多发性硬化研究进展

多发性硬化(MS)因其发病率增高而患病率有增高趋势。近来在研究其病因方面有些进展，认为外因(病毒感染)通过内因起作用，为治疗开拓了新思路。诊断方面引入了MRI并标准化了脑脊液寡克隆(IgG组分)区带。视神经脊髓受累者与经典的MS在其人白细胞抗原(HLA)等方面不同，多数认     

Translational research in multiple sclerosis

Translational research has become a challenge for the health care administration and Neurology Departments. The need to incorporate the results of basic research into the clinical setting and, vice versa, the orientation of basic research from the knowledge arising from clinical research, implies a new way of looking at the research concept. It also makes it necessary to reconsider the clinical health care and research infrastructures together with a need to define the functions health care neurologists and their involvement in the research tasks. Multiple sclerosis, due to its heterogeneous character, that is, clinical, pathogenic and pathological, is a paradigm of how translational research should help to improve knowledge of the clinical phenomena and to elaborate the therapeutic proposals based on said knowledge.     

Recent advances in neuroimaging of multiple sclerosis

Conventional magnetic resonance imaging (MRI) is sensitive in detecting abnormalities in multiple sclerosis (MS), but these tend not to be pathologically specific. The visible T2 lesions are diagnostically valuable and may allow earlier diagnosis of the disease and more accurate prognostication. Quantitative MR techniques such as volume measurement can reveal pathology in nonlesional tissue with some clinical correlation; however, accurate pathological interpretation at a cellular level is problematic given the current resolution of MRI. In this update, recent studies using conventional and quantitative MR techniques are discussed and new, promising non-MRI methodologies highlighted, including retinal nerve fiber layer estimation. The role of MRI in measuring metabolic function, such as functional measures and investigating nonlocomotor symptoms such as cognition, is also discussed as are future improvements to the techniques currently employed in research studies. With increased sophistication and improved analysis of these techniques, understanding of the pathology underlying MS may increase, and objective quantification of the natural history of MS is possible.     

Affective disorders in multiple sclerosis. Review and recommendations for clinical research

This review of research on affective disorders in multiple sclerosis was prepared by members of the Cognitive Function Study Group of the National Multiple Sclerosis Society (New York, NY) to call attention to the prevalence and seriousness of emotional disturbances in multiple sclerosis, and to encourage further investigation of these syndromes. We present English-language studies of euphoria, pathological laughing and weeping, depression, and bipolar disorder, describe methodological limitations, and suggest areas for future clinical research.     

Recent advances in amyotrophic lateral sclerosis research

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. Despite several genetic breakthroughs, the actual cause and mechanism of neurodegeneration in ALS remains a mystery. Nevertheless, recent scientific and clinical advances have led to the development of new therapeutic strategies for this progressive, fatal disorder. We review the progress of the most recent clinical trials in ALS, taking into account some of the hurdles encountered by these studies. We also discuss the potential role of retroviral infection as a cause or contributor to ALS, which is one of the most recent hypotheses for the pathogenesis of the disease. The genetic background of ALS is summarized and special attention is given to the newly identified ALS gene ALS2, and to those that are currently being investigated. The last part of this review is dedicated to the mutation in superoxide dismutase-1 (SOD1). The hypothesized deleterious mechanisms of mutant SOD1 are discussed, as well as the possibilities that the mutant protein activates the apoptotic cell death process and that these molecular alterations can be exploited to devise experimental neuroprotective therapies.     

Recent advances in the neuroimaging of multiple sclerosis

Neuroimaging studies continue to provide important insights into the central nervous system disease pathology of multiple sclerosis (MS). Although conventional magnetic resonance imaging remains the mainstay of diagnosis and laboratory assessment of therapeutic response in MS, quantitative techniques continue to extend our understanding of both macroscopic and microscopic disease processes. Over the past year, many published studies have investigated measures of brain atrophy, gray matter involvement, vascular properties, and myelin and neuronal loss and have examined their relationship to clinical disease expression, genotype, and therapy. An important trend continuing over the past year is the development of targeted agents to improve the pathologic specificity of imaging measures. Specific disease measures such as endothelial activation, microglial activation, and cell trafficking are accessible to neuroimaging and offer significant promise for improved characterization of central nervous system involvement in MS.     

Recent advances in the neuropathology of multiple sclerosis

Important insights from multiple sclerosis (MS) pathology have broadened our view of the disease during the last years. Details of the inflammatory response as well as mechanisms of demyelination were elucidated. Damage to neuronal processes was identified as the major predictor of persistent disability in MS patients. Abortive repair mechanisms are increasingly studied, and our increased understanding will pave the way to new therapeutic strategies. This overview highlights some of the current views on MS pathogenesis derived from human neuropathology.     

Recent progress in treatment for multiple sclerosis]

Multiple sclerosis (MS) is currently considered to be an autoimmune disease mediated by myelin antigen-specific Th 1 cells. Although the mechanism of MS remains to be elucidated, new disease modifying drugs have recently been introduced to MS treatment. Interferon-beta, copolymer 1 and intravenous administration of immunoglobulins have been shown to significantly reduce the relapse rate, progression of disease and increase of MRI lesion load in MS. However, as the effects of these drugs are nonspecific immunomodulation, specific immunomodulation therapy for MS is called for. T cell vaccination, altered peptide ligand and oral tolerance are possible candidates for specific immune therapy for MS. As in Asians there is such a distinct subtype of MS as HLA-DPB 1 * 0501-associated opticospinal MS, it is important to look for unique immune therapy for opticospinal MS in future.     

Recent therapeutic strategy for multiple sclerosis]

Multiple Sclerosis (MS) is an inflammatory demyelinating disease in the central nervous system (CNS), and it is clinically characterized by multiplicity in time (relapse and remission) and space (multiple lesions in CNS). In Asian countries including Japan, it has been pointed out that the prevalence rate of MS patients is extremely low and the frequency of the optic-spinal form of MS is high, compared with Western countries. Although the etiology remains unknown, it has been postulated that the pathogenesis of MS may involve immune mechanisms, virus-like infectious agents or genetic factors. MS should be attacked on two fronts: treatment to suppress the disease itself and alter its natural history, and treatment to improve the symptoms of MS and mask the deficits it causes. Although steroid therapy probably improves MS attacks by inhibiting the immune system and reducing inflammation, they seem ineffective in changing the natural history of the disease or preventing ultimate disability. Interferon beta has been approved as an effective drug for reducing the rate of MS attacks and the volume of MRI lesions and altering its natural history, based on positive results from large controlled trials in western countries as well as in Japan. Other immunomodulating treatments, such as glatiramer acetate, intravenous immunoglobulin, and mitoxantorone have been also approved as effective drugs for MS.     

Advances in multiple sclerosis research in 2009

The following review summarizes the progress in multiple sclerosis research published in the Journal of Neurology in 2009.     

Future research directions in multiple sclerosis therapies

The success of presently available injectable immunomodulatory therapies in treating multiple sclerosis has led to heightened interest in finding even more efficacious and better tolerated therapies. Several oral agents have shown efficacy in phase-II clinical trials and are now entering phase-III pivotal trials. In addition, monoclonal antibodies targeting surface receptors on various cells of the peripheral immune system have also shown efficacy in early studies and will soon be entering phase III. All of these approaches target immune molecules that are not specific for multiple sclerosis (MS) and carry inherent risk of infection and systemic side effects. Novel immunotherapies in preclinical or phases I to IIa testing are attempting to more selectively target pathogenic effector cells and thereby block abnormal immune cell activation without compromising normal healthy immune responses. The induction of tolerance to self-proteins continues to be a goal of MS immunotherapy, but as yet has not been accomplished outside of the laboratory. There is increasing awareness of the need to understand and modulate nonclassical immune targets as well as central nervous system degenerative processes. The roles of vitamins, antimicrobials, and hormones continue to be studied. The mechanisms of neurodegeneration in MS are likely multifactorial and include direct damage by T cells and humoral immunity as well as oxidative stress, glutamate-mediated excitotoxicity, and neuronal and oligodendrocyte apoptosis. Neuroprotective drugs that were once only considered for classical degenerative diseases, such as amyotrophic lateral sclerosis and Parkinson's disease, are now being considered in MS.     

Guidelines for neuropsychological research in multiple sclerosis

Acquisition of scientific information regarding the neuropsychological aspects of multiple sclerosis has been hampered by studies using small, inadequately described patient and control samples and a wide array of cognitive test procedures that hinder multicenter data pooling. Based on a review of key issues of clinical need and experimental interest, research guidelines are proposed for investigations in this burgeoning research area. The guidelines include suggestions for sampling methods, population characterization, and control groups as well as a recommended core battery of neuropsychological tests for use in this population. It is hoped that these guidelines will advance knowledge about the neuropsychology of multiple sclerosis by helping to promote sound experimental design, facilitate cross-study comparison, and encourage multicenter collaborative efforts.     

Recent developments in drug therapy for multiple sclerosis.

Symptomatic treatment of multiple sclerosis (MS) includes a diverse range of drugs intended to relieve the specific symptoms with which a patient may present at a particular point in the progression of the disease. These drugs, not specifically designed for the treatment of MS, may include antispastic agents (e.g. baclofen), drugs to reduce tremor (e.g. clonazepam), anticholinergics (e.g. oxybutynin) which relieve urinary symptoms, anti-epileptics (e.g. carbamazepine) to control neuralgia, stimulants to reduce fatigue (e.g. amantadine), and antidepressants (e.g. fluoxetine) to treat depression. The treatment of acute relapses or exacerbations is dominated by corticosteroids such as methylprednisolone. The most active area of current investigation is the development of drugs which will inhibit the progression of the disease process itself, and in this category the beta- and alpha-interferons are the most effective drugs currently available, although many new treatments are currently in trials, including immunoglobulin, copolymer-1. bovine myelin, T-cell receptor (TCR) peptide vaccines, platelet activating factor (PAF) antagonists, matrix metallo-proteinase inhibitors, campath-1, and insulin-like growth factor (IGF).