Acta neurologica Scandinavica. Supplementum最新文献

This consensus-based document on dementia diseases was worked out in 1988-1990 by Swedish dementia researchers. It comprises classification and nosology of dementia diseases taking into account brain-regional symptomatology and the pattern of degeneration. The significance of history-taking and 'bedside' examination is emphasized. Auxiliary diagnostic investigations are discussed, e.g. neuropsychological examination, brain imaging, and blood and cerebrospinal fluid analyses.

Background: Multiple sclerosis (MS) is characterized by perivascular inflammation and high levels of circulating T and B lymphocytes that respond to the myelin antigens myelin basic protein (MBP) and proteolipid protein (PLP), thereby suggesting a role for immunoregulatory cytokines.

Materials and method: Blood mononuclear cells (MNC) were prepared from patients with MS, optic neuritis (ON), myasthenia gravis (MG), other inflammatory (OIND) and non-inflammatory neurological diseases (OND), and from patients with HIV infection and healthy controls. MNC expressing cytokine mRNA were detected by in situ hybridization with radiolabelled cDNA oligonucleotide probes. Numbers of cytokine mRNA expressing cells were presented per standard numbers of MNC.

Results: MS patients had elevated numbers of MNC in blood expressing T helper type 1 (Th1) cell related interferon-gamma (IFN-gamma), Th2 cell associated interleukin-4 (IL-4) and the endogenously produced immunosuppressant transforming growth factor-beta (TGF-beta). IFN-gamma and TGF-beta correlated with MS disability: EDSS score < 3 was associated with high numbers of TGF-beta mRNA positive cells while IFN-gamma mRNA positive cells tended to be low. The reverse was seen in patients with EDSS > or = 3. Cultures of MNC in presence and absence of antigen revealed that MBP and PLP induced strong responses in MS reflected by high levels of IFN-gamma, IL-4 and TGF-beta mRNA expressing cells. Recombinant (r) TGF-beta 1 dose-dependently suppressed MBP-induced upregulation of the proinflammatory cytokines IFN-gamma, IL-4, IL-6, tumor necrosis factor-alpha, (TNF-alpha), TNF-beta and perforin, but not of the immunosuppressive and probably advantageous IL-10. Cytokine mRNA expressing cells were enriched in the MS patients' cerebrospinal fluid, as were the cytokine mRNA positive cells detected after culture in presence of MBP and PLP, reflecting an autonomy of the immune response in this compartment. ON, in many instances representing early MS, did not differ from clinically definite MS regarding profiles of IFN-gamma, IL-4 and TGF-beta. Also patients with MG had elevated numbers of IFN-gamma, IL-4 and TGF-beta mRNA expressing blood MNC. They were further augmented upon culture of the MG patients' MNC in presence of acetylcholine receptor (AChR). An upregulation of AChR-induced TGF-beta was observed in thymectomized patients. rTGF-beta suppressed AChR-induced upregulation of proinflammatory cytokines but not IL-10. Elevated numbers of IFN-gamma, IL-4 and TGF-beta mRNA expressing blood MNC were also found in patients with OIND (aseptic meningo-encephalitis, chronic inflammatory demyelinating polyneuropathy, polymyositis, Eaton-Lambert syndrome) and in HIV-infected patients. In HIV infection, numbers of IL-4 mRNA positive cells correlated inversely with CD4+ cell counts, reflecting the involvement of IL-4 in later stages of the disease. Patients with non

To further understand the control of brain tumor fluid balance and pH, the following studies were undertaken. The transport of a water soluble molecule across the brain and tumor capillary endothelium was studied during glucocorticoid and radiation treatment. The brain and brain-tumor acidity (pH) was evaluated as a single measurement in patients receiving a low maintenance dose of glucocorticoid. Transport changes and pH were measured in 61 patients with cerebral tumors using 82Rubidium (82Rb) and 11C-Dimethyloxa-zolidindione (11C-DMO), respectively, and Positron Emission Tomography (PET). Supplementary studies of tumor and contralateral brain blood flow and blood volume using the C15O2/PET and C15O/PET technique, respectively, were included to validate the 82Rb/PET model and obtain further information. A total of 125 PET scans were performed. Supplementary studies were undertaken to estimate delay of blood registration and form distribution of arterial blood isotope activity curves. Blood-to-tumor barrier transport was outlined at baseline and at 6 and 24 hours after the start of glucocorticoid treatment, finding a significant decrease in the transport. Radiation treatment (2-6 gray) did not alter the blood-to-tumor barrier transport when restudied within one hour in patients receiving glucocorticoid. In accordance with others, we observed pH values in gray and white matter in the range of 6.74-7.09 and 6.77-7.03 respectively. The pH in brain tumors was as high as 6.88-7.26, suggesting that tumors are more alkalotic than the normal brain. The permeability surface area product and the permeability coefficient were determined from the 82Rb/PET transport and C15O2/PET flow studies. Baseline permeability values were comparable to the literature values both for 82Rb and potassium. No difference in tissue blood volume was seen between 82Rb/PET and C15O/PET models and was of the same magnitude in the tumor and the contralateral tissue. The pH and fluid control in human brain tumors are perceived as metabolically controlled rather than, as previously believed, a result of simple passive exchange of alkalotic or osmotic active molecules between plasma and tumor interstitial space. Aspects of tumor alkalosis, tumor edema production, glucocorticoid edema clearance, and relationship between the anti-edema effect of glucocorticoid and the shown transport changes to 82Rb will be reviewed in the light of metabolic control mechanisms.

Lyme neuroborreliosis (LNB) has within the last few years become one of the most frequent neuroinfections. This thesis is based on 7 publications which have two main topics: (i) to improve and develop laboratory methods for routine diagnosis of LNB, (ii) to generate epidemiological data for LNB and to achieve a descriptive clinical delimitation of this disease. Laboratory diagnosis in Lyme borreliosis is based on detection of a Borrelia burgdorferi (Bb) specific immune response. Up till now serological assays have not achieved a sufficient diagnostic specificity and sensitivity. This is partly due to the use of test antigens consisting of all proteins of the spirochete including broadly cross-reacting antigens. In order to improve diagnostic antibody detection we isolated an immunodominant structural protein of Bb, the motility organelle the flagellum. The use of native, morphologically intact flagella as test antigen in ELISA led to a significantly increased diagnostic specificity, and, especially in early disease, to an improved diagnostic sensitivity. Reservations regarding the use of only one out of the over 100 proteins of Bb as a diagnostic antigen probe are groundless. The early as well as the late immune response to Bb always includes antibodies to the flagellum. The Bb flagellum is as a test antigen not completely Bb specific. Compared with all other antigen preparations however, the flagellum is at present the best compromise, if a sensitive and specific routine serology is requested. The diagnostic performance of specific IgM detection was improved with a mu-capture ELISA, which used biotin labelled Bb flagella. Compared to conventional indirect ELISA this technique avoids false positive results due to IgM rheumatoid factor interference and false low or false negative results due to IgG competition for the test antigen. The antibody response in Bb infection develops slowly. Patients with LNB can be antibody negative in blood up to 6-8 weeks after onset of neurological symptoms. Longstanding but seronegative disease in untreated patients is unlikely to occur. Expectations of further improvement of Lyme borreliosis serology focuses presently on the performance of the outer surface protein (Osp) C as a test antigen and on the genus specific domain of the Bb flagellin. Theoretically this region constitutes the best candidate for a better test antigen either as a recombinant or a synthetic peptide. In LNB a prominent Bb specific intrathecal antibody response develops.(ABSTRACT TRUNCATED AT 400 WORDS)

In patients with early, otherwise untreated Parkinson's disease, the abilities of selegiline (deprenyl) and tocopherol, antioxidative agents that act through complementary mechanisms, to delay the emergence of more severe disability requiring treatment with levodopa were evaluated. Eight hundred subjects were randomly assigned in a two-by-two factorial design to receive selegiline (10 mg per day), tocopherol (2000 IU per day), selegiline and tocopherol, or placebo and were followed up to determine the frequency of development of disability requiring treatment with levodopa, the primary end point. Interim analysis performed by an independent safety monitoring committee prompted a preliminary comparison of the 401 subjects assigned to tocopherol or placebo with the 399 subjects assigned to selegiline, alone or with tocopherol. During an average of 12 months of follow-up, only 97 subjects who received selegiline reached the end point. In contrast, 176 subjects who did not receive selegiline reached the end point during this period (P < 10(-8)). Selegiline was also found to be well tolerated and to have a small, but statistically significant symptomatic benefit. These results indicate that use of selegiline (10 mg per day) in patients with early, otherwise untreated Parkinson's disease, delays the emergence of more severe disability.