Outcomes in MS

What can happen to people with MS who are not treated?

What can happen to you depends upon the type of MS you have. Patients with relapsing-remitting MS can expect to have relapses with worsening neurological symptoms and remissions in which these symptoms get better. At a certain point, if you have relapsing-remitting MS, you can develop secondary progressive MS. If you have primary progressive MS, you can expect slow worsening of your symptoms over time. Patients with clinically isolated syndrome may or may not develop clinically definite MS. If you have RIS, your MRI may remain the same or worsen. You may or may not develop clinically definite MS.

Studies following groups of MS patients are called cohort studies. In a cohort study, an investigator chooses a group of individuals with multiple sclerosis and sees what happens to them. Cohort studies may be prospective or retrospective. In prospective studies people diagnosed with multiple sclerosis are seen initially and then followed over time to see what happens to them. In retrospective studies, an outcome has already occurred and the investigator looks at what has happened in the past. Retrospective studies are done by reviewing the medical records of multiple sclerosis patients who have been followed over various lengths of time.

Outcome measures are chosen by investigators to describe what happens to people with multiple sclerosis and to compare one group of patients with MS to another group. Outcome measures frequently used for relapsing-remitting MS patients are the relapse rate, which is the number of times per year that a person with MS has a relapse; the time it takes a patient with relapsing-remitting MS to reach secondary progressive MS; the expanded disability status scale (EDSS); and MRI findings. Common outcome measures used in progressive MS include the EDSS and MRI.

The EDSS is the most widely used method of quantifying the complex neurological exam and level of disability in MS. It is used to monitor changes in the level of disability over time. The scale runs from a score of 0 to 10 with zero corresponding to no signs or symptoms of neurologic dysfunction and 10 representing death.

Figure 1 Expanded Disability Status Scale (EDSS)

EDSS scores of 1.0 to 4.5 apply to people with MS who are able to walk without any aid and are based on measures of impairment on the neurological examination in eight neurologic systems. Each system is called a functional system (FS) and represents a network of neurons in the brain with responsibility for particular tasks. (htt1) Each functional system  is scored on a scale of 0 for no disability in this system to 5 or 6 indicating more severe disability. The eight functional systems are: (1) pyramidal – which measures muscle weakness or difficulty moving limbs; (2) cerebellar – loss of balance, incoordination or tremor; (3) brainstem – problems with speech, swallowing and eye movement; (4) sensory – numbness or loss of sensations; (5) bowel and bladder function; (6) visual function – problems with sight; (7) cerebral functions – problems with thinking and memory; and, (8) other.

Scores from 4 to 7 are determined by ambulatory ability and scores between 7 and 9.5 are based on the ability to carry out activities of daily living. (Uitdehaag 2017). The higher the score, the more severe is the disability. To document a permanent disability level and not one related to an acute relapse which may improve, disability worsening is generally measured as an EDSS score which is sustained over 3 to 6 months[iv].

Neurologists delineate major disability milestones for patients with MS. These are when a person first develops moderate disability in one functional system but still is able to walk without a problem (corresponding to an EDSS score of 3); severe disability in one functional system but remains self-sufficient even though they may have some limitation of ambulation (an EDSS score of 4); the need to use an adaptive aid such as a cane or walker to walk (EDSS 6); and, when they become wheelchair-bound (EDSS 7).

The main advantage of using the EDSS to describe disability in MS patients is that it has been a standard scale used in MS studies for many years.

The EDSS has several limitations. First is that it is difficult even for a neurologist to perform. This leads to variable scores when performed by different neurologists and sometimes even when performed by the same neurologist. Second, there is insufficient assessment of cognition, mood, energy level and quality of life (Uitdehaag, 2017). Note that all of these items may influence a person’s performance on the EDSS itself. Third, the scale is often criticized for its reliance on walking as the main measure of disability (htt2). Finally, it is a non-linear scale.

A linear scale has equal division for equal values such as inches on a ruler. A non-linear scale has unequally spaced division so that each score is not equal in size or value to other scores. This means that each score or step in the EDSS may not be of the same magnitude as other scores and movement along the EDSS does not progress in smooth equal gradations. For example, if someone worsens or improves by one point on the EDSS, this worsening or improvement means different things indifferent parts of the scale, Non-linearity also makes the EDSS difficult to use for statistical comparisons between groups of people with MS.

Studies of MS before the use of disease modifying therapy

A symptomatic therapy is a therapy designed to reduce the symptoms of a disease. Aspirin to lower the fever from an infection is an example of a symptomatic therapy. A disease-modifying therapy (DMT) is a category of medications used to slow down disease progression. To learn about what happens to untreated people with MS, it is useful to look at studies done before the use of disease modifying therapy.  There are three large multiple sclerosis studies that were begun before the common use of disease modifying therapy. These studies were done in Lyon France, Gothenburg Sweden, and London Ontario. Outcome measures in these studies include relapse rate and EDSS measurements. Worsening EDSS measurements were confirmed by re-examination in 5-12 months to see if the worsening represented a permanent decline.

Reviewing these studies, we must keep in mind that these studies and others like them show a lot of variability in what happens to individual patients. This means that there is no average person with multiple sclerosis. Some people with multiple sclerosis may become rapidly disabled while most do not. Similarly, the time it takes to reach certain levels of disability differs in individual patients. In view of the large variability in the outcomes for untreated people with MS, results of these studies are most often reported as median values for the group.

In these studies, the factor best predicting prognosis (disability) is whether your initial disease course is relapse remitting or primary progressive. This means that if you have been diagnosed with relapsing-remitting MS you are likely to take longer to become disabled than if you are initially diagnosed with primary progressive MS. After the type of MS you have, the next best predictor of how you will do is the age when your symptoms of MS began. People who are diagnosed with MS later in life are likely to become disabled over less time than people who are diagnosed with MS at a younger age. This is true in both relapsing-remitting, secondary progressive, and primary progressive forms of multiple sclerosis.

Although, in general, the time it takes for a person with relapsing-remitting MS to reach a significant level of disability is longer than that of someone with primary progressive MS, the median chronological age when patients reach milestones of severe disability in one functional system (EDSS 4), use of a cane (EDSS 6), and the use of a wheelchair (EDSS 7) is similar in both relapsing-remitting MS and primary progressive MS. In the Lyon, France cohort study these milestones occurred at ages of 47, 53, and 63 years irrespective of the initial clinical course. (Confavreux and Vukusic 2014)

The average time it takes for relapsing-remitting MS patients to become severely disabled in one functional system is significantly longer than for primary progressive MS. Even so, once a patient with relapsing-remitting MS becomes severely disabled in one functional system, the time of progression to needing a cane to ambulate is similar in relapse remitting and primary progressive MS. (Confavreux and Vukusic 2014)

In a review of the prognosis of MS, Confavreuz and Vukusic noted that, before you become severely disabled in one functional system (EDSS4), your accumulation of disability may be affected by your initial disease course but that by the time you reach or pass this milestone, further progression does not appear to be affected by an initial diagnosis of either relapsing-remitting MS or primary progressive MS (Confavreux and Vukusic 2014).

Despite the variability in how individual patients do with MS, over time, your neurologist may be able to get an idea of how you will do in the future because studies suggest that each individual patient’s rate of worsening seems to be fairly consistent. In many cases, how you will do in the future may be estimated by looking at how you have done in the past[v] (Confavreux and Vukusic 2014).

Life expectancy is only minimally reduced. A person with MS is likely to survive about 7 years less than someone without MS.

References

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