Differential diagnosis of suspected multiple sclerosis: a consensus approach

TLDR

MS diagnosis requires excluding other diseases, yet no systematic exclusion process has been defined. The study aims to recommend future research to validate and support consensus guidelines for MS differential diagnosis. An international panel of MS experts used literature review and consensus to develop guidelines that focus on excluding mimics, diagnosing isolated syndromes, and distinguishing MS from other inflammatory demyelinating disorders. The guidelines present red‑flag criteria, precise definitions of clinically isolated syndromes, algorithms for three common CISs, and a classification scheme for idiopathic inflammatory demyelinating disorders, offering a practical diagnostic path that improves accuracy for non‑MS specialists.

Abstract

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.