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Disease Courses

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In this article


Four disease courses that were originally identified in MS (Lublin & Reingold, 1996) were updated by the International Advisory Committee on Clinical Trials of MS in 2013 (Lublin et al.). The changes include: the addition of clinically isolated syndrome and the elimination of progressive relapsing MS. In addition, modifiers have been added to promote more effective conversations about disease actiivty and progression and shared decision-making about treatment options. 

Benign course

Natural history studies have demonstrated that a certain percentage of people with MS experience a benign course. However defining “benign MS” and determining the point at which a person can be classified as having a benign course, are the subject of some controversy.

Determining When the MS Disease Course is Benign

Natural history studies from Northern Ireland (McDonnell & Hawkins, 1998), Olmstead County, Minnesota (Pittock et al., 2004), South Wales (Hirst et al., 2008), and Gothenburg, Sweden (Andersen O. Natural course of MS: 50 years of follow-up. Multiple Sclerosis 2010; 16: S7–S392010), demonstrate conclusively that a certain percentage of people with MS experience a benign course, meaning no relapses and mild, stable disability over time. The estimate of 10% having benign disease after 20-30 years of illness seems realistic (Hutchinson, 2012).

The challenge lies in determining what the term “benign” really means, and how long into the disease course one has to wait in order to determine that the course is, in fact, benign. Natural history studies have relied heavily on the Expanded Disability Status Scale (EDSS) (.pdf) measure disease progression; however even within the studies cited here, there is variation in the score (<2 - <3) used to define benign MS. In addition, the EDSS places heavy emphasis on ambulation status, with little attention paid to other functions, including cognition (Balcer, 2001).

With increasing awareness of the potential for significant cognitive impairment in patients with CIS (Khalil et al., 2011) and in patients with little or no physical disability (Reuter et al., 2011; Amato et al., 2006), defining benign MS, and determining the patients for whom early and ongoing treatment with a disease-modifying agent is appropriate, are the subject of some debate: Hawkins, 2012 vs. Amato, 2012; Pittock et al., 2006 vs. Frohman et al., 2006.

Progressive course

Multiple sclerosis is a chronic, progressive disease that leads to increasing disability in most individuals. Descriptions of the disease have always included two types of clinical processes – an acute process involving relapses and a chronically persistent progressive process – for which the underlying pathogenic mechanisms of onset are unknown. The vast majority of individuals present with the acute relapsing-remitting form of the disease (Lublin & Reingold, 1996), and the treatments that are currently available to treat MS are most effective for these individuals. For the majority of those patients who eventually transition to secondary-progressive MS (SPMSP) and for those whose disease course is progressive from onset (primary progressive MS – PPMS), treatment options at this time primarily involve symptomatic management and rehabilitation to mitigate the impact of the disease progression.

In spite of the apparent differences in clinical manifestation between the disease courses, the consensus is that these differences are more quantitative than qualitative and that the relapsing and progressive courses of MS fall along a disease spectrum, with genetic and environmental factors contributing to the variations (Rice et al., 2013; Antel et al., 2012). While continuing to examine the apparent similarities and differences between the MS disease courses, the international MS community has come together to expedite the development of effective disease-modifying and symptom management therapies

for progressive forms of MS. The International Progressive MS Collaborative has identified the following five research priorities: experimental models for progressive MS; identification and validation of treatment targets and repurposing opportunities; proof-of-concept clinical trial strategies;  clinical outcome measures; and symptom management and rehabilitation strategies(Fox et al, 2012).

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