undergoing spinal fusion for AIS. SUMMARY OF BACKGROUND DATA: AIS is the most common pediatric spinal deformity and thousands of posterior fusions are performed annually. Surgery presents several postoperative challenges, such as pain control, delayed mobilization, and opioid-related morbidity. Optimizing perioperative care of AIS is a high priority to reduce morbidity and improving health care efficiency. MATERIALS AND METHODS: A total of 336 patients ages 10-18 were included in this study; 117 in the pre-Care Path cohort (2014-2015) and 219 in the post-Care Path cohort (2016-2019). Data compared included intraoperative details, length of stay, timing of mobilization, inpatient complications, emergency room (ER) visits, readmissions after discharge, postoperative complications, and reoperations. RESULTS: The post-Care Path cohort had improved mobilization on postoperative day 0 (pre 16.7%, post 53.3%, P<0.00001), reduced length of stay (pre 4.14 days, post 3.36 days, P=0.00006), fewer total inpatient complications (pre 17.1%, post 8.1%, P=0.0469), and fewer instances of postoperative ileus (pre 8.5%, post 1.9%, P=0.0102). Within 60 days of surgery, the post-Care Path cohort had fewer ER visits (pre 12.8%, post 7.2%, P=0.0413), decreased postoperative infections (pre 5.1%, post 0.48%, P=0.00547), decreased readmissions (pre 6.0%, post 0.48%, P=0.0021), and decreased reoperations (pre 5.1%, post 0.96%, P=0.0195). There was a decrease in inpatient oral morphine equivalents in the Care Path cohort (pre 118.7, post 84.7, P=0.0003). CONCLUSIONS: Our Care Path for AIS patients demonstrated significant improvements in postoperative mobilization and decreases in length of stay, complications, infections, ER visits, readmissions, and reoperations.

mRNP granule proteins Fmrp and Dcp1a differentially regulate mRNP complexes to contribute to control of muscle stem cell quiescence and activation.

BACKGROUND: During skeletal muscle regeneration, satellite stem cells use distinct pathways to repair damaged myofibers or to self-renew by returning to quiescence. Cellular/mitotic quiescence employs mechanisms that promote a poised or primed state, including altered RNA turnover and translational repression. Here, we investigate the role of mRNP granule proteins Fragile X Mental Retardation Protein (Fmrp) and Decapping protein 1a (Dcp1a) in muscle stem cell quiescence and differentiation. METHODS: Using isolated single muscle fibers from adult mice, we established differential enrichment of mRNP granule proteins including Fmrp and Dcp1a in muscle stem cells vs. myofibers. We investigated muscle tissue homeostasis in adult Fmr1-/- mice, analyzing myofiber cross-sectional area in vivo and satellite cell proliferation ex vivo. We explored the molecular mechanisms of Dcp1a and Fmrp function in quiescence, proliferation and differentiation in a C2C12 culture model. Here, we used polysome profiling, imaging and RNA/protein expression analysis to establish the abundance and assembly status of mRNP granule proteins in different cellular states, and the phenotype of knockdown cells. RESULTS: Quiescent muscle satellite cells are enriched for puncta containing the translational repressor Fmrp, but not the mRNA decay factor Dcp1a. MuSC isolated from Fmr1-/- mice exhibit defective proliferation, and mature myofibers show reduced cross-sectional area, suggesting a role for Fmrp in muscle homeostasis. Expression and organization of Fmrp and Dcp1a varies during primary MuSC activation on myofibers, with Fmrp puncta prominent in quiescence, but Dcp1a puncta appearing during activation/proliferation. This reciprocal expression of Fmrp and Dcp1a puncta is recapitulated in a C2C12 culture model of quiescence and activation: consistent with its role as a translational repressor, Fmrp is enriched in non-translating mRNP complexes abundant in quiescent myoblasts; Dcp1a puncta are lost in quiescence, suggesting stabilized and repressed transcripts. The function of each protein differs during proliferation; whereas Fmrp knockdown led to decreased proliferation and lower cyclin expression, Dcp1a knockdown led to increased cell proliferation and higher cyclin expression. However, knockdown of either Fmrp or Dcp1a led to compromised differentiation. We also observed cross-regulation of decay versus storage mRNP granules; knockdown of Fmrp enhances accumulation of Dcp1a puncta, whereas knockdown of Dcp1a leads to increased Fmrp in puncta. CONCLUSIONS: Taken together, our results provide evidence that the balance of mRNA turnover versus utilization is specific for distinct cellular states.

Cost and quality of life outcome analysis of postoperative infections after posterior lumbar decompression and fusion.

Surgical site infections (SSI) following spine procedures are serious and costly complications that may reduce patient quality of life (QOL). Deep SSIs may also extend hospitalizations and require surgical debridement or antibiotic therapy, increasing costs to both patients and the healthcare system. Here we sought to evaluate the effect of deep SSI on care cost and QOL outcomes in patients undergoing posterior lumbar decompression and fusion. To do so we performed a retrospective study of patients undergoing lumbar decompression and fusion between 2008 and 2012. Patients experiencing postoperative deep SSI were matched to controls not experiencing a deep SSI. Included patients had prospectively-gathered QOL outcome measures collected preoperatively and at 6 months postoperatively. Health resource utilization was recorded from patient electronic medical records over the 6-month follow-up. Direct costs were estimated using Medicare national payment amounts. Indirect costs were based on missed work days and patient income. We found both cohorts experienced significant improvements in QOL scores following surgery, and there were no significant differences between the cohorts. The average total cost was significantly higher in the infected cohort compared to controls ($37,009 vs. $16,227; p < 0.0001). Compared to controls, patients experiencing deep SSI had greater costs in each of the following categories: hospitalizations (p < 0.01), office visits (p = 0.03), imaging (p < 0.01), and medications (p < 0.01). Among those experiencing deep SSI, there are significant increases in costs, with minimal long-term impact on QOL outcomes as compared with controls at the six-month follow-up.

Rare Thymoma Metastases to the Spine: Case Reports and Review of the Literature.

BACKGROUND: We report a series of 3 cases of metastatic thymoma to the spine with spinal cord compression. An extensive literature review of thymic metastases to the spine was completed to provide a comprehensive appraisal of current prognostic indicators and potential treatment algorithms to help guide clinicians in treatment management. CASE DESCRIPTIONS: Between 2000 and 2017, 3 patients received diagnoses of thymic metastases to the spine at our institution. Metastasis presentation occurred from 2 to 8 years after the initial diagnosis with thymic cancer. All 3 patients presented with signs and symptoms of spinal cord/cauda equina compression, and underwent surgical intervention. Postoperative treatments varied among all 3 patients, 1 receiving chemotherapy, another undergoing radiation, and the third having had no further treatment because of extensive systemic disease. CONCLUSIONS: Upon review of the literature, 16 case reports/series described 28 total patients with spine metastases secondary to thymoma/thymic carcinoma. The presentations varied widely, including age, neurologic deficits, time from initial diagnosis to metastasis, and histologic grading. The only widely accepted prognostic factor is completeness of tumor resection, whereas clinical staging, histologic type, or both may also have prognostic value. Thus, gross total resection and spinal decompression should be prioritized in cases of surgical intervention. Chemotherapy and radiotherapy are generally recommended. However, given the lack of standardized treatment algorithms, individualized regimens should be formulated on a case-specific basis.

Intraneural nodular fasciitis of the radial nerve with rapidly progressive motor symptoms.

BACKGROUND: Nodular fasciitis is a benign mesenchymal tumor arising from fascia that typically presents as a rapidly growing, subcutaneous mass. Intraneural cases are very rare and can present with neurological symptoms, requiring surgical resection. CASE DESCRIPTION: A 31-year-old woman presented to us with painful paresthesias in her elbow and progressive motor deficits, for which she underwent surgery. CONCLUSION: The authors report the first case of intraneural nodular fasciitis occurring in the radial nerve and highlight the possibility of rapidly progressive motor deficit in patients presenting with this rare clinical entity.

A pilot study of the utility of a laboratory-based spinal fixation training program for neurosurgical residents.

OBJECTIVE Pedicle and lateral mass screw placement is technically demanding due to complex 3D spinal anatomy that is not easily visualized. Neurosurgical and orthopedic surgery residents must be properly trained in such procedures, which can be associated with significant complications and associated morbidity. Current training in pedicle and lateral mass screw placement involves didactic teaching and supervised placement in the operating room. The objective of this study was to assess whether teaching residents to place pedicle and lateral mass screws using navigation software, combined with practice using cadaveric specimens and Sawbones models, would improve screw placement accuracy. METHODS This was a single-blinded, prospective, randomized pilot study with 8 junior neurosurgical residents and 2 senior medical students with prior neurosurgery exposure. Both the study group and the level of training-matched control group (each group with 4 level of training-matched residents and 1 senior medical student) were exposed to a standardized didactic education regarding spinal anatomy and screw placement techniques. The study group was exposed to an additional pilot program that included a training session using navigation software combined with cadaveric specimens and accessibility to Sawbones models. RESULTS A statistically significant reduction in overall surgical error was observed in the study group compared with the control group (p = 0.04). Analysis by spinal region demonstrated a significant reduction in surgical error in the thoracic and lumbar regions in the study group compared with controls (p = 0.02 and p = 0.04, respectively). The study group also was observed to place screws more optimally in the cervical, thoracic, and lumbar regions (p = 0.02, p = 0.04, and p = 0.04, respectively). CONCLUSIONS Surgical resident education in pedicle and lateral mass screw placement is a priority for training programs. This study demonstrated that compared with a didactic-only training model, using navigation simulation with cadavers and Sawbones models significantly reduced the number of screw placement errors in a laboratory setting.