Diffuse axonal injury (DAI) that follows traumatic brain injury (TBI) is thought to be a major contributor to neurocognitive dysfunction that sometimes follows TBI. Conventional magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological tests (NPT) were performed on 38 TBI patients [hemorrhagic DAI (H-DAI, n=8), non-hemorrhagic (Nh-DAI, n=7), with no apparent DAI on conventional MRI (NA-DAI, n=23)] with a Glasgow Coma Scale score ranging between 9 and 13. The fractional anisotropy (FA) and mean diffusivity (MD) were quantified from different regions of the corpus callosum (CC), and peri-ventricular white matter (PWM) within 5-14 days and 6 months following TBI. Patients in all three groups showed decreased FA in the anterior limb of the internal capsule (ALIC) and the posterior limb of the internal capsule (PLIC), while the genu of the CC showed a decrease in the H-DAI group during the early period following TBI that persisted 6 months later, which appeared to be consistent with axonopathy. In patients without abnormalities on conventional MRI and DTI in the initial phase, a significant decrease in FA and increase in MD were observed in a few regions of the CC at 6 months, which was suggestive of demyelination/gliosis. The changes in FA and MD in the CC and PWM at 6 months follow-up showed significant correlation with some of the NPT performed in the three groups. DTI demonstrates axonopathy in the acute stage, as well as at secondary stages, at 6 months post-injury in the CC and PWM in regions of normal-appearing white matter on conventional MRI.
Clinical features along with several MRI characteristics such as open ring enhancement, peripheral restriction on DWI, venular enhancement, and presence of Glx on spectroscopy may be rewarding in differentiating TDLs from neoplastic lesions.
Purpose:To detect lesion-related focal Wallerian degeneration (WD) changes in different segments of the corpus callosum (CC) in patients with large middle cerebral arterial (MCA) territory stroke using diffusion tensor imaging (DTI). Materials and Methods:Eight patients underwent DTI scans at three different time points: six to eight weeks, 10 -12 weeks, and beyond six months of stroke onset. Eight healthy age-matched controls were also scanned using the same protocol at three different time points. Region-of-interest (ROI) analysis was performed on seven segments of the CC to determine the fractional anisotropy (FA), mean diffusivity (MD), and corresponding callosal cross-sectional areas. Results:On repeated-measures analysis of variance (ANOVA), a significant reduction in the FA values was observed from the first to the third study compared to controls, reflecting temporal degeneration in the rostrum, genu, rostral body, anterior midbody, and splenium of the CC. However, a significant temporal elevation in MD values was observed in only the rostral body and anterior midbody of the CC. This was associated with a significant regionspecific reduction in the cross-sectional areas at time points beyond six months, and appears to be consistent with the loss of callosal structural components due to interruption of the cortico-callosal fibers secondary to WD. Conclusion:These results indicate that cortico-callosal topographical changes exhibit a significant temporal decline in observed FA values that is suggestive of corticocallosal WD in patients with large MCA territory stroke.
The design and synthesis of a series of seven tricyclic 6-methylidene penems as novel class A and C serine beta-lactamase inhibitors is described. These compounds proved to be very potent inhibitors of the TEM-1 and AmpC beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. In combination with piperacillin, their in vitro activities enhanced susceptibility of all class C resistant strains from various bacteria. Crystallographic structures of a serine-bound reaction intermediate of 17 with the class A SHV-1 and class C GC1 enzymes have been established to resolutions of 2.0 and 1.4 A, respectively, and refined to R-factors equal 0.163 and 0.145. In both beta-lactamases, a seven-membered 1,4-thiazepine ring has formed. The stereogenic C7 atom in the ring has the R configuration in the SHV-1 intermediate and has both R and S configurations in the GC1 intermediate. Hydrophobic stacking interactions between the tricyclic C7 substituent and a tyrosine side chain, rather than electrostatic or hydrogen bonding by the C3 carboxylic acid group, dominate in both complexes. The formation of the 1,4- thiazepine ring structures is proposed based on a 7-endo-trig cyclization.
Summary: Purpose:The main objective of this study was to use diffusion tensor imaging (DTI) to search and quantify the extent of abnormality beyond the obvious lesions seen on the T 2 and fluid-attenuation inversion recovery (FLAIR) magnetic resonance images in patients with chronic traumatic brain injury (TBI) with and without epilepsy.Methods: DTI was performed on 23 chronic TBI patients (with late posttraumatic epilepsy, n = 14; without epilepsy, n = 9) and 11 age-matched controls. The ratios of fractional anisotropy (FA) and mean diffusivity (MD) between the regions of interest beyond the T 2 /FLAIR-visualized abnormality and the corresponding contralateral normal-appearing region were calculated. FA and MD ratios were compared for relative changes in these parameters among the TBI subjects with and without epilepsy and controls. Tissue volumes exhibiting abnormalities on DTI also were measured in these patients. Results:The mean regional FA ratio was significantly lower, whereas the mean regional MD value was higher in patients with TBI compared with controls. The mean regional FA ratio was significantly lower in TBI patients with epilepsy (0.57 ± 0.059) than in those without epilepsy (0.68 ± 0.039). Although the regional MD ratio was higher in TBI patients with epilepsy (1.15 ± 0.140) relative to those without epilepsy (1.09 ± 0.141), the difference did not reach statistical significance. The tissue volume with low FA value also was found to be higher in TBI patients with epilepsy than without.Conclusions: Severity of injury as predicted by the DTIderived increased volume of microstructure damage is associated with delayed posttraumatic epilepsy in TBI patients. These findings could be valuable in predicting epileptogenesis in patients with chronic TBI. Key Words: Diffusion tensor imaging-Traumatic brain injury-Posttraumatic epilepsyFractional anisotropy-Magnetic resonance imaging. Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality in developed countries, and posttraumatic epilepsy (PTE) is the major sequela (1,2). PTE is classified into three groups, depending on when seizures occur after TBI: (a) within 24 h, (b) during the first week, and (c) after >1 week (3,4). The first two groups are termed early PTE and are the result of direct response to the brain damage. The third category represents late PTE. The severity and type of brain injury appear to correlate with the incidence of PTE. The factors that are known to contribute to the risk of PTE are duration of unconsciousness, dura penetration, degree of direct cortical damage, and genetic predisposition to epilepsy (5). Structural damage resulting from trauma itself, or hypoxic damage and subsequent scarring and inadequate blood flow also are the major contributing factors to the risk of PTE. The investigation and management of patients after
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