Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines [RETIRED]

Abstract

Overview. Clinical types of MS.MS is a chronic recurrent inflammatory disorder of the CNS. The disease results in injury to the myelin sheaths, the oligodendrocytes, and, to a lesser extent, the axons and nerve cells themselves. [1][2][3][4][5] The symptoms of MS vary, depending in part on the location of plaques within the CNS. Common symptoms include sensory disturbances in the limbs, optic nerve dysfunction, pyramidal tract dysfunction, bladder or bowel dysfunction, sexual dysfunction, ataxia, and diplopia. 5Four different clinical courses of MS have been defined. 6 The first, relapsing-remitting MS (RRMS), is characterized by self-limited attacks of neurologic dysfunction. These attacks develop acutely, evolving over days to weeks. Over the next several weeks to months, most patients experience a recovery of function that is often (but not always) complete. Between attacks the patient is neurologically and symptomatically stable. The second clinical course, secondary progressive MS (SPMS), begins as RRMS, but at some point the attack rate is reduced and the course becomes characterized by a steady deterioration in function unrelated to acute attacks. The third clinical type, primary progressive MS (PPMS), is characterized by a steady decline in function from the beginning without acute attacks. The fourth type, progressive-relapsing MS (PRMS), also begins with a progressive course although these patients also experience occasional attacks. Outcome measures in MS clinical trials.Evaluation of the relative effectiveness of different therapies requires consideration of which outcome measure or measures are relevant to the goals of therapy. Clearly, the most important therapeutic aim of any disease-modifying treatment of MS is to prevent or postpone long-term disability. However, long-term disability in MS often evolves slowly over many years.1-3 Clinical trials, by contrast, study patients for only short periods of time (2 or 3 years) and, therefore, use only short-term outcome measures to assess efficacy. As a result, it is important to validate any short-term measure by its correlation with the actual patient outcome many years later. For a discussion of these issues, interested readers should consult the full-length assessment on the Neurology Web site at www.neurology.org.Scope of this guideline. The purpose of this assessment is to consider the clinical utility of these disease-modifying agents including the anti-inflammatory, immunomodulatory, and immunosuppressive treatments that are currently available.

Cell-based gene therapy experiments in murine experimental autoimmune encephalomyelitis

“…[40][41][42][43] A therapeutic approach which can downregulate pathogenic T cells while leaving the immune response otherwise intact may be an ideal solution. 44 We have previously developed an antigen-specific gene therapy treatment in which fibroblasts, secreting a mini-protein containing an encephalogenic epitope, when injected into EAE mice, cause a dramatic reduction in disease.…”

Immunotherapy in Peripheral Neuropathies

“…IFN-β1a IFN-β1a has proven efficacy in the treatment of multiple sclerosis [58]. The immunomodulatory properties of IFN-β1a that are believed to mediate its beneficial effects in MS suggest that it could also be effective in CIDP, leading to a prospective, open-label clinical trial studying the safety, tolerability, and efficacy of once-weekly IFN-β1a (Avonex; Biogen, Research Triangle Park, NC, USA) in a cohort of 20 patients with IVIG-resistant CIDP [59].…”

High Dose Oral Steroids Commonly Used to Treat Relapses in Canadian MS Clinics

“…Glucocorticoid treatment improves the speed of functional recovery of acute MS relapses but has not been shown to provide any long-term functional benefit. There is currently no convincing evidence that the clinical benefit is influenced by the route of glucocorticoid administration, the particular glucocorticoid prescribed, or the dosage of glucocorticoid 1,2 . Traditionally, IV administration of corticosteroid preparations has been used, but many patients prefer oral THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES therapy, which is less expensive and more convenient 3 .…”