Class of 87, Thirty years of nothing, where does it leave you?

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Our new news from the anals of neurology is that a group of people with clinically isolated syndrome who presented 30 years ago, have been followed up. At the population level there are some features that suggest that you may do more badly, but can it tell you where you will be in 30 years from diagnosis.?…I don’t need to give an answer as you know my opinion on MRI correlations.

Beta interferon came into play in the 1980s, which is over 30 years ago and in this cohort only 11 of 88 people recieved any treatment to slow disability. So is the important feature for progression.. MRI features? or that neuros did not activiety treat with a highly effective treatment? Whilst there was not much available when this study started, we need to know if the same would be true if people at radio-isolated or clinically isolated syndromw where treated with a highly effective DMT, what would happen?

I would hope the results would be different but basing our ideas on the effects of the original MS DMT aren’t going to tell us much. Here’s to the forty year follow-up.

A thirty year clinical and MRI observational study of multiple sclerosis and clinically isolated syndromes. Chung KK, Altmann D, Barkhof F, Miszkiel K, Brex PA, O’Riordan J, Ebner M, Prados F, Cardoso MJ, Vercauteren T, Ourselin S, Thompson A, Ciccarelli O, Chard DT. Ann Neurol. 2019. doi: 10.1002/ana.25637. [Epub ahead of print].

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes.

METHODS: 132 people presenting with a clinically isolated syndrome (CIS) were prospectively recruited between 1984-87, and followed up clinically and radiologically 1, 5, 10, 14, 20 and now 30 years later. All available notes and magnetic resonance imaging (MRI) scans were reviewed, and MS was defined according to the 2010 McDonald criteria.

RESULTS: Clinical outcome data was obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded disability status scale (EDSS) scores were available in 107 participants, of whom 77 had MS: thirty-two (42%) remained fully ambulatory (EDSS ≤3.5) all of whom had relapsing-remitting MS (RRMS), three (4%) had RRMS and EDSS >3.5, 26 (34%) had secondary progressive MS (all had EDSS >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 have been treated with a DMT. The strongest early predictors (within 5 years of presentation) of secondary progressive MS (SPMS) at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at one year.

INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, while others ran a more favourable long-term course. These outcomes could, in part, be predicted by radiological findings from within a year of first presentation.

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6 comments

  • Interesting study and I agree that this is one of the important points for research today: factors that can help to predict disability and progression.
    I just had a not too important question that perhaps is answered in the article: how was this a prospective recruitment of people with CIS in 1984-1987 since, as far as I know, the CIS term did not exist at that time?

    • This was a cohort of patients the majority of whom had optic neuritis (54%) who were followed up. It is not really representative of CIS in general as it is biased in favour of optic nerve involvement.

  • So the Institute of Neurology still has my MRI scans! In those days we were told not to tell our fellow patients what was wrong with us. Must have been a struggle to follow up CIS. Can’t see Moorfields on the research paper, Prof McDonald had a clinic there, I assume data was used from there too.

  • Also
    Engel et al 2019 – Intrathecal B-cell accumulation and axonal damage distinguish MRI-based benign from aggressive onset in MS

    Previous research has demonstrated that Neurofilament light chain (NfL) is a reliable biomarker of axonal damage and neurodegeneration in MS patients. Similarly, the ratio of CD20+/CD14+ (two different types of B cells) levels is correlated with a higher likelihood of disease progression. These researchers studied both NfL and CD20+/CD14+ in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis. The results of the study demonstrated that the most accurate prediction of disease severity can be obtained by combining the CD20+/CD14+ ratio and NfL levels in CSF and serum into a composite score. This composite score could help differentiate between benign and severe disease courses during the early stages of MS. These findings may help physicians make more personalized treatment decisions, but further research is needed to fully understand the practical implications of this research.

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