Bacille Calmette-Guérin (BCG) Vaccine In Radiologically Isolated Syndrome (RIS)

Multiple sclerosis (MS) witnessed relevant therapeutic progress in the last decade. This notwithstanding, safety, quality of life and overtreatment remain elements of strong concern for the subjects. Safe and manageable therapies that can be used since the (biological) onset of the disease, without risk of overtreatment, are important unmet needs in MS.

Following the extraordinary progress in the treatment of relapsing-remitting (RR) multiple sclerosis (MS), two major unmet needs remain to be addressed by translational research in this field: progressive MS and the "dream" of a world free of MS. As far as the latter is concerned, the investigators can hope to make the dream come true by understanding the etiology of the disease and hence design definitive cures. Unfortunately this perspective is neither at hand, nor it can be taken for granted that the etiologic targets, once discovered, will be readily treatable.

A more realistic and pragmatic perspective may be the prevention of the clinical onset of the disease, a research field that promises to become increasingly important as the integration of genetic data with endophenotypes, magnetic resonance imaging and other biomarkers ameliorates the ability to predict the development of the disease under clinical circumstance.

Epidemiological data supporting vitamin D supplementation and smoking avoidance are candidate approaches for primary and secondary prevention of the disease. Among other interventions that may have characteristics compatible with those of a preventive treatment, Bacille Calmette-Guerin (BCG) vaccine has been tested with encouraging results in early MS and clinically isolated syndrome (CIS). The knowledge that disease-modifying therapies work best when used early in the demyelinating process raises the question about whether to try this approach - which is safe, cheap and handy - in individuals with radiologically isolated syndrome (RIS).

Radiologically isolated syndrome is a new entity, diagnosed when the unanticipated magnetic resonance imaging (MRI) finding of brain spatial dissemination of focal white matter (WM) lesions highly suggestive of MS occurs in subjects without symptoms of MS, and with normal neurological examinations. Approximately one-third and two-thirds of individuals experience respectively clinical onset and/or radiological progression over a mean follow-up of five years. However, predictors (male sex, age < 37, spinal cord involvement) of higher risk of progression have been identified and conversion to clinically isolated syndromes (CIS) were described in 84% of RIS individuals with spinal cord lesions over a median time of 1.6 years from the date of the first MRI; the same predictors have recently been shown to precede evolution toward primary progressive MS. Whether or not to treat this condition remains currently a clinical conundrum.