What prognostic group are you in?

Background

MSology is an imperfect science. In short we can't predict the prognosis of an individual MSer very accurately. So don't let your neurologist fool you when he or she says you are likely to have benign MS. Benign MS is a relative term and can only be used retrospectively once you have had MS for many years, in fact decades. In the pre-DMT era most MSers, given sufficient time, would become disabled, which is why I prefer not to use the term benign MS. However, saying this is not sufficient and I suspect use of the term benign is not going to go away. I now use it as a treatment aim, i.e. we want all of our patients to have benign disease.

What we can do is apply population data to place you into a broad prognostic group. This is often helpful as it allows you to frame your disease it terms of potential outcomes and may help you balance the risks of some of the treatments against the potential impact of MS later on in your life.

Predicting outcomes in MS is an actuarial science. Just like an actuary working in the insurance industry we give you an average prognosis with a wide range of possibilities or errors. For this reason I try and keep it simple and classify MSers into three prognostic categories; poor, indeterminate or good.

Poor in this context simply means if you leave MS to its own devices and let it run its natural course the average person in this category will do badly. To be honest with you given sufficient time the majority of pwMS do badly, which is why I actively promote treatment based on the scientific rationale that if we prevent damage now we will protect your reserve capacity and improve your long-term outcome. This is the treatment philosophy behind the 'Brain Health: Time is Brain' initiative, which everyone with MS should take time to read.

The following is a list of factors that have been linked to poor prognosis. I suggest you add up how many you have and classify yourself into one of three groups. If you have less than 5 of these factors, you are more likely to have a good outcome. In comparison if you have 10 or more of these factors you fall into the poor prognostic group. In reality the majority of pwMS fall into the intermediate (indeterminate) prognostic group with 5-10 of these factors. Please note that some of these baseline factors are modifiable and hence it is up to you to make the effort to improve your own prognosis.

Please also note that these factors have been defined in groups of people who have not been on DMTs and hence only apply to MSers who are untreated. It is clear that treatment with DMTs are changing the outcome of MS.

Prognostic factors

1. Older age of onset (greater than 40 years).
2. Male sex.
3. “Multifocal“ onset. More than one site in the nervous system involved with the initial attack
4. Efferent or effector system is affected early. That is the motor (power), cerebellar (balance and coordination), or bladder & bowel function.
5. Partial or no recovery from initial relapses. Do you have residual deficits from your initial attacks?
6. High relapse rate in the first 2 years, i.e. more than 2 relapses
7. Early disability. If you have and EDSS > 3.0 within 5 years of symptom onset you are doing badly. If you don't know what your EDSS is you can calculate it using an online calculator (web-EDSS calculator).
8. Abnormal MRI with large lesion load. More than 9 T2 lesions (white blobs) on the baseline MRI
9. Active or enhancing lesions on your baseline MRI. Enhancing lesions imply that the lesions are new and actively inflamed
10. Posterior fossa lesions on the MRI. This refers to lesions in the back of the brain that involve the brainstem and cerebellum
11. Lesions in the spinal cord on MRI.
12. Obvious early brain atrophy on MR. Brain atrophy refers to premature shrinkage of the brain over and above what you would expect for age
13. Abnormal cerebrospinal fluid. Positive OCBs (oligoclonal IgG bands) in the spinal fluid.
14. Raised neurofilament levels in your spinal fluid. This test may not be part of routine care at your neurology centre. Neurofilaments are proteins that are released from damaged nerve fibres and high levels indicate greater damage and poorer outcome.
15. Low vitamin D levels. This is controversial, but several studies have shown that pwMS with low levels do worse. These observations do not necessarily imply causation, i.e. that by taking vitamin D you will do better. The observation may be an association in that the MS-associated inflammation uses up vitamin D and the more inflammation you have the worse your MS and hence the lower your vitamin D levels are. The latter is often referred to as reverse causation.
16. Smoking. Smokers with MS do worse than non-smokers. This is one reason why you should try and give up smoking.
17. Comorbidities. MSers who have diabetes, prediabetes, hypertension or a raised cholesterol do worse than pwMS without comorbidities.
18. Cognitive impairment. MSers with poor cognitive function do worse than MSers with good cognition. Please note you can't really assess your own cognition at present. You need to have it tested by a neuropsychologist.

Conclusions

Humans have an interesting psychology in that they tend to consider themselves to the exception to the rule. Gamblers don’t enter a casino to lose; they always believe they are going to win. When a person with lung cancer starts chemotherapy they believe they going to be one of the 10% who are cured. When some with MS is diagnosed they believe they going to be one of the 30% with benign disease. The current dogma is that 30% of untreated pwMS will have benign disease. This definition of benign MS is based on having no, or little disability at 15 years; i.e. an EDSS of 3.0 or less (no visible disability). The problem with this is when you interrogate people with benign MS you find that more than 50% of them have hidden symptoms of depression, anxiety and cognitive impairment. Can we really justify this definition of benign MS? What is more, when you follow people with benign MS past 15 years only 15% remain as benign at 25 years and 5% after 30 years. If you get to 40 years follow-up with benign MS half of these will become disabled over the next 10 years. Time is the killer. Some will state that these figures are now out of date and there are newer and better figures, which show MS is a more benign disease. You are right and there are several very good reasons for this. In population based studies the proportion of subjects with benign MS is greater than those in hospital or clinic-based studies; for example in the Ohlmstead Mayo Clinic population, about 45% have benign disease at 15 years. The reason for this is that pwMS with benign disease often drop-out of hospital follow-up and show up in population based studies. The earlier diagnosis of MS, diagnosing people with MS who would not have been diagnosed in the past (ascertainment bias), the changing definition of MS (CIS becoming MS) and the wide use of DMTs are all beginning to change the natural history of MS for the better. Despite these observations this should not change our treatment strategies and our aim of improving the outcome of all MSers.

I don’t think it is worth arguing over the exact figures; the message is that most MSers will not turn out have benign MS. Please note I say turn out. We simply cannot make an accurate call on this early in the course of the disease. What we should be focusing on is how can we maximise your chances of having benign disease. Treating pwMS with DMTs is one way of doing this and making sure that pwMS adopt a healthy lifestyle is other strategy that can be done in parallel.

The following figure illustrates what we are trying to do with DMTs. We are simply trying to move you to the left into a more favourable prognostic group. In other words we are trying to make sure you have benign MS.

Additional Reading

Giovannoni et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016 Sep;9 Suppl 1:S5-S48.