BACKGROUND: Initial demyelinating event (IDE) diagnosis and prognosis are not straightforward. OBJECTIVE: To identify potential diagnostic markers and outcome predictors of IDEs suggestive of multiple sclerosis (MS), that is, clinically isolated syndromes (CISs). METHODS: Clinically isolated syndrome cases (i.e., subjects with an IDE compatible with MS onset and no alternative explanation) with at least 1.5 years' follow-up were retrospectively identified. All cases underwent clinical, neurophysiological, MRI, and cerebrospinal fluid (CSF) assessment, including exploratory tau, 14-3-3, and cystatin C testing. CIS recovery, conversion to MS, and long-term neurological disability were used as outcome measures. Patients with neuromyelitis optica spectrum disorders, idiopathic acute transverse myelitis (IATM), Creutzfeldt-Jacob disease, and non-inflammatory/non-neurodegenerative disorders served as controls for CSF analysis. RESULTS: Forty-six CIS cases were included. Severe presentation was associated with incomplete recovery, while presence of at least 3 periventricular lesions on baseline MRI correlated with MS conversion. Initial pyramidal tract involvement, incomplete CIS recovery, and number of relapses predicted neurological disability. CSF tau, 14-3-3, and cystatin C did not correlate with any outcome measure. CIS cases had significantly lower tau and cystatin C levels compared to IATM. CONCLUSIONS: An extensive diagnostic evaluation of patients with an IDE is worthwhile to make prognostic predictions. More robust molecular biomarkers are needed.
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