1,721,031 research outputs found
Multiple sclerosis: symptomatic management
No full textSymptomatic management con improve quality of life in multiple sclerosis (MS) patients. Although only few symptoms and signs completely disappear through symptomatic treatment, substantial relief is possible in most patients. Especially bladder dysfunction and pain syndromes require accurate diagnosis in order to allow drug therapy that is based on the given pathogenetic context. The individual choice of drugs and careful dose adjustment is of great importance for sufficient treatment of patients. Particularly in case of spasticity, positive and negative aspects of drug therapy are closely adjacent. Finally, the benefit from physiotherapy and ergotherapy can not be overestimated
Multiple sclerosis: symptomatic management
No full textSymptomatic management con improve quality of life in multiple sclerosis (MS) patients. Although only few symptoms and signs completely disappear through symptomatic treatment, substantial relief is possible in most patients. Especially bladder dysfunction and pain syndromes require accurate diagnosis in order to allow drug therapy that is based on the given pathogenetic context. The individual choice of drugs and careful dose adjustment is of great importance for sufficient treatment of patients. Particularly in case of spasticity, positive and negative aspects of drug therapy are closely adjacent. Finally, the benefit from physiotherapy and ergotherapy can not be overestimated
New antiviral drugs
No full textThe number of available antiviral drugs increases constantly. Beyond antiretroviral compounds with activity against HIV, most of the recently introduced virustatic drugs unfold their activity against members of the Herpesvirus family, especially herpes-zoster- and herpes-simplex viruses. However, controlled studies on viral infections of the nervous system are rare, perhaps with the one exception of herpes zoster. Some studies on herpes zoster indicate that with modern antiviral substances like famiciclovir or valaciclovir acute zoster pain and post zoster neuralgia may be shortened in duration and reduced in frequency. Concerning the antiviral treatment of encephalitis with new virustatics, our experience is mainly based on case reports. Nevertheless, the broader spectrum of antiviral substances offers the possibility to treat individual encephalitis patients with drugs that have at least in vitro activity against the causative virus. In herpes-simplex-encephalitis, aciclovir remains the antiviral drug of first choice
Evidence for local and systemic elimination of macrophages from the injured peripheral nervous system
No full textTumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: Correlation with demyelinating activity and oligodendrocyte pathology
No full textThe precise role of tumour necrosis factor alpha (TNF alpha) in multiple sclerosis (MS) is still controversial. Most findings from the animal model experimental allergic encephalomyelitis have yet to be confirmed in multiple sclerosis. The aim of this study was to define the significance of TNF alpha with respect to the hallmark of MS, that is demyelination. Therefore, 78 lesion areas from diagnostic brain biopsies of 32 patients were analysed. Lesion demyelinating activity was classified by the presence of myelin degradation products in macrophages and macrophage activation markers. Nonradioactive in situ hybridisation tvas carried out to detect TNF alpha mRNA expressing cells. DNA fragmentation was visualised by TdT-mediated X-dUTP nick end labeling. A significantly higher number of cells expressed TNF alpha mRNA in active demyelinating lesions than in inactive or remyelinating lesions irrespective of the extent of the inflammatory infiltrate. TNF alpha mRNA expression correlated with the appearance of DNA fragmentation in T lymphocytes and oligodendrocytes within the lesions. In the periplaque white matter, expression of TNF alpha mRNA negatively correlated with oligodendrocyte numbers. These data support previous findings from animal models and in vitro experiments. Although not proving, the current study strongly suggests a pathogenic role of TNF alpha in demyelination in human multiple sclerosis and gives further support for TNF alpha-directed therapeutic strategies. (C) 2000 Wiley-Liss, Inc
Evidence for local and systemic elimination of macrophages from the injured peripheral nervous system
No full textA longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions
No full textSevere tissue destruction is the presumed histopathological correlate of hypointense multiple sclerosis (MS) lesions. In this study we correlated changes of lesion hypointensity over time with initial histopathological features in 14 biopsied MS lesions. The extent of hypointensity increased in initially demyelinated plaques and decreased in remyelinating lesions. The initial axonal loss determined the increase of hypointensity over time. In conclusion, both axonal loss and demyelinating activity determine the evolution of hypointensity over time
Acute axonal injury in multiple sclerosis - Correlation with demyelination and inflammation
No full textDamage to axons is taken as a key factor of disability in multiple sclerosis, but its pathogenesis is largely unknown. Axonal injury is believed to occur as a consequence of demyelination and was recently shown to be a feature even of the early disease stages. The present study was aimed at characterizing the association of axonal injury and histopathological hallmarks of multiple sclerosis such as demyelination, cellular infiltration and expression of inflammatory mediators. Therefore, axon reduction and signs of acute axonal damage were quantified in early lesion development of chronic multiple sclerosis and correlated with demyelinating activity and inflammation. Patients with secondary progressive multiple sclerosis revealed the most pronounced axonal injury, whereas primary progressive multiple sclerosis patients surprisingly showed relatively little acute axonal injury. Acute axonal damage, as defined by the accumulation of amyloid precursor protein (APP), was found to occur not only in active demyelinating but also in remyelinating and inactive demyelinated lesions with a large interindividual variability. Only few remyelinating lesions were adjacent to areas of active demyelination, In this minority of lesions, axonal damage may have originated from the neighbourhood. APP expression in damaged axons correlated with the number of macrophages and CD8-positive T lymphocytes within the lesions, but not with the expression of tumour necrosis factor-alpha (TNF-alpha) or inducible nitric oxide synthase (iNOS), Axonal injury is therefore, at least in part, independent of demyelinating activity, and its pathogenesis may be different from demyelination, This has major implications for therapeutic strategies, which aim at preventing both demyelination and axonal loss
Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time
No full textMultiple sclerosis is characterized morphologically by the key features demyelination, inflammation, gliosis and axonal damage. In recent years, it has become more evident that axonal damage is the major morphological substrate of permanent clinical disability. In our study, we investigated the occurrence of acute axonal damage determined by immunocytochemistry for amyloid precursor protein (APP) which is produced in neurones and accumulates at sites of recent axon transection or damage. The numbers of APP-positive axons in multiple sclerosis lesions were correlated with the disease duration and course. Most APP-positive axons were detected within the first year after disease onset, but acute axonal damage was also detected to a minor degree in lesions of patients with a disease duration of 10 years and more. This effect was not due to the lack of active demyelinating lesions in the chronic disease stage. Late remyelinated lesions (so-called shadow plaques) did not show signs of axon destruction. The number of inflammatory cells showed a decrease over time similar to that of the number of APP-positive axons. There was a significant correlation between the extent of axon damage and the numbers of CD8-positive cytotoxic T cells and macrophages/microglia. Our results indicate that a putative axon-protective treatment should start as early as possible and include strategies preventing T cell/macrophage-mediated axon destruction and leading to remyelination of axons
The relative number of macrophages/microglia expressing macrophage colony‐stimulating factor and its receptor decreases in multiple sclerosis lesions
No full textThe activation of macrophages/microglia in multiple sclerosis (MS) lesions plays a central role in the effector phase of myelin breakdown. The precise patterns of macrophage/microglia activation during demyelination have not yet been defined. The growth and activating factor macrophage-colony stimulating factor (M-CSF) and its specific receptor (M-CSFR) may be involved in this process. The present study investigated the expression of M-CSF and M-CSFR mRNA by in situ hybridization in 60 lesions from 32 MS patients. In the control and periplaque white matter, microglia was almost completely M-CSFR positive. Irrespective of the demyelinating activity, an increased number of cells expressed M-CSF or M-CSFR mRNA within the lesions. However, despite the tremendous increase in macrophages/microglia within the lesions, the relative number of these cells expressing M-CSF or M-CSFR decreased. There was no correlation of M-CSF or M-CSFR expression with active myelin breakdown. The correlation between the clinical course and the expression of M-CSF or M-CSFR mRNA revealed significant differences with the lowest expression in primary progressive MS. These results suggest a downregulation of M-CSF and M-CSFR inside the MS plaque probably due to the high amount of macrophage-derived cytokines or mediators. Nevertheless, the differences in the relative number of cells expressing the M-CSF/M-CSFR pathway implicate that this pathway may be an important contributory factor in different forms of MS pathology. (C) 2002 Wiley-Liss, Inc
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