Fatigue, Anxiety, Pain? It Could be MS

According to a new study from the University of British Columbia, the earliest warning signs of multiple sclerosis (MS) can appear more than a decade before the onset of classic neurological symptoms. The study, published in JAMA Network Open, analyzed the health data of more than 12,000 people in British Columbia and found that people with MS were more likely to use health services 15 years before the onset of the first MS symptoms. The findings challenge long-held assumptions about when the disease actually begins and provide the most comprehensive picture to date of how patients interact with a range of healthcare providers in the years before diagnosis as they seek answers to unclear medical problems.

First Symptoms Appear Many Years Before the Onset of MS

“Multiple sclerosis can be difficult to detect because many of the earliest signs—such as fatigue, headaches, pain, and mental health issues—are quite common and can easily be confused with other conditions,” said lead author Dr. Helen Tremlett, professor of neurology at the UBC Faculty of Medicine and researcher at the Djavad Mowafaghian Centre for Brain Health. “Our findings significantly push back the time when these early warning signs are likely to appear, potentially opening up new opportunities for earlier detection and intervention.”

The study used linked provincial clinical and administrative health data to track doctor visits in the 25 years before a patient’s MS symptoms appeared, which were confirmed by a neurologist based on a detailed medical history and clinical examinations. It is the first study to examine healthcare utilization this far back in a patient’s medical history. Most previous studies used administrative data to examine trends only in the five to ten years prior to a patient’s first demyelinating event (e.g., visual disturbances). This is much later than the date of symptom onset determined by the neurologist.

Doctor Visits Increase Even Before Symptoms Begin

The results showed that people with MS experienced a steady increase in healthcare utilization over a 15-year period compared to the general population, with different types of doctor visits increasing at specific points in time:

• 15 years before symptom onset: Visits to general practitioners increased, as did visits to other doctors for symptoms such as fatigue, pain, dizziness, and mental health conditions such as anxiety and depression.
• 12 years earlier: Visits to a psychiatrist increased.
• Eight to nine years earlier: Visits to neurologists and ophthalmologists increased, which could be related to problems such as blurred vision or eye pain.
• Three to five years earlier: Visits to emergency medicine and radiology increased.
• One year earlier: Visits to doctors in various specialties peaked, including neurology, emergency medicine, and radiology.

Early Intervention

“These patterns suggest that MS has a long and complex prodromal phase – where something is happening beneath the surface but has not yet manifested as MS,” said Dr. Marta Ruiz-Algueró, a postdoctoral fellow at UBC and first author of the study. “We are just beginning to understand what these early warning signs are, with mental health issues appearing to be among the earliest indicators.” The study builds on previous work by Dr. Tremlett and her team, which characterized the early stages of MS, known as the prodromal phase, when subtle symptoms appear before the typical signs become apparent. Prodromal phases are well known in other neurological diseases such as Parkinson’s disease, where mood swings, sleep disturbances, and constipation often occur years before the more familiar motor symptoms such as tremors and stiffness.

While the researchers point out that the vast majority of people who experience general symptoms will not develop MS, identifying and characterizing the prodromal phase of MS 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 through monitoring, support, or prevention strategies,” said Dr. Tremlett. According to the researchers, this opens up new avenues for research into early biomarkers, lifestyle factors, and other potential triggers that may play a role in this previously overlooked phase of the disease.