Multiple sclerosis develops long before your first neurological symptoms

Confirmation bias, i.e. a tendency to search for, interpret, favour, and recall recent information in a way that confirms or supports a belief that MS must be triggered by something.

Does COVID-19 or the COVID-19 vaccines cause MS?

Many people who develop MS look back over the preceding few weeks and months to identify potential triggers or cause(s) of their MS. A recent example is COVID-19. Many people who developed their first MS after COVID-19 or after receiving the COVID-19 vaccine are convinced that the infection or the vaccine triggered or caused their MS. This is a type of confirmation bias, i.e. a tendency to search for, interpret, favour, and recall recent information in a way that confirms or supports a belief that MS must be triggered by something. In my experience, this confirmation bias rarely extends beyond a year or two. It is often restricted to events in the few months before the onset of neurological symptoms. 

Photo by Google DeepMind on Unsplash

What is clear is that confirmation bias is inconsistent with what we know about the evolution of MS. There is good evidence that pwMS develop biological disease years before they have their first attack.

• 80% of subjects presenting with a clinically isolated lesion (CIS) compatible with demyelination have additional lesions on their MRI that are old, i.e. non-Gd-enhancing lesions. Similarly, many people with CIS already have evidence of end-organ damage that would have evolved over several years.

• Most people with radiologically-isolated syndrome (RIS) or asymptomatic MS who have an MRI for a reason unrelated to neurological symptoms, for example, as part of a medical to enter a pilot training programme, take years to have a neurological event that leads to a diagnosis of MS. 

• School leavers destined to develop CIS or MS in the next decade perform worse in high school examinations than school leavers who don’t develop CIS or MS in the future.

• Children who present with CIS/MS have smaller brains than children presenting with other inflammatory conditions of the brain that are not MS, e.g. ADEM (acute disseminated encephalomyelitis). 

• People diagnosed with CIS/MS have increased healthcare utilisation in the five years before their presentation. This is often referred to as prodromal MS. 

• Subtle changes are noted in areas of the brain months to years before a focal MS lesion is noted; i.e., something happens in the brains of people with MS long before focal inflammation occurs. I refer to this as the ‘field hypothesis’, i.e. focal inflammation, which causes MS lesions and relapses in responding to something in the tissue that is there many months or years before a lesion develops.

• People who are born in a high-risk country and migrate to a country of low risk take their MS risk with them, i.e. whatever causes MS is present many years before someone develops MS. 

What about EBV? 

I am in the camp that thinks the Epstein-Barr virus (EBV) is the cause of MS. We know that virtually 100% of people with MS (pwMS) are EBV positive when they are diagnosed with MS. Being EBV-negative protects you from getting MS. You also have to be infected with EBV before getting MS. People with symptomatic EBV infection or those who have infectious mononucleosis (IM) are at higher risk of getting MS than those who don’t get IM. From the time someone gets infected with EBV, there is a lag of close to 8 years before they present with their first neurological symptoms. In this period, from EBV exposure and first neurological symptoms, people destined to develop MS may have raised neurofilament levels indicative of subclinical damage to the nervous system or the beginning of biological MS.

All these observations tell us that MS takes years and possibly decades to develop. Therefore, things that happen in the months before your initial presentation are unlikely to play a causal role. However, these events may trigger relapses in people who already have MS. Before disease-modifying therapies (DMTs), it was shown that people with MS were more likely to have a relapse in the so-called ‘at-risk’ period surrounding an infection. The at-risk period is the week before and up to 5 weeks after the infection. This observation of infections triggering relapses is not observed in pwMS on DMTs, presumably because the DMT prevents the relapse from occurring.  Therefore, if you have developed biological MS already and are in the prodromal or asymptomatic stage, having an infection or a vaccination may stimulate the immune system and cause you to have your first clinical event. This infection and/or vaccine is not causing MS but is simply triggering a relapse.  

I hope this all makes sense to you and explains why I am confident that COVID-19 and COVID-19 vaccines do not cause MS. 

Does COVID-19 or the COVID-19 vaccines cause MS? NO

I would be interested to know if any of you had any events that you thought may have caused or triggered your MS.

Subscriptions and donations

MS-Selfie newsletters and access to the MS-Selfie microsite are free. In comparison, weekly off-topic Q&A sessions are restricted to paying subscribers. Subscriptions are being used to run and maintain the MS Selfie microsite, as I don’t have time to do it myself. You must be a paying subscriber if people want to ask questions unrelated to the Newsletters or Podcasts. If you can’t afford to become a paying subscriber, please email a request for a complimentary subscription (ms-selfie@giovannoni.net).

Important Links

MS-Selfie microsite

Donations to MS-Selfie

Prof. G’s Backstory and CV

Prof. G’s MS Blog Archive

Conflicts of Interest

X (Twitter) / LinkedIn / Medium

General Disclaimer

Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.