In some diseases, the underlying processes can start years before a diagnosis is made. A new study finds that people who later develop multiple sclerosis (MS) are more likely to have conditions like depression, constipation and urinary tract infections five years before their MS diagnosis than people who do not develop MS. The study, which is published in the December 5, 2023, online issue of Neurology^®, the medical journal of the American Academy of Neurology, also found that sexual problems and bladder infections, or cystitis, are more likely in people who later develop MS.

The conditions were also more likely to occur in people who had other autoimmune diseases, lupus and Crohn’s disease.

“Knowing that these conditions may be prodromal symptoms or even early-stage symptoms of MS would not necessarily lead to earlier diagnosis of the disease in the general population, since these conditions are common and could also be signs of other diseases, but this information could be helpful for people who are at a higher risk of developing MS, such as people with a family history of the disease or those who show signs of MS on brain scans but do not have any symptoms of the disease,” said study author Celine Louapre, MD, PhD, of Sorbonne University in Paris, France.

The study involved 20,174 people newly diagnosed with MS. They were each matched with three people who did not have MS of the same age and sex, for a total of 54,790 people. Then the people with MS were also compared to 30,477 people with Crohn’s disease and 7,337 people with lupus. MS, Crohn’s disease and lupus are all autoimmune diseases. They all affect women more often than men and affect young adults.

Then researchers used the medical records database to see whether the participants had any of 113 diseases and symptoms in the five years before and after their diagnosis, or before that matching date for the people who did not have an autoimmune disease.

The people with MS were 22% more likely to have depression five years before their diagnosis than the people without MS. They were 50% more likely to have constipation, 38% more likely to have urinary tract infections, 47% more likely to have sexual problems, and 21% more likely to have cystitis, or bladder infections.

For depression, 14% of the people with MS had prescriptions for antidepressants five years before diagnosis, compared to 10% of the people who did not have MS. By five years after diagnosis, 37% of people with MS had antidepressant prescriptions, compared to 19% of those without MS.

“Of course, not everyone who has these symptoms will go on to develop MS,” Louapre said. “We’re hoping that eventually these early signs will help us understand the biological mechanisms that occur in the body before the actual symptoms of the disease develop.”

A limitation of the study was that data was not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity and socioeconomic status.

Autologous haematopoietic stem cell transplantation, or aHSCT for short, is usually used to treat blood cancers, and involves harvesting stem cells from the person’s own bone marrow or blood followed by chemotherapy and antibody treatment.

Emerging evidence indicates that it is suitable for treating relapsing-remitting MS— characterised by distinct inflammatory episodes that cause varying degrees of residual disability. But aHSCT has yet to be included in most national clinical guidelines. 

The researchers therefore wanted to assess its safety and effectiveness when used in routine healthcare rather than under clinical trial conditions. 

They identified 231 patients with relapsing-remitting MS, 174 of whom had been treated with aHSCT before 2020: 2004 was when the first of these patients had been treated with aHSCT. Their average age when treated was 31, and nearly two thirds (64%) were women.

How well aHSCT worked was evaluated by analysing data collected from the Swedish MS registry. And its safety was assessed by scrutinising the patients’ electronic medical records for the 100 days following the procedure.

On average, patients had had their disease for more than 3 years and had received an average of 2 lots of standard treatment (disease modifying drugs) before aHSCT; 23 had not had any treatment. 

Around nearly 3 years, on average, after undergoing aHSCT, 20 patients (11%) were given a disease modifying drug.

This study showed no evidence of disease activity in nearly 3 out of 4 (73%) of those treated after 5 years and in almost two thirds (65%) after 10 years. 

Among the 149 MS patients with some disability to begin with, more than half (54%;80) improved, just over a third (37%; 55) remained stable, and around 1 in 10 (9%;14) got worse. 

The annualised relapse rate was 1.7 in the year before  aHSCT and 0.035 during the monitoring period, which averaged 5.5 years. Or put another way, on average, a patient had 1.7 relapses in the year before aHSCT treatment, and 1 relapse every thirtieth year after aHSCT treatment.

Five patients were required intensive care, and 61 developed a bacterial infection within 100 days of treatment. Febrile neutropenia (low white cell count accompanied by a high fever) was the most common side effect, affecting 68% of patients.

Other viral infections were verified in 23 patients (13%). Herpes zoster reactivation was documented in 3, and 3 had a confirmed localised fungal infection. None died as a result of their treatment.

This is an observational study, with no comparative group, which precludes definitive conclusions, the researchers acknowledge. 

Nevertheless, they summarise: “Our findings demonstrate that aHSCT for [relapsing-remitting MS] is feasible within regular healthcare and can be performed without compromising safety. 

“Our study corroborates the results observed in the only randomised controlled trial conducted to date. We believe that aHSCT could benefit a greater number of MS patients and should be included as a standard of care for highly active MS.”