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OBJECTIVE Return to work (RTW) is an important surgical outcome for patients who are employed, yet a significant number of patients with cervical spondylotic myelopathy (CSM) who are employed undergo cervical spine surgery and fail to RTW. In this study, the authors investigated factors associated with failure to RTW in the CSM population who underwent cervical spine surgery and who were considered to have a good surgical outcome yet failed to RTW. METHODS This study retrospectively analyzed prospectively collected data from the cervical myelopathy module of a national spine registry, the Quality Outcomes Database. The CSM data set of the Quality Outcomes Database was queried for patients who were employed at the time of surgery and planned to RTW postoperatively. Distinct multivariable logistic regression models were fitted with 3-month RTW as an outcome for the overall population to identify risk factors for failure to RTW. Good outcomes were defined as patients who had no adverse events (readmissions or complications), who had achieved 30% improvement in Neck Disability Index score, and who were satisfied (North American Spine Society satisfaction score of 1 or 2) at 3 months postsurgery. RESULTS Of the 409 patients who underwent surgery, 80% (n = 327) did RTW at 3 months after surgery. At 3 months, 56.9% of patients met the criteria for a good surgical outcome, and patients with a good outcome were more likely to RTW (88.1% vs 69.2%, p < 0.01). Of patients with a good outcome, 11.9% failed to RTW at 3 months. Risk factors for failing to RTW despite a good outcome included preoperative short-term disability or leave status (OR 3.03 [95% CI 1.66–7.90], p = 0.02); a higher baseline Neck Disability Index score (OR 1.41 [95% CI 1.09–1.84], p < 0.01); and higher neck pain score at 3 months postoperatively (OR 0.81 [95% CI 0.66–0.99], p = 0.04). CONCLUSIONS Most patients with CSM who undergo spine surgery reenter the workforce within 3 months from surgery, with RTW rates being higher among patients who experience good outcomes. Among patients with good outcomes who were employed, failure to RTW was associated with being on preoperative short-term disability or leave status prior to surgery as well as higher neck pain scores at baseline and at 3 months postoperatively.

Clinical Characteristics of patients imaged with [18F]DASA-23

Imaging of IC-2

Purpose:Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM.Experimental Design:[18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma.Results:In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood–brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation.Conclusions:We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy–induced normalization of aberrant cancer metabolism.

Purpose: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. Experimental Design: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. Results: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood–brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. Conclusions: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy–induced normalization of aberrant cancer metabolism.

Conventional ultrasound imaging is based on the scattering of sound from inhomogeneities in the density and the speed of sound and is often used in medicine to resolve pathologic compared to normal tissue. Here we demonstrate a difference-frequency ultrasound (dfUS) imaging method that is based on the interaction of two sound pulses that propagate non-collinearly and intersect in space and time. The dfUS signal arises primarily from the second-order non-linear coefficient, a contrast mechanism that differs from linear and harmonic US imaging. The distinct contrast mechanism allows dfUS to image anatomic features that are not identifiable in conventional US images of salmon and pig kidney tissue. Further, dfUS produces enhanced contrast of glioblastoma tumor implanted in the mouse brain, revealing its potential for improving medical diagnosis. Progress towards a real-time system is discussed.

Non-small cell lung cancer (NSCLC) metastatic to the brain leptomeninges is rapidly fatal, cannot be biopsied, and cancer cells in the cerebrospinal fluid (CSF) are few; therefore, available tissue samples to develop effective treatments are severely limited. This study aimed to converge single-cell RNA-seq and cell-free RNA (cfRNA) analyses to both diagnose NSCLC leptomeningeal metastases (LM), and to use gene expression profiles to understand progression mechanisms of NSCLC in the brain leptomeninges. NSCLC patients with suspected LM underwent withdrawal of CSF via lumbar puncture. Four cytology-positive CSF samples underwent single-cell capture (n = 197 cells) by microfluidic chip. Using robust principal component analyses, NSCLC LM cell gene expression was compared to immune cells. Massively parallel qPCR (9216 simultaneous reactions) on human CSF cfRNA samples compared the relative gene expression of patients with NSCLC LM (n = 14) to non-tumor controls (n = 7). The NSCLC-associated gene, CEACAM6, underwent in vitro validation in NSCLC cell lines for involvement in pathologic behaviors characteristic of LM. NSCLC LM gene expression revealed by single-cell RNA-seq was also reflected in CSF cfRNA of cytology-positive patients. Tumor-associated cfRNA (e.g., CEACAM6, MUC1) was present in NSCLC LM patients’ CSF, but not in controls (CEACAM6 detection sensitivity 88.24% and specificity 100%). Cell migration in NSCLC cell lines was directly proportional to CEACAM6 expression, suggesting a role in disease progression. NSCLC-associated cfRNA is detectable in the CSF of patients with LM, and corresponds to the gene expression profile of NSCLC LM cells. CEACAM6 contributes significantly to NSCLC migration, a hallmark of LM pathophysiology.

PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel positron emission tomography (PET) tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[(18)F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([(18)F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and GBM patients. EXPERIMENTAL DESIGN: [(18)F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [(18)F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next we produced [(18)F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers, and a pilot cohort of glioma patients. RESULTS: In mouse imaging studies, [(18)F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio (TBR) of 3.6 ± 0.5. In human volunteers, [(18)F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In GBM patients, [(18)F]DASA-23 successfully outlined tumors visible on contrast-enhanced magnetic resonance imaging (MRI). The uptake of [(18)F]DASA-23 was markedly elevated in GBMs compared to normal brain, and it identified a metabolic non-responder within 1-week of treatment initiation. CONCLUSION: We developed and translated [(18)F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [(18)F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

Background: This image report with technical notes is the first to illustrate and describe the technique used to treat spinal cerebrospinal fluid (CSF) leaks with the “snowman” muscle pledget. A 49-year-old male presented with orthostatic headaches as well as the left abducens nerve palsy. Patient’s workup including findings of diffuse meningeal enhancement on magnetic resonance imaging, lumbar puncture opening pressure of 4 cm H2O, and CT myelogram demonstrating evidence of ventral spinal thoracic CSF leak. Case Description: Procedure took place in a hybrid biplane operating room so that simultaneous digital subtraction myelogram may also be performed for intraoperative localization. Dural defect was identified intraoperatively and repaired with thoracic laminectomy and “snowman” muscle pledget technique. Postoperatively, the patient did well with resolution of his symptoms. Conclusion: The authors have proposed a grading scale to aid in the work up and management of intracranial hypotension. The use of a hybrid biplane operating room and “snowman” muscle pledget technique is a safe and effective technique to treat spontaneous spinal CSF leaks resulting from dural defects.

Cerebrospinal fluid (CSF) represents a promising source of cell-free DNA (cfDNA) for tumors of the central nervous system. A CSF-based liquid biopsy may obviate the need for riskier tissue biopsies and serve as a means for monitoring tumor recurrence or response to therapy. Spinal ependymomas most commonly occur in adults, and aggressive resection must be delicately balanced with the risk of injury to adjacent normal tissue. In patients with subtotal resection, recurrence commonly occurs. A CSF-based liquid biopsy matched to the patient’s spinal ependymoma mutation profile has potential to be more sensitive then surveillance MRI, but the utility has not been well characterized for tumors of the spinal cord. In this study, we collected matched blood, tumor, and CSF samples from three adult patients with WHO grade II intramedullary spinal ependymoma. We performed whole exome sequencing on matched tumor and normal DNA to design Droplet Digital™ PCR (ddPCR) probes for tumor and wild-type mutations. We then interrogated CSF samples for tumor-derived cfDNA by performing ddPCR on extracted cfDNA. Tumor cfDNA was not reliably detected in the CSF of our cohort. Anatomic sequestration and low grade of intramedullary spinal cord tumors likely limits the role of CSF liquid biopsy.

BACKGROUND The evidence base for many neurosurgical procedures has been limited. We performed a comprehensive and systematic analysis of study design, quality of reporting, and trial results of neurosurgical randomized controlled trials (RCTs). OBJECTIVE To systematically assess the design and quality characteristics of neurosurgical RCTs. METHODS From January 1961 to June 2016, RCTs with >5 patients assessing any 1 neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. RESULTS The median sample size in the 401 eligible RCTs was 73 patients with a mean patient age of 49.6. Only 111 trials (27.1%) described allocation concealment, 140 (34.6%) provided power calculations, and 117 (28.9%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 226 reports (56.4%), no difference between the procedures was found in 166 trials (41.4%), and significant harm was reported in 9 trials (2.2%). Trials with a larger sample size were more likely to report randomization mode, specify allocation concealment, and power calculations (all P < .001). Government funding was associated with better specification of power calculations (P = .008) and of allocation concealment (P = .026), while industry funding was associated with reporting significant efficacy (P = .02). Reporting of funding, specification of randomization mode and primary outcomes, and mention of power calculations improved significantly (all, P < .05) over time. CONCLUSION Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.

Leptomeningeal metastasis (LM), a spread of cancer to the meninges and cerebrospinal fluid, carries extremely poor prognosis due to fast progression and no effective treatment. Given that LM mostly develops in specific types of cancer, notably melanoma, breast and lung cancer, it is likely that predisposition for LMD is shaped by specific genetic footprints and/or anti-cancer therapies. In this regard, it is interesting that among all breast cancers the triple-negative (i.e. estrogen and progesterone receptor-negative and HER2 overexpression-negative) breast cancer (TNBC) type develops a disproportionally high percentage of LM, accounting for the majority (~40%) of all breast cancer LM cases. TNBCs trace their origin to the genomic instability stemming from defects in DNA repair (notably homology-directed repair, HDR). We have recently shown that the efficiency of HDR depends on dynamin 2 (DNM2) best known for its role in endocytic protein trafficking. Higher DNM2 was associated with more efficient HDR and the resistance to DNA-crosslinking chemotherapy. Importantly, elevated DNM2 was associated with lower relapse-free survival and shorter times to relapse after chemotherapy only in TNBCs and not in other types of breast cancer. As DNM2 also fuels migration and invasion, the cells with high DNM2 are not only the most resistant to chemotherapy but also are the most mobile, and thus may represent the core population of LM. Here we test the inhibition of the DNM2-dependent endocytic trafficking as a potential therapeutic strategy to halt LM in TNBC. As a model of LM we use the human-in-mouse model of brain metastasis based on internal carotid injection of MDA-MB-231-BR3 cells, which we have shown to faithfully recapitulate human LM. We show that DNM2 knockdown delays metastatic spread to the brain and potentiates the effect of DNA-crosslinking chemotherapeutic cyclophosphamide, providing justification for further testing of DNM2 inhibitors for targeted therapy of LM.

Introduction Randomized controlled trials (RCTs) have been critical in evaluating the safety and efficacy of functional neurosurgery interventions. Given this, we sought to systematically assess the quality of functional neurosurgery RCTs. Methods We used a database of neurosurgical RCTs (trials published from 1961 to 2016) to identify studies of functional neurosurgical procedures (N = 48). We extracted data on the design and quality of these RCTs and quantified the quality of trials using Jadad scores. We categorized RCTs based on the device approval status at the time of the trial and tested the association of device approval status with trial design and quality parameters. Results Of the 48 analyzed functional neurosurgery RCTs, the median trial size was 34.5 patients with a median age of 51. The most common indications were Parkinson's disease (N = 20), epilepsy (N = 10), obsessive-compulsive disorder (N = 4), and pain (N = 4). Most trials reported inclusion and exclusion criteria (95.8%), sample size per arm (97.9%), and baseline characteristics of the patients being studied (97.9%). However, reporting of allocation concealment (29.2%), randomization mode (66.7%), and power calculations (54.2%) were markedly less common. We observed that trial quality has improved over time (Spearman r, 0.49). We observed that trials studying devices with humanitarian device exemption (HDE) and experimental indications (EI) tended to be of higher quality than trials of FDA-approved devices (p = 0.011). A key distinguishing quality characteristic was the proportion of HDE and EI trials that were double-blinded, compared to trials of FDA-approved devices (HDE, 83.3%; EI, 69.2%; FDA-approved, 35.3%). Although more than one-third of functional neurosurgery RCTs reported funding from industry, no significant association was identified between funding source and trial quality or outcome. Conclusion The quality of RCTs in functional neurosurgery has improved over time but reporting of specific metrics such as power calculations and allocation concealment requires further improvement. Device approval status but not funding source was associated with trial quality.

Study design Retrospective survey review. Objective We seek to evaluate satisfaction scores in patients seen in neurosurgical spine versus neurosurgical nonspine clinics. Summary of background data The Press Ganey survey is a well-established metric for measuring hospital performance and patient satisfaction. These measures have important implications in setting hospital policy and guiding interventions to improve patient perceptions of care. Methods Retrospective Press Ganey survey review was performed to identify patient demographics and patient visit characteristics from January 1st, 2012 to October 10th, 2017 at Stanford Medical Center. A total of 40 questions from the Press Ganey survey were investigated and grouped in categories addressing physician and nursing care, personal concerns, admission, room, meal, operating room, treatment and discharge conditions, visitor accommodations and overall clinic assessment. Raw ordinal scores were converted to continuous scores of 100 for unpaired student t test analysis. We identified 578 neurosurgical spine clinic patients and 1048 neurosurgical nonspine clinic patients. Results Spine clinic patients reported lower satisfaction scores in aggregate (88.2 vs. 90.1; P=0.0014), physician (89.5 vs. 92.6; P=0.0002) and nurse care (91.3 vs. 93.4; P=0.0038), personal concerns (88.2 vs. 90.9; P=0.0009), room (81.0 vs. 83.1; P=0.0164), admission (90.8 vs. 92.6; P=0.0154) and visitor conditions (87.0 vs. 89.2; P=0.0148), and overall clinic assessment (92.9 vs. 95.5; P=0.005). Conclusions This study is the first to evaluate the relationship between neurosurgical spine versus nonspine clinic with regards to patient satisfaction. The spine clinic cohort reported less satisfaction than the nonspine cohort in all significant questions on the Press Ganey survey. Our findings suggest that efforts should be made to further study and improve patient satisfaction in spine clinics. Level of evidence Level III.

Trigeminal neuralgia is a rare neuropathic pain condition but can be very disabling. The hallmark is brief episodes of intense, radiating pain within the territory of trigeminal nerve distribution. It is typically unilateral, often accompanied by facial spasms and can be triggered by facial movements in a majority of patients. Microvascular compression of trigeminal ganglion is the etiology for most patients with classical trigeminal neuralgia. Some patients can have continuous facial pain in addition to paroxysms of pain. Trigeminal neuralgia is a clinical diagnosis, but MRI is done to rule out secondary causes or to detect microvascular compression. Pharmacological therapy with first-line agents—carbamazepine or oxcarbazepine—is the preferred treatment. Patients with failed pharmacological therapy are considered for surgical decompression, ablation procedures, or Gamma Knife surgery.

People generally prefer immediate rewards to rewards received after a delay, often even when the delayed reward is larger. This phenomenon is known as temporal discounting. It has been suggested that preferences for immediate rewards may be due to their being more concrete than delayed rewards. This concreteness may evoke an enhanced emotional response. Indeed, manipulating the representation of a future reward to make it more concrete has been shown to heighten the reward's subjective emotional intensity, making people more likely to choose it. Here the authors use an objective measure of arousal-pupil dilation-to investigate if emotional arousal mediates the influence of delayed reward concreteness on choice. They recorded pupil dilation responses while participants made choices between immediate and delayed rewards. They manipulated concreteness through time interval framing: delayed rewards were presented either with the date on which they would be received (e.g., "$30, May 3"; DATE condition, more concrete) or in terms of delay to receipt (e.g., "$30, 7 days; DAYS condition, less concrete). Contrary to prior work, participants were not overall more patient in the DATE condition. However, there was individual variability in response to time framing, and this variability was predicted by differences in pupil dilation between conditions. Emotional arousal increased as the subjective value of delayed rewards increased, and predicted choice of the delayed reward on each trial. This study advances our understanding of the role of emotion in temporal discounting. (PsycINFO Database Record

HD-YAS will study a cohort of young adult HD Gene Expansion Carriers (HDGEC) decades before expected symptom onset to characterize the very earliest signs of disease-related brain changes and identify whether there is any identifiable early functional impairment. Currently there is no detailed characterization of such a young adult HDGEC cohort and this represents the earliest time point after predictive genetic testing in which to gain disease insights. HD-YAS will be important in determining the earliest potential time window for therapeutic intervention. HD-YAS will recruit 120 participants-60 premanifest HDGECs and 60 gene negative or family controls-and will use a cross-sectional comparison with one visit per participant to assess the earliest time-point at which neurodegeneration can be detected. Participants will undergo 3T Volumetric MRI, rsfMRI and task fMRI, NODDI, and cognitive assessments including the CANTAB and EMOTICOM batteries, and biosamples such as CSF, blood and DNA will be collected to investigate biomarkers. Participants will be 18–40 years old and at-risk individuals must have a predictive genetic test; either carry the HD gene (gene-carrier) or not carry the HD gene (control). Individuals must not show any clinical symptoms of HD, have a disease burden score of ≤240, and must be willing and able to comply with the study visit and study procedures. HD-YAS began in August 2017 and is expected to complete by February 2019. HD-YAS collaborates with Enroll-HD, UK clinical genetics services and HD charity groups to identify potentially eligible participants throughout the UK. HD-YAS is funded by Wellcome, with CSF collection funded by CHDI. HD-YAS investigators – Participant Identification Site Investigators; Dr Oliver Quarrell, Dr Nayana Lahiri, Dr Andrea Nemeth, Dr Mary Porteous, Dr Elisabeth Rosser, Dr David Craufurd, Dr Rhona MacLeod, Dr Deborah Ruddy, Dr Roger Barker, Dr Simon Holden, Dr Hugh Rickards, Dr Anne Rosser, Dr Emma Hobson, Prof Angus Clarke, Dr Katherine Lachlan, Dr Reza Kiani, Dr Timothy Harrower. Thank you to the HDA, HDYO, SHA.

OBJECTIVEWhile conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus.METHODSThe authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls.RESULTSPatients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years).CONCLUSIONSDTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.

Cortical bone trajectory (CBT) is a novel pedicle insertion technique with comparable or superior mechanical properties and reduced invasiveness compared to traditional methods. We describe the screw accuracy, complications, and learning curve associated with CBT use. A prospective cohort study was performed involving 22 patients who underwent lumbar fusion with CBT screw placement. A total of 100 cortical screws were placed. Post-operative CT scans were reviewed to assess the adequacy of screw placement and calculate the incidence of vertebral body and pedicle breaches from cortical screw placement. Technique-related complications were examined. The entire surgical cohort was divided into two groups: early experience (first 11 patients) and late experience (last 11 patients), to study the effect of learning curve on CBT screw placement. Medial pedicle breach was observed in 6/100 cases and lateral vertebral body breach was observed in 1/100 cases. The incidence of durotomy related to the technique was 4.5% (N = 1/22). Post-surgical wound infection was seen in 9.1% of patients (N = 2/22). 66.7% (N = 4/6) of medial pedicle breaches, 100% (N = 1/1) of lateral breaches, 100% (N = 1/1) of CBT technique-related CSF leaks, and 100% (N = 2/2) of wound infections occurred in the early experience phase of our study (p = 0.0945). A shift in surgical technique and greater efficiency over time decreased the incidence of overall complications in the late cohort. The difference, however, did not reach statistical significance. A lateralized starting point for the cortical screw on the pars interarticularis and use of smaller diameter screws resulted in fewer medial pedicle out-fractures and breaches.

OBJECTIVEFast magnetic resonance imaging (fsMRI) sequences are single-shot spin echo images with fast acquisition times that have replaced CT scans for many conditions. Introduced as a means of evaluating children with hydrocephalus and macrocephaly, these sequences reduce the need for anesthesia and can be more cost-effective, especially for children who require multiple surveillance scans. However, the role of fsMRI has yet to be investigated in evaluating the posterior fossa in patients with Chiari I abnormality (CM-I). The goal of this study was to examine the diagnostic performance of fsMRI in evaluating the cerebellar tonsils in comparison to conventional MRI.METHODSThe authors performed a retrospective analysis of 18 pediatric patients with a confirmed diagnosis of CM-I based on gold-standard conventional brain MRI and 30 controls without CM-I who had presented with various neurosurgical conditions. The CM-I patients were included if fsMRI studies had been obtained within 1 year of conventional MRI with no surgical intervention between the studies. Two neuroradiologists reviewed the studies in a blinded fashion to determine the diagnostic performance of fsMRI in detecting CM-I. For the CM-I cohort, the fsMRI and T2-weighted MRI exams were randomized, and the blinded reviewers performed tonsillar measurements on both scans.RESULTSThe mean age of the CM-I cohort was 7.39 years, and 50% of these subjects were male. The mean time interval between fsMRI and conventional T2-weighted MRI was 97.8 days. Forty-four percent of the subjects had undergone imaging after posterior fossa decompression. The sensitivity and specificity of fsMRI in detecting CM-I was 100% (95% CI 71.51%–100%) and 92.11% (95% CI 78.62%–98.34%), respectively. If only preoperative patients are considered, both sensitivity and specificity increase to 100%. The authors also performed a cost analysis and determined that fsMRI was significantly cost-effective compared to T2-weighted MRI or CT.CONCLUSIONSDespite known limitations, fsMRI may serve as a useful diagnostic and surveillance tool for CM-I. It is more cost-effective than full conventional brain MRI and decreases the need for sedation in young children.

PURPOSE OF REVIEW: In this review, we seek to summarize the literature concerning the use of single-cell RNA-sequencing for CNS gliomas. RECENT FINDINGS: Single-cell analysis has revealed complex tumor heterogeneity, subpopulations of proliferating stem-like cells and expanded our view of tumor microenvironment influence in the disease process. SUMMARY: Although bulk RNA-sequencing has guided our initial understanding of glioma genetics, this method does not accurately define the heterogeneous subpopulations found within these tumors. Single-cell techniques have appealing applications in cancer research, as diverse cell types and the tumor microenvironment have important implications in therapy. High cost and difficult protocols prevent widespread use of single-cell RNA-sequencing; however, continued innovation will improve accessibility and expand our of knowledge gliomas.

Intracranial chondromas of the dural convexity are exceedingly rare with less than 30 reported in the literature to date. We report a massive intradural convexity chondroma in a patient initially thought to have a frontal gait neurodegenerative disorder. This large tumor required a complex, piecemeal surgical resection due to the dense, fibrous nature of the tumor and the proximity of crucial structures. The patient had complete resolution of her preoperative symptoms after surgical excision.

OBJECTIVEPreoperative depression has been linked to a variety of adverse outcomes following lumbar fusion, including increased pain, disability, and 30-day readmission rates. The goal of the present study was to determine whether preoperative depression is associated with increased narcotic use following lumbar fusion. Moreover, the authors examined the association between preoperative depression and a variety of secondary quality indicator and economic outcomes, including complications, 30-day readmissions, revision surgeries, likelihood of discharge home, and 1- and 2-year costs.METHODSA retrospective analysis was conducted using a national longitudinal administrative database (MarketScan) containing diagnostic and reimbursement data on patients with a variety of private insurance providers and Medicare for the period from 2007 to 2014. Multivariable logistic and negative binomial regressions were performed to assess the relationship between preoperative depression and the primary postoperative opioid use outcomes while controlling for demographic, comorbidity, and preoperative prescription drug–use variables. Logistic and log-linear regressions were also used to evaluate the association between depression and the secondary outcomes of complications, 30-day readmissions, revisions, likelihood of discharge home, and 1- and 2-year costs.RESULTSThe authors identified 60,597 patients who had undergone lumbar fusion and met the study inclusion criteria, 4985 of whom also had a preoperative diagnosis of depression and 21,905 of whom had a diagnosis of spondylolisthesis at the time of surgery. A preoperative depression diagnosis was associated with increased cumulative opioid use (β = 0.25, p < 0.001), an increased risk of chronic use (OR 1.28, 95% CI 1.17–1.40), and a decreased probability of opioid cessation (OR 0.96, 95% CI 0.95–0.98) following lumbar fusion. In terms of secondary outcomes, preoperative depression was also associated with a slightly increased risk of complications (OR 1.14, 95% CI 1.03–1.25), revision fusions (OR 1.15, 95% CI 1.05–1.26), and 30-day readmissions (OR 1.19, 95% CI 1.04–1.36), although it was not significantly associated with the probability of discharge to home (OR 0.92, 95% CI 0.84–1.01). Preoperative depression also resulted in increased costs at 1 (β = 0.06, p < 0.001) and 2 (β = 0.09, p < 0.001) years postoperatively.CONCLUSIONSAlthough these findings must be interpreted in the context of the limitations inherent to retrospective studies utilizing administrative data, they provide additional evidence for the link between a preoperative diagnosis of depression and adverse outcomes, particularly increased opioid use, following lumbar fusion.

Despite multimodal therapies extending patient survival, glioblastoma (GBM) recurrence is all but a certainty. To date, there are few single-center studies of reoperations. Our study aimed to assess GBM reoperation trends nationally in older patients, with emphasis on outcomes.The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was searched to identify patients 66 years and older with GBM from 1997 to 2010. The primary outcome was survival after diagnosis. Kaplan-Meier curves and multivariate analysis with proportional hazard ratios were used.Three thousand nine hundred sixty-three patients with recurrent GBM who initially received a surgical resection were identified (mean age = 74.7 years). Four hundred ninety-six (12%) of the patients with recurrent GBM underwent at least one reoperation at an average of 7.2 months after the initial diagnosis. Reoperation increased survival in patients compared with those who did not have surgical resection (12 vs. 5 months; P0.0001; hazard ratio [HR] = 0.666). Within the reoperated cohort, gross total resection improved median survival over subtotal resection (HR = 0.779). Two or more reoperations upon GBM recurrence improved survival to 17 months (P = 0.002). The overall complication rate was 21.7% in the initial resection-only group, versus 20.4% in the 1-reoperation group and 25.3% in the 2-reoperation group.Although definitive conclusions cannot be made given the lack of granularity, our national database study supports gross total resection as the initial treatment of choice, followed by reoperation at the time of recurrence, if tolerated, even in older patients.

Objective Open microsurgical and endoscopic approaches are the two main surgical options for excision of colloid cysts. Controversy remains as to which is superior. Previous studies consist of small cohort sizes. This topic has not been investigated using national administrative claims data which benefits from larger patient numbers. Methods Current Procedural Terminology (CPT) and International Classification of Disease version 9 (ICD-9) coding at inpatient visit was used to select for index surgical procedures corresponding to microsurgical or endoscopic excision of colloid cysts. Comorbidities, costs, and complications were collected. Results We identified a total of 483 patients. In all, 240 were from the microsurgical cohort and 243 were from the endoscopic cohort. The two groups displayed similar demographic and comorbidity profiles. Thirty-day post-operative complications were also similar between groups with the exception of seizures and thirty-day readmissions, both higher in the open surgical cohort. The seizure rates were 14.7 and 5.4% in the microsurgical and endoscopic cohorts, respectively (p = 0.0011). The thirty-day readmission rates were 17.3 and 9.6% in the microsurgical and endoscopic cohorts, respectively (p = 0.0149). Index admission costs and 90-day post discharge payments were higher in patients receiving microsurgical excision. Conclusion An analysis of administrative claims data revealed few differences in surgical complications following colloid cyst excision via microsurgical and endoscopic approaches. Post-operative seizures and thirty-day readmissions were seen at higher frequency in patients who underwent microsurgical resection. Despite similar complication profiles, patients undergoing microsurgical excision experienced higher index admission costs and 90-day aggregated costs suggesting that complications may have been more severe in this group.

Leptomeningeal metastases (LM), a diffuse form of brain metastases is rare and fatal progression of non-small cell lung cancer (NSCLC). In LM, metastatic cancer cells spread and resign on the brain meninges, the cerebrospinal fluid (CSF), cranial and spinal nerves. Rapid disease progression and scarce tissue availability hinder the progress of scientific study of LM and its treatment. To overcome the critical lack of tissue and to determine the genetic profile of NSCLC LM, we have developed methods to extract tumor-associated cell-free RNA from CSF, and isolated and sequenced circulating single cells from CSF. Herein, we used high throughput qPCR to target lung and brain-associated genes and identified NSCLC LM metastases-related RNA. Brain-specific gene signature (GFAP, NRGN, SNCB, ZBTB18) was detected in all CSF sample (control and metastases), whereas lung-specific genes (MUC1, SFTPB, SFTPD, SLC34A2) were detected in CSF of brain metastases patients. Normal, healthy CSF lacks cellular component, but CSF of patients with LM metastases inhabited with very low amount of circulating tumor cells. Single cells from CSF of 4 patients with NSCLC LM metastases were captured with microfluidic chip. Cells (n = 197) were clustered by significantly differential expressed genes demonstrating two distinct populations of white blood and tumor cells. These data identified specific cfRNA and single cell transcriptome profiles compared to normal cells or patients without NSCLC LM metastases, and highlighted metastases-associated carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) as highly expressed in patients with NSCLC LM metastases. CEACAM6 mRNA was detected in CSF of 86% of patients with NSCLC LM but not in the CSF of control patients. In vitro inhibition of CEACAM6 protein lead to decreased invasion in NSCLC cells which was rescued by overexpression of the protein. We have developed sensitive and robust techniques to leverage human CSF to study NSCLC LM.

Magnetic resonance–guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.