We examined a variety of strains of Sindbis virus for the genetic changes responsible for differences in neurovirulence in mice. SVlA (a low passage of the AR339 strain of Sindbis virus), a neuroadapted Sindbis virus (NSV), and two laboratory strains of Sindbis virus (HRSP and TotollOl) were examined. NSV causes severe encephalomyelitis with hind-limb paralysis and high mortality after intracerebral inoculation in weanling mice. In contrast, SV1A causes only mild, nonfatal disease in weanling mice; however, in suckling mice, SVlA causes a fatal encephalomyelitis after either intracerebral or subcutaneous inoculation. The two laboratory strains used have a greatly reduced neurovirulence for suckling mice and are aviruleit for weanling mice. The nucleotide sequences and encoded amino acid sequences of the structural glycoproteins of these four strains were compared. Hybrid genomes were constructed by replacing restriction fragments in a full-length cDNA clone of Sindbis virus, from which infectious RNA can be transcribed in vitro, with fragments froni cDNA clones of the various strains. These recombinant viruses allowed us to test the importance of each amino acid difference between the various strains for neurovirulence in weanling and suckling mice. Glycoproteins E2 and El were of paramount importance for neurovirulence in adult mice. Recombinant viruses containing the nonstructural protein region and the capsid protein region from an avirulent strain and the El and E2 glycoprotein regions from NSV were virulent, although they were less virulent than NSV. Furthermore, changes in either E2 (His-55 in NSV to Gln in SV1A) or El (Ala-72 in NSV to Val in SVlA and Asp-313 in NSV to Gly in SVIA) reduced virulence. For virulence in suckling mice, we found that a number of changes in E2 and El can lead to decreased virulence and that in fact, a gradient of virulence exists.

Mild traumatic brain injury (MTBI) is a common reason for hospital attendance and is associated with significant delayed morbidity. We studied a series of 80 persons with MTBI. Magnetic resonance imaging (MRI) and neuropsychological testing were used in the acute phase and a questionnaire for post-concussion syndrome (PCS) and return to work status at 6 months. In 26 subjects abnormalities were seen on MRI, of which 5 were definitely traumatic. There was weak correlation with abnormal neuropsychological tests for attention in the acute period. There was no significant correlation with a questionnaire for PCS and return to work status. Although non-specific abnormalities are frequently seen, standard MRI techniques are not helpful in identifying patients with MTBI who are likely to have delayed recovery.

ABSTRACT:Twelve fatal cases of encephalopathy associated with sepsis were examined in a ten-year retrospective study. The sources of infection and organisms isolated were variable. Six of the patients had focal neurologic signs; five had seizures. The level of consciousness varied from drowsiness to deep coma, and electroencephalograms revealed diffuse or multifocal abnormalities. Computed tomographic head scans and cerebrospinal fluid examinations were usually unremarkable. Eight patients had disseminated microabscesses in the brain at autopsy. Four patients had proliferation of astrocytes and microglia in the cerebral cortex, a feature associated with metabolic encephalopathies. Additional findings included cerebral infarcts, brain purpura, multiple small white matter hemorrhages, and central pontine myelinolysis. Although sepsis may cause encephalopathy by producing disturbances in cerebral synaptic transmission and cerebral energy production through a toxic mechanism, bacterial invasion of the brain with the formation of disseminated microabscesses is also an important cause.

Conventional structural imaging provides limited information on tumor characterization and prognosis. Advances in neurosurgical techniques, radiotherapy planning and novel drug treatments for brain tumors have generated increasing need for reproducible, noninvasive, quantitative imaging biomarkers. This Review considers the role of physiological MRI and PET molecular imaging in understanding metabolic processes associated with tumor growth, blood flow and ultrastructure. We address the utility of various techniques in distinguishing between tumors and non-neoplastic processes, in tumor grading, in defining anatomical relationships between tumor and eloquent brain regions and in determining the biological substrates of treatment response. Much of the evidence is derived from limited case series in individual centers. Despite their 'added value', the effect of these techniques as an adjunct to structural imaging in clinical research and practice remains limited.

Abstract. Th e pathogenesis of Venezuelan eq uine encephalitis (VEE) viru s infection was compared in intraperitoneally inoc ulated mice (n = 24, 6 to 8 weeks old) and ham sters (n = 9, 90-110 g) using histopathology and immunohistochemi cal localizati on ofVEE virus antigen. Infected mice developed paralysis, and the majority died by 9 da ys after inoculat ion . In contrast, ham sters did not survi ve beyond 3 days after inoculati on , and they did not develop any neu rologic signs. VEE virus antigen, dem onstrated by immunoperoxidase staining, and pathologic cha nges were present in extraneural organs of both mice and ham sters. There was more seve re involveme nt in hamsters, particularl y in Peyer' s patches of the distal small intestine. Th ere was a seve re encepha lomyelitis in mice, but path ologic cha nges were not well esta blished in the brain s of hamsters before death . VEE virus an tigen was wides pread in the central nervou s system of both mice and ham sters. VEE virus was found to be highly neurotrop ic in ham sters and had a simi lar distribut ion in the brain as in mice, but ham sters di ed from their extra neura l disease before major central nervous system disease developed.