Multiple sclerosis clinical course

The clinical course of multiple sclerosis has been described in four basic patterns relapsing remitting, secondary progressive, primary progressive, and progressive relapsing. 

FIGURE 26-3. Comparison of clinical course of multiple sclerosis by type. 

Assessing the effectiveness of a new drug candidate can be complex and often difficult. This is because some diseases or symptoms do not follow a predictable path. For example, acute conditions such as influenza or insomnia may resolve without intervention, while chronic conditions such as multiple sclerosis or arthritis follow a varying course of progression. Depending on age, treatment, and other risk factors, heart attacks and strokes may produce variable mortality rates. Additional difficulty is introduced by subjective evaluation, which can be influenced by the expectations of patients and physicians. Some of these issues can be addressed in controlled clinical trials. 

There are two main reasons for blinding the trial clinicians first, so that the use of non-trial treatments and interventions is not influenced by a knowledge of whether or not the patients received the trial treatment second, so that clinicians are not biased in then-assessment of clinical outcomes. The potential for bias depends on the subjectivity of the trial outcome. Biased assessment of neurological impairment and disability was clearly demonstrated in a multiple sclerosis trial in which blind and non-blind outcome assessment produced very different results (Noseworthy et al. 1994). Trials with blind assessment should also report whether or not blinding was effective. It is, of course, sometimes impossible to blind clinical assessment, but non-blind trials should report data on non-trial treatments given to patients during follow-up to ensure that these were not biased. 

Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis Results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on clinical trials of new agents in multiple sclerosis. Neurology 46 907-911. 

Jersild C, Eog T, Hansen GS, Thomsen M, Svejgaard A, Dupont B (1973) Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. Lancet 2 1221-5. 

Weinshenker BG, Bass B, Rice GP, Noseworthy J, Carriere W, BaskerviUe J, Ebers GC (1989) The natural history of multiple sclerosis A geographically based study. 2. Predictive value of the early clinical course. Brain 112(Pt 6) 1419-1428. 

FIGURE 53-2. Clinical course and treatment of multiple sclerosis. The horizontal axis represents time, and the vertical axis represents level of disability. The vertical dotted line represents the onset of the progressive disease phase. The progressive phase may evolve after a number of relapses or, in a subcategory of patients, may be the clinical course of the disease from the onset. (Reprinted with permission from Ann Neurol 1988 23 212.)... 

In the CNS, the major demyelinating disorder is multiple sclerosis (MS). MS should be differentiated from other disorders in which the histologic appearance of the lesions and the relapsing and remitting clinical course are similar. Acute MS lesions, in addition to plentiful foamy macrophages with increased proteases, have perivascular FCA-positive lymphocytes, EMA-positive and... 

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