The diagnosis of multiple sclerosis should be extended into the asymptomatic and prodromal phases of the disease in order to allow neurologists to treat the disease earlier, an international MS expert has told the ANZAN conference.

Professor Gavin Giovannoni, a leading UK expert in multiple sclerosis, said studies suggested that MS had a lengthy prodrome stage – defined as an early symptom indicating the onset of a disease or illness.

He said a definitive study proving the theory was a matched cohort study on health care use before a first demyelinating event. The trial involved 14,428 people with MS and 72,059 controls from a health administrative database.

The study showed that over a five-year period before people with MS put in their first MS related claim they were much more likely to visit their physician, be admitted to hospital and have a prescription compared to the controls.

“Which means they had a lot of symptoms prior to presenting with their first demyelinating event… and that’s what the prodrome is,” Professor Giovannoni said.

The researchers further validated their findings in a clinical cohort. Another Argentinian study also found evidence of significant cognitive impairment in children ahead of a diagnosis of MS.

“Clearly the disease has been there long before the first presenting symptom. So if you ask me how long the prodrome is it’s at least somewhere up to  10 years, maybe longer than that,” Professor Giovannoni told delegates.

According to Professor Giovannoni, from the Blizard Institute at Barts and The London School of Medicine and Dentistry, the diagnostic criteria for MS needed to be changed.

“I would argue that we should almost certainly be able to diagnose this condition a little earlier because then we could actually do something about it… we have an opportunity to modify the disease course,” he said.

He challenged delegates to think about MS as a biological disease.

He explained that the conventional definition is an “inflammatory disease of the CNS characterised by demyelination and variable degrees of axonal loss and gliosis”. Whereas a  ‘pre-theoretical or clinical definition’ is ‘objective CNS dysfunction i.e. involvement of two or more white matter structures (space) separated by time, with no other aetiology.

“There is a great opportunity, with some thinking, to link these two definitions up to improve our diagnostic criteria,” he said.

Vitamin D: The biggest opportunity and regret?

Moving on to discuss the potential to prevent MS, Professor Giovannoni said environmental factors that have been linked to MS included vitamin D levels or sunlight exposure, Epstein Barr Virus infection (EBV) and lifestyle factors such as smoking, alcohol intake and more recently childhood obesity.

He told delegates that he felt a little ‘guilty’ when it came to the potentially modifiable risk factor of vitamin D levels.

“I was actually quite junior when I went to my first task force meeting on how to design a vitamin D prevention study. I’ve now been to four meetings, three of them international, on how we as an MS community can design a vitamin D prevention trial but there’s been no consensus.”

“… and that’s embarrassing because the next generation of people with MS are going to look back at us and say, ‘you knew this, why didn’t you do something about it?”.

Professor Giovannoni said the expert groups had not known what age groups to tackle. There was also debate about dosing, and what the comparator should be. The best suggestion had been to take a population health approach and supplement one country and compare incidence rates with other countries.

The hypothesis, derived from immigration studies, is that vitamin D supplementation could reduce the incidence of MS by between 60 to 80 percent, he said.

The role of EBV could be key

Professor Giovannoni said he believed that EBV infection was a cause of MS.

“I had a Eureka moment back in 1995 when I went to a meeting on viruses in MS that I came away thinking EBV has to be the cause of this disease,” he told delegates.

“If you look at causation theory the virus ticks almost every one of Bradford Hill’s criteria [epidemiologic evidence of a causal relationship between a presumed cause and an observed effect]. The reason why people don’t think it’s important is because the RR is quite low – it’s 2 to 2.5. MS would be a rare manifestation of  common exposure and therefore RR of 2 to 2.5 can still be causal.”

Professor Giovannoni said he had recently taken up a co-director position of a new preventive neurology unit. One of its priorities was to look into an EBV vaccine study to prevent MS.