The MS Prodrome by Dr Helen Tremlett

Dr Helen Tremlett kicked off the first session of the virtual conference at 9am ET (14.00 GMT), joined by an audience of over 1,750 attendees from across the globe.

Delivering the Don Paty lecture, Helen argued that we need to formally recognise a prodromal phase in MS, referring to the period between initial symptoms or changes in function, and the first demyelinating event characterising the condition.

Helen evidenced that an MS prodrome is measurable via healthcare use between 5 and 10 years prior to a person with MS's first demyelinating event.

Symptoms causing access to healthcare providers and support in that period are wide ranging, and include:

• anxiety, depression, and / or mood disorders,
• migraine and / or headache,
• pain,
• fibromyalgia,
• anemia,
• reduced cognition,
• sleep disorders,
• irritable bowel,
• dermatological problems,
• behavioural and / or lifestyle changes,
• increased pharmaceutical prescriptions.

She also noted a pattern of elevated serum neurofilament levels (NFL) up to 6 years prior to an initial demyelinating event,suggesting there may be neuroaxonal damage evident in prodromal phase (Bjornevick, 2020).

Helen shared her thoughts on the implications this has for MS for prevention, suggesting that:

• Prodrome needs to be carefully considered when searching for risk factors for MS onset
• Increased awareness of the possibility of future MS in patients presenting with these sorts of complaints
• There could be a window of opportunity for early recognition and disability prevention
• Ultimately, in the future, there may be a place for neuroprotective clinical trials.

Evidence of the prodromal phase

She evidenced startling information around the level of access to healthcare services that people with MS have in the five years prior to their first demyelinating event.

In comparison with the general populace, those with MS in the 5 years prior to initial onset, are:

• 78% more likely to be hospitalised
• 88% more likely to have visited a healthcare professional
• 49% more likely to have had a prescription filled

These numbers increase even further when viewing just one year prior to a first event. In terms of people with MS's mental health, they also have 50% more psychiatrist visits in those five years prior to onset (Wijnands, 2019).

Other key evidence presented included:

• Fewer pregnancy-related visits occur, amongst women with MS, in the five years prior to onset of MS but an increase in oral contraceptives in those years, spiking in the year before the onset, may suggest that women with unexplained symptoms are delaying or avoiding pregnancy during this prodromal period.
• There was an increase in dermatology-related healthcare use, but there were 48% fewer dermatology visit for those who went on to develop PPMS when compared with RRMS in the five years before symptom onset. Helen queried whether skin problems might be an indicator of early inflammatory disorders.
• It is apparent that both sex and age may affect the prodrome. Anemia was more present in men who went on to have a demyelinating event than women. Pain, another prodromal marker, was affected by age, with increased age came increased reports of pain in the five years prior to MS onset (Yusuf, 2020).
• Cognitive decline is evident during the five years prior to MS onset, and evident up to 20 years before onset in PPMS (Cortese; 2016).
• In mothers who have a child with MS, their access to any physician, and also to mental health physicians, is higher compared to the general populace in the five years before their child's first demyelinating event. This may indicate paediatric prodrome affecting the mental health of family members, or that the mental health of a parent could be an environmental risk factor in paediatric MS development (Marrie, 2020).
• There are similar patterns regarding a higher prevalence of psychiatric disorders amongst people who go on to develop MS and other immune-mediated inflammatory diseases like rheumatoid arthritis and inflammatory bowel disease, in both five and even 10 years prior to disease onset, highlighting that these prodromal symptoms are not particular to MS alone (Marrie, 2018).