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Diffusion tensor and magnetization transfer MR imaging of early-onset multiple sclerosis.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) with the onset of symptoms typically occurring between the age of 20 and 40 years. However, in about 3% to 12% of the cases, the onset of the disease is before 16 years of age. This review summarizes the main results obtained by the application of conventional and non-conventional MRI techniques to the assessment of patients with early-onset MS, which showed that the overall amount of CNS damage in these subjects is mild, compared to that typically detected in the adult-form of the disease. This fits with the notion that an early onset of the disease is associated with a more favourable clinical evolution.

Adult↗

Microarray gene expression profiling of chronic active and inactive lesions in multiple sclerosis.

Multiple sclerosis, a primary autoimmune disease of the central nervous system has been characterized by the presence of the demyelinating lesions (plaques) in the CNS. To further understand the gene transcription status of the two most common lesions, chronic active and chronic inactive, we have performed a cDNA microarray analysis of these two lesion type. Comparative analysis of differential gene expression of chronic active and inactive lesions have confirmed the existence of a significant difference in the transcriptional profiles of these two lesion types in both marginal and central areas. Different sets of genes were highlighted, including genes of inflammatory characteristics, apoptosis related and stress-induced, indicating their potential role in MS pathogenesis.

Brain↗

Insights into the immunopathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Significant progress has been made in our understanding of the etiology of MS. MS is widely believed to be an autoimmune disease that results from aberrant immune responses to CNS antigens. T cells are considered to be crucial in orchestrating an immunopathological cascade that results in damage to the myelin sheath. This review summarizes the currently available data supporting the idea that myelin reactive T cells are actively involved in the immunopathogenesis of MS. Some of the therapeutic strategies for MS are discussed with a focus on immunotherapies that aim to specifically target the myelin reactive T cells.

Animals↗

Elevated plasma level of plasminogen activator inhibitor-1 (PAI-1) in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system and one of the earliest changes in inflammatory focus involves the activation of vascular endothelial cells. We determined the plasma level of plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis and cell migration, in patients with MS. The level of plasma PAI-1 was significantly higher in active MS cases when compared to stable MS and controls. Plasma concentrations of tissue plasminogen activator, transforming growth factor beta-1, and lipoprotein-a remained normal in spite of disease activity. These results suggested that PAI-1 plasma levels are associated with MS disease activity and is a good marker for MS relapse.

Adult↗

Additive effect of the HLA-DR15 haplotype on susceptibility to multiple sclerosis.

Multiple sclerosis (MS) has been associated with the human leukocyte antigen DR15 allele in Caucasians of North and Central European origin. However, the relative effect of the DR15 homozygous and the DR15 heterozygous genotypes on the disease susceptibility is unclear. Based upon results from three North European studies we have examined this by meta-analysis. Our results suggested that the effect of the DRB1*1501,DQA1*0102,DQB1*0602 haplotype on the susceptibility to MS is additive, perhaps reflecting that development of the disease is facilitated by a high density surface expression of the antigen presenting molecules encoded by this haplotype. Possible implications of our finding to future studies of the genetic background of MS is discussed.

Genetic Predisposition to Disease↗

Palliative care in patients with multiple sclerosis.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and can be characterized by acute exacerbations or gradual worsening of neurological function and disability. The course of the disease is highly variable and unpredictable, however, there are short and long-term favorable and unfavorable predictive factors, which may provide some information about the future pattern of the disease. Palliative care in MS is directed at symptom management, psychosocial support, and rehabilitation. The goal in palliative care is to achieve a high quality of life. The disease modifying agents, interferon beta, Glatiramer acetate and Mitoxantrone are the mainstay of treatment in MS. Symptomatic relief and counseling of patients with MS have a strong impact on quality of life.

Blindness↗

The neuro-ophthalmology of multiple sclerosis.

Multiple sclerosis (MS) is the most common disabling neurological disease in young people. Most CNS lesions involve neuroanatomically non-eloquent zones that often do not result in symptomatic complaints. By contrast, tissue-injury mechanisms involving inflammatory demyelination can involve more eloquent sites, such as the optic nerve and brainstem, which can correspondingly produce the development of well recognised syndromes such as optic neuritis and internuclear ophthalmoplegia, respectively. In this review we discuss the broad landscape of abnormalities that affect the afferent visual system and the ocular motor apparatus, and emphasise relevant features, the recognition and treatment of which are of importance to general neurological practice. The commonness of visual sensory and eye movement abnormalities in MS highlights the importance of understanding the principles addressed in this review.

Humans↗

[Infectious agents in the pathogenesis of multiple sclerosis].

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS) of a still unknown etiology. Genetic factors, environmental agents and an autoimmune response may play an important role in the pathogenesis of MS. In the paper the current opinion on the role of infectious agents in the pathogenesis of MS is presented. The results of epidemiological and serological studies are discussed as well as the results of viral isolation attempts and the search for virus structures in the CNS of MS patients. The most important findings in the field e.g. a potential role of Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and bacteria Chlamydia pneumoniae in MS are presented. Postulated mechanisms of virus-induced demyelination are also described.

Chlamydia Infections↗

The role of magnetic resonance imaging studies in multiple sclerosis.

Multiple sclerosis (MS) is a common cause of disability in young adults. Establishing a definitive diagnosis of the disease is often difficult, and there is much uncertainty concerning prognosis once the diagnosis is made. Magnetic resonance imaging (MRI) studies have proved to be a useful diagnostic test in the initial evaluation and monitoring of patients with MS. They also provide a means for quantitative assessment of disease activity and progression during clinical trials of MS therapies. Improvements in MRI technology show promise in providing more accurate measurements of disease extent. The new technique of magnetic resonance spectroscopy can be used to monitor the specific pathophysiology of evolving MS plaques in vivo and may provide insights that lead to a better understanding of the pathogenesis of MS.

Adult↗

Role of chemokines and their receptors in the pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the human central nervous system (CNS) of unknown etiology that causes demyelination and associated tissue injury. Trafficking of inflammatory T cells into the CNS is a crucial event in the pathogenesis of MS, a process in which chemokines and their receptors have been demonstrated to play an important role. Chemokines are key mediators of inflammation and have major effects on migration of cells to the sites of inflammation as well as activation of recruited and resident CNS cells. This paper summarizes recent and new information about the expression and function of elements of the chemokine system in MS and its animal model experimental allergic encephalomyelitis. Analysis of the chemokine system provides insights into mechanisms of CNS inflammatory reactions and may lead to new targets of therapeutic intervention in MS.

Chemokines↗

On the coincidence of cervical spondylosis and multiple sclerosis.

Multiple sclerosis (MS) and cervical spondylosis are relatively common diseases. It is therefore inevitable that the MS clinician will be confronted with patients with myelopathy in whom the two conditions coexist. When faced with an MS patient who has cord compression secondary to cervical spondylosis as well as cord demyelination, the issue of surgical decompression of the cord arises. Whether the trauma of cord compression aggravates the MS lesions is still a matter of debate and should not influence treatment decisions. There is little prospective evidence-based support for the notion of surgical cord decompression in cervical spondylosis without MS, and none at all for surgery in MS, with only small published retrospective series available. The clinician must therefore make a judgment-based treatment decision. Guidelines for the management of patients with coincidental cervical cord compression and MS are suggested.

Cervical Vertebrae↗

Overview of symptomatic management of multiple sclerosis.

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and often disabling disease of the central nervous system. Permanent disability may relate to axonal damage. The etiology of MS remains elusive; treatment may be episodic, symptomatic, and designed for partial disease modification. Its hallmark is unpredictability marked by relapses and remissions or disease progression. Despite the new immunomodulating agents that diminish some individuals' relapse rates and clinical worsening, there is no cure for MS. Thus symptom management is a key feature of MS nursing care. Adequate control of symptoms can result in maximal function, prevention of injury or trauma, restoration of a sense of control, and promotion of an acceptable quality of life. The nurse plays a vital role in the spectrum of MS care, none so critical as in the effort to moderate and modulate the symptomatic problems related to the disease.

Disability Evaluation↗

Retinal antigens are recognized by antibodies present in sera of patients with multiple sclerosis.

Multiple sclerosis (MS) is frequently accompanied by visual symptoms including those related to retinal disorders. Since they may be a consequence of an autoimmune reaction, we examined whether sera of patients with diagnosed MS and changes in visual-evoked potentials contain antibodies against retinal antigens (retAgs). Immunoblot analysis revealed that MS sera recognized mainly a 46-kD antigen, a 41-kD antigen, retinal arrestin, to a smaller extent also 70-, 56-, 43-, and 36-kD proteins. Patients whose sera showed the highest reactivity with 41- and 46-kD antigens had deficiencies in visual acuity, visual fields, ophthalmoscopy, and electroretinograms. Our observation suggests that antibodies to these retAgs may play a role in the origin of ophthalmologic impairment in MS.

Adult↗

[Clinical peculiarities of optic neuritis and alterations of local immune response in patients with multiple sclerosis].

Multiple sclerosis (MS) is a severe organic disease of the central nervous system (CNS) affecting mostly young people. Optic neuritis (ON) is one of the first manifestations of the disease in approximately 75% of cases. The autoimmune reactions to myelin antigens play a key role in ON pathogenesis of MS. The pro- and anti-inflammatory unbalance is the most important factor of the origin, development and stabilization of CNS changes. Presented are the data on alterations of the levels of pro- and anti-inflammatory cytokines TNF-alpha, IF-gamma and antibodies to MBP and anti DNA in patient's tears. The clinical peculiarities of ON in MS correlating with immunological alterations are established.

Adolescent↗

The initiation of the autoimmune response in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Most evidence supports the autoimmune pathogenesis of the disease. According to this hypothesis, the activation of autoreactive T-cells is a central event in the development of autoimmune response in MS. We examined molecular events involved in the initiation of autoimmune response in MS. Recent studies in our laboratory have reported an unexpectedly high degree of T-cell receptor (TCR) degeneracy and molecular mimicry as a frequent phenomenon that might play a role in the initiation of autoimmune response in MS. This paper provides insights into the physiologic and pathologic role of autoreactive T-cells, and characterizes structurally and functionally the specific targets for new therapies of MS.

Antigens, CD↗

Molecular pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is best understood as an inflammatory disease of the central nervous system (CNS) white matter characterized by demyelination, focal T cell and macrophage infiltrates, axonal injury and loss of neurological function. Our current understanding invokes proinflammatory cells and mediators that may be triggered by environmental factors to mediate disease in a genetically susceptible host. Five major themes which have been associated with the pathogenesis of MS lesions will be discussed: (1) The differential activation states of myelin-reactive T cells from MS patients vs. normal individuals, (2) the selective expression of chemokines, adhesion molecules and matrix metalloproteinases, (3) the proposed roles of the B7 costimulatory pathway, (4) the proinflammatory cytokines and (5) the role of molecular mimicry.

Autoimmunity↗

Functional roles and therapeutic targeting of gelatinase B and chemokines in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of autoreactive lymphocytes, and skewing of the extracellular proteinase balance, are targets for new therapies. Matrix metalloproteinase gelatinase B (MMP-9) is upregulated in MS and was recently shown to degrade interferon beta, one of the drugs used to treat MS. Consequently, the effect of endogenously produced interferon beta or parenterally given interferon beta may be increased by gelatinase B inhibitors. Blockage of chemotaxis or cell adhesion molecule engagement, and inhibition of hydroxymethyl-glutaryl-coenzyme-A reductase to lower expression of gelatinase B, may become effective treatments of MS, alone or in combination with interferon beta. This may allow interferon beta to be used at lower doses and prevent side-effects.

Animals↗

Multiple sclerosis.

Multiple sclerosis (MS) is the most common disabling neurologic disease of young people affecting between 350 and 450,000 individuals in the United States. Substantial advances have been made in the diagnostic assessment and treatment interventions over the last 10 years such that we are now able effectively to treat both the disease process and the associated symptomatic complaints associated with MS. Most patients consult with their primary care physician at the time when the first clinical manifestations of MS emerge. These physicians play a central role in the early identification and treatment of patients with MS. This article emphasizes the expanding diagnostic and therapeutic capabilities evolving for the MS patient and the crucial role played by primary care physicians in collaboration with neurologists in the coordination of the initial diagnostic and treatment plan.

Adult↗