The Radiologically Isolated Syndrome: Look (Again) Before You Treat

Abstract

The advent and wide use of magnetic resonance brain imaging has led to in the unexpected detection of lesions that appear typical of multiple sclerosis (MS) in otherwise asymptomatic patients. Several cohorts of patients with the "radiologically isolated syndrome (RIS)" have been studied mainly retrospectively, and a proportion of them do go on to have clinical symptoms of MS. This has led to the not infrequent clinical conundrum of whether or not to treat patients with MRI lesions suggestive of MS, given the knowledge that MS disease-modifying therapies work best when given early in the disease course. However, the decision to proactively treat patients with RIS is countered by the increasing risks associated with MS disease-modifying therapies as well as the uncertain prognostic outcome of RIS. This review will highlight what is and is not known about the long-term outcomes of RIS and present recommendations for clinicians when faced with this challenging situation.

Modeling of Cognitive Impairment by Disease Duration in Multiple Sclerosis: A Cross-Sectional Study

“…Moreover, our linear regression estimate suggests that cognitive decline associated with MS begun 1.2 years prior to the appearance of clinical symptomatology. This result is in accordance with reports on demyelinating lesions observed in asymptomatic healthy subjects years before the appearance of clinical symptomatology [45], [46], and with our recent study demonstrating a silent MS trait associated with suppressed expression of the nuclear receptor network and inhibited apoptosis of activated T-cells operating in the pre-disease stage of MS [47]. Similarly, in support of a latent, progressive pathogenic process, cognitive performance in subjects with radiologically isolated syndrome was significantly lower as compared with healthy subjects [48].…”

Radiologically isolated syndrome – incidental magnetic resonance imaging findings suggestive of multiple sclerosis, a systematic review

“…A summary of the most common indications is presented Figure 3. [26][27][28][29][30][31][32][33] Some patients in the RIS cohorts presented with cognitive impairment, which was also noted in four cases of 'subclinical MS' by Hakiki and colleagues. 28 Cognitive impairment has later been found in two more comprehensive RIS studies with neuropsychological testing.…”

“…The characteristics of the patients in current RIS cohorts are presented in Table 2 and the prognostic data from these cohorts are compiled in Table 3. The initial MRI 4,[6][7][8][9][10][11][12]23,[26][27][28][29][30][31][32][33] There are overlaps of the cohorts, which might mean that a patient has been registered more than once. For a complete description of all indications, please see the supplementary appendix in the online version of this article.…”

“Undiagnosing” multiple sclerosis

“…Prospective quantitative data on the characteristics of these patients, their correct diagnoses, and resulting patientphysician encounters is needed. Future research must also consider the impact of newly approved diagnostic imaging criteria 1 for MS as well as the implications of the increasingly recognized radiologically isolated syndrome 10 on misdiagnosis. Further study will help us to improve our diagnostic acumen, recognize our mistakes, and learn how to better communicate them to our patients.…”