Multiple sclerosis may start much earlier than previously thought

The earliest warning signs of multiple sclerosis (MS) may appear more than a decade before the first classic neurological symptoms, according to new research from the University of British Columbia.

A study published today in JAMA Network Open analyzed the medical records of more than 12,000 people in British Columbia and found that MS patients' frequency of seeking medical care increased 15 years before their first MS symptoms appeared.

These findings challenge long-held ideas about when the disease actually begins, offering the most comprehensive picture to date of how patients interact with different health care professionals in the years leading up to diagnosis as they try to find answers to unclear medical problems.

“MS can be difficult to recognize because many of the earliest signs — fatigue, headaches, pain, and mental health issues — can be quite general and easily mistaken for other illnesses,” said senior study author Dr. Helen Tremlett, a professor of neurology in the UBC Faculty of Medicine and a researcher at the Javad Mowafaghian Centre for Brain Health. “Our data significantly shifts the time frame for the onset of these early warning signs, potentially opening up opportunities for earlier detection and intervention.”

The study used linked clinical and administrative data from a provincial health system to track physician visits for 25 years before the onset of MS symptoms in patients, as determined by a neurologist based on a detailed medical history and clinical examination.

This is the first study to examine healthcare use this far back in a patient’s clinical history. Most previous studies have looked at trends only for the 5–10 years before the first demyelinating event (such as vision problems) using administrative data. This is a significantly later benchmark than the symptom onset date as determined by the neurologist.

The results showed that, compared with the general population, people with MS experienced a gradual increase in health care use over 15 years, with different types of health care visits increasing at different times:

• In the 15 years before symptom onset: There was an increase in visits to general practitioners and doctors for symptoms such as fatigue, pain, dizziness and mental health problems including anxiety and depression.
• Over 12 years: the number of visits to a psychiatrist has increased.
• Over 8–9 years: Increased visits to neurologists and ophthalmologists, which could be related to symptoms such as blurred vision or eye pain.
• Over 3-5 years: Increased visits to emergency departments and radiographic examinations.
• Over 1 year: Peak in visits to physicians in various specialties, including neurology, emergency care, and radiology.

“These patterns suggest that MS has a long and complex prodromal phase — a period where things are happening beneath the surface but don’t yet declare themselves as MS,” said Dr. Marta Ruiz-Alguero, a UBC postdoctoral fellow and first author of the study. “We’re just beginning to understand what these early warning signs are, with mental health issues appearing to be some of the earliest indicators.”

The study builds on previous work by Dr Tremlett and her team to characterise the early stages of MS, or prodromal phase, when subtle symptoms appear before the main signs of the disease become noticeable. Prodromal periods are well studied in other neurological diseases such as Parkinson’s disease, where mood changes, sleep disturbances and constipation often occur years before the onset of more familiar motor symptoms such as tremor and stiffness.

While the researchers caution that the vast majority of people with common symptoms will not develop MS, they believe that recognizing and characterizing the MS prodrome could one day help speed up diagnosis and improve outcomes for patients.

“By identifying these early warning signs, we may be able to intervene earlier – whether that’s monitoring, support or preventative strategies,” said Dr Tremlett. “This opens up new avenues of research into early biomarkers, lifestyle factors and other potential triggers that may play a role in this previously undetected phase of the disease.”