Wallace Brownlee showed how the 2017 Thompson criteria have allowed earlier diagnosis of MS, thanks to the inclusion of cortical lesions, symptomatic lesions and CSF-specific oligoclonal bands. As such, it has been estimated that 50% of patients previously diagnosed with clinically isolated syndrome (CIS) could be now be classified as having MS. However, rapid diagnosis comes with a risk of misdiagnosis, possibly occurring in up to 20% cases referred to MS clinics. Neurologists should carefully consider the characteristics of the clinical presentation and objective evidence of lesions (especially for historical symptoms), and delay diagnosis if further follow-up is thought to be necessary.
Christian Enzinger showed how MRI can support MS diagnosis (and help ruling out MS differentials). Lesion configuration, size, location, pattern, tissue destruction and contrast enhancement should be evaluated by experienced neuroradiologists. For instance, lesion location in the spinal cord and corpus callosum is very typical of MS and can help differentiation from age-related white matter changes. On the contrary, red flags for an alternate diagnosis are meningeal enhancement, indistinct (fluffy) lesions, microbleeds, infarcts, cavities or symmetric lesions.
Among possible differentials, a number of other neuro-inflammatory diseases should be considered, as clearly presented by Romain Marignier. Neuromyelitis optica spectrum disorders (NMOSD) are a very well-known cause of central nervous system neuroinflammation (both MOG-associated disease and AQ4+NMOSD should be considered). However, neurosarcoidosis, Behçet disease, Susac syndrome and anti-glial fibrillry acidic protein autoimmunity can also mimic the clinical, neuroradiological and CSF presentation of MS. Specific antibodies in the peripheral blood should be considered, along with involement of other systems (e.g., skin, lung, peripheral nerve).
Finally, Wolfgang Köhler reported on genetic conditions presenting with confluent and multifocal white matter disease that can appears similar to MS. Neuro-metabolic diseases (e.g., Fabry’s disease) present with neurological and not-neurological chronic progressive symptoms and, of note, can sometimes be treated, making their correct diagnosis very important. Genetic vasculopathies (e.g., CADASIL) can present with stroke like episodes (mimicking relapses), in the context of complex symptoms (e.g., migraine, mood disorders). Leukodystrophies are a large group of diseases primarily affecting the brain white matter (both with hypo-myelinating and de-myelinating aspects), presenting with progressive spastic paraparesis, movement disorders and/or early involvement of cognitive function. Diagnosis is genetic but family history, clinical features and pattern of white matter disease (e.g., symmetric diffuse or specific locations) can support the differential.
In conclusion, rapid and correct diagnosis of MS requires a thoughtful neurological history and examination, combined with appropriate neuroimaging and laboratory tests, within a multidisciplinary and specialised medical environment.