Early warning signs of multiple sclerosis (MS) have been found to appear as much as 15 years before its classic symptoms emerge. Future patients began visiting doctors more frequently with nonspecific complaints — such as anxiety and fatigue — long before the disease became evident.

Multiple sclerosis is a chronic condition in which the body’s immune system attacks the protective myelin sheath of nerve fibers in the brain and spinal cord, Naked Science reports. This damage disrupts the transmission of signals between the brain and the rest of the body, leading to a wide range of neurological symptoms — from fatigue and limb numbness to vision and coordination problems. The disease progresses unpredictably and can eventually result in significant disability.

The challenge of early MS diagnosis lies in the fact that its first signs are often highly nonspecific. Fatigue, headaches, mild mood changes, or general pain can point to dozens of other conditions. This creates what is known as a prodromal period — a phase in which pathological processes are already underway in the body, but there are no clear, recognizable signs of a specific disease. Such periods are well documented in other neurological disorders, such as Parkinson’s disease, where mood and sleep changes can occur years before tremors appear.

For a long time, it was believed that MS’s prodromal phase lasted between five and ten years. Most earlier studies examined medical records within that time frame, often starting from the first documented demyelinating event — such as inflammation of the optic nerve. However, this approach overlooked the very earliest stage of disease development, which could begin well before obvious neurological problems arose.

To determine when the first nonspecific signs might occur, researchers analyzed medical records from more than 12,000 people. The results of the new study were published in JAMA Network Open.

The team compared the healthcare histories of 2,038 patients with a confirmed MS diagnosis to a control group of 10,182 individuals without the disease. The groups were matched by sex, birth year, and socioeconomic status for maximum accuracy.

Unlike previous studies, the researchers examined records from up to 25 years before the symptom onset date, which was retrospectively determined by the treating neurologist based on detailed patient interviews and clinical evaluations. This approach allowed for a more accurate and earlier starting point, independent of diagnostic delays. The analysis revealed that people who later developed MS began using healthcare services more often long before the classic signs appeared.

The study identified a clear timeline of visits to various specialists. As early as 15 years before the established symptom onset, future patients more frequently visited general practitioners with vague complaints such as pain and fatigue. Around the same time — 14 to 15 years before onset — visits related to mental health, including anxiety and depression, also increased. Several years later, about 12 years before onset, consultations with psychiatrists became noticeably more common.

As the onset date drew closer, the pattern changed. About eight to nine years before the first major symptoms, patients began seeing neurologists and ophthalmologists more often, possibly due to early vision problems or eye pain. Three to five years before onset, emergency department visits and radiological exams — including MRI scans — increased.

The peak came in the year before classic symptoms appeared: during this period, visits to doctors of all specialties, especially neurologists, reached their highest point. For example, the number of neurologist visits rose more than fivefold.

The findings show that MS has a long and complex prodromal phase that begins much earlier than previously thought. The new data push back the timeline for the disease’s onset and highlight that mental health issues may be among its earliest indicators, appearing seven to eleven years before neurological complaints.

Studying this phase opens new possibilities for research aimed at identifying early biomarkers and risk factors. In the future, this could lead to strategies for earlier detection and intervention, potentially improving long-term outcomes for patients.