Multiple sclerosis and subclinical neuropathology in healthy individuals with familial risk: A scoping review of MRI studies

Abstract

Multiple genetic and non-heritable factors have been linked to the risk of multiple sclerosis (MS). These factors seem to contribute to disease pathogenesis before the onset of clinical symptoms, as suggested by incidental MRI evidence of subclinical MS neuropathology in individuals without clinical symptoms. Individuals with high familial risk for MS, such as first-degree relatives of patients with MS, can be studied by MRI to characterize the neuropathology during a subclinical period of MS. 16 studies published in English, which performed brain MRI on healthy individuals with high familial risk of MS were included in this scoping review. Studies suggest either no conclusive (5), or inconclusive yet considerable (4), or conclusive evidence (7) for the incidence of subclinical neuropathology, including focal and diffuse tissue damage. Across all studies, white matter lesions fulfilling MS criteria were observed in 86 of 613 individuals (14%). Future research is needed to evaluate the longitudinal dynamics and clinical relevance of preclinical imaging abnormalities in MS.

Keywords: Clinical discordance; Familial risk; Magnetic resonance imaging; Multiple sclerosis; Prodromal phase; Subclinical pathology.

Fig. 1

Article inclusion flowchart. First, the PubMed search engine was used to look for research reports that included any of our 6 different combinations of keywords, which described our target subject sample and data type (e.g., the combination “multiple sclerosis” AND “relatives” AND “imaging”). The abstract/summary of the initially found papers were screened to only include reports of in-vivo studies which included healthy/asymptomatic individuals at familial risk of MS and also used variables derived from MRI data as one of their main outcomes or screening measures. Then, the full reports of the nominated studies were read and only 16 studies were selected to be included in the review paper. These were studies in English language which aimed at or investigated MRI-based incidence of subclinical neuropathology in healthy subjects with high familial risk of MS.