October 17, 2025, 7:03 am | Read time: 7 minutes

Connection Between Early Symptoms and Disease Diagnoses Investigated

Multiple sclerosis is also called “the disease with a thousand faces” because it can present with a wide range of possible signs and symptoms. The frequency, form, and severity of disease flare-ups can vary greatly from patient to patient. This makes treatment, and especially diagnosis, challenging. A family history is an indicator of an increased MS risk. For example, if the parents are affected, the likelihood that the child may also develop the disease increases—but it is not guaranteed. Apparently, there are some early warning signs—previously not associated with the nerve disease—that suggest an initial outbreak of MS is imminent. According to the leaders of two studies, these can occur five to ten years before the actual disease and diagnosis.

Scientists from Sorbonne University in Paris analyzed health data from around 120,000 people from the United Kingdom and France, collected in “The Health Improvement Network.”¹ They were interested in which early symptoms could be associated with later disease diagnoses. To this end, the researchers analyzed and compared the data of:

• 20,174 MS patients
• 54,790 people who did not have multiple sclerosis,
• 30,477 Crohn’s disease patients, and
• 7,337 people diagnosed with lupus

The study leaders compared the health data of people with the mentioned autoimmune diseases with a medical checklist. This included 113 diseases and symptoms. The researchers were interested in whether the affected individuals had suffered from the listed complaints up to five years before their diagnosis. They also examined the data of the control group—people without autoimmune disease. Did they possibly have similar symptoms and complaints? If so, these obviously were not associated with a later developed autoimmune disease.

The Following Early Symptoms Were Already Present in MS Patients Years Before

Through their analysis, the scientists were able to identify five health complaints, symptoms, or diseases that seem to be associated with a later MS diagnosis.

These include:

• Depression
• Constipation
• Urinary tract infections
• Sexual disorders
• Bladder infections

Especially, Constipation and Sexual Disorders Could Be Linked to Later MS Diagnosis

The approximately 20,000 MS patients considered in the study were 50 percent more likely to suffer from constipation in the five years before their diagnosis. They experienced sexual disorders with a 47 percent higher probability, while urinary tract infections occurred with a 38 percent probability. Depression followed as a possible early warning sign for a later MS disease at 22 percent, and finally, bladder infections at 21 percent.

Fourteen percent of MS patients had already been prescribed antidepressants five years before they received the multiple sclerosis diagnosis. Among the examined people without MS, it was ten percent in the same period. Five years after the MS diagnosis, 37 percent of those affected took antidepressants. Among people without the autoimmune disease, it was 19 percent.²

Interpretation of Study Findings

With the findings from the data analysis, the French researchers hoped to expand the understanding of the development of multiple sclerosis or complaints that occur before the first officially recognized disease flare-up by doctors.

However, they also cautioned that the occurrence of the mentioned symptoms cannot always be considered early warning signs of MS. “Of course, not everyone who has these symptoms will later develop MS,” emphasized study author Celine Louapre in the university statement. They are too unspecific, could be caused by various lifestyle factors, or be associated with other diseases. “We hope that these early signs will help us understand the biological mechanisms that occur in the body before the actual symptoms of the disease appear.”

More on the topic

Autoimmune Disease Multiple Sclerosis: An Expert Explains Causes, Symptoms, and Treatment

Study on multiple sclerosis Certain vitamin could slow down the onset of MS

Study on the “MS Prodrome”

The study findings from 2023 are supported by a newer study from this year. In it, researchers—this time from England—also dealt with the “MS prodrome.”³ The “MS prodrome” is often referred to as the phase before the MS diagnosis (precursor stage), in which patients retrospectively identify various, sometimes diffuse complaints that are still poorly understood. Therefore, this study also aimed to examine possible early symptoms more closely.

Analysis of Health Data

The study is a retrospective analysis of health data from the Clinical Practice Research Datalink (CPRD). From the data, 15,029 MS patients who had received an MS diagnosis between 1990 and 2022 were identified. Each case was matched with an average of five age-matched controls without MS, resulting in a total of 81,027 controls. For all participants, at least five years of retrospective health data were available, and for some, even ten years or more.

In the next step, the researchers analyzed documented symptoms in the periods zero to two, two to five, and five to ten years before the MS diagnosis. The symptoms were divided into five categories: neurological, autonomic (such as bladder disorders), cognitive, psychiatric, and pain symptoms.

The Following Early Symptoms Occurred Most Frequently

Certain symptoms occurred significantly more frequently in those affected years before the MS diagnosis than in controls—most notably neurological complaints such as numbness or balance disorders. Specifically, the following frequencies and risk ratios (odds ratios; OR) were found:

• Neurological symptoms: About 44 percent of future MS patients already experienced neurological complaints such as numbness or balance disorders years before the diagnosis. In the comparison group without MS, it was only about 8 percent. Thus, the occurrence of such symptoms was almost eight times more common in future MS patients.
• Pain symptoms: About 43 percent of future MS patients reported pain, while this was the case for about 21 percent of the comparison group. Pain thus occurred about twice as often.
• Autonomic symptoms: Complaints such as bladder disorders occurred in nearly 38 percent of future MS patients, but only in about 21 percent of controls—also almost twice as often.
• Psychiatric symptoms: About 34 percent of future MS patients showed psychiatric abnormalities such as depression or anxiety, compared to 18 percent in the control group. The risk was thus about one and a half times higher.
• Cognitive symptoms: Memory or concentration problems were observed in about 1 percent of future MS patients, compared to 0.3 percent in the control group. These complaints thus occurred about two and a half times more frequently.

About 44 percent of the examined MS patients already had neurological symptoms before their diagnosis. The risk for these complaints was nearly eight times higher for them compared to the examined individuals without an MS diagnosis. Forty-three percent of MS patients had early pain symptoms, but since 21 percent of the control group—apparently independent of later MS—had such complaints, the risk for pain symptoms for MS patients was ultimately “only” doubled.

MS Does Not Appear Suddenly

Both studies provide valuable insights into the years before the official onset of multiple sclerosis. The disease, known for its flare-ups, does not appear suddenly but seems to manifest itself about five years earlier with more or less noticeable complaints. The difficulty is that these can vary greatly: from constipation to general pain, depression, and bladder complaints. Complaints that could also be attributed to many other causes.

It is clear, however, that further research into the MS precursor phase is necessary, and the possibility of impending MS should be considered with various symptoms (such as psychiatric, neurological, and pain).