ECTRIMS 2023: Sick days in years before diagnosis suggest MS prodrome

Multiple sclerosis (MS) patients had significantly more sickness-related work absences in the years leading up to their disease onset than people in the general population, a recent Swedish analysis showed.

Scientists believe the findings support the growing notion that there is an MS prodrome, during which early signs of illness begin to manifest before the classic symptoms of disease are evident.

“Analyzing and monitoring sick leave patterns might aid in identifying individuals at a higher risk of MS or those exhibiting early signs of MS, enabling timely diagnosis and intervention,” said Ali Manouchehrinia, PhD, a senior research specialist at the Karolinska Institutet in Sweden and research associate at the University of British Columbia in Canada.

Manouchehrinia presented the findings at the 9th European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) joint meeting, held Oct. 11-13 in Milan and online, in a talk titled, “The Prodromal Phase of MS: Sickness Absence Patterns in the Years Prior to Disease Onset.”

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Accumulating evidence suggests several inflammatory and neurological diseases, including MS, have a prodromal phase, or an early period of disease evolution that occurs before the typical clinical symptoms, Manouchehrinia explained.

For example, studies have indicated that people who will go on to develop MS have increased hospital admissions, physician visits, and prescriptions filled in the years before disease onset than others in the general population. Moreover, mental health issues, such as anxiety and depression, may be evident five years before MS onset, analyses have shown.

Manouchehrinia believes that understanding this prodromal phase of disease is “both intriguing and also … highly transformative,” namely in “how we understand MS, how we clinically manage MS, and how we do research on MS,” he said.

Knowing more about this phase could help in the development of prevention strategies against environmental risk factors for the disease, as well as early detection, diagnosis, and treatment.

“We know nowadays that the earlier diagnosis equals to earlier interventions, earlier treatment initiations, and we know that early treatment intervention is equivalent to better long-term and short-term outcomes,” the scientist said.

In the recent analysis, researchers used sickness-related work absences as a new metric for evaluating a possible MS prodrome.

This measurement may capture general declines in a person’s health, which is “very different, for example, from physicians visits or hospitalizations. It adds a new dimension to studying prodromal MS,” Manouchehrinia said.

The scientists looked at the relationship between sickness absences and MS in Sweden, where all residents 15 years or older with a work income can receive government benefits if they have reduced work capacity due to disease or injury.

These absences are recorded in the Swedish Social Insurance Agency if they last for 15 days or longer, and can be linked to multiple other clinical registries through a person’s unique identification number.

The analysis involved two groups of patients followed for at least five years prior to their MS onset, which occurred between the ages of 24-65. MS onset refers to the first record of symptoms indicative of the disease, but not necessarily the diagnosis.

A first group, called the administrative cohort, included 8,640 MS patients identified in Swedish inpatient or outpatient records. The other, the clinical cohort, included 6,527 patients from the Swedish MS registry.

In either group, each patient was matched with up to five people from the general population in terms of sex, age, county of residence, and time spent in Sweden. This added up to 43,259 controls in the administrative cohort and 32,589 in the clinical cohort.

Yearly absence rates examined in five years before MS onset

The scientists looked at yearly sickness absence rates in at least the five years prior to the date of MS onset, going back as far as possible for each patient. For some, they could go back as far as 18-19 years.

In the years leading up to MS onset, result showed “a general increase in the number of sickness absence days in MS patients, significantly more compared to controls,” Manouchehrinia said.

In the health administrative cohort, the increase started about 10-12 years before MS onset, drastically increasing in the year before onset to more than a 2.5 times higher rate of sickness absence days than that observed in the general population.

A similar pattern was observed in the clinical cohort, but with a less drastic increase in the year prior to diagnosis — MS patients had about 33% more days of absence due to sickness than controls.

“We observed an increased risk of sick leave in persons with MS,” Manouchehrinia said. This “highlights the prodromal phase, and this data might be used for early detections of patients with MS.”

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the 9th joint ECTRIMS-ACTRIMS meeting Oct. 11-13. Go here to see the latest stories from the conference.