FoxP1 orchestration of ASD-relevant signaling pathways in the striatum.

Mutations in the transcription factor Forkhead box p1 (FOXP1) are causative for neurodevelopmental disorders such as autism. However, the function of FOXP1 within the brain remains largely uncharacterized. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and patient-relevant heterozygous Foxp1 mouse brains. We demonstrate a role for FoxP1 in the transcriptional regulation of autism-related pathways as well as genes involved in neuronal activity. We show that Foxp1 regulates the excitability of striatal medium spiny neurons and that reduction of Foxp1 correlates with defects in ultrasonic vocalizations. Finally, we demonstrate that FoxP1 has an evolutionarily conserved role in regulating pathways involved in striatal neuron identity through gene expression studies in human neural progenitors with altered FOXP1 levels. These data support an integral role for FoxP1 in regulating signaling pathways vulnerable in autism and the specific regulation of striatal pathways important for vocal communication.

Accuracy of omni-planar and surface casting of epileptiform activity for intracranial seizure localization.

OBJECTIVE: Intracranial electroencephalography (ICEEG) recordings are performed for seizure localization in medically refractory epilepsy. Signal quantifications such as frequency power can be projected as heatmaps on personalized three-dimensional (3D) reconstructed cortical surfaces to distill these complex recordings into intuitive cinematic visualizations. However, simultaneously reconciling deep recording locations and reliably tracking evolving ictal patterns remain significant challenges. METHODS: We fused oblique magnetic resonance imaging (MRI) slices along depth probe trajectories with cortical surface reconstructions and projected dynamic heatmaps using a simple mathematical metric of epileptiform activity (line-length). This omni-planar and surface casting of epileptiform activity approach (OPSCEA) thus illustrated seizure onset and spread among both deep and superficial locations simultaneously with minimal need for signal processing supervision. We utilized the approach on 41 patients at our center implanted with grid, strip, and/or depth electrodes for localizing medically refractory seizures. Peri-ictal data were converted into OPSCEA videos with multiple 3D brain views illustrating all electrode locations. Five people of varying expertise in epilepsy (medical student through epilepsy attending level) attempted to localize the seizure-onset zones. RESULTS: We retrospectively compared this approach with the original ICEEG study reports for validation. Accuracy ranged from 73.2% to 97.6% for complete or overlapping onset lobe(s), respectively, and ~56.1% to 95.1% for the specific focus (or foci). Higher answer certainty for a given case predicted better accuracy, and scorers had similar accuracy across different training levels. SIGNIFICANCE: In an era of increasing stereo-EEG use, cinematic visualizations fusing omni-planar and surface functional projections appear to provide a useful adjunct for interpreting complex intracranial recordings and subsequent surgery planning.

Assessing the Readability of Online Patient Education Resources Related to Gynecomastia.

BACKGROUND: The Internet has a plethora of online patient education resources for many symptoms and diseases. National medical governing bodies recommend that patient education materials are written at or below the eighth-grade level, and the literature suggests that health literacy has been linked to increased adherence to treatment regimens and improved outcomes. The primary aim of the study is to assess the readability of online patient materials relating to gynecomastia and ascertain the availability of patient materials in non-English languages. METHODS: The readability of patient education materials relating to gynecomastia for academic-based websites and nonacademic websites was assessed using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), and Simple Measure of Gobbledygook (SMOG). The prevalence of non-English patient education materials was assessed for both academic-based and nonacademic websites. RESULTS: Fifty-eight documents were collected across academic websites. Overall median values were 10.7 for the FKGL, 47.0 for the FRE, and 11.4 for the SMOG. For the 10 nonacademic institutions, the overall median values were 10.6 for the FKGL, 45.2 for the FRE, and 10.8 for the SMOG. No appreciable differences were observed for readability when stratified by region or source. The prevalence of non-English patient materials was 19.1% across institutions. None of the noninstitutional materials had information in non-English languages. CONCLUSIONS: The readability of patient education materials related to gynecomastia is at higher levels than recommended by national organizations. There are limited non-English patient education materials. Future efforts should focus on improving the readability and accessibility of patient materials.

Audiogenic Seizures in the Fmr1 Knock-Out Mouse Are Induced by Fmr1 Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading monogenetic cause of autism. One symptom of FXS and autism is sensory hypersensitivity (also called sensory over-responsivity). Perhaps related to this, the audiogenic seizure (AGS) is arguably the most robust behavioral phenotype in the FXS mouse model-the Fmr1 knock-out (KO) mouse. Therefore, the AGS may be considered a mouse model of sensory hypersensitivity. Hyperactive circuits are hypothesized to underlie dysfunction in a number of brain regions in patients with FXS and Fmr1 KO mice, and the AGS may be a result of this. But the specific cell types and brain regions underlying AGSs in the Fmr1 KO are unknown. We used conditional deletion or expression of Fmr1 in different cell populations to determine whether Fmr1 deletion in those cells was sufficient or necessary, respectively, for the AGS phenotype in males. Our data indicate that Fmr1 deletion in glutamatergic neurons that express vesicular glutamate transporter 2 (VGlut2) and are located in subcortical brain regions is sufficient and necessary to cause AGSs. Furthermore, the deletion of Fmr1 in glutamatergic neurons of the inferior colliculus is necessary for AGSs. When we demonstrate necessity, we show that Fmr1 expression in either the larger population of VGlut2-expressing glutamatergic neurons or the smaller population of inferior collicular glutamatergic neurons-in an otherwise Fmr1 KO mouse-eliminates AGSs. Therefore, targeting these neuronal populations in FXS and autism may be part of a therapeutic strategy to alleviate sensory hypersensitivity.SIGNIFICANCE STATEMENT Sensory hypersensitivity in fragile X syndrome (FXS) and autism patients significantly interferes with quality of life. Audiogenic seizures (AGSs) are arguably the most robust behavioral phenotype in the FXS mouse model-the Fmr1 knockout-and may be considered a model of sensory hypersensitivity in FXS. We provide the clearest and most precise genetic evidence to date for the cell types and brain regions involved in causing AGSs in the Fmr1 knockout and, more broadly, for any mouse mutant. The expression of Fmr1 in these same cell types in an otherwise Fmr1 knockout eliminates AGSs indicating possible cellular targets for alleviating sensory hypersensitivity in FXS and other forms of autism.

Early seizure spread and epilepsy surgery: A systematic review.

OBJECTIVE: A fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing seizure activity early in ictus must be removed to avoid postoperative recurrence of seizures is an area of ongoing research. Seizure spread dynamics in the initial seconds of ictus are often correlated with postoperative outcome; there is neither a consensus definition of early spread nor a concise summary of the existing literature linking seizure spread to postsurgical seizure outcomes. The present study is intended to summarize the literature that links seizure spread to postoperative seizure outcome and to provide a framework for quantitative assessment of early seizure spread. METHODS: A systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Medline search identified clinical studies reporting data on seizure spread measured by intracranial electrodes, having at least 10 subjects and reporting at least 1-year postoperative outcome in the English literature from 1990 to 2019. Studies were evaluated regarding support for a primary hypothesis: Areas of early seizure spread represent cortex with seizure-generating potential. RESULTS: The search yielded 4562 studies: 15 studies met inclusion criteria and 7 studies supported the primary hypothesis. The methods and metrics used to describe seizure spread were heterogenous. The timeframe of seizure spread associated with seizure outcome ranged from 1-14 seconds, with large, well-designed, retrospective studies pointing to 3-10 seconds as most likely to provide meaningful correlates of postoperative seizure freedom. SIGNIFICANCE: The complex correlation between electrophysiologic seizure spread and the potential for seizure generation needs further elucidation. Prospective cohort studies or trials are needed to evaluate epilepsy surgery targeting cortex involved in the first 3-10 seconds of ictus.

Imaging in neurointerventional stroke treatment: review of the recent trials and what your neurointerventionalist wants to know from emergency radiologists.

Stroke is one of the leading causes of death and disability worldwide. Standard treatment for stroke is intravenous (IV) injection of tissue plasminogen activator (t-PA) rapidly after symptom onset. However, there are limitations of IV t-PA treatment, such as a short time window for administration and risk for hemorrhage. Recent trials have demonstrated the benefit of endovascular treatment when added to standard treatment to improve outcomes for patients. Advanced imaging was utilized in some trials to identify patients with proximal intracranial occlusion to target for endovascular reperfusion therapy, and to exclude patients with large infarct cores or poor collateral circulation who would not be expected to benefit from intervention. This article summarizes the use of imaging in recent stroke trials in details, provides a stroke imaging protocol, and provides tips which radiologists should know to help their neurointerventionalists.

Creating 3D models from Radiologic Images for Virtual Reality Medical Education Modules.

Virtual Reality (VR) is a powerful tool that has increasingly being used by medical field in recent years. It has been mainly used surgical training in particular laparoscopic procedures. VR can be used for the teaching of anatomy. The aim of the study is to show application of transforming 2D radiologic images into 3D model by using thresholding and segmentation and import into VR interface at an affordable cost. Four anatomy modules are created with inputs to control the rotational and translational movement of 3D models in the virtual space. These movements allow users to explore 3D models by using head tilt and gaze input. 3D models of the Circle of Willis, Vertebral Aneurysm, Spine, and Skull are rendered in the user's field of view at runtime. VR is constructed to have many potentials uses in radiology education. Visualization of 3D anatomic structures in a virtual environment give another tool for teaching to students and patients about anatomy of the body. Four anatomy modules described here demonstrate example user interaction patterns best suited for viewing contexts. Instead viewing stacked 2D images or 3D models confined to desktop applications, virtual reality increases user interactivity of education. An intuitive understanding of anatomic structures in 3D space enhances the learning experience for medical students, residents, and patients we are treating.

Autonomous and non-autonomous roles for ephrin-B in interneuron migration.

While several studies indicate the importance of ephrin-B/EphB bidirectional signaling in excitatory neurons, potential roles for these molecules in inhibitory neurons are largely unknown. We identify here an autonomous receptor-like role for ephrin-B reverse signaling in the tangential migration of interneurons into the neocortex using ephrin-B (EfnB1/B2/B3) conditional triple mutant (TMlz) mice and a forebrain inhibitory neuron specific Cre driver. Inhibitory neuron deletion of the three EfnB genes leads to reduced interneuron migration, abnormal cortical excitability, and lethal audiogenic seizures. Truncated and intracellular point mutations confirm the importance of ephrin-B reverse signaling in interneuron migration and cortical excitability. A non-autonomous ligand-like role was also identified for ephrin-B2 that is expressed in neocortical radial glial cells and required for proper tangential migration of GAD65-positive interneurons. Our studies thus define both receptor-like and ligand-like roles for the ephrin-B molecules in controlling the migration of interneurons as they populate the neocortex and help establish excitatory/inhibitory (E/I) homeostasis.

The p53 transcription factor modulates microglia behavior through microRNA-dependent regulation of c-Maf.

Neuroinflammation occurs in acute and chronic CNS injury, including stroke, traumatic brain injury, and neurodegenerative diseases. Microglia are specialized resident myeloid cells that mediate CNS innate immune responses. Disease-relevant stimuli, such as reactive oxygen species (ROS), can influence microglia activation. Previously, we observed that p53, a ROS-responsive transcription factor, modulates microglia behaviors in vitro and in vivo, promoting proinflammatory functions and suppressing downregulation of the inflammatory response and tissue repair. In this article we describe a novel mechanism by which p53 modulates the functional differentiation of microglia both in vitro and in vivo. Adult microglia from p53-deficient mice have increased expression of the anti-inflammatory transcription factor c-Maf. To determine how p53 negatively regulates c-Maf, we examined the impact of p53 on known c-Maf regulators. MiR-155 is a microRNA that targets c-Maf. We observed that cytokine-induced expression of miR-155 was suppressed in p53-deficient microglia. Furthermore, Twist2, a transcriptional activator of c-Maf, is increased in p53-deficient microglia. We identified recognition sites in the 3' untranslated region of Twist2 mRNA that are predicted to interact with two p53-dependent microRNAs: miR-34a and miR-145. In this article, we demonstrate that miR-34a and -145 are regulated by p53 and negatively regulate Twist2 and c-Maf expression in microglia and the RAW macrophage cell line. Taken together, these findings support the hypothesis that p53 activation induced by local ROS or accumulated DNA damage influences microglia functions and that one specific molecular target of p53 in microglia is c-Maf.

Development of a Predictive Model for Persistent Instability Following Conservative Management of Type II Odontoid Fractures.

BACKGROUND: Odontoid fractures are common cervical spine fractures; however, significant controversy exists regarding their treatment. Risk factors for failure of conservative therapy have been identified, although no predictive risk score has been developed to aid in decision-making. METHODS: A retrospective review was conducted of all patients evaluated at a level 1 trauma center. Patients identified with type II odontoid fractures as classified by the D'Alonzo Classification system who were treated with external orthosis were included in analysis. Patients were considered to have failed conservative therapy if they were offered surgical intervention. A machine learning method (Risk-SLIM) was then utilized to create a risk stratification score based on risk factors to identify patients at high risk for requiring surgical intervention due to persistent instability. RESULTS: A total of 138 patients were identified as presenting with type II odontoid fractures that were treated conservatively; 38 patients were offered surgery for persistent instability. The Odontoid Fracture Predictive Model (OFPM) was created using a machine learning algorithm with a 5-fold cross validation area under the curve of 0.7389 (95% CI: 0.671 to 0.808). Predictive factors were found to include fracture displacement, displacement greater than 5 mm, comminution at the fracture base, and history of smoking. The probability of persistent instability was <5% with a score of 0 and 88% with a score of 5. CONCLUSIONS: The OFPM model is a unique, quick, and accurate tool to assist in clinical decision-making in patients with type II odontoid fractures. External validation is necessary to evaluate the validity of these findings.

The Re-Evaluation of Frailty in Predicting Complications after Long-Segment Spinal Fusion for Adult Spinal Deformity.

OBJECTIVE: To evaluate on a national scale how frailty status (stratified using the 5-item Modified Frailty Index (mFI-5)) affects the operative characteristics of and complications after long-segment spinal fusion (LSF) for adult spinal deformity (ASD). METHODS: Adults undergoing LSF of ≥3 vertebrae in the National Surgical Quality Improvement Program database years 2015-2020 were split into 2 cohorts: nonfrail with mFI = 0 or 1; frail with mFI ≥2. Demographics, operative characteristics, and 30-day complications were contrasted between the cohorts using the Student's t-test, the Fisher's exact test, or a multivariate analysis when appropriate. RESULTS: In the 340 LSF cases collected, 268 fell into the nonfrail cohort and 72 into the frail cohort. The frail cohort constituted a high rate of geriatric age (65.3% vs. 38.1%; P < 0.001), higher body mass index (32.9 ± 0.86 vs. 30.2 ± 0.39; P = 0.005), and more comorbidities in 9 of 14 measures. After surgery, the frail cohort experienced more urinary tract infections (odds ratio [OR], 3.33; confidence interval [CI], 1.01-10.94; P = 0.04). However, the frail cohort shared similarities with the nonfrail cohort in terms of length of stay (5.11 ± 0.51 vs. 6.01 ± 1.62 days; P = 0.60), home discharge (OR, 0.76; CI, 0.42-1.39; P = 0.38), readmission (OR, 2.45; CI, 0.87-6.89; P = 0.09), and overall rate of complications (OR, 0.89; CI, 0.50-1.59; P = 0.70). CONCLUSIONS: Despite trends found in past studies of ASD, this analysis showed that the frailty status of mFI ≥2 is a poor predictor of surgical and hospitalization course and overall complications in LSF when examined up to 30 days postoperatively.

Patterns of Acute Ischemic Stroke Treatment from 2010 to 2020: An Evolving Landscape in Stroke Management Following Thrombectomy Trials.

Background and Objectives: Population-based studies on stroke can help guide the care of patients with acute ischemic stroke (AIS) by providing health care communities with information regarding the current usage of stroke treatments. It remains unclear how rapidly new techniques, particularly endovascular stroke treatment (EST), are being adopted and whether there is any disparity in their availability. Although studies using the National Inpatient Sample (NIS) have been conducted, updated studies over a longer period may provide further insights. This study aimed to understand patterns of AIS treatment, discharge disposition, in-hospital mortality, and mean length of stay (LOS) for each modality from 2010 to 2020 using the NIS database. Methods: This retrospective longitudinal study was conducted using NIS data from 2010 to 2020. Patients were categorized into groups based on whether they received intravenous recombinant tissue plasminogen activator (rt-PA), EST, both rt-PA and EST (combined therapy), or supportive care alone. Demographic, socioeconomic, regional, insurance, and hospital data were also obtained. The primary outcome was the proportion of patients receiving each modality, whereas the secondary outcomes were in-hospital mortality, mean LOS, and discharge disposition. Results: The usage rates increased (p < 0.001) in all groups between 2010 and 2020 (rt-PA: 5.09% to 8.39%, EST: 0.31% to 4.40%, and rt-PA+EST: 0.46% to 1.09%). The highest increase in usage was observed for EST, with a thirteen-fold increase. Mortality decreased from 2010 to 2020 in all groups (rt-PA: 8.45% to 3.54%, EST: 25.22% to 12.50%, and rt-PA+EST: 21.12% in 2010 to 9.30%) (p < 0.001). Combination therapy demonstrated the greatest improvement, with an 11.2% reduction in absolute mortality. Mean LOS was reduced for patients who received rt-PA (6.8 to 4.8 days), EST (9.3 to 8.9 days), and combined therapy (10.0 to 8.3 days) (p < 0.001) over the study period. The proportion of patients discharged to home increased for rt-PA (29.01% to 41.85%), EST (14.13% to 17.70%), and combined therapy (12.89% to 24.29%) (p < 0.001). Overall, stroke treatment usage was higher among the higher income groups, regardless of race. Higher usage was also observed for Whites in the West and Hispanic ethnicities in the South and West. Regardless of income or treatment method, utilization rates were lower for Black patients. Utilization rates were lower for Black patients with Medicare, Medicaid, or self-pay than for White patients. Discussion: Our study demonstrated that endovascular stroke treatment continues to expand, leading to better outcomes for mortality, LOS, and home discharge. Despite these positive patterns, there are visible inequities across regions, income status, and races.

Surgical site infection rates in open versus endoscopic lumbar spinal decompression surgery: A retrospective cohort study.

Background: Lumbar decompression is a commonly performed procedure for the operative management of several degenerative lumbar spinal pathologies. Although open approaches are considered the traditional method, endoscopic techniques represent a relatively novel, less-invasive option to achieve neural element decompression. Here within, we examine if the use of endoscopic techniques decreases the risk of post operative infections. Methods: We performed a retrospective cohort analysis to directly compare patients who underwent either open or endoscopic lumbar decompression at a single institution. Rates of postoperative outcomes such as surgical site infection, hospital length of stay, estimated blood loss, and others were compared between the two treatment groups. A multivariate logistic regression model was constructed using patient comorbidities and procedural characteristics to identify the risk factors for surgical site infection. Results: 150 patients were identified as undergoing lumbar spine decompression surgeries that met inclusion criteria for the study, of whom 108 (72.0%) underwent open and 61 (28.0%) underwent endoscopic approaches. Unpaired analysis revealed positive associations between operative duration, estimated blood loss, drain placement rates. Multivariate logistic regression did not reveal an association between surgical approach (open versus endoscopic) and the development of surgical site infection. Conclusions: Surgical site infections following endoscopic lumbar spine decompression are relatively uncommon, however, after adjusting for baseline differences between patient populations, surgical approach does not independently predict the development of postoperative infection.

Intraoperative cortical stimulation mapping with laryngeal electromyography for the localization of human laryngeal motor cortex.

OBJECTIVE: The objectives of this study were to describe the authors' clinical methodology and outcomes for mapping the laryngeal motor cortex (LMC) and define localization of the LMC in a cohort of neurosurgical patients undergoing intraoperative brain mapping. Because of mapping variability across patients, the authors aimed to define the probabilistic distribution of cortical sites that evoke laryngeal movement, as well as adjacent cortical somatotopic representations for the face (mouth), tongue, and hand. METHODS: Thirty-six patients underwent left (n = 18) or right (n = 18) craniotomy with asleep motor mapping. For each patient, electromyography (EMG) electrodes were placed in the face, tongue, and hand; a nerve integrity monitor (NIM) endotracheal tube with surface electrodes detected EMG activity from the bilateral vocal folds. After dense cortical stimulation was delivered throughout the sensorimotor cortex, motor responses were then mapped onto a three-dimensional reconstruction of the patient's cortical surfaces for location characterization of the evoked responses. Finally, stimulation sites were transformed into a two-dimensional coordinate system for probabilistic mapping of the stimulation site relative to the central sulcus and sylvian fissure. RESULTS: The authors found that the LMC was predominantly localized to a mid precentral gyrus region, dorsal to face representation and surrounding a transverse sulcus ventral to the hand knob. In 14 of 36 patients, the authors identified additional laryngeal responses located ventral to all orofacial representations, providing evidence for dual LMC representations. CONCLUSIONS: The authors determined the probabilistic distribution of the LMC. Cortical stimulation mapping with an NIM endotracheal tube is an easy and effective method for mapping the LMC and is simply integrated into the current neuromonitoring methods for brain mapping.

Lateral femoral cutaneous nerve transposition.

Lateral femoral cutaneous neuropathy, also known as meralgia paresthetica, is a pathology commonly encountered by neurosurgeons. Symptoms include numbness, tingling, and burning pain over the anterolateral thigh due to impingement on the lateral femoral cutaneous nerve (LFCN). Surgical treatment has traditionally involved nerve release or neurectomy. LFCN transposition is a relatively new approach that can provide excellent symptomatic relief. In this video, the authors highlight key operative techniques to ensure easy identification, adequate decompression, and transposition of the nerve. Key steps include ultrasound-guided wire localization, superficial decompression, opening of the inguinal ligament, deep decompression, and medial transposition. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2289.

Socioeconomic Disparities in Outcomes Following Conservative Treatment of Spinal Epidural Abscesses.

BACKGROUND: Primary spinal epidural abscess (SEA) is a rare but serious pathology that may result in severe neurologic injury. While certain literature has identified medical risk factors for failure of conservative therapy, no current evidence has been published regarding socioeconomic risk factors associated with failure of medical therapy. METHODS: A retrospective review was conducted of patients presenting with SEA from primary spinal infections. Patients presenting with magnetic resonance imaging evidence of SEA treated conservatively in the absence of neurologic deficits were included. Baseline clinical and socioeconomic characteristics were collected. Failure of medical management was defined as requiring surgical intervention despite maximal medical therapy due to the development of neurologic deficits or clinically significant deformity. RESULTS: A total of 150 patients were identified as presenting with magnetic resonance imaging evidence of SEAs without evidence of neurologic deficit. Of these patients, 42 required surgical intervention compared with 108 whose infection was successfully treated with medical therapy alone. Estimated average annual income was $64,746 vs $62,615 in those who successfully cleared their infection with medical management without requiring surgery, which was not statistically significant (P = 0.5). Insured patients were 5 times more likely to be successfully treated with antibiotics alone compared with uninsured patients (OR = 5.83, P = 0.008). Payer type, employment status, and incarceration status were not associated with failure of conservative therapy. CONCLUSIONS: In the treatment of primary SEA, absence of medical insurance is associated with failure of medical management. Payer status, employment status, average salary, and incarceration are not significant risk factors for failure of conservative management.

Peroneal Nerve Repair with Cross-Bridge Ladder Technique: Parallel End-to-Side Neurorrhaphies.

Background Multiple nerve transfer techniques are used to treat patients with nerve injuries when a primary repair is not possible. These techniques are categorized to end-to-end, end-to-side, and side-to-side neurorrhaphy. Our study aims to explore the utility of the cross-bridge ladder technique (H-shaped), which has shown promising results in animal models and probably underutilized clinically. Methods Four patients with significant loss of ankle dorsiflexion were seen in the clinic and underwent evaluation, including electrodiagnostic studies. A cross-bridge ladder repair technique was used between the tibial nerve as the donor and the common peroneal nerve as the recipient via one or two nerve grafts coapted in parallel with end-to-side neurorrhaphies. Dorsiflexion strength was measured preoperatively using the Medical Research Council (MRC) grading system and at each postoperative follow-up appointment. Results All four patients had suffered persistent and severe foot drop (MRC of 0) following trauma that had occurred between 6 and 15 months preoperatively. Three of the four patients improved to an MRC of 2 several months postoperatively. The last patient had an immediate improvement to an MRC of 2 by his first month and had a complete recovery of ankle dorsiflexion within 4 months from surgery. Conclusion We demonstrate the utility and clinical outcomes of the cross-bridge ladder technique in patients with persistent and prolonged foot drop following trauma. Both early and late recovery were seen while all patients regained motor function, with some patients continuing to improve up to the most recent follow-up. IRB Approval: Obtained 2013-1411-CP005.

Variant Sciatic Nerve Anatomy in Relation to the Piriformis Muscle on Magnetic Resonance Neurography: A Potential Etiology for Extraspinal Sciatica.

OBJECTIVE: To assess the prevalence and clinical implications of variant sciatic nerve anatomy in relation to the piriformis muscle on magnetic resonance neurography (MRN), in patients with lumbosacral neuropathic symptoms. MATERIALS AND METHODS: In this retrospective single-center study, 254 sciatic nerves, from 127 patients with clinical and imaging findings compatible with extra-spinal sciatica on MRN between 2003 and 2013, were evaluated for the presence and type of variant sciatic nerves, split sciatic nerve, abnormal T2-signal hyperintensity, asymmetric piriformis size and increased nerve caliber, and summarized using descriptive statistics. Two-tailed chi-square tests were performed to compare the anatomical variant type and clinical symptoms between imaging and clinical characteristics. RESULTS: Sixty-four variant sciatic nerves were identified with an equal number of right and left variants. Bilateral variants were noted in 15 cases. Abnormal T2-signal hyperintensity was seen significantly more often in variant compared to conventional anatomy (40/64 vs. 82/190; p = 0.01). A sciatic nerve split was seen significantly more often in variant compared to conventional anatomy (56/64 vs. 20/190; p < 0.0001). Increased nerve caliber, abnormal T2-signal hyperintensity, and asymmetric piriformis size were significantly associated with the clinically symptomatic side compared to the asymptomatic side (98:2, 98:2, and 97:3, respectively; p < 0.0001 for all). Clinical symptoms were correlated with variant compared to conventional sciatic nerve anatomy (64% vs. 46%; p = 0.01). CONCLUSION: Variant sciatic nerve anatomy, in relation to the piriformis muscle, is frequently identified with MRN and is more likely to be associated with nerve signal changes and symptomatology.

Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma.

PURPOSE: In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible. METHODS: In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR. RESULTS: Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis. CONCLUSION: Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.

Evaluation of Endoscopic Versus Open Lumbar Discectomy: A Multi-Center Retrospective Review Utilizing the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) Database.

INTRODUCTION: Endoscopic techniques in spine surgery continue to gain popularity due to their potential for decreased blood loss and post-operative pain. However, limited studies have evaluated these techniques within the United States. Additionally, given the limited number of practitioners with experience in endoscopy, most current studies are limited by a lack of heterogeneity. METHODS: The American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to evaluate the effect of endoscopic surgery on adverse events. Current Procedural Terminology (CPT) codes for open discectomy were compared with the relevant CPT codes for endoscopic lumbar discectomy. Baseline patient characteristics and adverse outcomes were then compared.  Results: A total of 38,497 single-level lumbar discectomies were identified and included. Of these, 175 patients undergoing endoscopic discectomy were compared with 38,322 patients undergoing open discectomy. Endoscopic discectomy demonstrated a shorter operative time of 88.6 minutes than 92.1 minutes in the open group. However, this was not significant (p=0.08). Patients in the endoscopic group demonstrated a shorter total length of stay of 0.81 days vs 1.15 days (p=0.014). Total adverse events were lower in the endoscopic group at 0.6% vs 3.4% in the open group (p=0.03). CONCLUSION:  Endoscopic discectomy demonstrated a significantly lower rate of adverse events and shorter total length of stay than open discectomy. Further research is necessary over time to evaluate larger patient populations as this technology is more rapidly incorporated.