A propensity score-matched comparative study of balloon guide catheters versus conventional guide catheters for concurrent mechanical thrombectomy with carotid stenting in tandem strokes: comparison of first pass effect, symptomatic intracranial hemorrhage, and 90-day functional outcomes.

BACKGROUND: Extensive clot burden in tandem strokes accounts for poor mechanical thrombectomy (MT) outcomes. Several studies have shown the benefit of balloon guide catheters (BGCs) in MT and carotid artery stenting. OBJECTIVE: In view of this potential benefit, to investigate the safety and effectiveness of proximal flow arrest using a BGC during concurrent MT and carotid revascularization for tandem stroke treatment in a comparative, propensity score-matched (PSM) study. METHODS: Patients with a tandem stroke identified from our endovascular database were dichotomized into groups treated with BGCs versus conventional guide catheters. One-to-one PSM adjustment for baseline demographics and treatment selection bias using nearest-neighbor matching was performed. Patient demographics, presentation characteristics, and procedural details were recorded. Outcomes assessed were final modified Thrombolysis in Cerebral Infarction (mTICI) grade, periprocedural symptomatic intracranial hemorrhage (sICH) rate, in-hospital mortality, and 90-day modified Rankin Scale (mRS) score. Mann-Whitney U test and multivariate logistic regression were performed to compare procedural parameters and clinical outcomes. RESULTS: Concurrent carotid revascularization (stenting with/without angioplasty) and MT was performed in 125 cases (BGC: 85; no BGC: 40). After PSM (40 patients/group), the BGC group had a significantly shorter procedure duration (77.9 vs 61.5 min; OR=0.996; P=0.006), lower discharge National Institutes of Health Stroke Scale score (8.0 vs 11.0; OR=0.987; P=0.042), and higher odds of 90-day mRS 0-2 score (52.3% vs 27.5%; OR=0.34; P=0.040). On multivariate regression, the BGC group had a significantly higher first pass effect rate (mTICI 2b or 3)(OR=1.115, 95% CI 1.015 to 1.432; P=0.013) and lower periprocedural sICH rate (OR=0.615, 95% CI 0.406 to 0.932; P=0.025). No difference in in-hospital mortality was observed (OR=1.591, 95% CI 0.976 to 2.593; P=0.067). CONCLUSION: BGCs used for concurrent MT-carotid revascularization with flow arrest were safe and resulted in superior clinical and angiographic outcomes in patients with a tandem stroke.

Expansion and Subsequent Rupture of Carotid Pseudoaneurysm After Tandem Carotid and Middle Cerebral Artery Occlusion Treated With Mechanical Thrombectomy and Carotid Stenting.

BACKGROUND AND IMPORTANCE: Extracranial carotid artery pseudoaneurysm is a rare entity with potential etiologies including infection, blunt trauma, postsurgical atherosclerotic disease, and invasive neoplasia. Although the natural history of carotid pseudoaneurysm is difficult to determine because of its rarity, complications such as stroke, rupture, and local mass effect may occur at staggering rates. CLINICAL PRESENTATION: In this case, a middle-aged man presented with a tandem carotid, middle cerebral artery occlusion that was treated with a carotid stent and mechanical thrombectomy. He returned 3 weeks later with a ruptured carotid pseudoaneurysm that was then treated with a covered stent. He made a full recovery and was neurologically intact on follow-up. CONCLUSION: This case illustrates a rare potential complication of carotid occlusion and stenting with possible catastrophic consequences. The goal of this report was to educate other clinicians in remaining vigilant in awareness of this complication and provide a framework for potential treatment if and when it occurs.

Effect of driver gas composition on production of scaled Friedlander waveforms in an open-ended shock tube model.

With the evolution of modern warfare and the increased use of improvised explosive devices (IEDs), there has been an increase in blast-induced traumatic brain injuries (bTBI) among military personnel and civilians. The increased prevalence of bTBI necessitates bTBI models that result in a properly scaled injury for the model organism being used. The primary laboratory model for bTBI is the shock tube, wherein a compressed gas ruptures a thin membrane, generating a shockwave. To generate a shock wave that is properly scaled from human to rodent subjects many pre-clinical models strive for a short duration and high peak overpressure while fitting a Friedlander waveform, the ideal representation of a blast wave. A large variety of factors have been experimentally characterized in attempts to create an ideal waveform, however we found current research on the gas composition being used to drive shock wave formation to be lacking. To better understand the effect the driver gas has on the waveform being produced, we utilized a previously established murine shock tube bTBI model in conjunction with several distinct driver gasses. In agreement with previous findings, helium produced a shock wave most closely fitting the Friedlander waveform in contrast to the plateau-like waveforms produced by some other gases. The peak static pressure at the exit of the shock tube and total pressure 5 cm from the exit have a strong negative correlation with the density of the gas being used: helium the least dense gas used produces the highest peak overpressure. Density of the driver gas also exerts a strong positive effect on the duration of the shock wave, with helium producing the shortest duration wave. Due to its ability to produce a Friedlander waveform and produce a waveform following proper injury scaling guidelines, helium is an ideal gas for use in shock tube models for bTBI.

Pediatric Subarachnoid Hemorrhage: Rare Events with Important Implications.

Rupture of an aneurysm is the leading cause of subarachnoid hemorrhage (SAH) which results in accumulation of blood between the arachnoid and pia mater, consequently increasing intracranial pressure. This often results in life threatening conditions like herniation or clinical presentations including focal neurological deficits. In children, these events, although rare, have significant implications. Pediatric SAH is associated with better outcomes in the hospital setting and may even be prevented proactively by the recognition of potential risk factors. Specifically, better recognition of genetic predispositions, metastatic lesions, and infectious causes of aneurysms is important to understand their growth and prevent hemorrhagic events. This review highlights the causes of pediatric SAH, reviews the models of current understanding of this etiology, and discusses the current treatment schema to provide a succinct summary and highlight gaps in current knowledge. This may lead to future investigations aimed at further improving prevention strategies, patient care, and patient outcomes.

Comparison of operating room variables, radiation exposure and implant costs for WEB versus stent assisted coiling for treatment of wide neck bifurcation aneurysms.

BACKGROUND: The WEB device offers another option for treating wide neck bifurcation aneurysms (WNBA). The objective was to compare procedure variables, radiation and implant cost between WEB and stent assisted coiling (SAC) for WNBA. METHODS: A retrospective comparison of similarly sized WNBA treated with SAC or WEB over 5-years was performed. The operating room (arrival-departure), anesthesia (intubation-extubation), procedure duration (puncture-closure), fluoroscopy time and radiation dose(m-Gy) were recorded from the patients' charts. Implant cost per case of all implants (stents, coils, WEB) that were opened whether deployed or not was captured including any coils used in the WEB cases. The implant cost represented the true cost incurred by the institution. RESULTS: There were 46 WEB and 41 SAC cases with no significant difference in aneurysm size. There were more MCA and ACOMM (p = 0.005) and more ruptured aneurysms (p = 0.02) in the WEB group. Regarding procedure variables (hours:minutes): Operating room time WEB 2:31 (±0:37) versus SAC 3:41 (±0:50) (p < 0.0001); anesthesia duration WEB 2:05 (±0:31) versus SAC 3:13 (±0:51) (p < 0.0001) and procedure duration WEB 1:16 (±0:29) versus SAC 2:09 (±0:46) (p < 0.0001). Regarding radiation: Fluoroscopy time WEB 0:34 (±0:18) versus SAC 1:06 (±0:35) (p < 0.0001) and radiation dose WEB 2392(±1086)m-Gy versus SAC 3442 (±1528)m-Gy (p = 0.0007). The implant cost was $17,028(±$5,527) for the WEB versus $23,813 (±$7,456) for the SAC group (p < 0.0001). CONCLUSION: The WEB group had significantly shorter operating room, procedure and anesthesia duration compared to the SAC group. The radiation dose and fluoroscopy time was lower for the WEB group. The total implant cost per case was significantly lower for the WEB versus the SAC group.

An autopsy report of basilar artery aneurysm flow diversion complicated by postoperative day 3 hemorrhage from vessel rupture.

A middle-aged patient presented with posterior circulation symptoms attributable to a large eccentric basilar trunk aneurysm. The planned treatment was flow diversion with loose coil packing which was successfully performed using a Pipeline Flex device deployed from the basilar to the left posterior cerebral artery. The complete procedure including live biplane fluoroscopy was digitally recorded. The patient had symptomatic improvement postoperatively and was discharged on day 1. The patient suffered a cardiac arrest on postoperative day 3 secondary to massive intraventricular and subarachnoid hemorrhage. An aneurysm rupture was suspected; however, postmortem examination showed an intact aneurysm sac. The hemorrhage was attributed to a small focal rent in the distal basilar artery next to an atheromatous plaque. The Pipeline device was visible through the rent. This is an autopsy report documenting an injury to the parent artery and not the aneurysm as a source of fatal delayed subarachnoid hemorrhage following flow diversion.

Utility of sodium fluorescein for achieving resection targets in glioblastoma: increased gross- or near-total resections and prolonged survival.

OBJECTIVE: It is commonly reported that achieving gross-total resection of contrast-enhancing areas in patients with glioblastoma (GBM) improves overall survival. Efforts to achieve an improved resection have included the use of both imaging and pharmacological adjuvants. The authors sought to investigate the role of sodium fluorescein in improving the rates of gross-total resection of GBM and to assess whether patients undergoing resection with fluorescein have improved survival compared to patients undergoing resection without fluorescein. METHODS: A retrospective chart review was performed on 57 consecutive patients undergoing 64 surgeries with sodium fluorescein to treat newly diagnosed or recurrent GBMs from May 2014 to June 2017 at a teaching institution. Outcomes were compared to those in patients with GBMs who underwent resection without fluorescein. RESULTS: Complete or near-total (≥ 98%) resection was achieved in 73% (47/64) of fluorescein cases. Of 42 cases thought not to be amenable to complete resection, 10 procedures (24%) resulted in gross-total resection and 15 (36%) resulted in near-total resection following the use of sodium fluorescein. No patients developed any local or systemic side effects after fluorescein injection. Patients undergoing resection with sodium fluorescein, compared to the non-fluorescein-treated group, had increased rates of gross- or near-total resection (73% vs 53%, respectively; p < 0.05) as well as improved median survival (78 weeks vs 60 weeks, respectively; p < 0.360). CONCLUSIONS: This study is the largest case series to date demonstrating the beneficial effect of utilizing sodium fluorescein as an adjunct in GBM resection. Sodium fluorescein facilitated resection in cases in which it was employed, including dominant-side resections particularly near speech and motor regions. The cohort of patients in which sodium fluorescein was utilized had statistically significantly increased rates of gross- or near-total resection. Additionally, the fluorescein group demonstrated prolonged median survival, although this was not statistically significant. This work demonstrates the promise of an affordable and easy-to-implement strategy for improving rates of total resection of contrast-enhancing areas in patients with GBM.

Magnetic Resonance Imaging Parameters and Their Impact on Survival of Patients with Glioblastoma: Tumor Perfusion Predicts Survival.

BACKGROUND: Many prognostic factors influence overall survival (OS) of patients with glioblastoma. Despite gross total resection and Stupp protocol adherence, many patients have poor survival. Perfusion magnetic resonance imaging may assist in diagnosis, treatment monitoring, and prognostication. METHODS: This retrospective study of 36 patients with glioblastoma assessed influence of preoperative magnetic resonance imaging parameters reflecting tumor cell density and vascularity and patient age on OS. RESULTS: The area under curve based on optimal receiver operating characteristic curves for the perfusion parameters normalized relative tumor blood volume (n_rTBV) and normalized relative tumor blood flow (n_rTBF) were 0.92 and 0.89, respectively, and the highest among all imaging parameters and age. OS showed strongly negative correlations with corrected n_rTBV (R = -0.70; P < 0.001) and n_rTBF (R = -0.67; P < 0.001). The Cox model, which included age and imaging parameters, demonstrated that n_rTBV and n_rTBF were most predictive of OS, with hazard ratios of 5.97 (P = 0.0001) and 8.76 (P = 0.0001), respectively, compared with 1.63 (P = 0.19) for age. Eighteen patients with corrected n_rTBV ≤2.5 (best cutoff value) had a median OS of 15.1 months (95% confidence interval (CI), 11.34-21.25) compared with 2.8 months (95% CI, 1.48-4.03; P < 0.001) for 18 patients with corrected n_rTBV >2.5. Twenty-four patients with n_rTBF ≤2.79 had a median OS of 12 months (95% CI, 10.46-17.9) compared with 2.8 months for 12 patients with n_rTBF >2.79 (95% CI, 1.31-4.2; P < 0.001). CONCLUSIONS: The dominant predictors of OS are normalized perfusion parameters n_rTBV and n_rTBF. Preoperative perfusion imaging may be used as a surrogate to predict glioblastoma aggressiveness and survival independent of treatment.

Blast Scaling Parameters: Transitioning from Lung to Skull Base Metrics.

Neurotrauma from blast exposure is one of the single most characteristic injuries of modern warfare. Understanding blast traumatic brain injury is critical for developing new treatment options for warfighters and civilians exposed to improvised explosive devices. Unfortunately, the pre-clinical models that are widely utilized to investigate blast exposure are based on archaic lung based parameters developed in the early 20th century. Improvised explosive devices produce a different type of injury paradigm than the typical mortar explosion. Protective equipment for the chest cavity has also improved over the past 100 years. In order to improve treatments, it is imperative to develop models that are based more on skull-based parameters. In this mini-review, we discuss the important anatomical and biochemical features necessary to develop a skull-based model.

Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?

Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion outcomes between patients < 65 years old (N=44) and those > 65 years old (N=36). Volume was estimated by the ABC/2 method. We observed a statistically significant difference between groups in use of anticoagulants χ2 =40.305 with p < 0.001, corrective platelet administration χ2 =19.380 with p < 0.001, gender χ2 =14.573 with p < 0.001, and Glasgow Coma Scale with χ2 =23.125 (p=0.026). Overall outcomes were similar in the two groups. Younger patients on average had worse presenting GCS scores, but recovered comparable to older patients. No significant difference in rate of volume expansion, resolution time, or need for surgical treatment was seen between these two groups. We conclude that the initial volume, size, and severity of subdural hematoma determined by the Glasgow Coma Scale score is more likely to predict surgery or future expansion than age of the patient. Patients on oral anti-coagulants that are given appropriate medical reversal agents early do quite well and no impact on the eventual outcome could be demonstrated. Further work is needed to establish better predictors of future volume expansion, and progression to chronic subdural hematoma based on improved severity scales.

Stereotactic radiosurgery planning based on time-resolved CTA for arteriovenous malformation: a case report and review of the literature.

Stereotactic radiosurgery has long been recognized as the optimal form of management for high-grade arteriovenous malformations not amenable to surgical resection. Radiosurgical plans have generally relied upon the integration of stereotactic magnetic resonance angiography (MRA), standard contrast-enhanced magnetic resonance imaging (MRI), or computed tomography angiography (CTA) with biplane digital subtraction angiography (DSA). Current options are disadvantageous in that catheter-based biplane DSA is an invasive test associated with a small risk of complications and perhaps more importantly, the two-dimensional nature of DSA is an inherent limitation in creating radiosurgical contours. The necessity of multiple scans to create DSA contours for radiosurgical planning puts patients at increased risk. Furthermore, the inability to import two-dimensional plans into some radiosurgery programs, such as Cyberknife TPS, limits treatment options for patients. Defining the nidus itself is sometimes difficult in any of the traditional modalities as all draining veins and feeding arteries are included in the images. This sometimes necessitates targeting a larger volume, than strictly necessary, with stereotactic radiosurgery for treatment of the AVM. In this case report, we show the ability to use a less-invasive and three-dimensional form of angiography based on time-lapsed CTA (4D-CTA) rather than traditional DSA for radiosurgical planning. 4D-CTA may allow generation of a series of images, which can show the flow of contrast through the AVM. A review of these series may allow the surgeon to pick and use a volume set that best outlines the nidus with least interference from feeding arteries or draining veins. In addition, 4D-CTA scans can be uploaded into radiosurgery programs and allow three-dimensional targeting. This is the first reported case demonstrating the use of a 4D CTA and an MRI to delineate the AVM nidus for Gamma Knife radiosurgery, with complete obliteration of the nidus over time and subsequent management of associated radiation necrosis with bevacizumab.

Lung cancer metastasis presenting as a solitary skull mass.

Lung cancer has been well documented to spread to bone and the axial skeleton after metastasis to adjacent organs. Bony metastasis is not, however, the typical presenting manifestation. The differential diagnosis for a tissue mass on the skull should warrant a workup for metastatic disease. Bony metastasis plays an important role in treatment and disease management. We report an exceptionally rare case of stage IV lung adenocarcinoma that presented with a solitary skull metastasis and a significant soft-tissue component. The lesion was treated by excision via craniotomy and subsequent medical management of the adenocarcinoma. This case illustrates a very rare presentation of lung adenocarcinoma and also represents what the authors believe to be the first report of a solitary skull mass originating from a lung primary. We also present a review of the literature surrounding bony metastasis to the skull and implications for patient care.

Giant calvarial intraosseous angiolipoma: a case report and review of the literature.

Intraosseous angiolipomas are very rare tumors occurring most commonly in the ribs and mandible. Only two cases with intracranial involvement have been reported in the literature. We report a case of a giant calvarial angiolipoma and its surgical treatment in a 30-year-old female who presented with a slowly expanding skull mass and discuss relevant radiological, histological and surgical findings.

Amelioration of nicotinamide adenine dinucleotide phosphate-oxidase mediated stress reduces cell death after blast-induced traumatic brain injury.

A total of 1.7 million traumatic brain injuries (TBIs) occur each year in the United States, but available pharmacologic options for the treatment of acute neurotrauma are limited. Oxidative stress is an important secondary mechanism of injury that can lead to neuronal apoptosis and subsequent behavioral changes. Using a clinically relevant and validated rodent blast model, we investigated how nicotinamide adenine dinucleotide phosphate oxidase (Nox) expression and associated oxidative stress contribute to cellular apoptosis after single and repeat blast injuries. Nox4 forms a complex with p22phox after injury, forming free radicals at neuronal membranes. Using immunohistochemical-staining methods, we found a visible increase in Nox4 after single blast injury in Sprague Dawley rats. Interestingly, Nox4 was also increased in postmortem human samples obtained from athletes diagnosed with chronic traumatic encephalopathy. Nox4 activity correlated with an increase in superoxide formation. Alpha-lipoic acid, an oxidative stress inhibitor, prevented the development of superoxide acutely and increased antiapoptotic markers B-cell lymphoma 2 (t = 3.079, P < 0.05) and heme oxygenase 1 (t = 8.169, P < 0.001) after single blast. Subacutely, alpha-lipoic acid treatment reduced proapoptotic markers Bax (t = 4.483, P < 0.05), caspase 12 (t = 6.157, P < 0.001), and caspase 3 (t = 4.573, P < 0.01) after repetitive blast, and reduced tau hyperphosphorylation indicated by decreased CP-13 and paired helical filament staining. Alpha-lipoic acid ameliorated impulsive-like behavior 7 days after repetitive blast injury (t = 3.573, P < 0.05) compared with blast exposed animals without treatment. TBI can cause debilitating symptoms and psychiatric disorders. Oxidative stress is an ideal target for neuropharmacologic intervention, and alpha-lipoic acid warrants further investigation as a therapeutic for prevention of chronic neurodegeneration.

Sleep disruption and the sequelae associated with traumatic brain injury.

Sleep disruption, which includes a loss of sleep as well as poor quality fragmented sleep, frequently follows traumatic brain injury (TBI) impacting a large number of patients each year in the United States. Fragmented and/or disrupted sleep can worsen neuropsychiatric, behavioral, and physical symptoms of TBI. Additionally, sleep disruption impairs recovery and can lead to cognitive decline. The most common sleep disruption following TBI is insomnia, which is difficulty staying asleep. The consequences of disrupted sleep following injury range from deranged metabolomics and blood brain barrier compromise to altered neuroplasticity and degeneration. There are several theories for why sleep is necessary (e.g., glymphatic clearance and metabolic regulation) and these may help explain how sleep disruption contributes to degeneration within the brain. Experimental data indicate disrupted sleep allows hyperphosphorylated tau and amyloid ß plaques to accumulate. As sleep disruption may act as a cellular stressor, target areas warranting further scientific investigation include the increase in endoplasmic reticulum and oxidative stress following acute periods of sleep deprivation. Potential treatment options for restoring the normal sleep cycle include melatonin derivatives and cognitive behavioral therapy.

Cumulative effects of repetitive mild traumatic brain injury.

The majority of traumatic brain injuries (TBI) in the USA are mild in severity. Sports, particularly American football, and military experience are especially associated with repetitive, mild TBI (mTBI). The consequences of repetitive brain injury have garnered increasing scientific and public attention following reports of altered mood and behavior, as well as progressive neurological dysfunction many years after injury. This report provides an up-to-date review of the clinical, pathological, and pathophysiological changes associated with repetitive mTBI, and their potential for cumulative effects in certain individuals.

Combination treatment of r-tPA and an optimized human apyrase reduces mortality rate and hemorrhagic transformation 6h after ischemic stroke in aged female rats.

Recombinant tissue plasminogen activator (r-tPA) is the only FDA-approved drug treatment for ischemic stroke and must be used within 4.5h. Thrombolytic treatment with r-tPA has deleterious effects on the neurovascular unit that substantially increases the risk of intracerebral hemorrhage if administered too late. These therapeutic shortcomings necessitate additional investigation into agents that can extend the therapeutic window for safe use of thrombolytics. In this study, combination of r-tPA and APT102, a novel form of human apyrase/ADPase, was investigated in a clinically-relevant aged-female rat embolic ischemic stroke model. We propose that successfully extending the therapeutic window of r-tPA administration would represent a significant advance in the treatment of ischemic stroke due to a significant increase in the number of patients eligible for treatment. Results of our study showed significantly reduced mortality from 47% with r-tPA alone to 16% with co-administration of APT102 and r-tPA. Co-administration decreased cortical (47 ± 5% vs. 29 ± 5%), striatal (50 ± 2%, vs. 40 ± 3%) and total (48 ± 3%vs. 33 ± 4%) hemispheric infarct volume compared to r-tPA alone. APT102 improved neurological outcome (8.9±0.6, vs. 6.8 ± 0.8) and decreased hemoglobin extravasation in cortical tissue (1.9 ± 0.1mg/dl vs. 1.4 ± 0.1mg/dl) striatal tissue (2.1 ± 0.3mg/dl vs. 1.4 ± 0.1mg/dl) and whole brain tissue (2.0 ± 0.2mg/dl vs. 1.4 ± 0.1mg/dl). These data suggest that APT102 can safely extend the therapeutic window for r-tPA mediated reperfusion to 6h following experimental stroke without increased hemorrhagic transformation. APT102 offers to be a viable adjunct therapeutic option to increase the number of clinical patients eligible for thrombolytic treatment after ischemic stroke.

SN79, a sigma receptor ligand, blocks methamphetamine-induced microglial activation and cytokine upregulation.

Methamphetamine (METH) abuse is associated with several negative side effects including neurotoxicity in specific brain regions such as the striatum. The precise molecular mechanisms by which METH usage results in neurotoxicity remain to be fully elucidated, with recent evidence implicating the importance of microglial activation and neuroinflammation in damaged brain regions. METH interacts with sigma receptors which are found in glial cells in addition to neurons. Moreover, sigma receptor antagonists have been shown to block METH-induced neurotoxicity in rodents although the cellular mechanisms underlying their neuroprotection remain unknown. The purpose of the current study was to determine if the prototypic sigma receptor antagonist, SN79, mitigates METH-induced microglial activation and associated increases in cytokine expression in a rodent model of METH-induced neurotoxicity. METH increased striatal mRNA and protein levels of cluster of differentiation 68 (CD68), indicative of microglial activation. METH also increased ionized calcium binding adapter molecule 1 (IBA-1) protein expression, further confirming the activation of microglia. Along with microglial activation, METH increased striatal mRNA expression levels of IL-6 family pro-inflammatory cytokines, leukemia inhibitory factor (lif), oncostatin m (osm), and interleukin-6 (il-6). Pretreatment with SN79 reduced METH-induced increases in CD68 and IBA-1 expression, demonstrating its ability to prevent microglial activation. SN79 also attenuated METH-induced mRNA increases in IL-6 pro-inflammatory cytokine family members. The ability of a sigma receptor antagonist to block METH-induced microglial activation and cytokine production provides a novel mechanism through which the neurotoxic effects of METH may be mitigated.

Overcoming challenges associated with upright imaging of the cervicothoracic junction: a case report involving a novel repurposing of the O-arm.

BACKGROUND: Prior to the mobilization of patients with spinal fractures following treatment, it is important to confirm stability in the upright position. METHODS: A patient presented with T2 and T3 vertebral body fractures visible on recumbent CT. Supine and upright plain x-rays with additional swimmer's views were deemed suboptimal prior to mobilization. The default configuration of the O-arm was modified to enable imaging in the upright position. RESULTS: Images utilizing the O-arm were satisfactory and anatomic alignment confirmed in an upright position. It is believed that this is the first time the O-arm has been used for upright diagnostic imaging (off-label application). Excellent visualization of the cervicothoracic junction and upper thoracic regions was obtained in the desired upright position. CONCLUSION: The O-arm was used successfully to image spinal trauma in the upright position and may represent a new application of the device, potentially fulfilling a frequently unmet medical imaging need.