How bad is my multiple sclerosis?
How bad is my multiple sclerosis?
Having some idea of how bad your MS is, or not, will allow you to discuss with your neurologist issues around what level of treatment is appropriate for you.
‘What is my prognosis?’ is one of the questions you need to answer to be able to make an informed decision about your MS treatment.
Other questions to ask yourself before starting a DMT
What prognostic group do I fall into?
What is the risk of not being treated with a disease-modifying therapy (DMT)?
Am I eligible for treatment with a DMT?
What is the difference between a maintenance/escalation DMT and an IRT (immune reconstitution therapy)?
Do I understand the difference between short-term intermittent and long-term continuous immunosuppression?
Do I understand the concept of treat-2-target?
What are the attributes of the specific DMTs?
How can I derisk or reduce my chances of getting certain adverse events on specific DMTs?
Prognosis
MSology is an imperfect science.
In short, we can't predict the prognosis of an individual person with MS 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 pwMS, 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 the use of the term benign is not going to go away. I now use it as a treatment aim, i.e. we want all pwMS 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 in 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 in fact an actuarial science. Just like an actuary working in the insurance industry we try to give you an average prognosis with a wide range of possibilities or errors. For this reason, I try and keep it simple and classify pwMS 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 help make the effort to improve your own prognosis, which is one of the reasons why I started MS-Selfie (Selfie is short for self-management).
Please also note that these factors have been defined in groups of people who have not been on DMTs and hence only apply to pwMS who are untreated. It is clear that treatment with DMTs is changing the outcome of MS.
Prognostic factors
Older age of onset (greater than 40 years)
Male sex
Multifocal onset - more than one site in the nervous system involved with the initial attack
Efferent or effector system is affected early - that is the motor (power), cerebellar (balance and coordination), or bladder & bowel function.
Partial or no recovery from initial relapses - do you have residual deficits from your initial attacks?
A high relapse rate in the first 2 years - more than 2 relapses
Early disability - if you have an 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)
Abnormal MRI with large lesion load - more than 9 T2 lesions (white blobs) on the baseline MRI
Active or enhancing lesions on your baseline MRI - enhancing lesions imply that the lesions are new and actively inflamed
Posterior fossa lesions on the MRI - this refers to lesions in the back of the brain that involve the brainstem and cerebellum
Lesions in the spinal cord on MRI
Obvious early brain atrophy on MR) - brain atrophy refers to premature shrinkage of the brain over and above what you would expect for your age. This information is unlikely to be available to you as it is often not measured or commented on by neuroradiologists.
Retinal thinning on optic coherence tomography or OCT - pwMS who have lost a lot of retinal nerve fibres do worse than people with a normal retina. Yes, the eye is truly a window into what is happening in the brain of someone with MS.
Abnormal cerebrospinal fluid - positive OCBs (oligoclonal IgG bands) in the spinal fluid.
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.
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.
Smoking - smokers with MS do worse than non-smokers. This is one reason why you should try and give up smoking.
Comorbidities - pwMS who are obese, have diabetes, prediabetes, hypertension or a raised cholesterol do worse than pwMS without comorbidities.
Cognitive impairment - pwMS with poor cognitive function do worse than pwMS 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 interesting psychology in that they tend to consider themselves to be 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 is 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 of follow-up with benign MS half of these will become disabled over the next 10 years. Time is the killer.
Many 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 Olmstead Mayo Clinic MS 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, but still show up in population-based studies.
The earlier diagnosis of MS, i.e. diagnosing people with MS who would not have been diagnosed in the past, is changing the definition of MS. For example, most people with CIS are now being diagnosed as having MS. The wide use of DMTs is also 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 pwMS.
I don’t think it is worth arguing over the exact figures; the message is that most pwMS will not turn out to have benign MS unless they are treated adequately. 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 another strategy that can be done in parallel.
The following figures illustrate what we are trying to do with DMTs. We are simply trying to move you to the right into a more favourable prognostic group. In other words, we are trying to make sure you have benign MS and to get you to old age with as healthy a brain as possible. What protects you from developing age-related cognitive impairment and dementia is your brain and cognitive reserves. MS reduces these both, which is why it is so important to protect these. This is why our treatment aim in MS has now moved beyond no evident inflammatory disease activity (NEIDA) to focus on the end-organ. This is why we now want to normalise your rate of MS-related brain volume loss and your neurofilament levels. Do you agree?
Subscriptions
I am raising funds from subscriptions to administer the MS-Selfie Newsletter and microsite. The subscriptions, for case studies only (all other newsletters are free), will be used to hire an administrator to proofread, curate and transfer the contents of the Newsletter onto the companion MS-Selfie microsite. If you find these Newsletters helpful and can afford to subscribe I would urge you to do so; it will help me and the MS community.
The MS-Selfie case study from the 16th of September is about a patient with rapidly evolving severe MS who is having doubts about the decision to be treated with cladribine. Should she abort the cladribine and have AHSCT? I discuss the issues around this treatment dilemma and the issues that COVID-19 raises in the management of this patient.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. If you have problems please tell your own healthcare professional who will be able to help you.
thank you for this information - this is really the kind of information you need to make informed decisions about treatment.
I took the EDSS-test and I was shocked to get a 3!
I have never been asked these kind of questions before, just the walking on the toes, and got a 0 because I can walk on my toes like a pro...
I appreciate your comments focusing on the hope for benign MS, that many newbies have, and your attempt to largely dispel that. I’ve “made it” all the way through from 28 to 64 but have some manageable deficits. I’ll die from something, but hopefully not too soon. I’ve seen or read about lots of others, not so “lucky”. MS totally changed my life, however, and I think that is the initial road block faced. Most think MS should be an illness that is curable and doesn’t involve sacrifice, inconvenience or any significant change of plans. Initially, one accepts no change. Then, a little- they can deal with it. Then a little more if they have to,.. on and on. In hind sight, one can look back and by then, they have been forced to accept the changes one way or another. Not putting up such a strong road block to change, initially, might lead to increased positive outcomes later? Perhaps an early invitation to consider alternative creative ways to have a happy life (just in case)? For many however, that would probably include a marked change in aspects of one’s philosophy of life. In my former profession, I think we used the term denial to describe not facing reality. The excuses are many and it runs from MS to Anti-vaxxers to Climate Science; to electing Presidents. I just thought it was noteworthy your sincere attempt to add some tough truth to your discussion.