Calculate your risk of developing MS from first presentation


We now understand that the early features of the condition matter; the more active the disease in the first five years the more likely you are to reaching the hard disability milestones (such as requiring a walking stick) that much sooner, than if the converse were true. But what about the development of MS (or CDMS, clinically definite MS) after the first clinical symptom (CIS, clinically isolated syndrome)?

The factors which convincingly predict this are as follows (not in any particular order):
– 10 or more T2 hyperintense lesions on the baseline MRI head scan
– presence of oligoclonal bands (OCBs), and
– elevated neurofilaments

In fact according to a recent publication by Costa et al., you can use a combination of these measures starting with your blood neurofilament level to determine exactly this, and assign a future risk score (see figure below):

Nomograms for predicting 2 and 5 year probabilities for McDonald 2017 MS according to baseline neurofilament light (NfL), CSF and brain MRI status. Categories for NfL: 0 (11.6 – 40.2 pg/ml, 1 (<11.6 pg/ml), 2 (>40.2 pg/ml). Categories for CSF OCBs: 0 (absent), 1 (present). Categories for MRI T2 lesions: 0 (0 lesions), 1 (1-3 lesions), 2 (4-9 lesions). To obtain 2 and 5 year survival probabilities, calculate trough use the first row of points for every person characteristic listed, then drop a vertical line from the total points row to the probabilities rows.

Prognostic value of serum neurofilaments in patients with clinically isolated syndromes

G Costa, V Martinelli, F Sangalli, L Moiola, B Colombo, M Radaelli, L Leocani, R Furlan, G Comi First published January 11, 2019, DOI:

Objective To assess the prognostic role of serum neurofilament light chains (NfL) for clinically defined multiple sclerosis (CDMS) and McDonald 2017 multiple sclerosis (MS) in patients with clinically isolated syndromes (CIS).

Methods We retrospectively analyzed data of patients admitted to our neurologic department between 2000 and 2015 for a first demyelinating event. We evaluated baseline serum NfL in addition to CSF, MRI, and clinical data.

Results Among 222 patients who were enrolled (mean follow-up 100.6 months), 45 patients (20%) developed CDMS and 141 patients (63.5%) developed 2017 MS at 2 years. Serum NfL (median 22.0, interquartile range 11.6–40.4 pg/mL) was noticeably increased in patients with a recent relapse, with a high number of T2 and gadolinium-enhancing lesions at baseline MRI. Serum NfL was prognostic for both CDMS and McDonald 2017 MS, with a threefold and a twofold respective reduction in CDMS and 2017 MS risk in those patients with low and extremely low levels of NfL. The results remained unchanged subsequent to adjustment for such established MS prognostic factors as oligoclonal bands, Gd-enhancing lesions, and a high T2 lesion load at baseline MRI. NfL was associated with disability at baseline but not at follow-up.

Conclusions Serum NfL have a prognostic value for CIS patient conversion to MS. NfL might play a twin role as biomarker in MS as peak level measurements can act as a quantitative marker of serious inflammatory activity, while steady-state levels can be a reflection of neurodegenerative and chronic inflammatory processes.

About the author

Neuro Doc Gnanapavan


  • NDG, are there any further studies on using exosomes in monitoring patients. I thought there was some research that showed distinct miRNA profiles for the newly diagnosed as well as patients who are progressing vs stabilized.

    • The work on exosomal microRNAs has been hampered by their reproducibility. Research groups have found differences in signatures between RRMS and SPMS for instance and may even be modulated by treatment (interferon beta and fingolimod). It is expensive to work on and much of the work is currently being done by pharma.

  • How many years away do you think we are from the use of NfL in daily clinical practice? Is it expensive for national health care systems to obtain the means to practice it?

    • The CSF neurofilament is already available on the NHS in the UK, and is being done by our centre. We have even had external requests. The blood neurofilament assay is a work in progress.

  • Neuro Doc G am I correct in my frustration or does it reflect my being a layperson and therefore ignore of critical aspects to the clinical processes of diagnosis?

    Whenever I read about things such as CIS or the benefits of treating early I think: ‘But what of those of us who weren’t promptly referred to a neurologist and promptly diagnosed?!?’ I’m confident of having had my first relapse 4 years before I was finally diagnosed and I also strongly suspect I had MS for a number of years before that.

    I’ve been treated with Alemtuzumab and whilst I take encouragement from reading about how effective it can be as an early first line treatment, I can’t help but consider the possibility I’ve actually come to it quite late in the course of my disease.

    Then there’s the worry about other family members such as my brother who has had EBV and one episode of blurred vision. When he mentioned MS to his GP he was told he’s not yet presenting with enough symptoms to merit a referral.

    In this rather neat and tidy research world where do the people in the real world sit?

    • You raise a good point, as specialists we know a lot about the disease, but a generalist may not. Educational programs are important for all to attend so that you keep abreast with changing areas in medicine.

      Although a person may be given a diagnosis of MS, we suspect the disease may have presented 10y prior to this. So the clinical diagnosis is just that and treating when the condition presents is important in order to avoid further delays.

      • Thanks for your reply. It provides some peace of mind to know that I may well have had MS for a number of years before diagnosis and not have presumed this incorrectly.

        It is also valuable to know that receiving Alemtuzumab within a year of diagnosis despite having reached EDSS 3 by then is likely to be pertinent to the question of efficacy.

        If ‘baseline’ is always from the point of actual diagnosis and doesn’t take into account the 10yrs prior that you mention then how is that allowed for in research and CARE-MS follow up etc ?



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