Postoperative analgesic options after spine surgery: finding the optimal treatment strategies.

INTRODUCTION: Spine surgery is one of the most common types of surgeries performed in the United States; however, managing postoperative pain following spine surgery has proven to be challenging. Patients with spine pathologies have higher incidences of chronic pain and resultant opioid use and potential for tolerance. Implementing a multimodal plan for postoperative analgesia after spine surgery can lead to enhanced recovery and outcomes. AREAS COVERED: This review presents several options for analgesia following spine surgery with an emphasis on multimodal techniques to best aid this specific patient population. In addition to traditional therapeutics, such as acetaminophen, non-steroidal anti-inflammatory medications, and opioids, we discuss intrathecal morphine administration and emerging regional anesthesia techniques. EXPERT OPINION: Several adjuncts to improve analgesia following spine surgery are efficacious in the postoperative period. Intrathecal morphine provides sustained analgesia and can be instilled intraoperatively by the surgical team under direct visualization. Local anesthetics deposited under ultrasound guidance by an anesthesiologist trained in regional techniques also provide the opportunity for single injections or continuous analgesia via an indwelling catheter.

Diffuse midline glioma, H3K27-altered, of the conus medullaris presenting as acute urinary retention: illustrative case.

BACKGROUND: Diffuse midline glioma (DMG), H3K27-altered, is a rare, highly malignant central nervous system neoplasm that arises in midline structures. They are more commonly encountered in children and are rarely encountered in adults, usually in the thalamus or spinal cord. The presence of the H3K27 mutation in the H3F3A gene automatically classifies a tumor as World Health Organization grade IV. These tumors carry a grim prognosis, with an overall median survival of less than 1 year. OBSERVATIONS: The authors report the case of a 38-year-old male presenting with acute-onset urinary retention who was found to have an expansile, well-circumscribed mass involving the conus medullaris at the level of T12-L1. A T12-L1 laminectomy and tumor debulking were performed. Pathology revealed glial cells with astrocytic morphology among Rosenthal fibers, microvascular proliferation, and cellular atypia. The H3K27 mutation was confirmed. LESSONS: DMG, H3K27-altered, is a rarely encountered entity that can present in numerous midline structures. If localized to the conus medullaris, it may present as acute-onset urinary retention in a previously asymptomatic patient. Further investigation is needed to characterize its molecular and clinical features in adults to improve the management of those presenting with these tumors.

Subsidence after lateral lumbar interbody fusion using a 3D-printed porous titanium interbody cage: single-institution case series.

OBJECTIVE: Cage subsidence is a well-known phenomenon after lateral lumbar interbody fusion (LLIF), occurring in 10%-20% of cases. A 3D-printed porous titanium (pTi) cage has a stiffness that mimics the modulus of elasticity of native vertebrae, which reduces stress at the bone-hardware interface, lowering the risk of subsidence. In this study, the authors evaluated their institutional rate of subsidence and resultant reoperation in patients who underwent LLIF using a 3D-printed pTi interbody cage. METHODS: This is a retrospective case series of consecutive adult patients who underwent LLIF using pTi cages from 2018 to 2020. Demographic and clinical characteristics including age, sex, bone mineral density, smoking status, diabetes, steroid use, number of fusion levels, posterior instrumentation, and graft size were collected. The Marchi subsidence grade was determined at the time of last follow-up. Outcome measures of interest were subsidence and resultant reoperation. Univariable logistic regression analysis was performed to assess the extent to which clinical and operative characteristics were associated with Marchi grade I-III subsidence. Significance was assessed at p < 0.05. RESULTS: Fifty-five patients (38 with degenerative disc disease and 17 with adult spinal deformity) were treated with 97 pTi interbody cages with a mean follow-up of 18 months. The mean age was 63.6 ± 10.1 years, 60% of patients were female, and 36% of patients had osteopenia or osteoporosis. Patients most commonly underwent single-level LLIF (58.2%). Sixteen patients (29.1%) had posterior instrumentation. The subsidence grade distribution was as follows: 89 (92%) grade 0, 5 (5%) grade I, 2 (2%) grade II, and 1 (1%) grade III. No patients who were active or prior smokers and no patients with posterior instrumentation experienced graft subsidence. No clinical or operative characteristics were significantly associated with graft subsidence. One patient (1.8%) required reoperation because of subsidence. CONCLUSIONS: In this institutional case series, subsidence of pTi intervertebral cages after LLIF occurred in 8% of operated levels, 3% of which were grade II or III. Only 1 patient required reoperation. These reported rates are lower than those reported for polyetheretherketone implants. Further studies are necessary to compare the impact of these cage materials on subsidence after LLIF.

Computed Tomography Hounsfield Units as a Predictor of Reoperation and Graft Subsidence After Standalone and Multilevel Lateral Lumbar Interbody Fusion.

BACKGROUND: Standalone single and multilevel lateral lumbar interbody fusion (LLIF) have been increasingly applied to treat degenerative spinal conditions in a less invasive fashion. Graft subsidence following LLIF is a known complication and has been associated with poor bone mineral density (BMD). Previous research has demonstrated the utility of computed tomography (CT) Hounsfield units (HUs) as a surrogate for BMD. In the present study, we investigated the relationship between the CT HUs and subsidence and reoperation after standalone and multilevel LLIF. METHODS: A prospectively maintained single-institution database was retrospectively reviewed for LLIF patients from 2017 to 2020, including single and multilevel standalone cases with and without supplemental posterior fixation. Data on demographics, graft parameters, BMD determined by dual-energy x-ray absorptiometry, preoperative mean segmental CT HUs, and postoperative subsidence and reoperation were collected. We used 36-in. standing radiographs to measure the preoperative global sagittal alignment and disc height and subsidence at last follow-up. Subsidence was classified using the Marchi grading system corresponding to disc height loss: grade 0, 0%-24%; grade I, 25%-49%; grade II, 50%-74%; and grade III, 75%-100%. RESULTS: A total of 89 LLIF patients had met the study criteria, with a mean follow-up of 19.9 ± 13.9 months. Of the 54 patients who had undergone single-level LLIF, the mean segmental HUs were 152.0 ± 8.7 for 39 patients with grade 0 subsidence, 136.7 ± 10.4 for 9 with grade I subsidence, 133.9 ± 23.1 for 3 with grade II subsidence, and 119.9 ± 30.9 for 3 with grade III subsidence (P = 0.032). Of the 96 instrumented levels in the 35 patients who had undergone multilevel LLIF, 85, 9, 1, and 1 level had had grade 0, grade I, grade II, and grade III subsidence, with no differences in the HU levels. On multivariate logistic regression, increased CT HU levels were independently associated with a decreased risk of reoperation after both single-level and multilevel LLIF (odds ratio, 0.98; 95% confidence interval, 0.97-0.99; P = 0.044; and odds ratio, 0.97; 95% confidence interval, 0.94-0.99; P = 0.017, respectively). Overall, the BMD determined using dual-energy x-ray absorptiometry was not associated with graft subsidence or reoperation. Using a receiver operating characteristic curve to separate the patients who had and had not required reoperation, the threshold HU level determined for single-level and multilevel LLIF was 131.4 (sensitivity, 0.62; specificity 0.65) and 131.0 (sensitivity, 0.67; specificity, 0.63), respectively. CONCLUSIONS: Lower CT HUs were independently associated with an increased risk of graft subsidence after single-level LLIF. In addition, lower CT HUs significantly increased the risk of reoperation after both single and multilevel LLIF with a critical threshold of 131 HUs. The determination of the preoperative CT HUs might provide a more robust gauge of local bone quality and the likelihood of graft subsidence requiring reoperation following LLIF than overall BMD.

The Effect of Sacroiliac Fusion and Pelvic Fixation on Rod Strain in Thoracolumbar Fusion Constructs: A Biomechanical Investigation.

STUDY DESIGN: In vitro biomechanical study. OBJECTIVE: Investigate effects of sacroiliac joint (SIJ) fusion and iliac fixation on distal rod strain in thoracolumbar fusions. SUMMARY OF BACKGROUND DATA: Instrument failure is a multifactorial, challenging problem frequently encountered by spinal surgeons. Increased rod strain may lead to instrumentation failure and rod fracture. METHODS: Seven fresh frozen human cadaveric specimens (T9-pelvis) used. Six operative constructs tested to investigate changes in rod strain at L5-S1 and S1-Ilium rods, posterior pedicle screws/rods from T10-S1 (PS), PS + bilateral iliac screw fixation, PS + unilateral iliac screw fixation (UIS), PS+UIS+3 unilateral SIJ screws, PS + 3 unilateral SIJ screws, and PS +6 bilateral SIJ screws. Uniaxial strain gauges were used to measure surface strain of rods during flexion-extension. RESULTS: In flexion-extension, bilateral iliac screws added significant strain to L5-S1 compared with long fusion constructs ending at S1 (PS) (P < 0.05). Unilateral iliac fixation exhibited highest strain to L5-S1 ipsilateral rod, was significantly higher compared with bilateral iliac fixation and PS construct. Unilateral and bilateral SIJ fusion did not significantly change L5-S1 rod strain compared with PS. When measuring S1-Ilium rod strain, unilateral pelvic fixation had highest reported rod strain, approached significance compared with bilateral iliac screws (P = 0.054). Addition of contralateral SIJ fusion did not affect rod strain at S1-ilium on side with unilateral fixation. CONCLUSION: Results showed additional fixation below S1 to pelvis added significant rod strain. Unilateral pelvic screws had highest rod strain; SIJ fusion did not affect rod strain. Findings can help guide surgeons when associated risk of rod failure is a consideration.Level of Evidence: N/A.

Radiculopathy with concomitant sacroiliac dysfunction and lumbosacral degenerative disease: illustrative case.

BACKGROUND: The sacroiliac joint (SIJ) is an important cause of low back pain and referred leg pain (RLP). Pain from SIJ dysfunction may occur in isolation or may result from a combination with lumbosacral area-mediated pain. SIJ fusion is one treatment modality for medically refractory symptoms and may also have a role in the treatment of RLP. OBSERVATIONS: The authors present a challenging case of concomitant lumbosacral degenerative disease and SIJ dysfunction in a patient with radiculopathy. They provide clinical characteristics and imaging findings and discuss difficulties in dealing with the intersection of these two distinct diagnoses. In addition, the authors offer a review of the relevant literature, elucidating the role of SIJ dysfunction in causing radicular lower extremity pain, the relationship to concomitant lumbosacral degenerative disease, and outcome data for SIJ fusion as it relates to RLP. LESSONS: With increasing numbers of patients undergoing spinal instrumentation in the setting of degenerative lumbosacral arthritis, as well as randomized controlled trial data demonstrating the efficacy of SIJ fusion for medically refractory SIJ dysfunction, it is important to recognize the challenges in understanding how both of these patient groups may present with radiculopathy. Failure to do so may result in incorrect patient selection, poor outcomes, and increased morbidity for at-risk patients.

The Effect of Elevated Mean Arterial Blood Pressure in Cervical Traumatic Spinal Cord Injury with Hemorrhagic Contusion.

OBJECTIVE: Hemorrhagic contusion in cervical spinal cord injury (CSCI) is poorly understood. We investigated hemorrhagic expansion in patients with CSCI with an assigned elevated mean arterial pressure (MAP) goal of >85 mm Hg. The change in hemorrhagic area and long-term follow-up data ≥6 months after injury was studied. METHODS: A retrospective review was performed from 2005 to 2016 to identify patients with motor complete CSCI with 2 cervical magnetic resonance imaging (MRI) scans within 7 days of injury showing evidence of hemorrhagic contusion and assigned a MAP goal of >85 mm Hg for 7 days. T2-weighted MRI was used to calculate the hemorrhagic surface area in the sagittal plane. A calculated MAP was recorded for each blood pressure measure between the initial and follow-up MRI scans. The American Spinal Injury Association impairment scale (AIS) and American Spinal Injury Association motor scores were recorded at the final follow-up examination at ≥6 months. RESULTS: A total of 193 patients were identified. The mean change in the hemorrhagic area was 24.0 mm2. Of the 193 patients, the AIS grade was A for 114 and B for 79 patients. Multiple logistic regression analysis demonstrated that the MAP and systolic blood pressure were nonsignificant predictors of hemorrhagic contusion expansion. An increased hemorrhagic contusion area on the follow-up MRI scan was associated with a reduced odds of AIS improvement of ≥1 and ≥2 points (odds ratio, 0.97; 95% confidence interval, 0.87-0.97; P = 0.028; and odds ratio, 0.92; 95% confidence interval, 0.99-1.13; P = 0.008, respectively) at the final ≥6-month follow-up examination. CONCLUSION: The present study investigated the clinical safety of elevated MAP goals for patients with CSCI and hemorrhagic contusion. Elevated MAPs did not significantly increase the risk of hemorrhagic expansion in those with CSCI. We have also reported the use of hemorrhagic contusion size as a potential radiographic biomarker for neurological outcomes.

Open Reduction and Decompression of Atlantoaxial Subluxation with Basilar Impression Due to Grisel Syndrome Using the Cervical Management Base Unit.

BACKGROUND: Intraoperative manipulation of the craniocervical junction with the Cervical Management Base Unit (CMBU) has been used as an adjunct for achieving optimal anatomic alignment during instrumented fusion procedures in a variety of disease settings. Here, we present our experience using the CMBU as a supplement to achieving a successful reduction and fixation of a reducible craniocervical subluxation with associated basilar impression/medullary compression in the setting of Grisel syndrome. CASE DESCRIPTION: Under fluoroscopy and neuromonitoring guidance, the elevator and axial translation mechanisms of the CMBU safely allowed for presurgical assessment of reducibility and facilitated complete reduction of the deformity with restitution of a normal atlantodental interval, spinolaminar line, and clivoaxial angle. Magnetic resonance imaging acquired 1 month after surgery and antibiotic therapy showed resolution of a large epidural abscess in the region of the dens and no evidence of residual neural impingement. Upright plain films at 9 months showed maintenance of the desired craniocervical alignment. CONCLUSIONS: Intraoperative manipulation of the craniocervical junction using the CMBU, when implemented under fluoroscopy and neuromonitoring, can safely facilitate an enduring anatomic correction of craniocervical deformity in the setting of Grisel syndrome. The dynamic utility of the CMBU for translation of the head and neck obviated the need to apply forces directly to hardware-bone interfaces, and its utility may extend to craniocervical disorders of other etiologies, especially those of a reducible nature and in the setting of poor bone quality and joint laxity.

Efficacy of Ultra-Early (< 12 h), Early (12-24 h), and Late (>24-138.5 h) Surgery with Magnetic Resonance Imaging-Confirmed Decompression in American Spinal Injury Association Impairment Scale Grades A, B, and C Cervical Spinal Cord Injury.

In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12-24 h), and 15 underwent decompressive surgery late (> 24-138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients (p = 0.009) and those with fracture dislocations (p = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score (p = 0.0004) and pre-operative IMLL (p = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively (p = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862-0.957; p < 0.001). We conclude that in patients with post-operative MRI confirmation of complete decompression following cervical TSCI, pre-operative IMLL, not the timing of surgery, determines long-term neurological outcome.

A biomechanical investigation of the sacroiliac joint in the setting of lumbosacral fusion: impact of pelvic fixation versus sacroiliac joint fixation.

OBJECTIVE: The sacroiliac joint (SIJ) is a known source of low-back pain. Randomized clinical trials support sacroiliac fusion over conservative management for SIJ dysfunction. Clinical studies suggest that SIJ degeneration occurs in the setting of lumbosacral fusions. However, there are few biomechanical studies to provide a good understanding of the effect of lumbosacral fusion on the SIJ. In the present study, researchers performed a biomechanical investigation to discern the effect of pelvic versus SIJ fixation on the SIJ in lumbosacral fusion. METHODS: Seven fresh-frozen human cadaveric specimens were used. There was one intact specimen and six operative constructs: 1) posterior pedicle screws and rods from T10 to S1 (PS); 2) PS + bilateral iliac screw fixation (BIS); 3) PS + unilateral iliac screw fixation (UIS); 4) PS + UIS + 3 contralateral unilateral SIJ screws (UIS + 3SIJ); 5) PS + 3 unilateral SIJ screws (3SIJ); and 6) PS + 6 bilateral SIJ screws (6SIJ). A custom-built 6 degrees-of-freedom apparatus was used to simulate three bending modes: flexion-extension (FE), lateral bending (LB), and axial rotation (AR). Range of motion (ROM) was recorded at L5-S1 and the SIJ. RESULTS: All six operative constructs had significantly reduced ROM at L5-S1 in all three bending modes compared to that of the intact specimen (p < 0.05). In the FE mode, the BIS construct had a significant reduction in L5-S1 ROM as compared to the other five constructs (p < 0.05). SIJ ROM was greatest in the FE mode compared to LB and AR. Although the FE mode did not show any statistically significant differences in SIJ ROM across the constructs, there were appreciable differences. The PS construct had the highest SIJ ROM. The BIS construct reduced bilateral SIJ ROM by 44% in comparison to the PS construct. The BIS and 6SIJ constructs showed reductions in SIJ ROM nearly equal to those of the PS construct. UIS and 3SIJ showed an appreciable reduction in unfused SIJ ROM compared to PS. CONCLUSIONS: This investigation demonstrated the effects of various fusion constructs using pelvic and sacroiliac fixation in lumbosacral fusion. This study adds biomechanical evidence of adjacent segment stress in the SIJ in fusion constructs extending to S1. Unilateral pelvic fixation, or SIJ fusion, led to an appreciable but nonsignificant reduction in the ROM of the unfused contralateral SIJ. Bilateral pelvic fixation showed the greatest significant reduction of movement at L5-S1 and was equivalent to bilateral sacroiliac fusion in reducing SIJ motion.

AOSpine Subaxial Cervical Spine Injury Classification System: The Relationship Between Injury Morphology, Admission Injury Severity, and Long-Term Neurologic Outcome.

OBJECTIVE: The AOSpine Subaxial Cervical Spine Injury Classification System was introduced to improve communication, clinical management, and research. Here, the system was studied in relation to injury severity along with admission and long term neurologic follow-up. METHODS: A retrospective study was performed in subaxial cervical spine injury patients. Morphology was classified using the AOSpine Subaxial Cervical Spine Injury Classification System. Six major morphology subtypes were selected for analysis. The American Spinal Injury Association (ASIA) motor and Abbreviated Injury Severity (AIS) scores were recorded at admission and at follow-up >6 months. Admission intramedullary lesion length (IMLL) on MRI was recorded. RESULTS: In all, 82 patients met criteria for analysis. The mean follow-up time was 11 months (range, 6-33 months). The were 36 patients with morphology subtypes A0, 4 with A1/A2, 9 with A3/A4, 8 with B2, 11 with B3, and 14 with C. The A1/2 subtype had the least severe injuries on admission. The C and A3/A4 subtypes had the most severe injuries. The subtype C had the lowest ASIA Motor Score (AMS) and second highest percentage of complete injuries. A3/A4 patients had the highest percentage of complete injuries on admission. At follow-up, A3/A4 patients had the lowest AMS, and 33% of patients continued to have complete injuries. C subtype injuries all converted to AIS incomplete injuries on follow-up (P = 0.04). IMLL was found to be significantly different compared across multiple morphologic subtypes. Surgical management for each morphology subtype was reported. CONCLUSION: The AOSpine Subaxial Cervical Spine Injury Classification System successfully associated injury morphology with IMLL along with admission and long-term neurologic function and recovery.

Thoracic Discectomy Through a Unilateral Transpedicular or Costotransversectomy Approach With Intraoperative Ultrasound Guidance.

BACKGROUND: The disc location, extent of calcification, limited visualization of the ventral cord, and tenuous blood supply to the thoracic spinal cord pose unique technical challenges when surgically treating thoracic disc herniation. OBJECTIVE: To report our initial experience with a series of cases in which intraoperative ultrasound image guidance was used for thoracic discectomy through a unilateral transpedicular or costotransversectomy approach. METHODS: Five patients (n = 5) underwent a transpedicular approach and five (n = 5) underwent costotransversectomy for thoracic discectomy. Pre- and postoperative clinical records, operative reports, disc location/calcification, and complications were reviewed. RESULTS: There were 6 (n = 6) males and 4 (n = 4) females with an average age of 54 yr (range: 33-74). All patients had symptoms attributable to a single-level of thoracic disc herniation. Discs were classified as central (n = 5) and paracentral (n = 5). Preoperative CT and/or intraoperative visualization demonstrated calcified disc material in 6 (n = 6) patients. Final outcomes data at last follow-up was available for 9 of 10 patients. Eight of these nine patients experienced a return to normal baseline functional status. Postoperative imaging confirmed that no wrong-level surgeries were performed. The mean length of follow-up was 20.4 wk (range 4-48). CONCLUSION: Thoracic discectomy with ultrasound visualization via a unilateral transpedicular or costotransversectomy approach is safe and effective for treatment of central and paracentral calcified disc herniations. This tool improves the safety profile of thoracic discectomy and allows for treatment of thoracic discs through less invasive approaches.

Extent of Spinal Cord Decompression in Motor Complete (American Spinal Injury Association Impairment Scale Grades A and B) Traumatic Spinal Cord Injury Patients: Post-Operative Magnetic Resonance Imaging Analysis of Standard Operative Approaches.

Although decompressive surgery following traumatic spinal cord injury (TSCI) is recommended, adequate surgical decompression is rarely verified via imaging. We utilized magnetic resonance imaging (MRI) to analyze the rate of spinal cord decompression after surgery. Pre-operative (within 8 h of injury) and post-operative (within 48 h of injury) MRI images of 184 motor complete patients (American Spinal Injury Association Impairment Scale [AIS] grade A = 119, AIS grade B = 65) were reviewed to verify spinal cord decompression. Decompression was defined as the presence of a patent subarachnoid space around a swollen spinal cord. Of the 184 patients, 100 (54.3%) underwent anterior cervical discectomy and fusion (ACDF), and 53 of them also underwent laminectomy. Of the 184 patients, 55 (29.9%) underwent anterior cervical corpectomy and fusion (ACCF), with (26 patients) or without (29 patients) laminectomy. Twenty-nine patients (16%) underwent stand-alone laminectomy. Decompression was verified in 121 patients (66%). The rates of decompression in patients who underwent ACDF and ACCF without laminectomy were 46.8% and 58.6%, respectively. Among these patients, performing a laminectomy increased the rate of decompression (72% and 73.1% of patients, respectively). Twenty-five of 29 (86.2%) patients who underwent a stand-alone laminectomy were found to be successfully decompressed. The rates of decompression among patients who underwent laminectomy at one, two, three, four, or five levels were 58.3%, 68%, 78%, 80%, and 100%, respectively (p < 0.001). In multi-variate logistic regression analysis, only laminectomy was significantly associated with successful decompression (odds ratio 4.85; 95% confidence interval 2.2-10.6; p < 0.001). In motor complete TSCI patients, performing a laminectomy significantly increased the rate of successful spinal cord decompression, independent of whether anterior surgery was performed.

Bullough's bump: unusual protuberant fibro-osseous tumor of the temporal bone. Case report.

Scalp and calvarial masses are common in children and the differential diagnosis is broad. The authors recently cared for a child with an unusual fibro-osseous lesion of the temporal bone that has previously not been described in the pediatric neurosurgery literature. A 10-year-old girl presented with a firm, slowly enlarging protuberant mass arising from the squamous suture of the temporal bone without intracranial extension. The mass was removed en bloc through a temporal craniectomy and cranioplasty was performed. The patient had a smooth postoperative course. Histological examination showed multiple oval osseous islands dispersed throughout a bland fibrous stroma. The pathological diagnosis was "Bullough's bump," a rare, benign fibro-osseous neoplasm first described in 1999, and only 8 reported cases appear in the literature. Here the authors report the first case of Bullough's bump in a child.

The effect of working memory capacity on conflict monitoring.

The conflict adaptation effect, a reduced interference effect upon the detection of a conflict signal (e.g., following an incongruent trial), has been interpreted as evidence for active regulation of top-down cognitive control. We hypothesized that the extent of conflict adaptation should be related to individuals' working memory capacity (WMC), which has been repeatedly demonstrated to reflect the level of cognitive control. Using the Simon task, in Experiment 1, we quantified the conflict adaptation ratio (CAR) transiently as the ratio of the conflict effect following an incongruent trial to the conflict effect following a congruent trial, controlling for the reaction time that often correlates with WMC. We observed that the CAR varied from highly negative with low WMC scores to near-zero with high WMC scores. This result suggests that high WMC individuals, when detecting conflict, adjust the level of cognitive control optimally so that their performance is less susceptible to the presence of a distractor. In Experiment 2, we quantified the CAR in a sustained manner as the ratio of the conflict effect from predominantly incongruent blocks to the conflict effect from predominantly congruent blocks. Again, the CAR varied from negative to zero as WMC increased. These results suggest that WMC may reflect, in addition to the ability to maintain a level of control, the ability to adjust the level of control appropriately to the contextual demands.

CNTF receptor subunit α as a marker for glioma tumor-initiating cells and tumor grade: laboratory investigation.

OBJECT: Tumor-initiating cells are uniquely resilient to current treatment modalities and play an important role in tumor resistance and recurrence. The lack of specific tumor-initiating cell markers to identify and target these cells presents a major obstacle to effective directed therapy. METHODS: To identify tumor-initiating cell markers in primary brain tumors, the authors compared the proteomes of glioma tumor-initiating cells to their differentiated progeny using a novel, nongel/shotgun-based, multidimensional liquid-chromatography protein separation technique. An in vivo xenograft model was used to demonstrate the tumorigenic and stem cell properties of these cells. Western blot and immunofluorescence analyses were used to confirm findings of upregulated ciliary neurotrophic factor receptor subunit-α (CNTFRα) in undifferentiated tumor-initiating cells and gliomas of increasing tumor grade. Sequencing of the CNTFRα coding regions was performed for mutation analysis. Finally, antibody-dependent cell-mediated cytotoxicity was used to establish the role of CNTFRα as a potential immunotherapeutic target. RESULTS: Ciliary neurotrophic factor receptor subunit-α expression was increased in tumor-initiating cells and was decreased in the cells' differentiated progeny, and expression levels increased with glioma grade. Mutations of CNTFRα are not common in gliomas. Functional studies using CNTF treatment in glioma tumor-initiating cells showed induction of differentiation through the CNTFRα pathway. Treatment with anti-CNTFRα antibody resulted in increased antibody-dependent cell-mediated cytotoxicity in CNTFRα expressing DAOY cells but not in cell lines that lack CNTFRα. CONCLUSIONS: These data indicate that CNTFRα plays a role in the formation or maintenance of tumor-initiating cells in gliomas, is a marker that correlates with histological grade, may underlie treatment resistance in some cases, and is a potential therapeutic target.

MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells.

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis.

The effect of a PP2A inhibitor on the nuclear receptor corepressor pathway in glioma.

OBJECT: Nuclear receptor corepressor (N-CoR) forms a complex that maintains neural stem cells in an undifferentiated state through transcriptional repression. Recently, it has been shown that N-CoR is overexpressed in glioblastoma multiforme (GBM) tumor stem cells and has a putative role in maintaining these cells in an undifferentiated immortal state. To determine the effects of disruption of N-CoR complex function by serine/threonine protein phosphatase 2A (PP2A) inhibition on GBM tumor cell differentiation and proliferation, the authors developed and investigated a competitive small molecule inhibitor (LB1) of PP2A in GBM. METHODS: The authors investigated the effects of LB1 on GBM proliferation and molecular differentiation pathways using in vitro and in vivo studies. RESULTS: The LB1 inhibited PP2A, leading to increased levels of phosphorylated Akt kinase and decreased NCoR expression, as well as dose-dependent antiproliferative activity in cultured U87 and U251 malignant glioma cells (dose range 1-10 microM). Systemic LB1 treatment (1.5 mg/kg/day for 21 days) had significant tumor antiproliferative effects in mice harboring U87 glioma xenografts (73% mean reduction in tumor volume compared with controls; p < 0.001). Moreover, a reduction in PP2A expression and activity after LB1 treatment in vivo correlated with increased Akt phosphorylation, reduced nuclear N-CoR expression and N-CoR cytoplasmic translocation, and increased accumulation of acetylated core histones, which coincided with the appearance of glial fibrillary acidic protein-expressing tumor cells. CONCLUSIONS: These findings indicate that PP2A inhibition effectively disrupts N-CoR complex function/expression and leads to cytoplasmic translocation of N-CoR with subsequent tumor cell differentiation and/or death. Therapeutic paradigms that target N-CoR function in the cancer stem cell component of malignant gliomas may have treatment utility.

Identification of a novel proliferation-related protein, WHSC1 4a, in human gliomas.

Dynamic changes in the expression of multiple genes appear to be common features that distinguish transformed cells from their normal counterparts. We compared the proteomic profiles of four glioblastoma multiforme (GBM) tissue samples and four normal brain cortex samples to examine the molecular basis of gliomagenesis. Trypsin-digested protein samples were separated by capillary isoelectric focusing with nano-reversed-phase liquid chromatography and were profiled by mass spectrometric sequencing. Wolf-Hirschhorn syndrome candidate 1 (WHSC1), along with 103 other proteins, was found only in the GBM proteomes. Western blot and immunohistochemistry verified our proteomic findings and demonstrated that 30-kDa WHSC1 expression increases with ascending tumor proliferation activity. RNA interference could suppress glioma cell growth by blocking WHSC1 expression. Our novel findings encourage the application of proteomic techniques in cancer research.