Effect of steroids on edema and sodium uptake of the brain during focal ischemia in rats.Surprising as it may sound cerebral edema is a fairly common pathophysiological entity which sheroids encountered in many clinical conditions. Many of these conditions present as medical and surgical emergencies. Pathophysiology of cerebral edema at cellular level is complex. Damaged cells swell, injured blood vessels leak and blocked absorption pathways force fluid to enter brain tissues. Cellular and blood vessel damage follows synthesis of testosterone from androstenedione how do steroids decrease cerebral edema an injury cascade.
Cerebral Edema and its Management
The mechanisms by which the glucocorticoid dexamethasone produces its therapeutic action in patients with intracranial tumors still remain unclear. The purpose of this study was to investigate whether dexamethasone affects cerebral perfusion and water molecule diffusion by using quantitative dynamic susceptibility contrast perfusion MR imaging DSC-MR imaging and diffusion tensor MR imaging DT-MR imaging. There was, however, an increase in edematous brain CBF These data suggest that dexamethasone does not significantly affect tumor blood flow but may, by reducing peritumoral water content and local tissue pressure, subtly increase perfusion in the edematous brain.
Because of its rapid and beneficial clinical effects, the synthetic glucocorticoid dexamethasone has been routinely used in the management of patients with intracranial tumors for the past 3 decades. Studies in both humans and animal models suggest that its principal effect is to reduce edema formation, hence lowering intracranial pressure. Unfortunately, those studies performed to date that have investigated how steroids affect cerebral perfusion have produced contradictory results, both in terms of the magnitude and direction of perfusion changes.
In view of the conflicting data and these methodologic problems, a pilot study was performed in which dynamic susceptibility contrast perfusion MR imaging DSC-MR imaging was used to measure quantitative values of cerebral blood flow CBF , cerebral blood volume CBV , and mean transit time MTT for enhancing tumor, nonenhancing peritumoral edematous brain, and normal-appearing contralateral white matter in a group of patients with high-grade glioma before and 48—72 hours after dexamethasone treatment.
By measuring these parameters before and after treatment in the 3 regions, it is possible to determine whether and by how much cerebral perfusion is altered by dexamethasone and whether the changes are localized to the tumor region or are more global in nature.
Ten consecutive patients 8 men and 2 women; age range, 40—76 years; mean age, Their radiologic data did not suggest any neurologic disorders other than the primary neoplasm.
The tumor type was histologically confirmed in all patients following MR imaging. At the time of imaging, none of the patients had 1 begun steroid treatment, 2 had any prior radiation therapy or chemotherapy, or 3 undergone any prior cranial surgery. They also had no contraindications to MR imaging. The local ethics committee approved the study and informed consent was obtained from each patient. At least one of the sections was taken through a prominent anatomic landmark so as to minimize any deviation in section location in the second scan.
Computational image realignment techniques were then used to warp the images in the second examination to the first, thereby minimizing any small remaining positioning differences. Five acquisitions consisting of a baseline T2-weighted echo-planar EP image and 6 diffusion-weighted EP images, a total of 35 EP images, were collected per section position.
The acquisition parameters for the EP imaging sequence were 15 axial sections of 5-mm thickness and 1. Cerebral perfusion was measured by imaging the dynamic signal intensity change following a bolus injection of a gadolinium-based contrast agent.
Thirty-four volumes of 15 axial sections of 5-mm thickness and 1. Following the DSC-MR imaging protocol, a contrast-enhanced T1-weighted volume sequence was also collected by using the following acquisition parameters: The concentration-time curves were fitted by using a gamma-variate function to estimate and remove the difference in bolus arrival time and recirculation artifacts.
Singular value decomposition was used to perform the deconvolution of the AIF and tissue concentration-time curves. To allow regions of enhancing tumor to be accurately positioned on the cerebral perfusion and water diffusion parametric maps for both scans, the contrast-enhanced T1-weighted volume images from the presteroid treatment scan were registered directly onto the corresponding T2-weighted EP images by using image boundary and internal landmark information in SPM www.
The effects of dexamethasone on cerebral perfusion and water diffusion in these tissue types were quantified by using the following region of interest analysis. Nonenhancing peritumoral edematous brain was then defined for each section as the largest region of signal intensity hyperintensity on the T2-weighted EP images, which extended beyond enhancing tumor Fig 1.
Overall mean cerebral perfusion and water diffusion values for the entire enhancing tumor and peritumoral edematous brain volumes in each patient were then calculated from this multisection data. These volume measurements were typically obtained from thousands of voxels in 5—12 sections for enhancing tumor and peritumoral edematous brain and hundreds of voxels in a single section for normal-appearing contralateral white matter in centrum semiovale.
Images obtained from patient 4. A, Presteroid treatment contrast-enhanced T1-weighted volume image with region of interest indicating enhancing tumor. Pre- B and 72 hours C poststeroid treatment T2-weighted EP images with shaded and unshaded region of interest indicating enhancing tumor and nonenhancing peritumoral edematous brain.
Figure 1 shows presteroid treatment contrast-enhanced T2-weighted volume and pre- and poststeroid treatment T2-weighted EP images for a representative section location acquired from a year-old woman patient 4. Regions corresponding to enhancing tumor and nonenhancing peritumoral edematous brain are indicated by shaded and unshaded regions of interest in the T2-weighted EP images.
Note the very subtle reduction in signal intensity of peritumoral edematous brain between the pre- and poststeroid treatment T2-weighted EP images.
This subtle reduction in edematous brain T2-weighted signal intensity was also seen in several other patients. In 3 patients 2, 5, and 10 , there was no evidence of edema on T2-weighted EP imaging.
For this patient group, average enhancing tumor CBF was practically unchanged There was an increase in edema CBF Several previous imaging studies have investigated whether dexamethasone affects cerebral perfusion in intracranial tumors. Unfortunately, the results of these studies are contradictory possibly because of methodologic differences and heterogeneous tumor patient populations. Here, in the largest MR imaging study to date, quantitative cerebral perfusion parameters were measured in a group of patients with high-grade glioma to address further this question.
After 48—72 hours of steroid treatment, tumor CBF was practically unchanged, whereas edematous brain CBF increased on average by Several other studies produced results that are consistent with this observation. Van Roost et al 8 used xenon-enhanced CT Xe-CT to assess the effects of daily dose 0—32 mg , cumulative dose 0 to mg , and duration of dexamethasone treatment 0—36 days on cerebral perfusion in 26 patients with GBM.
They found that, although CBF was inversely correlated with daily dose of dexamethasone in several gray and white matter regions within the contralateral hemisphere, CBF of solid and necrotic tumor was not correlated with any of the dexamethasone treatment parameters. Furthermore, they found that edematous brain CBF was positively correlated with both duration and total dose of dexamethasone treatment.
Apart from a reduction in CBF in some normal tissue regions, these findings of no alterations in tumor CBF and an increase in edematous brain CBF are similar to those presented above. In brief, they argue that the raised extracellular water content of edematous brain produces an increase in the local tissue extravascular pressure, which in turn reduces peritumoral blood flow by collapsing the capillaries and raising the local cerebrovascular resistance.
As dexamethasone reduces edematous brain water content, the local tissue pressure is also reduced leading to an increase in peritumoral blood flow. This may be one of the mechanisms responsible for the increase in edematous brain perfusion seen in the current study. The view that dexamethasone produces no change in tumor perfusion and an increase in edematous brain perfusion is contradicted by results from the studies by Leenders et al 6 and Behrens et al.
In that study, it was hypothesized that dexamethasone causes vasoconstriction by inhibiting the release of prostacyclin, a powerful vasodilator, from vascular endothelial cells. They also found that CBF in contralateral cortex and white matter was significantly reduced compared with values measured in a control group of 10 patients with Parkinson disease; however, because all the patients were undergoing steroid treatment at the time of imaging and no baseline scans were acquired, it is not possible to determine completely the effects of dexamethasone on cerebral perfusion from this study.
In addition, except for the patient with CNS lymphoma, they found that both peritumoral gray and white matter rCBF did not show any systematic change after steroid treatment data not shown.
Differences in imaging methodology, steroid dosage, and time to imaging after steroid administration, however, make direct comparison of these studies difficult. Similarly, the relatively low spatial resolution of EP images may lead to partial-volume averaging of artery and tissue signals, which will affect the characterization of the AIF and hence the measured perfusion parameters.
Different tissue characteristics will also affect the accuracy of the perfusion data. In view of these problems, several authors have compared DSC-MR imaging with other imaging methods that generate quantitative measures of cerebral perfusion. However, in light of the increasing use of DSC-MR imaging to characterize perfusion in a range of different pathologies, further studies are required to investigate the accuracy of perfusion measured by using DSC-MR imaging and its relationship to data obtained from other imaging modalities in both healthy and diseased brain.
In addition to the small number of subjects scanned in this study, a further problem in determining the significance of the current results is demonstrated by Tables 1 and 2 , which show how variable tumor and peritumoral edematous brain perfusion is from patient to patient, even in a group of subjects with the same tumor type.
High-grade gliomas are characterized by their highly abnormal microvasculature, which gives rise to extremely variable and heterogeneous blood flow patterns, 18 so perhaps this is to be expected. This indicates that the effect size of perfusion changes in peritumoral edematous brain after 48—72 hours of steroid treatment is small. In addition to performing much larger studies, the effect size for edematous brain perfusion changes could be increased by performing imaging at time points beyond 48—72 hours of treatment, whereas the study of Van Roost et al 8 suggests that increases in perfusion relative to baseline might become more significant.
Such time-series data on the longer-term effects of steroids on cerebral perfusion will be vital in studies assessing the efficacy of angiogenesis-inhibiting drugs, 19 because patients will most likely be taking steroids concurrently with these newer treatments.
After 48—72 hours of treatment, no significant change in CBF, CBV, or MTT was observed in enhancing tumor or normal-appearing contralateral white matter, but nonenhancing peritumoral edematous brain CBF was increased by These data suggest that dexamethasone does not significantly affect tumor blood flow, but may subtly increase perfusion in edematous brain by reducing peritumoral water content and hence local tissue pressure.
Larger studies in homogeneous groups of patients are now required to replicate these findings, and to investigate further the longer-term effects of steroids on cerebral perfusion in intracranial tumors.
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We do not capture any email address. This article has not yet been cited by articles in journals that are participating in Crossref Cited-by Linking. Skip to main content. American Journal of Neuroradiology February , 27 2 ;. Methods Patients Ten consecutive patients 8 men and 2 women; age range, 40—76 years; mean age, Results Figure 1 shows presteroid treatment contrast-enhanced T2-weighted volume and pre- and poststeroid treatment T2-weighted EP images for a representative section location acquired from a year-old woman patient 4.
View inline View popup. Discussion Several previous imaging studies have investigated whether dexamethasone affects cerebral perfusion in intracranial tumors.
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Experimental comparison and preliminary results.