What are the implications?
Dr. Tremlett said the immediate impact of these observations about the prodrome is focused on research, particularly investigation of risk factors for MS. “If we want to know what causes MS, we have to be very careful that we are not detecting prodromal symptoms and mistaking that for a causal MS risk factor. We need to make sure we look further back than just the last few years when looking for risk factors.”
She gave the example of the observation that women in the years before MS diagnosis are less likely to have a pregnancy and more likely to fill a prescription for contraception. “This has led to the idea that avoiding pregnancy and using contraceptives increases the risk of MS, but I interpret it as these women know that something odd is going on and make the lifestyle decision not to become pregnant.”
She believes the longer-term impact of the prodrome is going to require much thought. “There is no such diagnosis of prodromal MS at the moment, but there could be in future. But the idea that we can use this information to detect MS earlier is going to require collaboration from many international stakeholders and MS organizations. We can’t automatically suspect MS in people who have these symptoms because they are so nonspecific. I think to request an MRI in patients experiencing headaches/fatigue/bowel issues is jumping the gun at the present moment as these symptoms are very common.”
On the idea of measuring NfL in patients with some of these symptoms, she believes that may be a possibility in the future but much more data are required.“We do have some evidence suggesting that the NfL blood biomarker is raised before MS diagnosis, and this was from a very well-designed study, but it was small so I think it is too early to start looking at this in clinical practice,” she said. “But it does justify doing this as part of a research study. We definitely need more data on this. We must be cautious as NfL is not specific for MS – many other conditions are also associated with raised levels, but it is certainly an interesting marker if used carefully.”
Following in the footsteps of Parkinson disease
She suggested that the way forward will be to package up these symptoms with information on biomarkers, such as NfL and imaging information, to enhance the ability to identify prodromal MS. “We could create a risk score and when a certain level of confidence is reached that this could be prodromal MS, then these patients could be enrolled in an intervention research study.”
Dr. Tremlett pointed out that, in the Parkinson disease field, a set of validated criteria for a prodrome have already been identified. “This is not used in clinical practice yet, but it is being used to identify patients for enrollment into clinical trials. I’m hoping that MS will follow in their footsteps.”
Commenting on the presentation, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, said: “There is no doubt that the MS disease process begins prior to the first attack (in the case of relapsing MS) or the onset of overt disability progression (in the case of primary progressive MS).”
He explained that this is demonstrated by the presence of old lesions on MRI in most patients at the time of presentation, the existence of so-called radiologically isolated syndrome (patients without symptoms of MS who undergo MRI for another reason and are found to have lesions suggesting of MS, many of whom go on to develop MS at a later date), and the occurrence of a variety of symptoms 5-10 years before presentation to a neurologist.
“Those symptoms are ones that are common in MS, though not specific for MS,” Dr. Cohen noted. “The main implication is that the timeline for MS needs to be moved earlier – for diagnosis, categorization of disease course, prognostic studies, and treatment. The issue is that the symptoms of the prodrome are rather nonspecific and most people with those symptoms do not have MS.”
New incoming president of ECTRIMS, Maria Pia Amato, MD, professor of neurology at the University of Florence (Italy), added: “The million-dollar question is when does progression really begin? This plenary talk tells us the disease is there years and years before it manifests itself with first demyelinating event. This opens up an immense opportunity for research and to open the window to the possibility of earlier diagnosis and treatment.”
Dr. Tremlett reports an investment in Precision NanoSystems.
A version of this article originally appeared on Medscape.com.