What’s a prodrome and what does it mean in MS?



MS is a disease of young adults who are often diagnosed in their twenties. 

However, epidemiology studies suggest that you develop the risk for MS in your mid teens.

So can MS be picked up before diagnosis is there a Prodrome, which is an early symptom indicating the onset of the condition?

We know from exam results done in Argentina, that people destined to develop MS, can do a bit worse in their exams. This suggests that MS is present before it rears its head. We know there is diasease activity before MS as this is occasionally caught by  people who have an MRI and show a radiologically isolated syndrome.
In this study they look to see if there are symptoms that suggest that MS is coming. 
Here they search through health records 5 years before the first noticed clinical event, leading to the diagnosis of MS.


Wijnands JM, Zhu F, Kingwell E, Zhao Y, Ekuma O, Lu X, Evans C, Fisk JD, Marrie RA, Tremlett H. Mult Scler. Five years before multiple sclerosis onset: Phenotyping the prodrome.  2018:1352458518783662.

BACKGROUND:The multiple sclerosis (MS) prodrome is poorly characterized.
OBJECTIVE:To phenotype the MS prodrome via health care encounters.
METHODS:Using data from a population-based cohort study linking administrative and clinical data in four Canadian provinces, we compared physician and hospital encounters and prescriptions filled (via International Classification of Diseases chapters, physician specialty or drug classes) for MS subjects in the 5 years before the first demyelinating claim in an administrative cohort or the clinical symptom onset in an MS clinic-derived cohort, to age-, sex- and geographically matched controls. Rate ratios (RRs), 95% confidence intervals (95% CIs) and proportions were estimated.
RESULTS:The administrative and clinical cohorts included 13,951/66,940 and 3202/16,006 people with and without MS (cases/controls). Compared to controls, in the 5 years before the first demyelinating claim or symptom onset, cases had more physician and hospital encounters for the nervous (RR (range) = 2.31; 95% CI: 1.05-5.10 to 4.75; 95% CI: 3.11-7.25), sensory (RR (range) = 1.40; 95% CI: 1.34-1.46 to 2.28; 95% CI: 1.72-3.02), musculoskeletal (RR (range) = 1.19; 95% CI: 1.07-1.33 to 1.70; 95% CI: 1.57-1.85) and genito-urinary systems (RR (range) = 1.17; 95% CI: 1.05-1.30 to 1.59; 95% CI: 1.48-1.70). Cases had more psychiatrist and urologist encounters (RR (range) = 1.48; 95% CI: 1.36-1.62 to 1.80; 95% CI: 1.61-2.01), and higher proportions of musculoskeletal, genito-urinary or hormonal-related prescriptions (1.1-1.5 times higher, all p < 0.02). However, cases had fewer pregnancy-related encounters than controls (RR = 0.78; 95% CI: 0.71-0.86 to 0.88; 95% CI: 0.84-0.92).
CONCLUSION: Phenotyping the prodrome 5 years before clinical recognition of MS is feasible


My comments

People with MS had twice the number of nervous system related events but the others were marginally above the norm. The conclusion is that the prodrome is feasible, but one would need to see if there is any specificity for MS here. I doubt it. Would there be any real predictive value probably not. 

The next question we have to think about is, if there was an MS prodrome what would you do about it?

To date efforts to prevent MS are thin on the ground. Maybe stopping people getting glandular fever would be a start.

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  • Thanks for a great article MD, especially the comment about stopping glandular fever – can you update readers on the possible links between glandular fever and MS? From a personal observation I had glandular fever in my mid-teens and did nothing about it and wonder if that was a key event for my later MS.

  • "but one would need to see if there is any specificity for MS here. I doubt it. "

    "To date efforts to prevent MS are thin on the ground"

    Professor G mission made difficult


  • " I had glandular fever in my mid-teens and did nothing about it.."

    Cause if you've got it you've got it for life..there's no cure. Good Luck.


    CD8 T cell deficiency impairs control of Epstein–Barr virus and worsens with age in multiple sclerosis:

    "..infected memory B cells, which are resistant to the apoptosis that occurs during normal B-cell homeostasis because they express virus-encoded anti-apoptotic molecules."

    • interesting.
      I am a patient of Prof G. I didn't know of his work relating to EBV and I also had no idea of a link between Glandular fever until recently.

      I was hospitalised in my teens due to it, and it affected me quite badly afterwards. I had issues with fatigue, did much worse in my a levels and seemed to change (withdraw).. I didn't really link it to the glandular fever, no one told me to expect anything. in fact, it was almost handled like it wasn't a big deal.

      it cant be coincidence so many of us had it!

      is there a link between the severity of the glandular fever, and prognosis of MS? or is that what is looking to investigate?

      Ill mention to him about my experience, at our next appointment.

    • Absolutely yes. if you have EBV it increases your risk of MS AND IF YOU HAVE HAD GLANDULAR FEVER THE RISK IS EVEN HIGHER

  • "There is substantial evidence that stress increases multiple sclerosis disease activity, but limited evidence on its association with the onset of multiple sclerosis."

    "Conclusion:Cases were more likely to report a serious illness in the previous 12 months, which could suggest that a non-specific illness provides an additional strain to an already predisposed immune system."


  • I got a Ph.D. in maths at 24 and had lots of signs of MS by 27. Would I have been Stephen Hawkins if I hadn't had MS? Seriously, this study suggests you can tell things about an MS prodome at a population level but not for any individual, doesn't it?

  • Hello All
    I am a researcher – focused on diagnosing MS early- as you can imagine its very challenging. Wanted to know if any of you would be interested in talking with me. I am focusing on (1) prodrome – prior to being diagnosed with MS the very first time and (b) if there is a similar phenomenon just prior to symptoms. Many thanks to all of you for expressing yourselves in this forum.

    • I had thought that the insurance studies proved rather conclusive that there was an occult prodrome? Ie that medical spend and work absences for the five years preceding an MS diagnosis were substantially higher than in the age-equivalent general population.

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