Larger Lesion Volumes Research Articles

Lactoferrin Reduces Chorioretinal Damage in the Murine Laser Model of Choroidal Neovascularization

Purpose: To determine whether lactoferrin, specifically endogenous mouse lactoferrin and exogenous intraperitoneal lactoferrin treatment, plays a role in reducing the chorioretinal damage in the laser-induced model of choroidal neovascularization. Materials and methods: Four 532-nm argon laser spots were placed between the retinal vessels of each eye. At Day 7, Fluorescein Angiography was performed to grade the lesions. The mice were perfused with fluorescein-labeled tomato lectin and sacrificed. The retinal pigment epithelium-choroid-sclera complex was flat-mounted and analyzed with a confocal microscope to measure the volume of the lesions. The effect of endogenous lactoferrin was studied by comparing lactoferrin knockout and wild-type (WT) mice. The effect of exogenous lactoferrin treatment was studied by comparing lactoferrin knockout and WT mice treated with lactoferrin for seven days to their respective controls. Results: Lactoferrin knockout mice demonstrated 47% larger lesion volumes than WT mice (p < 0.001). Intraperitoneal treatment with Lactoferrin reduced the lesion volume in Lactoferrin knockout mice by 26% (p < 0.04). Regarding the fluorescein angiography, lesions indicating the greatest damage (grade 2B) occurred more frequently in control lactoferrin knockout mice compared with control WT mice (16% versus 5%). Intraperitoneal treatment with Lactoferrin reduced the grade 2B lesions from16% to 2% in Lactoferrin knockout mice. Conclusion: The endogenous lactoferrin present in WT mice appears to reduce the choroidal neovascularization in the laser-induced choroidal neovascularization model in mice. Treatment with exogenous lactoferrin is capable of reducing the choroidal neovascularization in lactoferrin knockout mice but does not add a significant protective effect to WT.

Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit.

Abstract W MP95: Deletion of the Hemopexin or Heme Oxygenase-2 Gene Aggravates Brain Injury Following Stroma-free-hemoglobin Induced Intracerebral Hemorrhage

Introduction: The breakdown of heme-hemoglobin released after intracerebral hemorrhage (ICH) contributes to brain injury. Hemopexin (HPX) has highest binding affinity to heme as its transporter and heme oxygenase 2 (HO2) is heme rate-limiting enzyme for its degradation. However, the significance and role of HPX and HO2 on hemoglobin clearance in brain remains understudied. Methods: Intracerebral injection of stroma-free hemoglobin (SFHb) was used in our study to induced ICH. The HPX or HO2 knockout (KO) mice were injected with 10μL SFHb into the striatum. Behavioral/functional tests were performed along with anatomical changes. Iron deposition and neuronal degeneration was shown by Perl’s or Fluoro Jade B staining, respectively. Immunohistochemistry with anti-Iba1 was used to detect microglial activation around the injured site. Result: This study reveals that microglia contribute to hemoglobin clearance after SFHb injection. Deletion of HPX or HO2 aggravated the SFHb-induced brain injury. Both of HPX or HO2 KO mice showed larger lesion volume (P&lt;0.05) and more degenerating neurons (P&lt;0.01) compared with the littermate controls in peri-lesion area at 24h post-injection. However, their activated microglial cells in peri-lesion area were significantly decreased (P&lt;0.05), accompanied with markedly increased iron positive glial cells (both P&lt;0.001), which are confirmed to be microglial cells by double-staining. The data suggested that activated microglia engulfed the injected SFHb and conferred protective effects after ICH. To further address this point, primary microglial cells were treated with SFHb and the results showed that microglial cells take up extracellular SFHb and that SFHb can activate microglial cells. In addition, our in vivo work revealed that activated microglial cells were increased from 24h to 72h after injection in both HPX KO and HO2 KO mice (P&lt;0.05). Also, notable improvements on neurological deficits scoring and locomotor activities indicated that the brain damages in mice were recovering from 24h to 72h post-injection, supporting activated microglia exerted beneficial effects after ICH. Conclusions: This study suggests that HPX and HO2 contribute to hemoglobin clearance after ICH and microglia play the crucial role.

Transurethral convective water vapor as a treatment for lower urinary tract symptomatology due to benign prostatic hyperplasia using the Rezūm(®) system: evaluation of acute ablative capabilities in the human prostate.

BackgroundThe purpose of this study was to assess the acute ablative characteristics of transurethral convective water vapor (steam) using the Rezūm® system in men with benign prostatic hyperplasia through histologic and radiographic studies.MethodsSeven patients were treated with transurethral intraprostatic injections of sterile steam under endoscopic visualization followed by previously scheduled adenectomies. The extirpated adenomas were grossly examined followed by whole mount sectioning and staining with triphenyl-tetrazolium chloride (TTC) to evaluate thermal ablation. Histology was performed after hematoxylin and eosin staining on one prostate. After review of results from the first patient cohort, an additional 15 patients with clinical benign prostatic hyperplasia were treated followed by gadolinium-enhanced magnetic resonance imaging (MRI) at one week.ResultsIn the first patient cohort, gross examination of TTC-stained tissue showed thermal ablation in the transition zone. In addition, there was a distinct interface between viable and necrotic prostatic parenchyma. Histopathologic examination revealed TTC staining-outlined necrotic versus viable tissue. Gadolinium-enhanced MRIs in the cohort of 15 patients demonstrated lesion defects in all patients at 1 week post-procedure. Coalesced lesions were noted with a mean (± standard deviation) lesion volume of 9.6±8.5 cm3. The largest lesion volume was 35.1 cm3. Ablation using vapor was rapid and remained confined to the transition zone, consistent with the thermodynamic principles of convective thermal energy transfer.ConclusionThermal ablation was observed in all specimens. The resulting coalescing ablative lesions, as seen on MRI, were confined to the transition zone. These studies confirm the ablative capabilities of vapor, validate the thermodynamic principles of convective heating, and allow for further clinical studies.

Parametric sensitivity analysis of radiofrequency ablation with efficient experimental design

The aim of this research is to analyze the efficacy of radiofrequency ablation (RFA) for varying electrothermal parameters. An attempt has been made to study the RFA for the effect of thermal conductivity, electrical conductivity and blood perfusion rate with Taguchi's design of experiments methodology. Their combined effect was analyzed quantitatively in different tissues. It was found that ablation volume for temperature control algorithm is mostly affected by blood perfusion followed by electrical conductivity and thermal conductivity. Smallest ablation volume was observed in kidney tissue while largest lesion volume was obtained in muscle tissue. Based on the results some insightful corollaries were drawn which may be translated as qualification of RFA for the respective tissue treatment protocol. Moreover, quantification of parameter sensitivity translates to efficient design of control algorithm for power delivery. It is intended that these conclusions will help the radiologist in the treatment planning stage and would serve as broad guidelines for the application of RFA in varying biological environment.

Association Between Cerebral Lesions and Emotional Changes in Acute Ischemic Stroke Patients

Controversies and interest are present in the associations between specific brain locations and depression or anxiety. This study investigated the association between stroke location and emotional changes in stroke patients. This prospective observational study analyzed the neuroimages and neuropsychiatric conditions of 26 patients with acute middle cerebral artery infarction. Each patient's neurological and psychiatric condition was evaluated 1 week as well as 1 month after the stroke. We found that the right superior and middle temporal gyrus was associated with anxiety at 1 month after stroke. Moreover, better mentality is associated with deterioration of anxiety within 1 month after stroke, and larger lesion volume is associated with deterioration of depression within 1 month after stroke.

Abstract TP21: Impact Of Complete Recanalization On The Relationships Between Pretreatment Dwi Volume And Clinical Outcome In Patients Treated By Endovascular Treatment.

Objectives: To evaluate the relationships between pre-treatment DWI volume and clinical outcome following endovascular therapy. Methods: Patients from the REcanalisation using Combined intravenous Alteplase and Neurointerventional ALgorithm for acute Ischemic StrokE (RECANALISE) study who suffered an acute hemispheric infarction with a large vessel occlusion and underwent DWI before endovascular treatment were enrolled. DWI volumes were automatically calculated by the RAPID software. Recanalization was graded using the TIMI scale. Outcomes assessed were favorable outcome (mRS 0-2) and death at 90 days. Findings: 66% (138/210) of the patients were eligible for this substudy. Mean age was 69.6 years (+/-17.6), median NIHSS 16 (IQR: 10-21) median time to MRI 110 min (IQR 77-178), and median time to treatment 149 min (IQR: 115-250). Median DWI volume was 14mL (IQR: 5 to 43) and was categorized into tertiles.Median volume per tertile were: Small: 3mL(IQR:1-5); Moderate 14mL(IQR:10-20) and Large 60mL(IQR:43-104)including 19 patients with a very large DWI lesion (&gt;70mL). TIMI 3 was achieved in 47%[median delay 238 min, (IQR, 206 to 285)]and TIMI 2 in 38%; [median delay 269 min, (IQR, 219 to 350)]. Overall, the rate of favorable outcome decreased and the death rate increased gradually with DWI volume.( cf Table) After adjustment for age and NIHSS, complete recanalization was associated with a higher rate of favorable outcome and decreased death rate in the moderate and large DWI volume tertiles.(cf table)This relationship was not observed in patients with very large (&gt;70 mL) or small DWI volumes. Conclusion: In patients undergoing endovascular treatment, our results demonstrate that increasing DWI volumes were associated with a worse outcome while a complete recanalization was associated with a significant better clinical outcome in patients with a moderate to large DWI lesion. This relationship was not observed in small or very large DWI lesion volume (&gt;70 mL). /&gt;

Feasibility and toxicity of hypofractionated image guided radiation therapy for large volume limited metastatic disease

PurposeHypofractionated image guided radiation therapy (HIGRT) is increasingly used for limited metastases. Reported studies have mostly treated small volume tumors. Here, we report the toxicity and oncologic outcomes following treatment of large volume metastases. Methods and MaterialsHIGRT patients treated from October 2005 to March 2010 were reviewed. Gross tumor volumes (GTV) and planning target volumes (PTV) were obtained from planning software. A metastasis was considered large volume if the treated PTV exceeded 50 cc. Patients were treated with either 10-fraction (4-5 Gy per fraction) or 3-5 fraction (8-14 Gy per fraction) regimens. Toxicity was obtained from both prospectively collected databases and retrospectively from patient charts. ResultsSixty-four patients with 93 treated lesions >50 cc were identified. The median GTV and PTV volumes were 41 and 119 cc, respectively. The median number of treated large volume lesions was 1, and a maximum of 3 large volume lesions were treated in a single patient. Primary malignancies included non–small cell lung cancer, renal cell, colorectal, breast, bladder, pituitary, small cell lung cancer, sarcoma, head-and-neck cancer, and hepatocellular cancer. Treated sites included lung (n = 33), regional lymph nodes (n = 20), bone (n = 17), adrenal (n = 9), and liver (n = 6). The most frequently used treatment regimen was 50 Gy in 5 Gy fractions. The median follow-up was 27 months for surviving patients. Treated lesion control was 78%. Low rates of acute and late grade 3 or higher toxicity were reported, with 3 and 5 patients experiencing each, respectively. ConclusionsHIGRT to large volume oligometastatic disease is tolerable and feasible with promising tumor control. Local radiation therapy should be considered in patients with large volume, limited metastatic disease.

Is Antiplatelet Treatment Effective on the Progression of White Matter Hyperintensity? - 5 Year Follow Up, Propensity Score Adjusted, Observational Study (P04.203)

Objective: We performed this study to assess the effects of antiplatelet treatment on the progression of white matter change. Background White matter hyperintensity on MRI is commonly observed in asymptomatic elderly, and chronic ischemic insult is one of the postulated mechanisms. However, there is no consensus on the treatment of these patients, including the usage of antiplatelet. Design/Methods: From 2003 to 2005, subjects who performed brain MRI for health check up and showed mild white matter change only without any significant lesion on were selected, and follow up MRI were performed in 2010. During this period, patients were prescribed either antiplatelet or not according to the attending physician9s preference. White matter hyperintensity volume in FLAIR was blindly assessed by one investigator using 3D slicer imaging analysis software. For statistical comparison, propensity score weighting method was used. Results: Among 192 screened patients, 93 patients were followed and analyzed. The average interval between initial and follow up MR was 5.2 years. Male was 33 and mean age at the time of initial MR was 60.6 years old. Among them, 54 patients were taking antiplatelet during follow up period. Between the antiplatelet group and control, there was no difference in demographic and risk factor profiles except hypertension, which was more prevalent in those taking antiplatelet (38.9 vs. 15.4%, P=0.002). Compared to the control, the antiplatelet group also showed more severe baseline white matter lesion volume (1953 vs. 3963 mm3, P=0.002) and more progression of white matter change (1010 vs. 2944 mm3, P=0.001). When we adjusted the variables using inverse probability treatment weighting method, there was no difference between the two groups. Conclusions: Subjects with large white matter lesion volume on MRI were more likely to take antiplatelet, but there was no effect of antiplatelet on the progression of white matter hyperintensity. Disclosure: Dr. Rha has nothing to disclose. Dr. Park has nothing to disclose. Dr. Park has nothing to disclose. Dr. Yoo has nothing to disclose.

Malignant CTA Collateral Profile Is Highly Specific for Large Admission DWI Infarct Core and Poor Outcome in Acute Stroke

Large admission DWI lesion volumes are associated with poor outcomes despite acute stroke treatment. The primary aims of our study were to determine whether CTA collaterals correlate with admission DWI lesion volumes in patients with AIS with proximal occlusions, and whether a CTA collateral profile could identify large DWI volumes with high specificity. We studied 197 patients with AIS with M1 and/or intracranial ICA occlusions. We segmented admission and follow-up DWI lesion volumes, and categorized CTA collaterals by using a 5-point CS system. ROC analysis was used to determine CS accuracy in predicting DWI lesion volumes >100 mL. Patients were dichotomized into 2 categories: CS = 0 (malignant profile) or CS>0. Univariate and multivariate analyses were performed to compare imaging and clinical variables between these 2 groups. There was a negative correlation between CS and admission DWI lesion volume (ρ = -0.54, P < .0001). ROC analysis revealed that CTA CS was a good discriminator of DWI lesion volume >100 mL (AUC = 0.84, P < .001). CS = 0 had 97.6% specificity and 54.5% sensitivity for DWI volume >100 mL. CS = 0 patients had larger mean admission DWI volumes (165.8 mL versus 32.7 mL, P < .001), higher median NIHSS scores (21 versus 15, P < .001), and were more likely to become functionally dependent at 3 months (95.5% versus 64.0%, P = .003). Admission NIHSS score was the only independent predictor of a malignant CS (P = .007). In patients with AIS with PAOs, CTA collaterals correlate with admission DWI infarct size. A malignant collateral profile is highly specific for large admission DWI lesion size and poor functional outcome.

Abstract 3615: Degree of CTA Collaterals determines the Early and Final MRI DWI Lesion Volumes in Endovascular Treatment of Acute Ischemic Stroke

Background: Large pre-treatment DWI lesion volumes have been correlated with poor response to intra-arterial (IA) stroke therapies. In patients with large intracranial vessel occlusion, the degree of collateral vessel seen on CT Angiography (CTA) has also been correlated with patient outcomes. However, the relationship between the degree of collaterals on CTA and DWI lesion volume early on and after intervention has not been described and may be useful in patient selection for acute therapies. Objectives: To assess the relationship of CTA collaterals and DWI lesion volumes in patients eligible for IA stroke therapy, and to assess pre-treatment CTA collaterals with final infarct volume in patients receiving IA therapy for acute stroke. Methods: Single tertiary center retrospective review of patients considered for IA stroke therapy from May 2010 to June 2011. CTA collaterals were assessed as 0 - no collaterals, 1 - minimal collaterals (&lt;50% of affected territory), 2- partial collaterals (&gt; 50% of affected territory), and 3 - full collaterals. DWI volumes on initial MRI scans and post-treatment MRI scans (done 24-96 hours) were calculated by region of interest analysis. Univariate and multivariate analyses were performed (STATA, College Station, TX) Results: 71 patients were available for analysis. Acute CTA imaging revealed no collaterals in 6 patients, minimal collaterals in 5 patients, partial collaterals in 33 patients and full collaterals in 27 patients. Baseline NIHSS correlated inversely with the degree of collaterals: In patients with no collaterals the median NIHSS was 20.5 (IQR 11.5 - 25.5), with minimal collaterals 18 (IQR 14-23.5), and with partial or full collaterals 13 (IQR 10-17). Initial DWI lesion volume correlated well in an inverse fashion with CTA collaterals as follows: none or minimal collaterals 88.7cc (intraquartile range (IQR) 51.6cc - 177.43cc), partial 19.7cc (IQR 13.7cc - 36.9cc) and full collaterals 9.7cc (IQR 4.7cc - 29.6cc). Final DWI lesion volumes also inversely correlated as follows: none 152.0cc (IQR 76.0cc - 204.4cc), minimal 118.8cc (IQR 57.5cc - 141.1cc), partial 34.9cc (IQR 14.2cc - 107.4cc), and full 17.2cc (IQR 8.6cc - 47.9cc). On multivariate analysis, baseline NIHSS and CTA collaterals were significantly correlated with DWI lesion volume of &gt; 80cc (P&lt;0.05) Conclusion: The degree of CTA collaterals are significantly inversely correlated with DWI lesion volumes before and after IA therapy for acute stroke

Stereotactic radiosurgery for arteriovenous malformations, Part 6: multistaged volumetric management of large arteriovenous malformations

The object of this study was to define the long-term outcomes and risks of arteriovenous malformation (AVM) management using 2 or more stages of stereotactic radiosurgery (SRS) for symptomatic large-volume lesions unsuitable for surgery. In 1992, the authors prospectively began to stage the treatment of anatomical components to deliver higher single doses to AVMs with a volume of more than 10 cm(3). Forty-seven patients with such AVMs underwent volume-staged SRS. In this series, 18 patients (38%) had a prior hemorrhage and 21 patients (45%) underwent prior embolization. The median interval between the first-stage SRS and the second-stage SRS was 4.9 months (range 2.8-13.8 months). The median target volume was 11.5 cm(3) (range 4.0-26 cm(3)) in the first-stage SRS and 9.5 cm(3) in the second-stage SRS. The median margin dose was 16 Gy (range 13-18 Gy) for both stages. In 17 patients, AVM obliteration was confirmed after 2-4 SRS procedures at a median follow-up of 87 months (range 0.4-209 months). Five patients had near-total obliteration (volume reduction > 75% but residual AVM). The actuarial rates of total obliteration after 2-stage SRS were 7%, 20%, 28%, and 36% at 3, 4, 5, and 10 years, respectively. The 5-year total obliteration rate after the initial staged volumetric SRS with a margin dose of 17 Gy or more was 62% (p = 0.001). Sixteen patients underwent additional SRS at a median interval of 61 months (range 33-113 months) after the initial 2-stage SRS. The overall rates of total obliteration after staged and repeat SRS were 18%, 45%, and 56% at 5, 7, and 10 years, respectively. Ten patients sustained hemorrhage after staged SRS, and 5 of these patients died. Three of 16 patients who underwent repeat SRS sustained hemorrhage after the procedure and died. Based on Kaplan-Meier analysis (excluding the second hemorrhage in the patient who had 2 hemorrhages), the cumulative rates of AVM hemorrhage after SRS were 4.3%, 8.6%, 13.5%, and 36.0% at 1, 2, 5, and 10 years, respectively. This corresponded to annual hemorrhage risks of 4.3%, 2.3%, and 5.6% for Years 0-1, 1-5, and 5-10 after SRS. Multiple hemorrhages before SRS correlated with a significantly higher risk of hemorrhage after SRS. Symptomatic adverse radiation effects were detected in 13% of patients, but no patient died as a result of an adverse radiation effect. Delayed cyst formation did not occur in any patient after SRS. Prospective volume-staged SRS for large AVMs unsuitable for surgery has potential benefit but often requires more than 2 procedures to complete the obliteration process. To have a reasonable chance of benefit, the minimum margin dose should be 17 Gy or greater, depending on the AVM location. In the future, prospective volume-staged SRS followed by embolization (to reduce flow, obliterate fistulas, and occlude associated aneurysms) may improve obliteration results and further reduce the risk of hemorrhage after SRS.

Parenchymal hematoma and total lesion volume in combined IV/IA revascularization stroke therapy

Background and purposeA positive correlation between large parenchymal hematoma (PH) volume and large CT lesion volume in subjects treated with intravenous (IV) recombinant tissue plasminogen activator (rtPA) as well as...

Isolated lateral thalamic infarction: the role of posterior cerebral artery disease

Lateral thalamic infarction (LTI) is usually caused by small vessel disease (SVD), i.e., occlusion of the deep perforator. However, focal atherosclerotic posterior cerebral artery disease (PCAD) may produce LTI via thrombotic occlusion of the perforator. We aimed to investigate the prevalence of PCAD in LTI and differences in clinical and imaging findings between LTIs associated with PCAD and SVD. We retrospectively evaluated 58 consecutive patients with isolated LTI who underwent diffusion-weighted imaging (DWI) and MR angiography (MRA) within 7 days after stroke onset. Patients were divided into two groups: those with PCAD and those with SVD. Clinical syndromes were divided into pure sensory stroke (PSS) and sensory stroke plus (SS-plus), i.e., the concomitant presence of motor dysfunction or ataxia. Clinical and imaging findings were compared between these two groups. Of the 58 patients, 13 (22.4%) had PCAD. PSS was more frequently associated with SVD than with PCAD (57.8% vs. 23.1%, P=0.032). Initial DWI lesion volume (cm³) was significantly larger in PCAD than in patients with SVD (0.38±0.13 vs. 0.33±0.22, P=0.025). Among the 23 patients (39.7%) who underwent follow-up DWI, patients with PCAD showed a significantly greater increase in subacute lesion volume than those with SVD (P=0.019). Although National Institutes of Health Stroke Scale scores did not differ at admission (P=0.185), they were significantly higher at discharge in PCAD than in patients with SVD (P=0.012). Our data suggest that PCAD is an important cause of LTI, being related to SS-plus, larger lesion volume, and worse clinical outcomes.

Stereologic Analysis of Tibial-Plateau Cartilage and Femoral Cancellous Bone in Guinea Pigs With Spontaneous Osteoarthritis

Two strains of guinea pig develop spontaneous osteoarthritis of the knee. Although the disease evolves at different rates in the two strains, it is not known whether these differences are reflected in the structure of the cartilage and cancellous bone. We determined whether the three-dimensional structure of the tibial-plateau cartilage and femoral cancellous bone differed between the two strains. Six Dunkin-Hartley and six GOHI/SPF guinea pigs were evaluated. The animals were sacrificed at 11 months of age. The 24 proximal tibias were used for a stereologic histomorphometric analysis of the tibial-plateau cartilage. The 24 femurs were used for a site-specific, three-dimensional quantitative analysis of the cancellous bone by micro-CT. Compared to the GOHI/SPF guinea pigs, the tibial-plateau cartilage of the Dunkin-Hartley strain had a larger lesion volume (3.8% versus 1.5%) and a thicker uncalcified cartilage layer (0.042 versus 0.035 mm), but a thinner calcified cartilage zone (0.008 versus 0.01 mm) and a thinner subchondral cortical bone plate (0.035 versus 0.039 mm). The femoral cancellous bone in the Dunkin-Hartley strain had a lower bone mineral density (477 versus 509 mg/cm(3)). However, the trabeculae were thicker (3.91 versus 3.53 pixels) and farther apart (7.8 versus 5.6 pixels). The osteoarthritic changes in the cartilage were topographically mirrored in the subchondral bone. They were most severe on the medial side of the joint, particularly in the anterior region. Spontaneous osteoarthritis in the guinea pig is associated with site-specific changes in the articular cartilage layer, which are topographically mirrored in the underlying subchondral bone. Three-dimensional structural information not revealed by two-dimensional radiography may help characterize the stages of osteoarthritis.

Myelin‐associated glycoprotein protects neurons from excitotoxicity

In addition to supporting rapid nerve conduction, myelination nurtures and stabilizes axons and protects them from acute toxic insults. One myelin molecule that protects and sustains axons is myelin-associated glycoprotein (MAG). MAG is expressed on the innermost wrap of myelin, apposed to the axon surface, where it interacts with axonal receptors that reside in lateral membrane domains including gangliosides, the glycosylphosphatidylinositol-anchored Nogo receptors, and β1-integrin. We report here that MAG protection extends beyond the axon to the neurons from which those axons emanate, protecting them from excitotoxicity. Compared to wild type mice, Mag-null mice displayed markedly increased seizure activity in response to intraperitoneal injection of kainic acid, an excitotoxic glutamate receptor agonist. Mag-null mice also had larger lesion volumes in response to intrastriatal injection of the excitotoxin NMDA. Prior injection of a soluble form of MAG partially protected Mag-null mice from NMDA-induced lesions. Hippocampal neurons plated on proteins extracted from wild-type rat or mouse myelin were resistant to kainic acid-induced excitotoxicity, whereas neurons plated on proteins from Mag-null myelin were not. Protection was reversed by anti-MAG antibody and replicated by addition of soluble MAG. MAG-mediated protection from excitotoxicity was dependent on Nogo receptors and β1-integrin. We conclude that MAG engages membrane-domain resident neuronal receptors to protect neurons from excitotoxicity, and that soluble MAG mitigates excitotoxic damage in vivo.

Electrocortical Pathology in a Rat Model of Penetrating Ballistic-Like Brain Injury

Traumatic brain injury (TBI) causes severe disruption of cerebral electrical activity and electroencephalography (EEG) is emerging as a standard tool to monitor TBI patients in the acute period of risk for secondary injuries. However, animal studies of EEG pathology in the context of TBI are surprisingly sparse, largely because of the lack of real-time continuous EEG (cEEG) monitoring in animal TBI models. Here, we performed long-term EEG monitoring to study nonconvulsive seizures (NCS), periodic epileptiform discharges (PED), and EEG power spectra following three injury severity levels in a rat model of penetrating ballistic-like brain injury (PBBI). EEG signals were recorded continuously from bilateral hemispheres of freely behaving rats for 72 h and for 2 h on days 7 and 14 after the injury. We report that the incidence of NCS and PED positively correlated with the injury severity, where 13%, 39%, and 59% of the animals exhibited NCS, and 0%, 30%, and 65% of the animals exhibited PED following 5%, 10% and 12.5% PBBI, respectively. Similar correlations existed for the number of NCS and PED events and their duration. NCS and PED occurred either independently or in tandem. Longer NCS durations were associated with larger lesion volumes. Significant EEG slowing evidenced by the EEG power shift toward the δ frequency band (0.5-4 Hz) occurred within 2 h after PBBI, which resolved over time but persisted longer after greater injury severity. In contrast, decreases in higher frequency power (i.e., 30-35 Hz) remained depressed throughout 14 days. This is the first long-term cEEG study of the acute injury phase in a rat model of severe TBI, demonstrating common occurrences of clinically observed electrocortical pathology, such as NCS, PED, and cortical slowing. These EEG pathologies may serve as critical care biomarkers of brain injury, and offer clinically relevant metrics for studying acute therapeutic interventions.

Diffusion tensor imaging correlates with lesion volume in cerebral hemisphere infarctions

BackgroundBoth a large lesion volume and abnormalities in diffusion tensor imaging are independently associated with a poor prognosis after cerebral infarctions. Therefore, we assume that they are associated. This study assessed the associations between lesion volumes and diffusion tensor imaging in patients with a right-sided cerebral infarction.MethodsThe lesion volumes of 33 patients (age 65.9 ± 8.7, 26 males and 7 females) were imaged using computed tomography (CT) in the acute phase (within 3-4 hours) and magnetic resonance imaging (MRI) in the chronic phase (follow-up at 12 months, with a range of 8-27 months). The chronic-phase fractional anisotropy (FA) and mean diffusivity (MD) values were measured at the site of the infarct and selected white matter tracts. Neurological tests in both the acute and chronic phases, and DTI lateralization were assessed with the Wilcoxon signed-rank test. The effects of thrombolytic therapy (n = 10) were assessed with the Mann-Whitney U test. The correlations between the measured parameters were analysed with Spearman's rho correlation. Bonferroni post-hoc correction was used to compensate for the familywise error rate in multiple comparisons.ResultsSeveral MD values in the right hemisphere correlated positively and FA values negatively with the lesion volumes. These correlations included both lesion area and healthy tissue. The results of the mini-mental state examination and the National Institutes of Health Stroke Scale also correlated with the lesion volume.ConclusionsA larger infarct volume is associated with more pronounced tissue modifications in the chronic stage as observed with the MD and FA alterations.

Abstract #9: Gender Related Outcome Differences after Experimental Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) has been less well studied than moderate or severe injuries. Emerging clinical evidence from sports related mTBI suggests that females may have worse outcomes than males, yet few animal studies have addressed this issue. The present study compared neurobehavioral and neuropathological outcomes after experimental mTBI in male versus female mice subjected to controlled cortical impact (CCI) brain injury. Male and female C57BL/6 mice (20–25 g) were subjected to mild CCI (each n = 13) or sham injury (each n = 7). Fine motor co-ordination was evaluated by a beam walk (BW) test at 1 day, 3 days, 7 days, 14 days, and 21 days after injury and cognitive function was assessed using the Morris water maze (MWM) at 15–18 days after injury. T2-weighted MRI was performed on all mice at 21 days after mild CCI, and the injury-mediated lesion volume in each mouse brain was calculated. Mild CCI caused only a slight increase in the number of foot faults in BW in both male and female mice, without significant gender differences. In the MWM, injured male mice did not show impairments in learning and memory, compared with shams. In contrast, in female mice the latency to locate a submerged platform was significantly increased when compared with either sham or male animals (p In contrast to long-held views that females may be somewhat protected from brain trauma by virtue of estrogen or progesterone, recent clinical evidence in mTBI suggests otherwise. The current study supports these clinical observations and demonstrates that cognitive impairments are found in female but not male mice following mTBI, with parallel larger lesion volumes. This model may be used to address potential mechanisms that may account for these gender differences.

Is sagittal sinus resection in falcine meningiomas a factor of bad surgical outcome?

Objective:Meningiomas arising purely from the falx below the longitudinal sinus represents a surgical challenge for the neurosurgeon. The authors discuss the new aspects of surgical details that may avoid complications and determine the prognosis.Materials and Methods:We retrospectively evaluated our surgical experience from June 2004 to January 2010. Seventy patients harboring falcine meningiomas were included and submitted for surgical resection. All historical records, office charts and images were reviewed in order to sample the most important data regarding epidemiology, clinical pictures, radiological findings and surgical results, as well as the main complications. The patients were divided into three main groups: anterior third 32 patients (Group A), middle third 15 patients (Group B), 23 patients in the posterior third of falx (Group C).Results:In Group A, total macroscopic resection was achieved in 31 out of 32 cases (96.87%). Twenty five patients had Rankin 0, five patients had Rankin 1-2, two patients had Rankin 6. In Group B (15 patients), 10 patients had gross resection and Rankin 0, four patients had Rankin 1-2 and one patient had Rankin 6. In Group C (23 patients), 20 patients were absolutely able, Rankin score 0, after six months postoperative period (83.3% had excellent results) and no mortality. Four cases had Rankin score 1 – 2 (16.6%). Ten cases (43.47%) had Simpson I resection and ten cases (43.47%) had Simpson II.Conclusion:Despite larger lesion volumes, Group A meningiomas had a better outcome due to the position they were in, the tumor and surrounding structures. The preoperative preparation and surgical planning can preserve sagittal sinus; but in some cases, this is not possible. Sagittal sinus resection, as proven by this paper, is still a factor of bad surgical outcome. In the middle and posterior third, resection of sagittal sinus is a factor of a bad outcome, due to cerebral infartion.