A prodrome for MS?

Study in Neurology evaluated the associations between diseases and symptoms diagnosed in primary care

The researchers show that, on a population scale, the frequency of disorders such as depression, constipation, and urinary tract infections is associated with a diagnosis of multiple sclerosis five years later. These results outline a prodromal phase of the disease.

Several studies have already suggested that, in some patients, subtle symptoms were present up to ten years before a diagnosis of MS. What remained was to quantify this phenomenon at the population scale to rigorously define a ‘prodromal phase’, i.e. a period during which the disease takes hold discreetly. A better understanding of early symptoms of MS could help researchers pinpoint the exact moment when the inflammatory process that causes lesions in the central nervous system begins.

“One of the major difficulties with multiple sclerosis is that we do not observe a strict correspondence between the severity of lesions on nerve fibres and patients’ symptoms. This considerably limits our ability to predict the course of the disease,” said Professor Céline Louapre, a Neurologist at Pitié-Salpêtrière Hospital and Head of Paris Brain Institute’s clinical investigation center.

“The challenge today is to detect the disease as early as possible, well before the lesions are visible on MRI, in the hope of delaying the onset of disability. Of course, not everyone who has these symptoms will go on to develop MS.’ She added that all four are ‘common’ and ‘could also be signs of other diseases’.

Professor Louapre, accompanied by Octave Guinebretière and Thomas Nedelac, compared the health data of 20,174 patients with multiple sclerosis, 54,790 patients without multiple sclerosis, and 37,814 patients affected by two autoimmune diseases which, like MS, mainly affect women and young adults—namely 30,477 patients with Crohn’s disease and 7,337 with lupus.

The researchers observed that five symptoms were significantly associated with a later diagnosis of multiple sclerosis: depression, sexual disorders, constipation, cystitis, and other urinary tract infections.

“This association was sufficiently robust at the statistical level for us to state that these are early clinical warning signs, probably related to damage to the nervous system, in patients who will later be diagnosed with multiple sclerosis,” Professor Louapre explains. “The overrepresentation of these symptoms persisted and even increased over the five years after diagnosis.”

However, these five symptoms also appeared in the prodromal phase of lupus and Crohn’s disease, which means they are not specific to MS. Most importantly, they are also widespread in healthy people.

A prodrome for MS?

“These signs alone will not be enough to make an early diagnosis, but they will certainly help us better understand the mechanisms of multiple sclerosis—which has many causes—and reconstruct its natural history. Finally, these new data support the idea that the disease begins well before the onset of classic neurological symptoms,” concludes Professor Louapre.