Aggressive immunosuppressive treatment of Susac's syndrome in an adolescent: using treatment of dermatomyositis as a model

We describe aggressive immunosuppressive treatment of an adolescent with Susac's syndrome (SS), a disease of the microvasculature in the brain, retina, and inner ear. Because the immunopathogenesis of SS appears to have much in common with that of juvenile dermatomyositis (JDM), the patient was treated with an approach that has been effective for severe JDM. The patient's outcome provides evidence for the importance of prompt, aggressive, and sustained immunosuppressive treatment of encephalopathic SS

Discussion: “Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties” (Rowland, E. M., Mohamied, Y., Chooi, K. Y., Bailey, E. L., and Weinberg, P. D., 2015, ASME J. Biomech. Eng., 137(10), p. 101003): An Alternative Approach Using Segmentation Based on Local Hemodynamics

The biological response of living arteries to mechanical forces is an important component of the atherosclerotic process and is responsible, at least in part, for the well-recognized spatial variation in atherosusceptibility in man. Experiments to elucidate this response often generate maps of force and response variables over the arterial surface, from which the force–response relationship is sought. Rowland et al. discussed several statistical approaches to the spatial autocorrelation that confounds the analysis of such maps and applied them to maps of hemodynamic stress and vascular response obtained by averaging these variables in multiple animals. Here, we point out an alternative approach, in which discrete surface regions are defined by the hemodynamic stress levels they experience, and the stress and response in each animal are treated separately. This approach, applied properly, is insensitive to autocorrelation and less sensitive to the effect of confounding hemodynamic variables. The analysis suggests an inverse relation between permeability and shear that differs from that in Rowland et al. Possible sources of this difference are suggested

Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue

BACKGROUND: The arachnoid granulations (AGs) are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF) to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. METHODS: Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7–10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7–10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144) and their expression was quantified using flow cytometry analysis. RESULTS: Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. CONCLUSION: To our knowledge, this is the first report of the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow

Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex

<p>Abstract</p> <p>Background</p> <p>The arachnoid granulations (AGs) are herniations of the arachnoid membrane into the dural venous sinuses on the surface of the brain. Previous morphological studies of AGs have been limited in scope and only one has mentioned surface area measurements. The purpose of this study was to investigate the topographic distribution of AGs on the superior surface of the cerebral cortex.</p> <p>Methods</p> <p><it>En face </it>images were taken of the superior surface of 35 formalin-fixed human brains. AGs were manually identified using Adobe Photoshop, with a pixel location containing an AG defined as 'positive'. A set of 25 standard fiducial points was marked on each hemisphere for a total of 50 points on each image. The points were connected on each hemisphere to create a segmented image. A standard template was created for each hemisphere by calculating the average position of the 25 fiducial points from all brains. Each segmented image was mapped to the standard template using a linear transformation. A topographic distribution map was produced by calculating the proportion of AG positive images at each pixel in the standard template. The AG surface area was calculated for each hemisphere and for the total brain superior surface. To adjust for different brain sizes, the proportional involvement of AGs was calculated by dividing the AG area by the total area.</p> <p>Results</p> <p>The total brain average surface area of AGs was 78.53 ± 13.13 mm²(n = 35) and average AG proportional involvement was 57.71 × 10^-4± 7.65 × 10^-4. Regression analysis confirmed the reproducibility of AG identification between independent researchers with r²= 0.97. The surface AGs were localized in the parasagittal planes that coincide with the region of the lateral lacunae.</p> <p>Conclusion</p> <p>The data obtained on the spatial distribution and <it>en face </it>surface area of AGs will be used in an <it>in vitro </it>model of CSF outflow. With an increase in the number of samples, this analysis technique can be used to study the relationship between AG surface area and variables such as age, race and gender.</p

Mechanism of CSF Outflow Through Human Arachnoid Granulations

We have evidence of outflow of CSF through arachnoid granulations(AG) using both an in-vitro and ex-vivo perfusion model

Mechanism of CSF Outflow Through Human Arachnoid Granulations Using In Vitro and Ex-Vivo Perfusion Models

In IIH disturbed CSF dynamics may result from an increased resistance to CSF outflow at the arachnoid granulations(AGs). We modeled the outflow of CSF through human AGs using cell culture(in-vitro) and whole tissue(ex-vivo) perfusion models