Key Questions Answered
Q: How early can signs of multiple sclerosis appear?
A: The study found increased healthcare usage related to MS symptoms up to 15 years before official diagnosis.
Q: What early symptoms did people with MS report?
A: General symptoms like fatigue, pain, dizziness, anxiety, and depression appeared years before neurological symptoms.
Q: Why is this research important?
A: It challenges traditional MS diagnostic timelines and opens the door to earlier detection and intervention strategies.
Summary: A large-scale analysis of health records reveals that subtle signs of multiple sclerosis (MS) may appear more than a decade before diagnosis. People who eventually develop MS began increasing healthcare visits—especially for general symptoms like fatigue, pain, and anxiety—15 years before neurologists identified their first demyelinating event.
These findings suggest a lengthy prodromal phase for MS, similar to early-stage Parkinson’s disease, where nonspecific symptoms quietly precede more recognizable ones. Identifying this earlier timeline could lead to proactive support, monitoring, and even future prevention strategies.
Key Facts
- Long Prodrome: Healthcare usage increased steadily over 15 years before MS diagnosis.
- Early Indicators: Fatigue, dizziness, mental health issues, and eye problems were among the first signs.
- Clinical Shift: Results challenge the belief that MS only begins with clear neurological symptoms.
Source: University of British Columbia
The earliest warning signs of multiple sclerosis (MS) may emerge more than a decade before the first classical neurological symptoms occur, according to new research from the University of British Columbia.
Published today in JAMA Network Open, the study analyzed the health records of more than 12,000 people in British Columbia and found that those with MS began using healthcare services at elevated rates 15 years before their first MS symptoms appear.
The findings challenge long-held assumptions about when the disease truly begins, offering the most comprehensive picture to date of how patients engage with a range of healthcare providers in the years leading up to a diagnosis as they search for answers to ill-defined medical challenges.
“MS can be difficult to recognize as many of the earliest signs—like fatigue, headache, pain and mental health concerns—can be quite general and easily mistaken for other conditions,” said senior author Dr. Helen Tremlett, professor of neurology at UBC’s faculty of medicine and investigator at the Djavad Mowafaghian Centre for Brain Health.
“Our findings dramatically shift the timeline for when these early warning signs are thought to begin, potentially opening the door to opportunities for earlier detection and intervention.”
The study used linked clinical and administrative provincial health data to track physician visits in the 25 years leading up to the onset of a patient’s MS symptoms, as determined by a neurologist through detailed medical history and clinical assessments.
It is the first study to examine healthcare usage this far back in a patient’s clinical history. Most previous studies only examined trends in the five to 10 years leading up to a patient’s first demyelinating event (such as vision problems) using administrative data. This is a much later benchmark compared to the neurologist-determined date of symptom onset.
The findings revealed that, when compared to the general population, people with MS had a steady build-up of healthcare engagement over 15 years with different types of doctor visits increasing at distinct points in time:
• 15 years before symptom onset: Visits to general practice physicians increased, as did visits to any physician for symptoms like fatigue, pain, dizziness and mental health conditions including anxiety and depression.
• 12 years before: Visits to a psychiatrist increased.
• Eight to nine years before: Visits to neurologists and ophthalmologists increased, which could relate to issues like blurry vision or eye pain.
• Three to five years before: Emergency medicine and radiology visits increased.
• One year before: Physician visits across multiple specialties peaked, including neurology, emergency medicine and radiology.
“These patterns suggest that MS has a long and complex prodromal phase—where something is happening beneath the surface but hasn’t yet declared itself as MS,” said Dr. Marta Ruiz-Algueró, a postdoctoral fellow at UBC and the study’s first author.
“We’re only now starting to understand what these early warning signs are, with mental health-related issues appearing to be among the earliest indicators.”
The study builds on previous work by Dr. Tremlett and her team to characterize the early stages of MS, or prodromal phase, when subtle symptoms appear before the hallmark signs become recognizable.
Prodromal periods are well established in other neurological disorders, like Parkinson’s disease, where mood changes, sleep disturbances and constipation often arise years before the more familiar motor symptoms like tremors and stiffness.
While the researchers caution that the vast majority of people who experience general symptoms will not go on to develop MS, they say recognizing and characterizing the MS prodrome could one day help accelerate diagnosis and improve outcomes for patients.
“By identifying these earlier red flags, we may eventually be able to intervene sooner—whether that’s through monitoring, support or preventive strategies,” said Dr. Tremlett.
“It opens new avenues for research into early biomarkers, lifestyle factors and other potential triggers that may be at play during this previously overlooked phase of the disease.”
About this multiple sclerosis research news
Author: Reyhana Heatherington
Source: University of British Columbia
Contact: Reyhana Heatherington – University of British Columbia
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Healthcare use before multiple sclerosis symptom onset” by Helen Tremlett et al. JAMA Network Open
Abstract
Healthcare use before multiple sclerosis symptom onset
Importance
Health care use increases before multiple sclerosis (MS) onset. However, most studies have focused on the 5 to 10 years preceding the first demyelinating disease code from administrative data. Few studies have examined patterns before clinically determined MS symptom onset from clinical records.
Objective
To examine health care use 25 years before MS symptom onset in a clinical cohort from British Columbia, Canada.
Design, Setting, and Participants
This matched cohort study accessed data prospectively collected from January 1991 to September 2018. All data were released mid-2024 for analysis. The study was conducted in British Columbia using publicly funded universal health insurance data. Patients with MS were identified from MS clinic records and matched with up to 5 individuals randomly selected without replacement from the general population by sex, birth year, socioeconomic status, and postal code of residency.
Main Outcomes and Measures
Linked clinical and administrative data were used to compare physician visit rates 25 years before MS onset using adjusted negative binomial models and 15 years before MS onset by International Classification of Diseases, Ninth Revision (ICD-9) chapter and physician specialty.
Results
A total of 2038 patients with MS (mean [SD] age at symptom onset, 37.9 [10.9] years; 1508 female [74.0%]) and 10 182 matched individuals were included. All-cause physician visit rate ratios (RRs) for patients with MS were consistently elevated from 14 years before onset (adjusted RR [ARR], 1.19; 95% CI, 1.07-1.33), peaking the year before MS onset (ARR, 1.28; 95% CI, 1.21-1.35).
The RRs for ill-defined symptoms and signs were consistently elevated 15 years before onset, exceeding 1.15 and peaking at 1.37 (95% CI, 1.19-1.56) the year before MS onset. Mental health–related RRs from 14 years before onset were significant (excluding years 7, 5, and 4), with RRs in the 3 years before MS onset ranging from 1.30 (95% CI, 1.05-1.58) to 1.38 (95% CI, 1.12-1.68).
Sensory, musculoskeletal, and nervous system RRs were elevated 8, 5, and 4 years before onset, respectively, with, for example, a peak of 2.42 (95% CI, 1.90-3.07) for nervous system concerns the year before MS onset. By physician specialty, general practice visit RRs were significantly elevated in each of the 15 years before MS onset, reaching 1.23 (95% CI, 1.17-1.30) in the year before onset.
Psychiatry visit RRs were elevated 12 years before onset (2.59; 95% CI, 1.23-5.47). Neurology and ophthalmology RRs were significantly higher up to 8 to 9 years before onset, peaking the year before MS onset at 5.46 (95% CI, 4.30-6.93) for neurology and 1.64 (95% CI, 1.30-2.08) for ophthalmology.
Conclusions and Relevance
In this matched cohort study of people with and without MS, health care use was higher among patients with MS 14 to 15 years before MS symptom onset, suggesting that MS may have started earlier than previously thought. Mental health and psychiatric issues along with ill-defined signs and symptoms might be among the earliest features of the prodromal period preceding nervous system–related and neurologic visits by 7 to 11 years.
