Secondary progressive MS — do we need a calculator?
Would a tool to self-diagnose secondary progressive multiple sclerosis be helpful?
Returning to my theme of secondary progressive MS and as a follow-up to my post on ‘What’s really new in SPMS?’. #
I have frequently argued that what drives progressive MS, i.e. loss of axons and neurones, is there from the start of the MS disease process and defining a point in time when SPMS starts is ridiculous. The only reason why pwMS don’t notice they have SPMS early on in the course of their disease is that they compensate for the damage and only become aware of progression when the compensatory mechanisms become exhausted. In people who take their nervous systems to the extreme notice progressive MS much much earlier.
Case 1
Take the marathon runner with so-called RRMS doing well on glatiramer acetate. She has an EDSS of 1.0 and her last relapse was 3 years ago. Her latest MRI showed only one new lesion, which according to her neurologist was not sufficient to trigger an escalation in her therapy. This patient noticed that when she got to about 15 miles in her long training runs or a race, her right foot would start to drop and she would occasionally catch the tip of her running shoe on the road. This symptom is almost certainly due to fatigable weakness in the neuronal, or motor, pathway supplying her right leg.
Six months later this symptom would now develop at the 10-mile mark. This person is fully functional, i.e normal when doing her standard activities of daily living, but it takes the stress of a long run to bring out the worsening disability. She asked me if she had SPMS. What should I say? Should I tell her she has SPMS? What are the implications for writing it down in her medical notes?
Case 2
Another example is world renowned high-flying 34-year investigative journalist with a 7-year history of RRMS who is NEDA (no evident disease activity) on dimethyl fumarate. He used to be able to burn the midnight oil and get along with 3–4 hours of sleep for days on end when completing a project. This happened with most of his publication deadlines. However, he had noticed that over the last 2–3 years that his attention span and concentration were falling off. He could now only work a maximum of 2 hours at a stretch and needs at least 6 hours of sleep to function the next day. He is simply not the same journalist he was 3 years ago.
To the average person, you would say this is just ageing; but he is only 34 years of age, which in my book is too young to blame his loss of cognitive stamina on age-related cognitive fall-out. In reality, age-related cognitive slowing only really starts from 35–40 years of age. When I finally agree to send him for a full neuropsychological assessment, he and I were not surprised when the report comes back that he has problems with both visuospatial memory and executive function. This patient knew his cognition was failing; put another way he knows he has secondary progressive MS - he is not a fool. He didn’t need the neuropsychological assessment to prove this. However, I probably did, simply to document his deficits in his medical records. This patient has an EDSS of 1.5; I wonder how many other neurologists would label him as being SPMS?
These two cases illustrate that if you are prepared to look for worsening disability in pwMS, using functional stress tests in the form of endurance exercise, tests of subtle motor dysfunction such as complex keyboard tasks, or cognitive testing, you will find the deficits and almost certainly be able to document their worsening. Does this help us manage MS? No, and possibly, yes; I am not sure.
No in the sense that we really have no idea if switching someone with worsening MS with no evidence of inflammatory activity, i.e. someone with no relapses and no focal inflammatory activity on MRI (NEDA 1&2), would benefit from a treatment change. We have equipoise here, i.e. a gap in our clinical evidence-base. These sorts of patients should be randomised to clinical trials, i.e. stay on their treatment or escalated to a treatment that at least has been shown to have an impact on end-organ damage markers (brain volume loss). Or they should be randomised to add-on neuroprotection trials. This is the next frontier in MS. I am sure these two patients have smouldering MS, which has not been halted by glatiramer acetate nor dimethyl fumarate.
The philosophical question that arises from this discussion is that both these patients have become aware of their progressive disease independent of what I as a neurologist has to say. They don’t need me to say, yes, you have SPMS. In fact, if I say, ‘Yes, you have SPMS’ and write it down in their notes I would be doing them a disservice. Currently, there are no treatments licensed for SPMS and according to NHS England’s guidelines we are meant to stop their treatments. Yes, stop their treatment. These scenarios show you how perverse the current NHS England stopping criteria are; they are not evidence-based nor have they been formulated on any coherent scientific rationale.
Another debate these scenarios raise is whether or not we should provide patients with the tools and knowledge to diagnose themselves as having SPMS? I say yes. However, a lot of my colleagues and other MS stakeholders are saying no. This is patronising-doctors.org all over again. Why shouldn’t we tell people they have worsening or SPMS? Or at least empower them to make that diagnose themselves? Their argument against this proactive approach is that you can do nothing about it. This is the wrong attitude to have. If we recognise worsening MS in these patients we should ask why? Do they have evidence of sub-clinical inflammatory activity that we can target? Are there lifestyle interventions and comorbidities that need addressing? Are there any trials that are actively recruiting patients with early SPMS? If a large enough group of these patients are recognised then they may be able to lobby the MS Society and other funding agencies to fund trials and research into smouldering MS. Another possibility is a treatment switch. If, for example, siponimod gets a licensed for SPMS and greenlighted by NICE, then both these patients may become eligible for siponimod. Finally, giving pwMS the ability to self-monitor and show they are getting worse across one or two domains may make them eligible for specific trials in the future. Not having this information, on the other hand, may make them ineligible for the trials.
Do you have any opinions on the issues raised in this post? Would you want to use a calculator to assess whether or not you have SPMS? If yes, please complete a short online survey. Thank you.
CoI: multiple