Challenges in diagnosing and treating progressive MS

One of the main questions neurologists ask about progressive MS is whether it is easy to recognise it early. Dr Xavier Montalban (University of Toronto, Canada) thinks this is very complex, elaborating on the example that “some patients with an apparent clinically isolated syndrome (CIS) and incomplete recovery, do in fact have progressive MS.

"This is typical for male patients in their forties or fifties, who generally have primary progressive MS.” Also, in patients with relapsing-remitting MS, it can be difficult to identify progression because EDSS is not very sensitive nor commonly used, even in experienced MS clinics. This also applies to other tests, such as the 9-Hole Peg Test and Timed 25-Foot Walk. Cognition is not studied in many centres either. Digital health technology is now evolving as very useful tool, Dr Montalban mentioned. “Typically, neurologists see MS patients every 6 months or every year, and a number of events happening during the year are not captured.” The use of digital and remote communication technologies are useful tools for MS management because they provide more complete information about the patient. [1].

In describing the treatment landscape for patients with progressive MS, Dr Montalban started to mention 3 reasons why drugs fail in progressive MS. Firstly, pathogenic mechanisms in the progressive phase are completely different from those in the relapsing phase of MS (see Table). A second reason is that patient populations included in trials are not appropriate, “probably because they are either too old or it is too late to intervene”, he added. Thirdly, clinical outcomes are not sensitive enough and clinical trials are not smart enough to detect the worsening of disease over this period of time.

Table. Pathological mechanisms in progressive MS [2]



A recent study showed an association of chronic active MS lesions with disability in vivo. Chronic active, slowly expanding, smouldering lesions are visible on an MRI scan. This type of lesion is of special clinical and biological interest for its accumulation of microglia and/or macrophages at the lesion edge, subtle opening of the blood-brain barrier, and repair/remyelination failure with axonal loss [3].

According to Dr Montalban, the most important question is: Do we have any treatment for progressive MS? Over the years, many drugs have been approved for the treatment of relapsing MS (see Figure). “For primary progressive MS, the only drug we have available is ocrelizumab.” Dr Montalban ended by recommending reading the ECTRIMS-EAN clinical practice guidelines for pharmacological management of MS [4], as well as a recently published review regarding treatment approaches for progressive MS [5].

Figure. Evolving therapeutic landscape in MS

1. Marziniak M, et al. JMIR Rehabil Assist Technol. 2018;5:e5.
2. Ontaneda D. Continuum (Minneap Minn). 2019;25:736-752.
3. Absinta M, et al. JAMA Neurol. 2019 Aug 12.
4. Montalban X, et al. Mult Scler. 2018;24:96-120.
5. Faissner S, et al. Nat Rev Drug Discov. 2019 Aug 9.

Posted on 8 November 201925 March 2024