What happens before presentation of clinical symptoms

What happens before presentation of clinical symptoms

Have you recently been diagnosed with multiple sclerosis (MS)? If the answer to that question is yes, then this article is just for you.

Damage to the brain and the breakdown of brain cells, development of brain lesions, and the faster loss of brain volume seen in MS can start early in the disease process, even before the emergence of any symptoms.1-6 And this can have long-term consequences for people living with MS if a management plan is not initiated quickly after diagnosis.1,7-9

This article has been created to emphasise the importance of starting treatment as soon as possible in people who have just been diagnosed with MS. We will take a look at the changes that happen before the appearance of symptoms and the impact that these early changes can have if they are left unaddressed.

Early MS disease activity can go unnoticed

Your brain has what is described as a neurological reserve – an inbuilt capacity to retain function by changing the pathways that are used.10 This means that your brain can compensate for damaged or destroyed connections that are caused by early MS disease activity.10 So if one part of the brain is damaged, your brain may be able to use other parts of it to work around the problem.10


This can help to explain why you would have been unaware of early neuronal injury caused by MS before your diagnosis. Neurological reserve helps to mask early damage and without experiencing any symptoms, you wouldn’t have known that anything was wrong.10


What changes happen before the emergence of MS symptoms?

Brain atrophy is the gradual loss of brain volume over time, and it is caused by the damage and breakdown of neurons (nerve cells) in the brain.10 This happens in everyone as a result of aging. But for people living with MS, brain atrophy takes place a little faster.10
Accelerated brain atrophy is a key component of MS which is present throughout the entire disease course, and can even be seen on brain scans in people who don’t have any symptoms but later go on to develop the disease.1-4,10,11


Long-term underlying MS disease activity contributes to the faster rate of brain atrophy that is seen in MS.6,12 Similarly to brain atrophy, this ongoing activity is also present before people with MS experience any signs or symptoms of the disease.6 Therefore, it is ‘silent’ early on, meaning that people are unaware of it occurring. Alongside age, brain atrophy, continuous ‘smouldering MS’ disease in the absence of relapses, and the activation of certain immune cells in the brain, this early activity is considered a driver of disease progression in MS.12-16

Discuss treatment options with your doctor as soon as possible after diagnosis

Early MS disease activity should not be overlooked, as it can have potential consequences many years down the line. For example, the extent of brain atrophy at disease onset is now considered a predictor of physical impairment in the long term.4,7,8 It may also impact cognitive function much later in life.4,9
As there is such profound evidence linking early disease activity with the development of poor long-term outcomes, it’s hugely important to take swift action against MS following a diagnosis. If you have just been diagnosed with MS, you should discuss your options with your doctor, to ensure that you find the right treatment for you and that this is started as soon as possible. Early initiation of MS treatment is associated with better long-term outcomes for people living with MS, so talking to your doctor about your treatment options, without delay, could make a really positive difference to the course of your disease.17


Recognition of the earliest signs of MS can be very challenging and often means that potentially damaging disease activity has already happened pre-diagnosis.17 Therefore, action must be taken quickly when symptoms do arise and become noticeable.

Although treating early is the most ideal scenario, there is increasing evidence that disease modification is still possible in the later stages of MS disease – even if walking function has been lost.1 This recent research should offer you some reassurance that the right MS management can still help to stop or delay any further damage, even if your treatment is started later than hoped.

If you’re concerned about the management of your MS or the potential impact that early disease activity might have on you in the future, discuss it with your doctor. To help you have conversations about these topics with your healthcare team, why not create your own Talk To Your Doctor Guide.


1.    Cerqueira JJ, et al. J Neurol Neurosurg Psychiatry 2018; 89(8): 844–850.
2.    George IC, et al. Mult Scler 2021; 27(1): 130–133.
3.    Azevedo CJ, et al. Neurol Neuroimmunol Neuroinflamm 2015; 2(3): e102.
4.    Healthline – Drug May Slow Brain Atrophy in People with Progressive MS. Available at: https://www.healthline.com/health-news/drug-slow-brain-atrophy-in-people-with-progressive-ms. Last accessed: April 2021.
5.    MS Trust – Lesions. Available at: https://mstrust.org.uk/a-z/lesion. Last accessed: April 2021.
6.    Suthiphosuwan S, et al. JAMA Neurol 2020; 77(5): 653–655.
7.    Rojas JI, et al. Arq Neuropsiquiatr 2012; 70(10): 765–768.
8.    Popescu V, et al. J Neurol Neurosurg Psychiatry 2013; 84: 1082–1091.
9.    Bakirtzis C, et al. Open Neurol J 2018; 12: 31–40.
10.    Giovannoni G, et al. Brain health: Time matters in multiple sclerosis. Last updated: August 2018.
11.    Rocca M, et al. Neurology 2017; 88: 403–413.
12.    Elliott C, et al. Mult Scler 2019; 25(14): 1915–1925.
13.    NIH – Smouldering spots in the brain may signal severe MS. Available at: https://www.nih.gov/news-events/news-releases/smoldering-spots-brain-may-signal-severe-ms. Last accessed: April 2021.
14.    Absinta M, et al. JAMA Neurol 2019; 76(12): 1474–1483.
15.    MSAA – Understanding Progression in MS. Available at: https://mymsaa.org/PDFs/Understanding_Progression_in_MS.pdf. Last accessed: April 2021.
16.    Scalfari A. Mult Scler 2019; 25(7): 902–904.
17.    MS International Federation – Signs of MS may start five years before diagnosis. Available at: https://www.msif.org/news/2018/08/26/signs-of-ms-may-start-five-years-before-diagnosis/. Last accessed: April 2021.


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