Inflammatory central nervous system demyelination: Correlation of magnetic resonance imaging findings with lesion pathology

Magnetic resonance imaging (MRI) is widely used to evaluate and monitor disease activity in inflammatory demyelinating central nervous system (CNS) diseases such as multiple sclerosis. The present study aimed at correlating MRI findings with histological parameters in 6 cases of biopsy-proven inflammatory demyelination of the CNS. The earliest stages of demyelinating activity manifested as almost isointense lesions with a massive gadolinium-DTPA (Gd-DTPA) enhancement in T1-weighted scans. In T2-weighted scans, early active lesions formed a border of decreased intensity compared with the lesion center and the perifocal edema. The morphological correlate of this pattern in our patients was activated macrophages in the zone of myelin destruction at the plaque border. Late active lesions were hypointense in T1 and hyperintense in T2 scans. Inactive demyelinated and remyelinating lesions were hyperintense in T2 scans and enhanced inhomogenously after Gd-DTPA application. T1 scans revealed major differences in the degree of hypointensity that correlated with the extent of axonal damage, extracellular edema, and the degree of demyelination or remyelination.     

Cortical,subcortical and spinal alterations in neuroimmunological diseases

Journal of Neurology - Inflammatory and immune mediated diseases of the nervous system are reflected by a broad spectrum of different clinical deficits. The reason for this is that inflammation may...     

Effects of clonidine on the stimulation-evoked release of3H-noradrenaline from superfused rat brain slices as a function of the biophase concentration

The influence of clonidine on the stimulation-evoked overflow of tritium was studied in brain slices preincubated with 3H-noradrenaline. The slices were prepared from parietal cortex (Cx), nucleus anterior hypothalami (nah) and nucleus tractus solitarii (nts). After preincubation, the tissues were superfused at 23 degrees C or 37 degrees C with a medium containing the noradrenaline uptake inhibitor desipramine. Electrical field stimulation was applied using stimulation frequencies of 0.3-10 Hz. At 23 degrees C/0.3 Hz, clonidine concentration-dependently inhibited the evoked overflow of tritium in all three brain regions. In contrast, at 23 degrees C/3 Hz the inhibitory effect of the drug in the Cx was abolished and a facilitation was observed in the nah and nts. When tested at increasing frequencies of stimulation in the nts at 23 degrees C, clonidine exerted a dual action, characterized by a reduction of electrically evoked responses at frequencies below 1 Hz and a facilitation at frequencies above 1 Hz. At 37 degrees C, clonidine concentration-dependently decreased the evoked overflow in all brain regions studied, this effect being more pronounced at 0.3 Hz than at 3 Hz. The apparent lack of an effect of clonidine on the stimulation-evoked overflow of tritium in the Cx at 23 degrees C/3 Hz was turned to a facilitation when noradrenaline (0.01 mumol/l) was included in the superfusion medium. Conversely, an inhibitory effect of clonidine was seen when the uptake blocker desipramine (as well as noradrenaline) was omitted from the superfusion medium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ganglioside GM1, a molecular target for immunological and toxic attacks: similarity of neuropathological lesions induced by ganglioside-antiserum and cholera toxin

Summary Ganglioside-antisera, the ganglioside G_M1-ligands, cholera toxin (CT), and CT subunit B, respectively, were injected into the lumbosacral subarachnoid space of normal rats. The cytotoxic effects of the injected compounds on the peripheral and central nervous system were investigated by light and electron microscopy; the severity of CNS lesions was evaluated by quantitation of macrophages containing debris. In contrast to control sera and G_M2-antiserum, antisera against a mixture of the major brain gangliosides G_M1, G_D1a, G_D1b, and G_T1b (MaBG) or against G_M1 induced demyelination in spinal roots and spinal cord, as well as alterations of astroglia. CT induced the same cytotoxic effects as MaBG- and G_M1-antisera, whereas CT subunit B was without effect. The ineffectiveness of G_M2-antiserum is obviously due to the very low concentration of the specific binding target, G_M2, on cell surfaces; that of CT subunit B to the lack of the cytotoxic operator, subunit A. Our results indicate that a similar pattern of neuropathological lesions may be effected by different cytotoxic mechanisms through attachment of the cytotoxic agent onto the cell surface via a common target molecule, and further substantiate the role of G_M1-antibodies in the pathogenesis of demyelination.Dedicated to Prof. F. Seitelberger on the occasion of his seventieth birthdaySupported by Austrian Science Research Fund, Project Nos. S-25/04, S-25/06, and P 5354     

The immunopathology of multiple sclerosis: an overview

Multiple sclerosis (MS) is traditionally seen as an inflammatory demyelinating disease, characterized by the formation of focal demyelinated plaques in the white matter of the central nervous system. In this review we describe recent evidence that the spectrum of MS pathology is much broader. This includes demyelination in the cortex and deep gray matter nuclei, as well as diffuse injury of the normal-appearing white matter. The mechanisms responsible for the formation of focal lesions in different patients and in different stages of the disease as well as those involved in the induction of diffuse brain damage are complex and heterogeneous. This heterogeneity is reflected by different clinical manifestations of the disease, such as relapsing or progressive MS, and also explains at least in part the relation of MS to other inflammatory demyelinating diseases.     

Thyroid cancer in childhood: management strategy, including dosimetry and long-term results

Thyroid cancer, although very rare in childhood, represents the most common pediatric endocrine neoplasia. The low incidence and the resulting limited availability of prospective, randomized trials lead to a lack of evidence- based recommendations for treatment strategies. Total thyroidectomy and lymphadenectomy, when indicated, followed by ablative radioiodine treatment, are considered the cornerstones of initial patient management which decrease the risk of relapse. On the other hand, less aggressive treatment modalities should also be aimed at due to the high life expectancy of this special patient group and the potential impairment of the quality of life. These considerations have led to individualized "tailored" therapeutic approaches based on prior risk stratification. This article mainly deals with novel nuclear medicine concepts for dosing regimens in radioiodine therapy.     

The increased frequency of the Lewis negative blood group in a diabetic population

Summary The Lewis negative (Le a– b –) red blood cell phenotype was observed three times more frequently in 170 diabetics (29%) irrespective of their clinical type, than in 100 controls (10%). This difference could not be accounted for by factors influencing the serological typing (ABH secretion and ABO groups) nor by the geographic origin of the populations tested. The Lewis substances are primarily soluble antigens present in blood, saliva and other fluids and absorbed on red blood cells. In 61 diabetics saliva was also analysed. Blood cell and saliva results were concordant allowing the interpretation of the Lewis negative red cell phenotype to indicate the absence of the Lewis antigen. The higher frequency of the Lewis negative phenotype was not related to the severity or the duration of the diabetes and therefore was unlikely to depend on metabolic factors. It probably indicates an increased frequency of (le, le) genotype in the diabetic population. The similarity between the results for insulin dependent and insulin independent diabetes seems to indicate that these two clinical types of diabetes are genetically related.