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Markus M. Luedi, Sanjay K. Singh, Jennifer C. Mosley, Islam S. A. Hassan, Masumeh Hatami, Joy Gumin, Lukas Andereggen, Erik P. Sulman, Frederick F. Lang, Frank Stueber, Gregory N. Fuller, Rivka R. Colen and Pascal O. Zinn

OBJECTIVE

Dexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug’s impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug’s impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort.

METHODS

Expression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520).

RESULTS

The mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature.

CONCLUSIONS

The authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients’ prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

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Hidehisa Nishi, Akira Ishii, Ichiro Nakahara, Shoji Matsumoto, Nobutake Sadamasa, Yasutoshi Kai, Ryota Ishibashi, Michio Yamamoto, Satoshi Morita and Izumi Nagata

OBJECTIVE

The clinical outcomes of a direct aspiration first-pass technique (ADAPT) and stent retriever (SR) have been reported to be similar in several observational studies. In this study, procedural and clinical outcomes with ADAPT and SR for the treatment of acute ischemic stroke with large artery occlusion were compared in different time periods.

METHODS

In each specific time period, SR and ADAPT were used as the first-line treatment approach for acute ischemic stroke patients with large artery occlusion at the authors’ institution. Baseline characteristics, procedural variables, and functional outcome at 90 days were compared between patients treated with SR and those treated with ADAPT. These 2 groups were divided into 3 sequential subgroups to assess the learning curve effects of the endovascular team and individual operators on the procedural variables of each treatment strategy.

RESULTS

Overall, 89 patients were treated. In the SR group, the recanalization rate was higher (84% vs 65%; p = 0.01) and the procedure time was shorter than in the ADAPT group (median 42 minutes vs 76 minutes, p = 0.04). On the subgroup analysis of the learning curve, the SR group showed more rapid improvement in procedure time than the ADAPT group (p = 0.01 for the team; p < 0.01 for individual operators).

CONCLUSIONS

In this initial experience, a higher recanalization rate and shorter procedure time were achieved with SR than with ADAPT. A high recanalization rate with SR was possible with relatively less clinical experience, whereas procedure time dramatically decreased with experience. These observed effects on the learning curve might be useful when choosing the method for initial endovascular treatment of acute ischemic stroke at relatively small stroke centers.

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Kristy Tan, Avital Meiri, Wenzhu B. Mowrey, Rick Abbott, James T. Goodrich, Adam L. Sandler, Asif K. Suri, Michael L. Lipton and Mark E. Wagshul

OBJECTIVE

The object of this study was to use diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to characterize the long-term effects of hydrocephalus and shunting on white matter integrity and to investigate the relationship of ventricular size and alterations in white matter integrity with headache and quality-of-life outcome measures.

METHODS

Patients with shunt-treated hydrocephalus and age- and sex-matched healthy controls were recruited into the study and underwent anatomical and DTI imaging on a 3-T MRI scanner. All patients were clinically stable, had undergone CSF shunt placement before 2 years of age, and had a documented history of complaints of headaches. Outcome was scored based on the Headache Disability Inventory and the Hydrocephalus Outcome Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial, radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the corpus callosum and internal capsule with manual region-of-interest delineation and in other regions with TBSS. Paired t-tests, corrected with a 5% false discovery rate, were used to identify regions with significant differences between patients and controls. Within the patient group, linear regression models were used to investigate the relationship between FA or ventricular volume and outcome, as well as the effect of shunt-related covariates.

RESULTS

Twenty-one hydrocephalus patients and 21 matched controls completed the study, and their data were used in the final analysis. The authors found significantly lower FA for patients than for controls in 20 of the 48 regions, mostly posterior white matter structures, in periventricular as well as more distal tracts. Of these 20 regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3 showed decreased AD. No areas of increased FA were observed. Higher FA in specific periventricular white matter tracts, tending toward FA in controls, was associated with increased ventricular size, as well as improved clinical outcome.

CONCLUSIONS

The study shows that TBSS-based DTI is a sensitive technique for elucidating changes in white matter structures due to hydrocephalus and chronic CSF shunting and provides preliminary evidence that DTI may be a valuable tool for tailoring shunt procedures to monitor ventricular size following shunting and achieve optimal outcome, as well as for guiding the development of alternate therapies for hydrocephalus.

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David H. Shin, Kristopher G. Hooten, Brian D. Sindelar, Brian M. Corliss, William R. Y. Carlton Jr., Christopher P. Carroll, Jeffrey M. Tomlin and W. Christopher Fox

Military neurosurgery has played an integral role in the development and innovation of neurosurgery and neurocritical care in treating battlefield injuries. It is of paramount importance to continue to train and prepare the next generation of military neurosurgeons. For the Army, this is currently primarily achieved through the military neurosurgery residency at the National Capital Consortium and through full-time out-service positions at the Veterans Affairs–Department of Defense partnerships with the University of Florida, the University of Texas–San Antonio, and Baylor University. The authors describe the application process for military neurosurgery residency and highlight the training imparted to residents in a busy academic and level I trauma center at the University of Florida, with a focus on how case variety and volume at this particular civilian-partnered institution produces neurosurgeons who are prepared for the complexities of the battlefield. Further emphasis is also placed on collaboration for research as well as continuing education to maintain the skills of nondeployed neurosurgeons. With ongoing uncertainty regarding future conflict, it is critical to preserve and expand these civilian-military partnerships to maintain a standard level of readiness in order to face the unknown with the confidence befitting a military neurosurgeon.

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Ziev B. Moses, John H. Chi and Ram V. S. R. Chavali

The authors report on a 47-year-old woman with a symptomatic thoracic spinal arachnoid cyst (SAC) who underwent a novel procedure that involves direct puncture of the SAC to visualize, diagnose, and potentially treat these rare spinal lesions. The method described utilizes 3D fluoroscopy to gain access to the SAC, followed by injection of myelographic contrast into the cyst. A characteristic “jellyfish sign” was observed that represents the containment of the contrast within the superior aspect of the cyst and a clear block of cranial flow of contrast, resulting in an undulating pattern of movement of contrast within the cyst. Following balloon fenestration of the cyst, unimpeded flow of contrast was visualized cranially throughout the thoracic subarachnoid space. The patient was discharged the following day in good condition, and subsequently experienced 1 year free from symptoms. This is the first reported case of a successful direct puncture of an SAC with balloon fenestration, and the first noted real-time fluoroscopic “behavior” of CSF within an arachnoid cyst.

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Krzysztof Zapałowicz and Maciej Radek

OBJECTIVE

The objective of the present study was to determine experimentally the distribution of lesions caused in the cadaveric brachial plexus (BP) by excessive stretching. The authors attempted to delineate the correlation between the direction of stretching and sites of lesions.

METHODS

Fifteen specimens (each comprised the spinal segment C4–T2 with 2 BPs) were harvested from adult cadavers. Each BP was stretched in a mechanical testing machine at a constant speed of 200 mm/min. Specimens were divided into 3 groups: in group A the BPs were stretched caudally at a 45° angle to the spinal midline; in group B they were stretched perpendicularly to the spinal midline; and in group C the stretching was caudally parallel to the midline. Lesions of each BP were identified and analyzed. A graph of load against dislocation was registered when stretching to delineate the maximal force (Fmax), defined as the maximum load at which BP failure occurs.

RESULTS

Based on macroscopic examination, 140 sites of mechanical damage were identified in 30 BPs. Preganglionic injuries (63.6% of lesions), defined as avulsions of the spinal ganglia with their rootlets, were found in 89 spinal nerves. In group B—in which specimens were stretched perpendicularly to the spinal segment—preganglionic injuries were significantly more frequent (41 avulsed spinal nerves) than in groups A and C (21 and 27 avulsed spinal nerves, respectively). Postganglionic lesions equivalent to neurotmesis were found in 51 sites (36.4% of all lesions) along spinal nerves, trunks, divisions, and cords. Postganglionic lesions in group B were much less frequent (8) as compared with groups A and C (24 and 19, respectively).

CONCLUSIONS

Predominance of preganglionic lesions suggests that attachments of the BP to the spine are more susceptible to traction than postganglionic elements. Preganglionic lesions were mainly produced in C7, C8, and T1 spinal nerves, suggesting their weaker attachment to the spine than in the case of C5 and C6 nerves. Preganglionic lesions were highly correlated with a traction perpendicular to the spine, whereas postganglionic lesions were provoked mainly by traction directed at 45° caudally or by means of caudal traction parallel to the midline. This discrepancy implies a relationship between mechanical resistance of pre- and postganglionic elements of the BP and the vector of force.

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Benjamin F. Mundell, Marcus J. Gates, Panagiotis Kerezoudis, Mohammed Ali Alvi, Brett A. Freedman, Ahmad Nassr, Samuel F. Hohmann and Mohamad Bydon

OBJECTIVE

From 1994 to 2006 outpatient spinal surgery increased 5-fold. The perceived cost savings with outcomes comparable to or better than those achieved with inpatient admission for the same procedures are desirable in an era where health expenditures are scrutinized. The increase in outpatient spine surgery is also driven by the proliferation of ambulatory surgery centers. In this study, the authors hypothesized that the total savings in outpatient spine surgery is largely driven by patient selection and biases toward healthier patients.

METHODS

A meta-analysis assessed patient selection factors and outcomes associated with outpatient spine procedures. Pooled odds ratios and mean differences were calculated using a Bayesian random-effects model. The authors extended this analysis in a novel way by using the results of the meta-analysis to examine cost data from an administrative database of academically affiliated hospitals. A Bayesian approach with priors informed by the meta-analysis was used to compare costs for inpatient and outpatient performance of anterior cervical discectomy and fusion (ACDF) and lumbar laminectomy.

RESULTS

Sixteen studies with a total of 370,195 patients met the inclusion criteria. Outpatient procedures were associated with younger patient age (mean difference [MD] −2.34, 95% credible interval [CrI] −4.39 to −0.34) and no diabetes diagnosis (odds ratio [OR] 0.78, 95% CrI 0.54–0.97). Outpatient procedures were associated with a lower likelihood of reoperation (OR 0.42, 95% CrI 0.16–0.80), 30-day readmission (OR 0.39, 95% CrI 0.16–0.74), and complications (OR 0.29, 95% CrI 0.15–0.50) and with lower overall costs (MD −$121,392.72, 95% CrI −$216,824.81 to −$23,632.92). Additional analysis of the national administrative data revealed more modest cost savings than those found in the meta-analysis for outpatient spine surgeries relative to inpatient spine surgeries. Estimated cost savings for both younger patients ($555 for those age 30–35 years [95% CrI −$733 to −$374]) and older patients ($7290 for those age 65–70 years [95% CrI −$7380 to −$7190]) were less than the overall cost savings found in the meta-analysis.

CONCLUSIONS

Compared to inpatient spine surgery, outpatient spine surgery was associated with better short-term outcomes and an initial reduction in direct costs. A selection bias for outpatient procedures toward younger, healthier patients may confound these results. The additional analysis of the national database suggests that cost savings in the outpatient setting may be less than previously reported and a result of outpatient procedures being offered more frequently to younger and healthier individuals.

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Martijn J. A. Malessy, Job Eekhof and Willem Pondaag

OBJECTIVE

The results of lateral femoral cutaneous nerve (LFCN) decompression to treat idiopathic meralgia paresthetica (iMP) vary widely. Techniques to decompress the LFCN differ, which may affect outcome, but in MP it is unknown to what extent. The authors present a new technique using dynamic decompression and discuss the outcomes.

METHODS

A retrospective cohort study was performed in a consecutive series of 19 cases. The goal of decompression was pain relief and recovery of sensation. The plane ventral to the LFCN was decompressed by cutting the fascia lata and the inferior aspect of the inguinal ligament. The plane dorsal to the LFCN was decompressed by cutting the fascia of the sartorius muscle. Subsequently, the thigh was brought in full range of flexion and extension/abduction. The authors identified and additionally cut fibers that tightened and caused compression at various locations of the LFCN during movement in all patients, referring to this technique as dynamic decompression. Postoperatively, an independent neurologist scored pain and sensation on a 4-point scale: completely resolved, improved, not changed, or worsened. Patients scored their remaining pain or sensory deficit as a percentage of the preoperative level. Statistical assessment was done using ANOVA to assess the association between outcome and duration of preoperative symptoms, BMI, and length of follow-up.

RESULTS

In 17 of the 19 cases (89%), the pain and/or paresthesia completely resolved. Patients in the remaining 2 cases (11%) experienced 70% and 80% reduction in pain. Sensation completely recovered in 13 of the 19 cases (69%). In 5 of the 19 cases (26%) sensation improved, but an area of hypesthesia remained. Four of these 5 patients indicated a sensory improvement of more than 75%, and the remaining patient had 50% improvement. Sensation remained unchanged in 1 case (5%) with persisting hypesthesia and mild hyperesthesia. There was no significant impact of preoperative symptom duration, BMI, and length of follow-up on postoperative outcome.

CONCLUSIONS

Dynamic decompression of the LFCN is an effective technique for the treatment of iMP. Most patients become completely pain free and sensation recovers considerably.