Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis

Abstract

Following the extraordinary progress in the treatment of multiple sclerosis (MS), two major unmet needs remain: understanding the etiology of the disease and, hence, designing definitive cures (this perspective is neither at hand, nor it can be taken for granted that the etiologic targets will be readily treatable); the prevention of an overt and disabling disease, which seems to be a more realistic and pragmatic perspective, as the integration of genetic data with endophenotypes, MRI, and other biomarkers ameliorates our ability to identify early neuroinflammation. Radiologically isolated syndrome (RIS; diagnosed when the unanticipated MRI finding of brain spatial dissemination of focal white matter lesions highly suggestive of MS occurs in subjects without symptoms of MS, and with normal neurological examinations) and the recently focused “prodromal MS” are conditions at risk of conversion toward overt disease. Here, we explore the possibility of secondary prevention approaches in these early stages of neuroinflammation. RIS and prodromal MS are rare conditions, which suggest the importance of Study Groups and Disease Registry to implement informative clinical trials. We summarize ongoing preventive approaches in the early stages of the demyelinating process, especially in RIS conditions. Moreover, we highlight the importance of the biomarkers and the predictors of evolution to overt disease, which may be useful to select the individuals at risk of conversion to clinically isolated syndrome (CIS) and/or clinically definite MS. Finally, we illustrate the importance of the endophenotypes to test the frontline immunomodulatory approach for preventive strategies. Future investigations, especially in relatives of patients, based on MRI techniques and biological studies (better with integrated approaches) may provide opportunities to understand the MS early causal cascade and may help to identify a “therapeutic window” to potentially reverse early disease processes.

Inflammatory bowel disease and immune-mediated inflammatory diseases: looking at the less frequent associations

“…TherapeuTic advances in Gastroenterology considered to be the prodromic stage of evolving MS by most of the authors. In this case, a strict follow-up of the patient by both gastroenterologist and neurologist is mandatory, as theoretically anti-TNF therapy may have a deleterious effect, as for MS. 156,157 Respiratory diseases Asthma. Asthma is a chronic respiratory disease characterized by recurrent attacks of breathlessness and wheezing, with variable clinical severity and temporal frequency.…”

“…Another particular clinical picture is that of the so-called ‘radiologically isolated MS’, that is considered to be the prodromic stage of evolving MS by most of the authors. In this case, a strict follow-up of the patient by both gastroenterologist and neurologist is mandatory, as theoretically anti-TNF therapy may have a deleterious effect, as for MS. 156 , 157…”

Upper Limb Sensory-Motor Control During Exposure to Different Mechanical Environments in Multiple Sclerosis Subjects With No Clinical Disability

“…Asymptomatic MS describes a clinically silent disease state of MS usually incidentally discovered after imaging or other diagnostic exams performed, for example, for routine check-ups. Magnetic resonance imaging (MRI) and clinical tests have suggested that in asymptomatic MS subjects despite the morphological evidence of subclinical disease, the CNS damage remains very limited, and unknown protective mechanisms prevent its clinical manifestation in these individuals (Stefano et al, 2006 ; Siva, 2013 ; Amato et al, 2022 ).…”

Presymptomatic MS or radiologically isolated syndrome should be actively monitored and treated: Commentary

“…Finally, we need to consider potential barriers related to sustainability in different health care systems given that DMT cost is the largest component of healthcare expenditures for MS. 8 RIS diagnosis, monitoring and treatment give us the unique opportunity to implement early preventive interventions in MS. To achieve this goal, we need biomarkers with high diagnostic accuracy which will allow us to stratify 'higher risk' RIS individuals 9 who may benefit most from disease-modifying treatment and from targeting of modifiable risk factors such as smoking, obesity, low vitamin D levels and physical activity, as well as environmental exposures. 1 This, however, may not be so straightforward; therefore, it is advisable that individuals with RIS should be managed by neurologists in tertiary centres with long-standing journals.sagepub.com/home/msj clinical and radiological expertise in the diagnosis and treatment of demyelinating diseases.…”

“…The evidence that the biological onset of multiple sclerosis (MS) can anticipate the clinical onset by several years has led to an ever-growing number of studies aimed at characterizing and monitoring the preclinical phase of MS. 1 Individuals with incidental brain or spinal cord lesions highly suggestive of central nervous system (CNS) demyelination without related symptoms and signs are classified as having a radiologically isolated syndrome (RIS). 2 These individuals have a 34% risk of conversion to MS over 5 years 3 and a 51% risk over 10 years 4 especially if they are young, with infratentorial or spinal cord lesions, with cerebrospinal fluid (CSF)-restricted oligoclonal bands, and development of new gadolinium-enhancing lesions on follow-up magnetic resonance imaging (MRI) scans.…”