The Sonya Slifka Longitudinal Multiple Sclerosis Study: methods and sample characteristics

The Sonya Slifka Longitudinal Multiple Sclerosis Study follows a population-based cohort of approximately 2000 people with multiple sclerosis (MS) to study demographic and clinical characteristics, course of illness, utilization and cost of health services, provider characteristics, use of MS specialists and disease modifying agents, and neurologic, economic and psychosocial outcomes. This report describes the study methodology, presents baseline demographic and clinical data, and evaluates the representativeness of the sample. A stratified random sample of persons with established and recently-diagnosed MS selected from the National Multiple Sclerosis Society (NMSS) mailing lists was supplemented with recently-diagnosed patients recruited through systematic nationwide outreach. Baseline data were collected by computer-assisted telephone interviews derived from standardized instruments; data collection continues at six-month intervals. The cohort was comparable to population-based and clinical samples with respect to demographics, course, relapse rate, symptoms, and severity of disability. Almost two-thirds of the cohort needed help with activities of daily living, three-quarters were limited in work or other activities, and half had emotional problems that compromised quality of life. The Slifka Study cohort is broadly representative of the MS population and the database can be used to address questions not answered by natural history studies, clinical databases, or population-based surveys.     

A Longitudinal Magnetic Resonance Imaging Study of the Cervical Cord in Multiple Sclerosis

This study was performed to evaluate the correlation between changes of crosssectional cord area and disability in multiple sclerosis. Axial magnetic resonance images at the C-5 spinal level were obtained at entry and 12 months later for 29 patients with clinically definite multiple sclerosis. The degree of disability was inversely correlated at entry and follow-up with the crosssectional area and the transverse diameter of the spinal cord. In addition, changes in disability correlated inversely with changes in cross-sectional area (r = -0.4, p = 0.04). These findings suggest that cross-sectional cord area at C-5 might be a useful marker of disease evolution.     

Disease-modifying agents in multiple sclerosis

Since 1993, six disease-modifying therapies for multiple sclerosis (MS) have been proven to be of benefit in rigorous phase III clinical trials. Other agents are also available and are used to treat MS, but definitive data on their efficacy is lacking. Currently, disease-modifying therapy is used for relapsing forms of MS. This includes clinically isolated syndrome/first-attack high-risk patients, relapsing patients, secondary progressive patients who are still experiencing relapses, and progressive relapsing patients. The choice of agent depends upon drug factors (including affordability, availability, convenience, efficacy, and side effects), disease factors (including clinical and neuroimaging prognostic indicators), and patient factors (including comorbidities, lifestyle, and personal preference). This review will discuss the disease-modifying agents used currently in MS, as well as available alternative agents.     

多发性硬化患者抑郁的研究

目的研究多发性硬化(MS)患者抑郁的发生率、特点及其相关因素。方法通过汉密尔顿抑郁量表(Hamilton depression，HAMD)了解作者医院32例MS患者的抑郁状况，进而以扩展残疾状况评分(expanded disability status scale，EDSS)评估其神经功能缺损程度，并与其他神经免疫性疾病患者、非免疫性中枢神经系统疾病患者和健康者各30名进行比较；同时分析MS患者年龄、性别、病程、EDSS评分与患者抑郁的相关性。结果MS患者抑郁的发生率为43．6％，明显高于各对照组；患者神经功能缺损程度与抑郁呈正相关；MS患者年龄、性别、病程与抑郁无明显相关。结论MS患者抑郁发生率很高，应引起临床关注；抑郁的发生可能与其中枢神经系统病灶及免疫学异常有关。     

Vaccines in Multiple Sclerosis

Vaccinations help prevent communicable disease. To be valuable, a vaccine’s ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection—particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.     

自噬在多发性硬化中的研究进展

多发性硬化(MS)是一种自身免疫性疾病,其发病机制尚不明确,可能是多因素共同致病的结果。自噬,即细胞内的"自食"现象,可清除细胞内多余的细胞器和蛋白质,是维持机体正常生理功能的重要机制。近年研究发现,自噬参与了MS和实验性自身免疫性脑脊髓炎(EAE)的发生发展过程,EAE是一种用中枢神经系统髓鞘抗原免疫易感动物的自身免疫性疾病模型,是目前最常用于研究MS的动物模型。对自噬的干预有望能为阐明MS的发病机制和开发更多治疗措施提供新的依据,文中就自噬在MS中的研究进展做一综述。     

Sphingolipids in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the CNS. Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), are target cells in MS. Although the etiology of MS is poorly known, new insights suggest oligodendrocyte apoptosis as one of the critical events followed by glial activation and infiltration of lymphocytes and macrophages. A major breakthrough in delineation of the mechanism of cell death, perivascular cuffing, and glial activation came from elucidation of the sphingolipid signal transduction pathway. The sphingolipid signal transduction pathway induces apoptosis, differentiation, proliferation, and growth arrest depending upon cell and receptor types, and downstream targets. Sphingomyelin, a major component of myelin membrane formed by mature oligodendrocytes, is abundant in the CNS and ceramide, its primary catabolic product released by activation of either neutral or acidic sphingomyelinase, serves as a potential lipid second messenger or mediator molecule modulating diverse cellular signaling pathways. Similarly, under certain conditions, sphingosine produced from ceramide by ceramidase is phosphorylated by sphingosine kinases to sphingosine-1 phosphate, another potent second messenger molecule. Both ceramide and sphingosine-1 phosphate regulate life and death of many cell types including brain cells and participate in pathogenic processes of MS. In this review, we have made an honest attempt to compile recent findings made by others and us relating to the role of sphingolipids in the disease process of MS.