Who Develops Secondary-Progressive Multiple Sclerosis?

Some Signs That Relapsing-Remitting MS May Become Secondary-Progressive MS

An estimated 85% of people with multiple sclerosis (MS) are initially diagnosed with relapsing-remitting MS (RRMS). Some of these people will eventually develop secondary-progressive MS (SPMS), which is characterized by a more steady progression of symptoms and disability and fewer or no relapses.

Before disease-modifying treatments became widely available, 80 to 90% of people with RRMS would eventually develop SPMS within 25 years (50% within 10 years). It is now unclear what effect these medications will have on MS progression, but it is assumed (and hoped) that this proportion will be much lower and slower to develop.

Who Is More Likely to Move From RRMS to SPMS?

People who have had MS for 5 to 20 Years: People can change from having RRMS to SPMS at any time. However, this transition usually occurs within 5 to 20 years of the onset of disease.

Men: It seems that men with RRMS are more likely to move from RRMS to SPMS.

People with later age of onset: RRMS tends to move into SPMS around age 40. This means that people who were diagnosed with RRMS at a later age tend to move more quickly into SPMS. Again, this is in untreated RRMS.

What Are Some Signs that RRMS Has Become or Is Becoming SPMS?

'CRAB drugs' don't work well: Despite our best efforts and adherence, some people with RRMS that are on the current disease-modifying drugs (Copaxone, Rebif, Avonex, Betaseron and Tysabri), will begin to show increasing disability and lesion burden on MRI scans. This is an indication that we are no longer responding to the drugs and that we could be moving into SPMS. This could mean that the drug should be switched. For instance, if neutralizing antibodies to one of the interferon-based drugs are present, Copaxone might be a better choice. It is also possible that Tysabri could still delay the onset of progressive disease.

Relapses are changing: The natural history of RRMS is to have the number of relapses actually decrease over time. However, the relapses that do occur may be much more severe, bringing multiple symptoms, rather than just affecting one area of function. Recovery from the relapses tends to be incomplete, meaning that even after the acute phase of the relapse is past, some symptoms and/or disability remains. Additionally, the person no longer responds as well (or at all) to Solu-Medrol during these relapses.

Greater degree of disability: When measured by the Expanded Disability Status Scale (EDSS), people with RRMS tend to have a score of four or less. People with SPMS usually have a score of six or higher, meaning that some form of assistance is needed to walk. People with RRMS who reach a level of 4 to 5.5 (indicated by the inability to walk more than 500 meters without resting) usually develop SPMS within a fairly short time period.

There will also be more abnormalities found during the neurological exam. This shows that the brain can no longer compensate for the demyelination from the MS.

Lastly, people that develop SPMS tend to exhibit more cognitive disturbances. This is most likely due to the greater degree of atrophy in the brain, which is highly correlated to cognitive dysfunction. What this really means is that the brain can no longer compensate for the damage, especially where there is complete axonal destruction, resulting in black holes.

Large amount of damage seen on MRI:

Greater lesion burden: This means that there is a greater total number of lesions, which tend to be:

• Around the ventricles (the cavities in the brain that are filled with cerebrospinal fluid)
• Overlapping
• Concentrated in the brain stem, brain stem and spinal cord

More axonal damage and “black holes:" Areas that show up as dark (hypointense) spots on a T1 scan for more than 6 months are referred to as “black holes.” These are areas where there has been repeated inflammation, leading to complete destruction of both myelin and the axons themselves. These areas strongly correspond to disability.

Enlargement of CSF-filled ventricles in the brain: This is a measure of atrophy, as there is less brain tissue, so the spaces around and within the brain get bigger.

Decrease in gadolinium-enhancing lesions: Paradoxically, the number of new, active (gadolinium-enhancing lesions) decreases in later stages of RRMS. This is because the disease is most likely becoming more degenerative than inflammatory, which is seen by more axonal damage, including atrophy and black holes.

_Sources:

Coyle, Patricia K. and Halper, June. Living with Progressive Multiple Sclerosis: Overcoming the Challenges (2nd Ed.) New York: Demos Medical Publishing. 2008.

Tremlett H, Yinshan Zhao , Devonshire V. Natural history of secondary-progressive multiple sclerosis. Mult Scler. 2008 Apr;14(3):314-24.