摘要:

The classical demyelinating diseases include the ‘autoimmune’ inflammatory demyelinating diseases, the inflammatory demyelinating diseases of infectious aetiology, and the demyelinating or dysmyelinating diseases of genetic/hereditary background. In addition, primary demyelination is present in other conditions, such as brain ischaemia and intoxication. Irrespective of the primary aetiology, selective demyelination can be mediated through various pathogenetic pathways: the immune-mediated inflammatory pathway; the metabolic pathway; and the ischaemic/excitotoxic pathway. These pathways are only partly segregated with distinct aetiologies of demyelinating diseases, but they also reflect the way in which the patient copes with the disease-inciting event in relation to their particular genetic background. For future therapeutic strategies it will be important to interfere with the specific pathogenetic pathways of demyelination, which may be common to various demyelinating diseases, but may differ in subgroups of patients who suffer from a particular clinical demyelinating disease entity.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The cause of multiple sclerosis is generally considered to be entirely T cell mediated. However, recent reports of studies in a variety of animal models of inflammatory demyelinating disease, coupled with detailed pathological analysis and neuroimaging studies of multiple sclerosis patients, indicate that the events involved in the formation of the multiple sclerosis lesion may be more complicated. This complex pathogenesis is reflected in the variable response of multiple sclerosis patients to immunomodulatory therapy.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Renewed interest in axonal injury in multiple sclerosis has significantly shifted the focus of research into this disease toward neurodegeneration. During the past year magnetic resonance and morphologic studies have continued to confirm and extend the concept that axonal transection begins at disease onset, and that cumulative axonal loss provides the pathologic substrate for the progressive disability that most long-term MS patients experience. Although inflammation and chronic demyelination are probable causes of axonal transection, little is known about the molecular mechanisms that are involved. The view that MS can also be considered an inflammatory neurodegenerative disease has important clinical implications for therapeutic approaches, monitoring of patients, and future treatment strategies.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Magnetic resonance imaging methods allow observation of pathological changesin vivo. Magnetic resonance-based studies have provided a number of important insights into the spatio-temporal evolution of the pathology of multiple sclerosisin vivo, particularly with respect to the relation between pathology and progression of disability. Magnetic resonance techniques have shown that this pathology is not restricted to the plaques that are evident at autopsy, but also involve the so-called normal-appearing white matter. Nonconventional magnetic resonance imaging strategies such as magnetization transfer imaging and spectroscopic imaging provide measures with higher pathological specificity for myelin and axonal injury. These and other advanced magnetic resonance techniques (such as the measurement of atrophy, lesion relaxation spectra, and lesion dynamics) are affording opportunities to use observations of patients to test biologically specific hypotheses. This should help us to better define new targets for drug therapy and to assess responses to new therapeutic agents.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Demyelination and inflammation both contribute to the neurological deficits characteristic of multiple sclerosis and Guillain-Barré syndrome. Conduction deficits attributable to demyelination are well known, but it is becoming clear that factors such as nitric oxide, endocaine, cytokines, and antiganglioside antibodies also play significant roles. Demyelination directly affects conduction and also causes changes in both the distribution and repertoire of expressed axolemmal ion channels, which in turn affect impulse propagation and can promote hyperexcitability. In conducting axons, sustained trains of impulses can produce intermittent conduction failure, and, in the presence of nitric oxide exposure, can also cause axonal degeneration. Other factors impairing impulse transmission include nodal widening, glutamate toxicity, and disturbances of both the blood-brain barrier and synaptic transmission.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The present review of the recent literature focuses on antigen-specific immune reactions in multiple sclerosis. New techniques have allowed precise quantitative analysis of the antigen-receptor repertoire of infiltrating T cells in the multiple sclerosis brain. Novel candidate autoantigens, including B-cell autoantigens, have been identified. ‘Humanized’ animal models allow the functional characterization of human immune moleculesin vivo. Finally, several therapeutic trials have recently assessed the clinical benefit of selective immunotherapies.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The combined application of recently developed techniques for genetic and biochemical analysis, neuroimaging and the ability to create animal models has led to remarkable advances in the field of leukodystrophy research. The present review focuses on recent developments in X-linked adrenoleukodystrophy, Alexanders disease, Canavans disease, metachromatic leukodystrophy, globoid cell leukodystrophy (Krabbes disease) and Pelizaeus-Merzbacher disease, and briefly discusses new data on six other rare inherited leukodystrophies. Of the leukodystrophies, 12 can now be diagnosed precisely using noninvasive techniques, and the molecular defect has been identified in nine of these. Disease incidence can be reduced through genetic counselling. Presymptomatic diagnosis provides an opportunity for therapeutic intervention. Study of animal models facilitates elucidation of pathogenic mechanisms and identifies pathways that could be targeted by future therapies.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The molecular mechanisms that underlie the primary headaches - migraine, cluster headache and tension-type headache - have not yet been clarified. On the basis of studies in headache induced by intravenous infusions of glyceryl trinitrate (an exogenous nitric oxide donor) and histamine (which liberates nitric oxide from vascular endothelium), it has been suggested that nitric oxide is a likely candidate responsible molecule. The present review deals with the biology of this small messenger molecule, and the updated scientific evidence that suggests a key role for this molecule in primary headaches. This evidence suggests that the release of nitric oxide from blood vessels, perivascular nerve endings or from brain tissue is an important molecular trigger mechanism in spontaneous headache pain. Pilot trials have shown efficacy of a nitric oxide synthase inhibitor in both migraine attacks and chronic tension-type headache. These observations suggest new approaches to the pharmacological treatment of headache.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The normal female lifecycle is associated with hormonal milestones, including menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. Attacks of migraine without aura, but not with aura, are more likely to occur 2 days before onset and on the first 2 days of menses, but they are not more severe than those that occur outside the perimenstrual period. Oral sumatriptan and naratriptan are effective as short-term perimenstrual prophylaxis. Postdural headache can occur during the postpartum period. The International Headache Society Task Force assessed the efficacy of treatment of women who had migraine with combined oral contraceptives and hormone replacement therapy, as well as the risk of ischemic stroke associated with their use. There is no contraindication to the use of oral contraceptives in women with migraine in the absence of migraine aura or other risk factors. There is a potentially increased risk of ischemic stroke in women with migraine who are using combined oral contraceptives and have additional risk factors that cannot easily be controlled, including migraine with aura. There is no compelling evidence that postmenopausal hormone replacement therapy either decreases or increases stroke risk.

ISSN:1350-7540    

出版商:OVID    

年代:2001

数据来源: OVID