Early multiple sclerosis: diagnostic challenges in clinically and radiologically isolated syndrome patients

Purpose of review: With the introduction of new diagnostic criteria, the sensibility for multiple sclerosis (MS) diagnosis increased and the number of cases with the clinically isolated syndrome (CIS) decreased. Nevertheless, a misdiagnosis might always be around the corner, and the exclusion of a 'better explanation' is mandatory.There is a pressing need to provide an update on the main prognostic factors that increase the risk of conversion from CIS or from radiologically isolated syndrome (RIS) to MS, and on the potential 'red flags' to consider during the diagnostic workup. Recent findings: We discuss diagnostic challenges when facing patients presenting with a first demyelinating attack or with a RIS, with a focus on recently revised diagnostic criteria, on other neuroinflammatory conditions to be considered in the differential diagnosis and on factors distinguishing patients at risk of developing MS.A correct definition of a 'typical' demyelinating attack, as well as a correct interpretation of MRI findings, remains crucial in the diagnostic process. The cerebrospinal fluid examination is warmly recommended to confirm the dissemination in time of the demyelinating process and to increase the diagnostic accuracy. Summary: An early and accurate diagnosis of MS requires careful consideration of all clinical, paraclinical and radiological data, as well the reliable exclusion of other mimicking pathological conditions. This is advocated to promptly initiate an appropriate disease-modifying therapy, which can impact positively on the long-term outcome of the disease.