Plot thickens: McDonald criteria for MS

Interested in reading about a Catch-22?

Eur J Neurol. 2017 Oct 11. doi: 10.1111/ene.13476. [Epub ahead of print]

Low clinical conversion rate in clinically isolated syndrome (CIS) patients – diagnostic benefit of McDonald 2010 criteria?

Rosenkranz SC, Kaulen B, Neuhaus A, Siemonsen S, Köpke S, Daumer M, Stellmann JP, Heesen C.



New diagnostic criteria of Multiple Sclerosis (MS) increase the number of patients being diagnosed with MS while a substantial part might not convert to clinically definite MS (CDMS).


Diagnostic accuracy of the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an unselected cohort of patients in whom a MS diagnostic workup was decided.


We analyzed clinical, MRI and CSF data in all patients who presented with symptoms suspicious for MS at the University based MS outpatient clinic between 2006 and 2010 (n=165).


Follow-up was available for 131 patients. During the mean follow-up period of 2 years, 19% of patients developed clinically definite multiple sclerosis (CDMS) whereas 64% of the patients fulfilling McDonald2010 criteria did not convert to CDMS.

CONCLUSION: The low clinical conversion rate indicates that new diagnostic criteria may increase the incidence of MS cases with a less active disease course.

If 2016 was the year to end all years, 2017 is surely the year of activists and dissidents. On balance, destabilization is a good thing; I like others feel science has followed the views of the majority for far too long.

In questions of science, the authority of a thousand is not worth the humble reasoning of a single individual.”
                                                     ― Galileo Galilei

Recently, I posted on the value of CSF analysis in MS; a procedure, which if we’re not careful may disappear altogether in MS. Rosenkranz et al. in their publication also question whether the science/neurology community were too precipitous in our blind reliance of the MRI diagnostic criteria in suspected MS cases?

There are a number of MRI criteria in practice, they all vary in their sensitivity (ability to correctly identify those with the disease) and specificity (ability to correctly identify those without the disease). But, what is apparent is that through the years the various iterations have improved sensitivity substantially, but at the cost of ever decreasing specificity. Not surprisingly, the authors state that ‘the validity for MRI as a diagnostic and prognostic tool is a matter of ongoing discussion’.

In their study, Rosenkranz et al. identified 131 individuals with initial presentation of demyelination (clinically isolated syndrome, CIS). During the follow-up period of 2 years, 19% developed clinically definite MS based on the Poser criteria (click on the hyperlink of CSF analysis in MS to view this criteria). Conversely, 45% fulfilled the 2010 McDonald criteria (this figure was lower when the 2005 criteria was applied). In short, the 2010 criteria lead to more MS diagnosis at the CIS stage, including those who do not then go onto experience further clinical events!

The catch-22 of this scenario is that we don’t truly know the long term prognosis/outcomes of these individuals. How can we then judge whether there is harm from early treatment or if there are long-term benefits to be had? I’m conflicted in all of this as I am an early treatment advocate and believe in pushing the boundaries.

About the author

Neuro Doc Gnanapavan


  • The neurologist who confirmed a diagnosis of MS told me that despite clear evidence via my MRI the only test to be sure of the diagnosis was a lumbar puncture, so I choose to have one. It has since been suggested to me that the LP was unnecessary and that all that was required was a MRI.
    It has occurred to me that the procedures undertaken to diagnose took place via my (then) private healthcare and that a cash-strapped NHS may find it appealing and convenient to take the solo route of MRI.
    Then there's the question of how many symptoms suffice? My brother has had one episode of blurred vision and now finds he needs the toilet urgently, but when he mentioned MS to his GP (also like me having had the EBV) he was told he's not evidencing sufficient symptoms to merit a scan.
    I had presented with symptoms, over the years, that were each addressed individually, even my first relapse symptoms were deemed to be as a consequence of a degenerative disc!
    All of this before the question of any treatment. I'm sold on the logic behind the induction approach, but the escalation approach definitely dominates in the UK.
    I don't suppose it comes as any surprise that I suspect there are large numbers with MS who remain undiagnosed and consequently untreated. Maybe the future will allow for EBV vaccination or routine screening of those who've had the virus – and not just for MS – my sister had the virus and has Sarcoidosis.

    • A lumbar puncture is not diagnostic but aids in the diagnostic process however a scan can show lesions in time (different lesion ages) and space (lesions in different places which is used to make diagnosis.

      I can't comment on the case as one needs to get all the facts but you always seek a second opinion, or a private scan.

      You mention about undiagnosed MS, a pathologist by the name of Ingrid Allen a pathologist from Northern Ireland said she saw lots of undiagnosed cases

  • Is it correct that 90% of people with CIS will go on to have a diagnosis of clinically definite MS?

    I look hard at statistics and on hearing this pushed for a LP that led to the confirmation. Only then was I eligible to access treatment.

    More research, breakdown of stats (that with intense breakdown often didn't look as appealing as pharma would like us to believe), led me to induction treatment options.

    I just don't see the point in delaying the very likely inevitable. Especially when we now have the opportunity to drastically slow or even halt progression of this disease.

    • The figures for likelihood of conversion are based on the number of lesions at the baseline scan. If MRI is normal it's 10-20% over most people's lifetime. If 1-4 lesions it's 40-90%. If 4+ lesions it's 80-90% but also greater short term risk of 80%.
      Is there such a thing as benign MS in the long term – it depends what you think qualifies as benign MS?

    • Thanks. I had around 7 small lesions with only very mild sensory symptoms. I had Lemtrada. I'll never know whether my disease would have had a more benign course. But I do know I hit it hard in an attempt to halt progression and make sure it had minimal impact on my life. The risk:benefit profile was still worth it in my mind since the risks of Lemtrada are largely mitigated and treatable with monthly monitoring. I couldn't spend my life waiting for progression knowing that there was a treatment that had the potential to halt that.

  • Hi Professor,

    I was hoping you could answer a question for me. I am currently living in a country where CIS diagnosed individuals like myself can only be prescribed older generation DMDs (Rebif). Given the efficacy of new treatments, should I push for a spinal tap to confirm MS? My neurologist promised to offer Ocrevus or Lemtrada as soon as I converted (as that would mean I failed Rebif). I have another MRI in a few months and currently have no disability.

    • So you are not alone, I think in the UK, we are in the same situation.
      In Europe, Lemtrada has a liberal license and disease needs to be active, so that could be an MRI lesion. In Europe we are still waiting to hear what the regulators do about ocrelizumab. Your new scan will show if there are lesions in time, which is part of the diagnosis.

      I am sorry but the neuros can't give individual advise, so can only give generalised information



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