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The prognosis for patients with malignant gliomas continues to be dismal. The high degree of resistance of gliomas to nitrosourea-based chemotherapy is one major factor in poor treatment outcome. The identification of O6-alkylguanine-DNA alkyltransferase (AGAT) as a major determinant of nitrosourea resistance has resulted in the development of several agents to inactivate this repair protein and counteract tumor cell resistance. However, a major problem in preclinical trials has been the marked nitrosourea dose limitations imposed by the prior administration of AGAT-depleting agents. We investigated the AGAT depletion and selective enhancement of BCNU activity of intraarterial (i.a.) O6-benzylguanine ( O6BG) in the human malignant glioma xenograft D-456 MG growing intracranially (i.c.) in athymic rats. Whereas i.a. O6BG at 2.5 mg/kg produced 100% inhibition of D-456 MG AGAT i.c. activity 8 h after administration, intraperitoneal (i.p.) O6BG at this dose produced only 40% inhibition, requiring dose escalation to 10 mg/kg to produce 100% AGAT depletion. Prior administration of i.p. O6BG (10 mg/kg) and i.a. O6BG (2.5 mg/kg) limited maximum tolerated intravenous (i.v.) BCNU doses (37.5 mg/kg when given alone) to 6.25 and 25 mg/kg, respectively. Higher doses of BCNU alone or in combination with O6BG produced histopathologic evidence of cerebral and hepatic toxicity. Therapy experiments revealed a significantly improved median survival for rats treated with O6BG i.a. (2.5 mg/kg) plus BCNU i.v. (25 mg/kg, days 61 and 59 in duplicate experiments) compared with saline (day 21, P=0.001), O6BG i.a. or i.p. (days 22 and 23, P=0.001), BCNU i.v. (37.5 mg/kg, day 29, P=0.001), and O6BG i.p. (10 mg/kg) plus BCNU i.v. (6.25 mg/kg, day 37, P<0.001). Therefore, O6BG i.a., by virtue of rapid AGAT depletion and selective uptake into i.c. tumors, offers significant potential for regional chemomodulation of AGAT-mediated nitrosourea resistance in malignant human gliomas with concomitant reduction of systemic toxicity. [ABSTRACT FROM AUTHOR]

A young man had an open fracture of the tibia with bone and soft tissue loss in the distal part of the left leg following a crush injury. The circumferential skin defect was successfully treated with controlled lengthening of the distal skin by the Ilizarov technique using nylon wires and skin staples to apply traction. This was combined with limb reconstruction done simultaneously using orthofix external fixator. This case report highlights the use of an orthopaedic technique to provide skin cover in distal leg.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for assessing spinal cord injury (SCI) that has historically been challenged by the presence of metallic stabilization hardware. This study leverages recent advances in metal-artifact resistant multi-spectral DW-MRI to enable diffusion quantification throughout the spinal cord even after fusion stabilization. Twelve participants with cervical spinal cord injuries treated with fusion stabilization and 49 asymptomatic able-bodied control participants underwent multi-spectral DW-MRI evaluation. Apparent diffusion coefficient (ADC) values were calculated in axial cord sections. Statistical modeling assessed ADC differences across cohorts and within distinct cord regions of the SCI participants (at, above, or below injured level). Computed models accounted for subject demographics and injury characteristics. ADC was found to be elevated at injured levels compared with non-injured levels (z = 3.2, p  = 0.001), with ADC at injured levels decreasing over time since injury (z = -9.2, p < 0.001). Below the injury level, ADC was reduced relative to controls (z = -4.4, p < 0.001), with greater reductions after more severe injuries that correlated with lower extremity motor scores (z = 2.56, p  = 0.012). No statistically significant differences in ADC above the level of injury were identified. By enabling diffusion analysis near fusion hardware, the multi-spectral DW-MRI technique allowed intuitive quantification of cord diffusion changes after SCI both at and away from injured levels. This demonstrates the approach's potential for assessing post-surgical spinal cord integrity throughout stabilized regions.

Study Design: A modified Delphi study., Objective: To assess current practice patterns in the management of cervical spinal cord injury (SCI) and develop a simplified, practical classification system which offers ease of use in the acute setting, incorporates modern diagnostic tools and provides utility in determining treatment strategies for cervical SCI., Methods: A three-phase modified Delphi procedure was performed between April 2020 and December 2021. During the first phase, members of the AOSpine SCI Knowledge forum proposed variables of importance for classifying and treating cervical SCI. The second phase involved an international survey of spine surgeons gauging practices surrounding the role and timing of surgery for cervical SCI and opinions regarding factors which most influence these practices. For the third phase, information obtained from phases 1 and 2 were used to draft a new classification system., Results: 396 surgeons responded to the survey. Neurological status, spinal stability and cord compression were the most important variables influencing decisions surrounding the role and timing of surgery. The majority (>50%) of respondents preferred to perform surgery within 24 hours post-SCI in clinical scenarios in which there was instability, severe cord compression or severe neurology. Situations in which <50% of respondents were inclined to operate early included: SCI with mild neurological impairments, with cord compression but without instability (with or without medical comorbidities), and SCI without cord compression or instability., Conclusions: Spinal stability, cord compression and neurological status are the most important variables influencing surgeons' practices surrounding the surgical management of cervical SCI. Based on these results, a simplified classification system for acute cervical SCI has been proposed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

There is a paucity of data comparing the demographics, mechanism of injury, and outcomes of upper versus lower cervical spinal cord injuries (cSCI). The study objective was to define different clinical manifestations of cSCI. Data were collected prospectively through centers of the North American Clinical Trials Network (NACTN). Data was collected on 470 patients (21% women, mean age 50 years). Cervical vertebral level was analyzed as an ordinal variable to determine a natural demarcation to classify upper versus lower cSCI. For continuous variable analysis, falls were associated with C3 more than C4 vertebral level injuries (60% vs. 42%; p  = 0.0126), while motor vehicle accidents were associated with C4 more than C3 (40% vs. 29%; p  = 0.0962). Motor International Standards for Neurological Classification of Spinal Cord Injury scores also demonstrated a natural demarcation between C3 and C4, with C3 having higher median American Spinal Injury Association (ASIA) motor scores (40 [4-73] vs. 11 [3-59], p  = 0.0227). There were no differences when comparing C2 to C3 nor C4 to C5. Given the significant differences seen between C3 and C4, but not C2 and C3 nor C4 and C5, upper cSCI was designated as C1-C3, and lower cSCI was designated as C4-C7. Compared with a lower cSCI, patients with an upper cSCI were more likely to have a fall as their mechanism of injury (54% vs. 36%; p  = 0.0072). Patients with an ASIA C cSCI were likely to have an upper cervical injury: 23% vs. 11% ( p  = 0.0226). Additionally, patients with an upper cSCI were more likely to have diabetes prior to injury: 37% versus 22%, respectively ( p  = 0.0084). Lower cSCI were more likely injured through sports (19% vs. 8%, p  = 0.0171) and present with ASIA A (42% vs. 25%, p  = 0.0186) neurological grade. Patients with lower cSCI were also significantly more likely to have complications such as shock, pulmonary embolism, and pleural effusion. In conclusion, there appears to be a natural demarcation of injury type between C3 and C4. Upper cSCI (C1-C3) was more associated with falls and diabetes, whereas lower cSCI (C4-C7) was more associated with sports, worse ASIA scores, and more complications. Further research will be needed to understand the mechanistic and biological differences between these two groups and whether different treatments may be appropriate for each of these groups.

Traumatic injuries of the spine are associated with long-term morbidity and mortality. Timely diagnosis and appropriate management of mechanical instability and spinal cord injury are important to prevent further neurologic deterioration. Spine surgeons require an understanding of the essential imaging techniques concerning the diagnosis, management, and prognosis of spinal cord injury. We present a review in the role of computed tomography (CT) including advancements in multidetector CT (MDCT), dual energy CT (DECT), and photon counting CT, and how it relates to spinal trauma. We also review magnetic resonance imaging (MRI) and some of the developed MRI based classifications for prognosticating the severity and outcome of spinal cord injury, such as diffusion weighted imaging (DWI), diffusion tractography (DTI), functional MRI (fMRI), and perfusion MRI.

Objectives: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM)., Design: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM., Participants and Setting: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation., Results: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered 'answered'. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an 'answered' research question. Respondents from South America were also most likely to submit 'answered' questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4)., Conclusions: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics., Competing Interests: Competing interests: BD, JB, ODM, IS, ES, MGF and MRNK have voluntary roles at Myelopathy.org, an international DCM charity., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This study investigated tissue diffusion properties within the spinal cord of individuals treated for cervical spondylotic myelopathy (CSM) using post-decompression stabilization hardware. While previous research has indicated the potential of diffusion-weighted MRI (DW-MRI) markers of CSM, the metallic implants often used to stabilize the decompressed spine hamper conventional DW-MRI., Methods: Utilizing recent developments in DW-MRI metal-artifact suppression technologies, imaging data was acquired from 38 CSM study participants who had undergone instrumented fusion, as well as asymptomatic (non-instrumented) control participants. Apparent diffusion coefficients were determined in axial slice sections and split into four categories: a) instrumented levels, b) non-instrumented CSM levels, c) adjacent-segment (to instrumentation) CSM levels, and d) non-instrumented control levels. Multi-linear regression models accounting for age, sex, and body mass index were used to investigate ADC measures within each category. Furthermore, the cord diffusivity within CSM subjects was correlated with symptom scores and the duration since fusion procedures., Results: ADC measures of the spinal cord in CSM subjects were globally reduced relative to control subjects ( p = 0.005). In addition, instrumented levels within the CSM subjects showed reduced diffusivity relative to controls ( p = 0.003), while ADC within non-instrumented CSM levels did not statistically deviate from control levels ( p = 0.107)., Discussion: Multi-spectral DW-MRI technology can be effectively employed to evaluate cord diffusivity near fusion hardware in subjects who have undergone surgery for CSM. Leveraging this advanced technology, this study had identified significant reductions in cord diffusivity, relative to control subjects, in CSM patients treated with conventional metallic fusion instrumentation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koch, Nencka, Klein, Wang, Kurpad, Vedantam and Budde.)

Secondary damage obstructs functional recovery for individuals who have sustained a spinal cord injury (SCI). Two processes significantly contributing to tissue damage after trauma are spinal cord hemorrhage and inflammation: more specifically, the recruitment and activation of immune cells, frequently driven by pro-inflammatory factors. Cytokines are inflammatory mediators capable of modulating the immune response. While cytokines are necessary to elicit inflammation for proper healing, excessive inflammation can result in destructive processes. The pro-inflammatory cytokines IL-12 and IL-23 are pathogenic in multiple autoimmune diseases. The cytokine subunit IL-12p40 is necessary to form bioactive IL-12 and IL-23. In this study, we examined the relationship between spinal cord hemorrhage and IL-12-related factors, as well as the impact of IL-12p40 (IL-12/IL-23) on secondary damage and functional recovery after SCI. Using in vivo magnetic resonance imaging and protein tissue analyses, we demonstrated a positive correlation between IL-12 and tissue hemorrhage. Receptor and ligand subunits of IL-12 were significantly upregulated after injury and colocalized with astrocytes, demonstrating a myriad of opportunities for IL-12 to induce an inflammatory response. IL-12p40 -/- mice demonstrated significantly improved functional recovery and reduced lesion sizes compared to wild-type mice. Targeted gene array analysis in wild-type and IL-12p40 -/- female mice after SCI revealed an upregulation of genes associated with worsened recovery after SCI. Taken together, our data reveal a pathogenic role of IL-12p40 in the secondary damage after SCI, hindering functional recovery. IL-12p40 (IL-12/IL-23) is thus an enticing neuroinflammatory target for further study as a potential therapeutic target to benefit recovery in acute SCI., (© 2022 Wiley Periodicals LLC.)

Background and Purpose: In traumatic spinal cord injury, DTI is sensitive to injury but is unable to differentiate multiple pathologies. Axonal damage is a central feature of the underlying cord injury, but prominent edema confounds its detection. The purpose of this study was to examine a filtered DWI technique in patients with acute spinal cord injury., Materials and Methods: The MR imaging protocol was first evaluated in a cohort of healthy subjects at 3T ( n  = 3). Subsequently, patients with acute cervical spinal cord injury ( n  = 8) underwent filtered DWI concurrent with their acute clinical MR imaging examination <24 hours postinjury at 1.5T. DTI was obtained with 25 directions at a b-value of 800 s/mm 2 . Filtered DWI used spinal cord-optimized diffusion-weighting along 26 directions with a "filter" b-value of 2000 s/mm 2 and a "probe" maximum b-value of 1000 s/mm 2 . Parallel diffusivity metrics obtained from DTI and filtered DWI were compared., Results: The high-strength diffusion-weighting perpendicular to the cord suppressed signals from tissues outside of the spinal cord, including muscle and CSF. The parallel ADC acquired from filtered DWI at the level of injury relative to the most cranial region showed a greater decrease (38.71%) compared with the decrease in axial diffusivity acquired by DTI (17.68%)., Conclusions: The results demonstrated that filtered DWI is feasible in the acute setting of spinal cord injury and reveals spinal cord diffusion characteristics not evident with conventional DTI., (© 2021 by American Journal of Neuroradiology.)

Study Design: The study examined and compared four artificial cervical disks using validated finite element models., Purpose: To compare and contrast the biomechanical behavior of four artificial cervical disks by determining the external (range of motion) and internal (facet force and intradiscal pressure) responses following cervical disc arthroplasty (CDA) and to elucidate any device design effects on cervical biomechanics., Overview of Literature: Despite CDA's increasing popularity most studies compare the CDA procedure with anterior cervical discectomy and fusion. There is little comparative evaluation of different artificial disks and, therefore, little understanding of how varying disk designs may influence spinal biomechanics., Methods: A validated C2-T1 finite element model was subjected to flexion-extension. CDAs were simulated at the C5-C6 level with the Secure-C, Mobi-C, Prestige LP, and Prodisc C prosthetic disks. We used a hybrid loading protocol to apply sagittal moments. Normalized motions at the index and adjacent levels, and intradiscal pressures and facet column loads were also obtained., Results: The ranges of motion at the index level increased after CDA. The Mobi-C prosthesis demonstrated the highest amount of flexion, followed by the Secure-C, Prestige LP, and Prodisc C. The Secure-C demonstrated the highest amount of extension, followed by the Mobi-C, Prodisc C, and Prestige LP. The motion decreased at the rostral and caudal adjacent levels. Facet forces increased at the index level and decreased at the rostral and caudal adjacent levels following CDA. Intradiscal pressures decreased at the adjacent levels for the Mobi-C, Secure-C, and Prodisc C. Conversely, the use of the Prestige LP increased intradiscal pressure at both adjacent levels., Conclusions: While all artificial disks were useful in restoring the index level motion, the Secure-C and Mobi-C translating abilities allowed for lower intradiscal pressures at the adjacent segments and may be the driving mechanism for minimizing adjacent segment degenerative arthritic changes. The facet joint integrity should also be considered in the clinical decision-making process for CDA selection.

Objective: To test the hypothesis that sensorimotor complete traumatic cervical spinal cord injury (SCI) is a heterogenous clinical entity comprising several subpopulations that follow fundamentally different trajectories of neurologic recovery., Methods: We analyzed demographic and injury data from 655 patients who were pooled from 4 prospective longitudinal multicenter studies. Group-based trajectory modeling was applied to model neurologic recovery trajectories over the initial 12 months postinjury and to identify predictors of recovery trajectories. Neurologic outcomes included upper extremity motor score, total motor scores, and American Spinal Injury Association Impairment Scale (AIS) grade improvement., Results: The analysis identified 3 distinct trajectories of neurologic recovery. These clinical courses included (1) marginal recovery trajectory, characterized by minimal or no improvement in motor strength or change in AIS grade status (remained grade A); (2) moderate recovery trajectory, characterized by low baseline motor scores that improved approximately 13 points or AIS conversion of 1 grade point; (3) good recovery trajectory, characterized by baseline motor scores in the upper quartile that improved to near maximum values within 3 months of injury. Patients following the moderate or good recovery trajectories were younger, had more caudally located injuries, had a higher degree of preserved motor and sensory function at baseline examination, and exhibited a greater extent of motor and sensory function in the zone of partial preservation., Conclusion: Cervical complete SCI can be classified into one of 3 distinct subpopulations with fundamentally different trajectories of neurologic recovery. This study defines unique clinical phenotypes based on potential for recovery, rather than baseline severity of injury alone. This approach may prove beneficial in clinical prognostication and in the design and interpretation of clinical trials in SCI., (© 2021 American Academy of Neurology.)

Many artificial discs for have been introduced to overcome the disadvantages of conventional anterior discectomy and fusion. The purpose of this study was to evaluate the performance of different U.S. Food and Drug Administration (FDA)-approved cervical disc arthroplasty (CDA) on the range of motion (ROM), intradiscal pressure, and facet force variables under physiological loading. A validated three-dimensional finite element model of the human intact cervical spine (C2-T1) was used. The intact spine was modified to simulate CDAs at C5-C6. Hybrid loading with a follower load of 75 N and moments under flexion, extension, and lateral bending of 2 N·m each were applied to intact and CDA spines. From this work, it was found that at the index level, all CDAs except the Bryan disc increased ROM, and at the adjacent levels, motion decreased in all modes. The largest increase occurred under the lateral bending mode. The Bryan disc had compensatory motion increases at the adjacent levels. Intradiscal pressure reduced at the adjacent levels with Mobi-C and Secure-C. Facet force increased at the index level in all CDAs, with the highest force with the Mobi-C. The force generally decreased at the adjacent levels, except for the Bryan disc and Prestige LP in lateral bending. This study demonstrates the influence of different CDA designs on the anterior and posterior loading patterns at the index and adjacent levels with head supported mass type loadings. The study validates key clinical observations: CDA procedure is contraindicated in cases of facet arthroplasty and may be protective against adjacent segment degeneration., (Copyright © 2021 by ASME.)

Objective: The objective of this study was to evaluate the characteristics and performance of current prediction models in the fields of spine metastasis and degenerative spine disease to create a scoring system that allows direct comparison of the prediction models., Methods: A systematic search of PubMed and Embase was performed to identify relevant studies that included either the proposal of a prediction model or an external validation of a previously proposed prediction model with 1-year outcomes. Characteristics of the original study and discriminative performance of external validations were then assigned points based on thresholds from the overall cohort., Results: Nine prediction models were included in the spine metastasis category, while 6 prediction models were included in the degenerative spine category. After assigning the proposed utility of prediction model score to the spine metastasis prediction models, only 1 reached the grade of excellent, while 2 were graded as good, 3 as fair, and 3 as poor. Of the 6 included degenerative spine models, 1 reached the excellent grade, while 3 studies were graded as good, 1 as fair, and 1 as poor., Conclusions: As interest in utilizing predictive analytics in spine surgery increases, there is a concomitant increase in the number of published prediction models that differ in methodology and performance. Prior to applying these models to patient care, these models must be evaluated. To begin addressing this issue, the authors proposed a grading system that compares these models based on various metrics related to their original design as well as internal and external validation. Ultimately, this may hopefully aid clinicians in determining the relative validity and usability of a given model.

Aims and Objectives: The human spine degenerates with age. Intervertebral disc degeneration occurs in the cervical spine. The objective of this study is to determine the effects of degenerative disc diseases on the range of motion (ROM) of the human cervical spinal column using a validated finite-element model., Materials and Methods: The validated intact and healthy C2-T1 finite-element model simulated the cortical shell, cancellous core, posterior elements of the vertebrae, and spinal ligaments (longitudinal, capsular, spinous and ligamentum flava, and nucleus and annulus of the discs). Three different stages of the disc disease, that is, mild, moderate, and severe, were simulated at the C5-C6, C6-C7, and C5-C6-C7 discs, respectively, and they were termed as upper single level, lower single level, and bi-level (BL) models, respectively. The material properties and geometry of the disc(s) were altered to simulate the different stages of degeneration. The external mechanical loading was applied in the sagittal mode, via flexion-extension motions and the magnitude was 2.0 Nm for each mode. They were applied to each of the healthy and disc degeneration models, and for each of the three severities of degeneration. The ROM at adjacent and index levels was extracted and normalized with respect to the healthy (baseline) spine., Results: A nonuniform distribution in the ROM was found for different disc degeneration states, segmental levels, and flexion-extension loading modes. The specific results for each and level are reported in the results section of the paper., Conclusion: Closer follow-up times may be necessary in symptomatic patients with progressive disease, especially with BL involvements., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Craniovertebral Junction and Spine.)

Clinical methods for determining the severity of traumatic spinal cord injury (SCI) and long-term functional outcome in the acute setting are limited in their prognostic accuracy because of the heterogeneity of injury and dynamic injury progression. The aim of this study was to evaluate the time course and sensitivity of advanced magnetic resonance imaging (MRI) methods to neurological function after SCI in a rat contusion model. Rats received a graded contusion injury at T10 using a weight-drop apparatus. MRI consisted of morphological measures from T 2 -weighted imaging, quantitative T 2 imaging, and diffusion-weighted imaging (DWI) at 1, 30, and 90 days post-injury (dpi). The derived metrics were compared with neurological function assessed using weekly Basso, Beattie, and Bresnahan (BBB) locomotor scoring and return of reflexive micturition function. At the acute time point (1 dpi), diffusion metrics sensitive to axonal injury at the injury epicenter had the strongest correlation with time-matched BBB scores and best predicted 90-dpi BBB scores. At 30 dpi, axonal water fraction derived from DWI and T 2 values were both correlated with time-matched locomotor scores. At the chronic time point (90 dpi), cross-sectional area was most closely correlated to BBB. Overall, the results demonstrate differential sensitivity of MRI metrics at different time points after injury, but the metrics follow the expected pathology of acute axonal injury followed by continued degeneration and finally a terminal level of atrophy. Specificity of DWI in the acute setting may make it impactful as a prognostic tool while T 2 imaging provided the most information about injury severity in chronic injury.

Objective: William P. Van Wagenen pursued a research fellowship in Europe early in his career under the recommendation of Harvey Cushing. Later, Van Wagenen would be instrumental in the establishment of the William P. Van Wagenen Fellowship, a postgraduate fellowship for neurosurgeons from the AANS that requires study outside of a fellow's country of residency training with plans to return to academic practice., Methods: Since 1968, 54 Van Wagenen Fellowships have been awarded, sending 54 fellows from 31 institutions to 13 different countries. The academic productivity of fellows was studied to determine the academic "return on investment" of the fellowship., Results: Almost all fellows have spent some time in academic neurosurgery (94%), with the vast majority remaining in academics for their entire career (87%); 52% of fellows have received NIH funding, and 55% have been promoted to professor. The numbers are even more striking for the first half of Van Wagenen Fellows (who received the fellowship from its inception in 1968 to 1994) with at least 25 years of career development who remained in academics: 65% received NIH funding, 86% were promoted to professor, and 62% became chairs of academic departments. The Hirsch index of fellows, defined as h papers from an individual with at least h citations, is higher than the national mean and median values for academic neurosurgeons at every academic rank. Fellows have served on national committees and as AANS and CNS presidents and have given back financially to the Neurosurgery Research and Education Foundation (NREF) to fund future research activities of neurosurgical residents and young faculty., Conclusions: The Van Wagenen Fellowship will continue to provide young neurosurgeons with opportunities to pursue novel research and network with peers internationally and to motivate young neurosurgeons to transform neurosurgery. The legacy of Cushing and Van Wagenen continues today through the Van Wagenen Fellowship, a legacy that will only continue to grow.

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p  = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p  < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI.

Objectives: To establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM)., Design: A cross-sectional, observational study., Setting: Patients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity., Participants: 481 individuals suffering from DCM completed the online survey fully., Main Outcome Measures: Functional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain (Visual Analogue Scale) and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains (arm and hand function, walking, upper body/trunk function, sexual function, elimination of pain, sensation and bladder/bowel function) in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significance p <0.05., Results: Of 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment ( p <0.005) who prioritised walking, even among patients with lower pain scores., Conclusions: This is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs., Competing Interests: Competing interests: JSH reports being a Medical Advisor for Depuy Synthes and Ethicon, being an Educational Speaker at Globus Medical and research funding from AO Spine. MGF reports consulting for Fortuna Fix. MK declares a grant from the National Institute for Health Research, travel support from AO Spine and is founder of Myelopathy.org, the first charity for patients with cervical myelopathy. The remaining authors have nothing to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Diffusion tensor imaging (DTI), based on the property of preferential diffusion of water molecules in biological tissue, is seeing increasing clinical application in the pathologies of the central nervous system. Spinal cord injury (SCI) is one such area where the use of DTI allows for the evaluation of changes to microstructure of the spinal cord not detected on routine conventional magnetic resonance imaging. The insights obtained from pre-clinical models of SCI indicate correlation of quantitative DTI indices with histology and function, which points to the potential of DTI as a non-invasive, viable biomarker for integrity of white matter tracts in the spinal cord. In this review, we describe DTI alterations in the acute phase of SCI in both animal models and human subjects and explore the underlying pathophysiology behind these changes.

Objective: Cervical spondylotic myelopathy (CSM) is a common cause of spinal cord dysfunction. Recently, it has been shown that diffusion tensor imaging (DTI) may be a better biomarker than T2-weighted signal intensity (T2SI) on MRI for CSM. However, there is very little literature on a comparison between the quantitative measurements of DTI and T2SI in the CSM patient population to determine disease severity and recovery., Methods: A prospective analysis of 46 patients with both preoperative DTI and T2-weighted MRI was undertaken. Normalized T2SI (NT2SI), regardless of the presence or absence of T2SI at the level of maximum compression (LMC), was determined by calculating the T2SI at the LMC/T2SI at the level of the foramen magnum. Regression analysis was performed to determine the relationship of fractional anisotropy (FA), a quantitative measure derived from DTI, and NT2SI individually as well their combination with baseline preoperative modified Japanese Orthopaedic Association (mJOA) score and ∆mJOA score at the 3-, 6-, 12-, and 24-month follow-ups. Goodness-of-fit analysis was done using residual diagnostics. In addition, mixed-effects regression analysis was used to evaluate the impact of FA and NT2SI individually. A p value < 0.05 was selected to indicate statistical significance., Results: Regression analysis showed a significant positive correlation between FA at the LMC and preoperative mJOA score (p = 0.041) but a significant negative correlation between FA at the LMC and the ΔmJOA score at the 12-month follow-up (p = 0.010). All other relationships between FA at the LMC and the baseline preoperative mJOA score or ∆mJOA score at the 3-, 6-, and 24-month follow-ups were not statistically significant. For NT2SI and the combination of FA and NT2SI, no significant relationships with preoperative mJOA score or ∆mJOA at 3, 6, and 24 months were seen on regression analysis. However, there was a significant correlation of combined FA and NT2SI with ∆mJOA score at the 12-month follow-up. Mixed-effects regression revealed that FA measured at the LMC was the only significant predictor of ΔmJOA score (p = 0.03), whereas NT2SI and time were not. Goodness-of-fit analysis did not show any evidence of lack of fit., Conclusions: In this large prospective study of CSM patients, FA at LMC appears to be a better biomarker for determining long-term outcomes following surgery in CSM patients than NT2SI or the combination values at LMC.

OBJECTIVE The presence, extent, and distribution of intraventricular hemorrhage (IVH) have been associated with negative outcomes in aneurysmal subarachnoid hemorrhage (SAH). Several qualitative scores (Fisher grade, LeRoux score, and Graeb score) have been established for evaluating SAH and IVH. However, no study has assessed the radiodensity within the ventricular system in aneurysmal SAH patients with IVH. Prior studies have suggested that hemorrhage with a higher radiodensity, as measured by CT Hounsfield units, can cause more irritation to brain parenchyma. Therefore, the authors set out to investigate the relationship between the overall radiodensity of the ventricular system in aneurysmal SAH patients with IVH and their clinical outcome scores. METHODS The authors reviewed the records of 101 patients who were admitted to their institution with aneurysmal SAH and IVH between January 2011 and July 2015. The following data were collected: age, sex, Glasgow Coma Scale (GCS) score, Hunt and Hess grade, extent of SAH (none, thin, or thick/localized), aneurysm location, and Glasgow Outcome Scale (GOS) score. To evaluate the ventricular radiodensity, the initial head CT scan was loaded into OsiriX MD. The ventricular system was manually selected as the region of interest (ROI) through all pertinent axial slices. After this, an averaged ventricular radiodensity was calculated from the ROI by the software. GOS scores were dichotomized as 1-3 and 4-5 subgroups for analysis. RESULTS On univariate analysis, younger age, higher GCS score, lower Hunt and Hess grade, and lower ventricular radiodensity significantly correlated with better GOS scores (all p < 0.05). Subsequent multivariate analysis yielded age (OR 0.936, 95% CI 0.895-0.979), GCS score (OR 3.422, 95% CI 1.9-6.164), and ventricular density (OR 0.937, 95% CI 0.878-0.999) as significant independent predictors (p < 0.05). A receiver operating characteristic curve yielded 12.7 HU (area under the curve 0.625, p = 0.032, sensitivity = 0.591, specificity = 0.596) as threshold between GOS scores of 1-3 and 4-5. CONCLUSIONS This study suggests that the ventricular radiodensity in aneurysmal SAH patients with IVH, along with GCS score and age, may serve as a predictor of clinical outcome.

Chronic subdural hematoma (cSDH) is a common neurosurgical pathology associated with older age and complicated by antiplatelet/anticoagulant therapies. With improving medical care in an aging population, the incidence of cSDH will likely increase over the next 25 years, placing a burden on health care costs. Consequently, a simple and inexpensive treatment option is desirable. As such, we report a basic, but novel, technique to drain cSDH with an Integra Camino bolt. This technique was employed in two patients, where the significant resolution of cSDH and associated clinical symptoms were observed without complications., Competing Interests: There are no conflicts of interest.

Study Method: Systematic review (update)., Objective: Degenerative cervical myelopathy (DCM) is a degenerative spine disease and the most common cause of spinal cord dysfunction in adults worldwide. The objective of this study is to determine the natural history of DCM by updating the systematic review by Karadimas et al. The specific aims of this review were (1) to describe the natural history of DCM and (2) to determine potential risk factors of disease progression., Method: An updated search based on a previous protocol was conducted in PubMed and the Cochrane Collaboration library for studies published between November 2012 and February 15, 2015., Results: The updated search yielded 3 additional citations that met inclusion criteria and reported the incidence of spinal cord injury and severe disability in patients with DCM. Based on 2 retrospective cohort studies, the incidence rate of hospitalization for spinal cord injury is 13.9 per 1000 person-years in patients with cervical spondylotic myelopathy and 4.8 per 1000 person-years in patients with myelopathy secondary to ossification of the posterior longitudinal ligament (OPLL). In a third small prospective study, the risk of being wheelchair bound or bedridden was 66.7% in DCM patients with OPLL., Conclusion: The overall level of evidence for these estimated rates of hospitalization following spinal cord injury was rated as low., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The objective of this study is to develop guidelines that outline the appropriate type and timing of rehabilitation in patients with acute spinal cord injury (SCI)., Methods: A systematic review of the literature was conducted to address key questions related to rehabilitation in patients with acute SCI. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the type and timing of rehabilitation. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest., Results: Based on the findings from the systematic review, our recommendations were: (1) We suggest rehabilitation be offered to patients with acute spinal cord injury when they are medically stable and can tolerate required rehabilitation intensity (no included studies; expert opinion); (2) We suggest body weight-supported treadmill training as an option for ambulation training in addition to conventional overground walking, dependent on resource availability, context, and local expertise (low evidence); (3) We suggest that individuals with acute and subacute cervical SCI be offered functional electrical stimulation as an option to improve hand and upper extremity function (low evidence); and (4) Based on the absence of any clear benefit, we suggest not offering additional training in unsupported sitting beyond what is currently incorporated in standard rehabilitation (low evidence)., Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care, decreasing the heterogeneity of management strategies and encouraging clinicians to make evidence-informed decisions., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Network analysis based on graph theory depicts the brain as a complex network that allows inspection of overall brain connectivity pattern and calculation of quantifiable network metrics. To date, large-scale network analysis has not been applied to resting-state functional networks in complete spinal cord injury (SCI) patients. To characterize modular reorganization of whole brain into constituent nodes and compare network metrics between SCI and control subjects, fifteen subjects with chronic complete cervical SCI and 15 neurologically intact controls were scanned. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI). Correlation analysis was performed between every ROI pair to construct connectivity matrices and ROIs were categorized into distinct modules. Subsequently, local efficiency (LE) and global efficiency (GE) network metrics were calculated at incremental cost thresholds. The application of a modularity algorithm organized the whole-brain resting-state functional network of the SCI and the control subjects into nine and seven modules, respectively. The individual modules differed across groups in terms of the number and the composition of constituent nodes. LE demonstrated statistically significant decrease at multiple cost levels in SCI subjects. GE did not differ significantly between the two groups. The demonstration of modular architecture in both groups highlights the applicability of large-scale network analysis in studying complex brain networks. Comparing modules across groups revealed differences in number and membership of constituent nodes, indicating modular reorganization due to neural plasticity.

Introduction: Traumatic spinal subdural hematoma involving the retroclival region and upper cervical spine is a rare pathology. To our knowledge, there have only been 2 prior cases in an adult trauma patient. We describe a patient with preexisting Chiari 1 malformation, who recently sustained a unilateral type 1 occipital condyle fracture with associated disruption of the tectorial membrane and transverse ligament, which returned with a retroclival subdural hematoma extending down to C7, causing spinal cord compression and symptomatic obstructive hydrocephalus., Case Presentation: A 30-year-old female sustained a motor vehicle collision. Computed tomography C spine revealed a type I occipital condyle fracture. Magnetic resonance imaging C spine demonstrated disruption of the tectorial membrane and avulsion of the transverse ligament at its attachment to the left C1 tubercle; moreover, there was a Chiari 1 malformation. The patient was neurologically intact. A halo was recommended, but the patient opted for an aspen collar with close management. She was discharged but returned 3 days later with apneic episodes, along with bradycardia and hypertension. She was promptly intubated. Computed tomography head showed interval ventricular enlargement. Magnetic resonance imaging C spine revealed a new ventral hematoma spanning the retroclival region to C7, most pronounced at C2-C3. On examination, she opened her eyes to pain, her pupils were equal and reactive, and she withdrew in all extremities. An external ventricular drain was emergently placed. She underwent a suboccipital craniectomy, C1-3 laminectomies, and occiput-C4 instrumented fusion. The dura was significantly tense, and no epidural hematoma was observed during lateral exploration. Postoperatively, she woke up well, exhibiting a nonfocal neurologic examination. A diagnostic angiogram was negative. She was extubated uneventfully, and the external ventricular drain was weaned off in 4 days., Conclusion: Traumatic spinal subdural hematoma involving both the retroclival region and upper cervical spine can lead to bulbar signs and symptomatic obstructive hydrocephalus. There should be vigilance for this pathology in patients with high-energy craniocervical trauma. Disruption of the tectorial membrane and therapeutic anticoagulation may be risk factors. The clinical scenario can be complicated in the setting of a preexisting Chiari 1 malformation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI)., Methods: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest.", Results: The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) "We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI"; (2) "We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option"; and (3) "We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI.", Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome., Methods: A systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as "we recommend," whereas a weak recommendation is presented as "we suggest.", Results: Conclusions from the systematic review included (1) isolated studies reported statistically significant and clinically important improvements following early decompression at 6 months and following discharge from inpatient rehabilitation; (2) in one study on acute central cord syndrome without instability, a marginally significant improvement in total motor scores was reported at 6 and 12 months in patients managed with early versus late surgery; and (3) there were no significant differences in length of acute care/rehabilitation stay or in rates of complications between treatment groups. Our recommendations were: "We suggest that early surgery be considered as a treatment option in adult patients with traumatic central cord syndrome" and "We suggest that early surgery be offered as an option for adult acute SCI patients regardless of level." Quality of evidence for both recommendations was considered low., Conclusions: These guidelines should be implemented into clinical practice to improve outcomes in patients with acute SCI and central cord syndrome by promoting standardization of care, decreasing the heterogeneity of management strategies, and encouraging clinicians to make evidence-informed decisions., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The objective of this guideline is to outline the role of magnetic resonance imaging (MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury (SCI)., Methods: A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI. This review focused on longitudinal studies that controlled for baseline neurologic status. A multidisciplinary Guideline Development Group (GDG) used this information, their clinical expertise, and patient input to develop recommendations on the use of MRI for SCI patients. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest.", Results: Based on the limited available evidence and the clinical expertise of the GDG, our recommendations were: (1) "We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention, when feasible, to facilitate improved clinical decision-making" (quality of evidence, very low) and (2) "We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome" (quality of evidence, low)., Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Systematic review., Objectives: The primary objective of this systematic review was to define the change in impairment, disability, and pain following surgical intervention in patients with degenerative cervical myelopathy (DCM). Secondary objectives included to assess the impact of preoperative disease severity and duration of symptoms on outcomes and to summarize complications associated with surgery., Methods: A systematic literature search was conducted to identify prospective studies evaluating the effectiveness and safety of operative treatment in patients with DCM. Outcomes of interest were functional status, disability, pain, and complications. The quality of each study was evaluated using the Newcastle-Ottawa Scale, and the strength of the overall body of evidence was rated using guidelines outlined by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) Working Group., Results: Of the 385 retrieved citations, 32 met inclusion criteria and are summarized in this review. Based on our results, pooled standard mean differences showed a large effect for improvement in Japanese Orthopaedic Association or modified Japanese Orthopaedic Association score from baseline at short-, medium-, and long-term follow-up: 6 to 12 months (1.92; 95% confidence interval [CI] = 1.41 to 2.43), 13 to 36 months (1.40; 95% CI = 1.12 to 1.67), and ≥36 months (1.92; 95% CI = 1.14 to 2.69) (moderate evidence). Surgery also resulted in significant improvements in Nurick, Neck Disability Index, and Visual Analogue Scale scores (low to very low evidence). The cumulative incidence of complications was low (14.1%; 95% CI = 10.1% to 18.2%)., Conclusion: Surgical intervention for DCM results in significant improvements in functional impairment, disability, and pain and is associated with an acceptably low rate of complications., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The objective of this study is to develop evidence-based guidelines that recommend effective, safe and cost-effective thromboprophylaxis strategies in patients with spinal cord injury (SCI)., Methods: A systematic review of the literature was conducted to address key questions relating to thromboprophylaxis in SCI. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest.", Results: Based on conclusions from the systematic review and expert panel opinion, the following recommendations were developed: (1) "We suggest that anticoagulant thromboprophylaxis be offered routinely to reduce the risk of thromboembolic events in the acute period after SCI;" (2) "We suggest that anticoagulant thromboprophylaxis, consisting of either subcutaneous low-molecular-weight heparin or fixed, low-dose unfractionated heparin (UFH) be offered to reduce the risk of thromboembolic events in the acute period after SCI. Given the potential for increased bleeding events with the use of adjusted-dose UFH, we suggest against this option;" (3) "We suggest commencing anticoagulant thromboprophylaxis within the first 72 hours after injury, if possible, in order to minimize the risk of venous thromboembolic complications during the period of acute hospitalization.", Conclusions: These guidelines should be implemented into clinical practice in patients with SCI to promote standardization of care, decrease heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Systematic review., Objective: To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI)., Methods: An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI., Results: The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved outcomes; however, the quality of evidence was deemed very low due to selection bias. Seven studies reported MRI predictors of neurologic or functional outcomes. There was moderate-quality evidence that longer intramedullary hemorrhage (2 studies) and low-quality evidence that smaller spinal canal diameter at the location of maximal spinal cord compression and the presence of cord swelling are associated with poor neurologic recovery. There was moderate-quality evidence that clinical outcomes are not predicted by SCI lesion length and the presence of cord edema., Conclusions: Certain MRI characteristics appear to be predictive of outcomes in acute SCI, including length of intramedullary hemorrhage (moderate-quality evidence), canal diameter at maximal spinal cord compression (low-quality evidence), and spinal cord swelling (low-quality evidence). Other imaging features were either inconsistently (presence of hemorrhage, maximal canal compromise, and edema length) or not associated with outcomes. The paucity of literature highlights the need for well-designed prospective studies., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4.6-50 μM). This data suggests acid ceramidase as a novel drug target for adjuvant pediatric brain tumor therapies. Of these acid ceramidase inhibitors, carmofur has seen clinical use in Japan since 1981 for colorectal cancers and is a promising drug to undergo further animal studies and subsequently a clinical trial as a treatment for pediatric patients with brain tumors.

Background Diminishing volume of intracranial cerebrospinal fluid (CSF) in patients with space-occupying masses have been attributed to unfavorable outcome associated with reduction of cerebral perfusion pressure and subsequent brain ischemia. Objective The objective of this article is to employ a ratio of CSF volume to brain volume for longitudinal assessment of space-volume relationships in patients with extra-axial hematoma and to determine variability of the ratio among patients with different types and stages of hematoma. Patients and methods In our retrospective study, we reviewed 113 patients with surgical extra-axial hematomas. We included 28 patients (age 61.7 +/- 17.7 years; 19 males, nine females) with an acute epidural hematoma (EDH) ( n = 5) and subacute/chronic subdural hematoma (SDH) ( n = 23). We excluded 85 patients, in order, due to acute SDH ( n = 76), concurrent intraparenchymal pathology ( n = 6), and bilateral pathology ( n = 3). Noncontrast CT images of the head were obtained using a CT scanner (2004 GE LightSpeed VCT CT system, tube voltage 140 kVp, tube current 310 mA, 5 mm section thickness) preoperatively, postoperatively (3.8 ± 5.8 hours from surgery), and at follow-up clinic visit (48.2 ± 27.7 days after surgery). Each CT scan was loaded into an OsiriX (Pixmeo, Switzerland) workstation to segment pixels based on radiodensity properties measured in Hounsfield units (HU). Based on HU values from -30 to 100, brain, CSF spaces, vascular structures, hematoma, and/or postsurgical fluid were segregated from bony structures, and subsequently hematoma and/or postsurgical fluid were manually selected and removed from the images. The remaining images represented overall brain volume-containing only CSF spaces, vascular structures, and brain parenchyma. Thereafter, the ratio between the total number of voxels representing CSF volume (based on values between 0 and 15 HU) to the total number of voxels representing overall brain volume was calculated. Results CSF/brain volume ratio varied significantly during the course of the disease, being the lowest preoperatively, 0.051 ± 0.032; higher after surgical evacuation of hematoma, 0.067 ± 0.040; and highest at follow-up visit, 0.083 ± 0.040 ( p < 0.01). Using a repeated regression analysis, we found a significant association ( p < 0.01) of the ratio with age (odds ratio, 1.019; 95% CI, 1.009-1.029) and type of hematoma (odds ratio, 0.405; 95% CI, 0.303-0.540). Conclusion CSF/brain volume ratio calculated from CT images has potential to reflect dynamics of intracranial volume changes in patients with space-occupying mass.