Study Examines Factors That Increase Risk of Progressing from RRMS to SPMS

Study Examines Factors That Increase Risk of Progressing from RRMS to SPMS

Age at disease onset, number of early relapses, and the extent of brain damage at baseline can help identify those who are at high risk of progression from relapsing-remitting multiple sclerosis into the secondary progressive phase of the disease, a new study shows.

The study with that finding, “The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis,” was published in the journal Neurology.

Relapsing-remitting multiple sclerosis (RRMS) sometimes can evolve into a secondary progressive (SPMS) phase, which is much harder to treat. Unfortunately, the progression from RRMS to SPMS is largely unpredictable as little is known about the mechanisms that lead to the development of SPMS.

A lack of predictive biomarkers also makes it more difficult to identify patients at risk of developing SPMS, who consequently would require much more aggressive therapies.

The brain is divided into two types of tissue — white matter and gray matter. Injury to the gray matter of the brain plays a major role in the accumulation of long-term disability in patients with MS. In particular, studies have suggested that cortical lesions and cortical atrophy — representing damage to a part of the brain known as the cerebral cortex — can account for the transition to SPMS.

In an effort to learn more about the progression to SPMS, researchers set out to investigate the relationship between cortical changes, the number of early relapses, and the long-term course of MS.

Researchers assessed a number of parameters, such as the number of cortical lesions, white matter lesions, and cortical thickness at both onset of MS and at follow-up (mean of 7.9 years) in a group of 219 patients with RRMS.

After a mean of 6.1 years, researchers determined that 59 patients, or 27 percent, developed SPMS.

Patients who had a larger number of cortical lesions at onset had a higher risk of developing SPMS. Specifically, patients with two cortical lesions had a 2.16-fold greater risk of developing SPMS, patients with five cortical lesions had a 4.79-fold greater risk of developing SPMS, and patients with seven cortical lesions or more had a 12.3-fold higher risk of developing SPMS.

Patients with more cortical lesions also tended to have a shorter time to SPMS progression.

Patients were grouped by early relapse (ER) numbers during the first two years, including the low-ER group (one ER), mid-ER group (two ERs), and the high-ER group (three or more ERs).

Patients in the high-ER group compared to the low-ER and mid-ER groups had a larger volume of cortical lesions at onset and developed more cortical lesions. They also had larger volume of white matter lesions, experienced more severe cortical atrophy over time, and progressed to the SPMS more quickly.

Statistical analysis showed that an older age at onset, greater baseline cortical lesion numbers, larger white matter lesion volume, early changes in global cortical thickness, and three or more early relapses independently predicted a higher probability of developing SPMS.

Researchers hypothesize that this is likely due to the fact that extensive cortical damage at disease onset is associated with high levels of inflammatory activity and predisposes patients to more quickly develop SPMS.

Based on the results, the team concluded: “Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy.”


  1. Robin says:

    Almost had to laugh at this. I wasn’t diagnosed with MS until it became SPMS; before that, it was “stress” or “hypochondria.”

    • ALAN S says:

      I’m sorry to hear that. I went through 2 doctors, one who said it was a virus and then on the next relapse, that it was panic. It took a bit of yelling and camping plug in the clinic to get my diagnosis.

      • sonja says:

        Alan can you please tell me how much time between your 1st and 2nd relapse? My son just got diagnosed immediately because he got optic neuritis. 3 lesions on the MRI so now I am constantly worrying about a relapse. We do not know how often they can happen 🙁

        • Gary Green says:

          Hi Sonja, I realize your post is kind of old, but my first symptom was also optic neuritis 13 yrs ago. I was 40. I have not had a relapse of that symptom. Been on Copaxone since then. Everyone is different and while I have experienced the exhaustion common among MS patient I have been very lucky in not experiencing other symptoms of note.

    • Gwendolyn E Mugliston says:

      I had my first problems with MS at age 27 while sitting in a library when my visual horizon became fractured. I was diagnosed as have a “mental condition” due to stress and anxiety related to taking a rigorous scholastic schedule. The doctor was very dismissive and actually derogatory (a pattern I have observed in many male MD specialists since that first encounter). Because the SS went away quickly and not wanting to repeat the humiliating experience with another doctor, I did not return to medical care due to problems until I was in my 50’s. MRI’s quickly picked up the white matter plaques. Not one single doctor “believed” my history.
      My take on all of this is if you get a doctor who believes your SS and has you on a “good” and working med, how lucky you are. I do not and will die from wobbly legs,visual spots, weakness, muscles that don’t take you where you expect to go, etc.
      And then there is the mixed dx when RA is added to the pie.
      I go to the VA because finally I needed help as I couldn’t keep my job due “episodes”. It has taken years to get the correct tests, really smart doctors and finally I have some relief but sorting the symptoms out between MS and RA, I think cannot be done at this time…the two diseases have very similar Clinical Signs and even laboratory values of anti-CCP and DNA testing is helpful. Anti CCP is now considered to be the best test for RA. I do not know what is the best test for MS.
      Of course all this is my opinion after living in this body for almost 80 years and eating an organic NGMO diet, making sure “I lived an uncontaminated life.” However, I have a very dim view of what lies ahead as my friends have died off, my children are all over the world and I live in a place like PA.

    • NairbM47 says:

      I had my first episode in my mid twenties & I am now 72 having had multiple ‘attacks’ subsequently but without a definite period between each of them.
      I am, not unexpectedly, a retired ‘Chest Physician’. Although I still have acute flare ups from time to time, and am left with a combination of right sided weakness and not insignificant pain. I have not encountered any system which enables any patient or physician to ‘accurately’ & repetitively ‘assess and measure’ the pain that one is affected by so that it is trackable on an ongoing basis
      If anyone knows the specific details of such a tool please let me know so that I may investigate it further and then determine its’ relevance both clinically and scientifically.

    • Steve says:

      I am 60 and for 32 years Doctors told me they thought I had MS. About 4 years it seems I moved from RRMS to SPMS. Now I am feeling all the symptoms. Wish I had listened way back.

  2. Mario Venter says:

    What about sauth Africa ms treatment price and therapy its verry spensive can there be help for SA?

  3. Steve says:

    Re:“Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy.”

    This study tells us nothing new. More cortical lesions. or inflammation in the cortex, leads to earlier profession from arms to spms.

  4. Who cares? People like me with SPMS would love to hear that something can treat this stage not all the talk. I really do not hold out a lot of confidence that a cure or even a treatment is on the horizon.

  5. Marybeth DeSanti says:

    That is so frustrating to hear. I was diagnosed with RRMS in 1997 however, back then I had no idea what MS was. No one can possibly understand what anyone feels including doctors unless they live with this Disease. Saying some is a hypochondriac is ridiculous.
    I recently had a relapse however, it did not show on my MRI but I knew because I was dragging my left leg, tripping walking up the stairs and losing my balance. I’m much better now thank god because of the steroids.

  6. Carol says:

    I was told by my consultant my back pain was due to “wear and tear”. After having an MIR scan. Unfortunately, after more tests were undertaken, it turned out to be PPMS! I now use a powered wheelchair to get around.
    I personally think more people with RRMS develope SRMS than this study shows.

    • Jackie says:

      I was diagnosed at 32. Back then it was rrms I’m sure now I have PP MS. I also use a power wheelchair. I reside n a nursing home. Can’t use my arms or legs. I am now 51 years old. but no lesions show up in my MRI. so there goes that theory

  7. Pam Houser says:

    Marybeth S. Thank you for your comments…I am now in SPMS after RRMS from 1994ish and I am having left sided numbness-weakness. Feels like a stroke. I too am dragging my left foot, swelling my left side of body, choking on liquids at times, dropping things…etc. My Service Dog is continually sniffing my left side. Tests show no stroke though. Low level oxygen in small blood vessels. ? Due to sleep apnea. Hang in there. Glad to hear there is possible relief in sight.

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