Summary: A new study finds that people can show early signs of multiple sclerosis up to five years before clinical diagnosis.
Source: University of British Columbia
People with multiple sclerosis (MS) may begin to show changes and increased health-care use up to five years before the condition is clinically recognized, according to a new analysis of Canadian health records.
The study, published in Lancet Neurology, identified a measurable prodromal phase for MS — an earlier-than-expected period in which patients seek medical care more often than the general population. Detecting such a prodrome could help clinicians spot red flags sooner, open an earlier window for intervention, and guide research into triggers or causes of MS.
“Finding that people with MS alter their patterns of health-care use in the five years before the earliest medical recognition of the disease is important because it suggests researchers must look even further back to understand how MS begins,” said Helen Tremlett, senior author and professor in the department of medicine at the Djavad Mowafaghian Centre for Brain Health.
MS is believed to involve immune-mediated damage to myelin, the insulating layer around neurons. After diagnosis, clinicians commonly try to determine when the disease began, often referring to a patient’s first demyelinating event — symptoms such as vision loss, numbness, or motor weakness.
To look for a prodromal period, researchers analyzed health administrative and clinical databases across four Canadian provinces: British Columbia, Saskatchewan, Manitoba, and Nova Scotia. The analysis included health records from 14,428 people with MS and 72,059 matched controls, spanning two decades. The team compared patterns of hospital admissions, physician visits, and prescription fills in the five years before a first demyelinating claim or reported symptom onset.
Prodromes are recognized for other neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, where early symptom patterns have provided clues about how those diseases begin and have spurred new research into potential causes or triggers. This MS study used similar principles to search for early signs in routine health-care interactions.
Results showed that, according to health administrative data, patients who later received an MS diagnosis used health-care services more frequently than controls across the five-year interval, with use rising steadily from five years to one year before the first demyelinating claim. Rate ratios increased for hospital admissions, physician claims, and prescription drug classes. In a clinical cohort with available symptom onset dates, similar trends in physician claims and prescriptions were observed, although individual year-by-year differences were generally smaller and often did not reach statistical significance.
“There’s something going on that makes this group different,” said José Wijnands, first author, postdoctoral fellow, and Michael Smith Foundation for Health Research trainee. “When degenerative brain diseases show a prodrome, it suggests an underlying process that might be detectable before classic symptoms appear.”
The authors plan further work to identify what drove the increased health-care use. They will examine whether specific patterns of illnesses or prescriptions point to a recognizable cluster of early symptoms that clinicians could use to screen for MS earlier. Understanding these patterns may reveal biological or environmental processes active before a conventional diagnosis and could inform earlier therapeutic strategies.
Funding: This research was supported by the National Multiple Sclerosis Society (U.S.). The study used Canadian health administrative and clinical data, which enabled comparison of health-care system use across multiple provinces.
Source: Heather Amos – University of British Columbia
Original research: Abstract for “Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study” by José M. A. Wijnands et al., published in Lancet Neurology. Published online April 20, 2017. DOI: 10.1016/S1474-4422(17)30076-5.
Background
Neurodegenerative processes can begin many years before clinical symptoms appear. This study examined whether a prodromal period for MS exists by assessing patterns of health-care use prior to a first demyelinating event.
Methods
The matched cohort study used linked administrative and clinical databases from four Canadian provinces to compare hospital admissions, physician visits, and prescription use between people who developed MS and matched general population controls during the five years preceding a first demyelinating disease claim or recorded symptom onset. Rate ratios were estimated using negative binomial regression and combined across provinces with random-effects models. The primary outcome was all-cause health-care use in each of the five years before the index date.
Findings
The health administrative cohort included 14,428 MS cases and 72,059 controls (data available from April 1984 to April 2014). Annual health-care use rose steadily in the MS group compared with controls between five years and one year before the first demyelinating claim, across hospital admissions, physician claims, and prescription drug classes. A clinical cohort with symptom onset dates showed similar trends for physician claims and prescriptions, though year-to-year differences were less consistently statistically significant.
Interpretation
Greater and increasing use of health care in the five years before a first demyelinating event supports the existence of a measurable MS prodrome. These findings have clinical and research implications, including the potential to identify and intervene earlier in the disease course.
Funding
National Multiple Sclerosis Society.