Background: Monitoring disease evolution in Multiple sclerosis (MS) subjects may aid in decision making for personalizing treatment and disease evolution prediction. We investigate the use of disability progression, using clinical features, the expanded disability status scale (EDSS), and their relationship with texture features and Amplitude Modulation-Frequency Modulation (AM-FM) features extracted from MRI MS detectable lesions for the prognosis of future disability on magnetic resonance imaging (MRI). Methods: MS detectable brain lesions from N=38 symptomatic untreated subjects diagnosed with clinically isolated syndrome (CIS), were manually segmented, by an experienced MS neurologist, on transverse T2-weighted (T2W) images obtained from serial brain MRI scans at the baseline (Time0M) and the repeat (Time6-12M) examinations. The subjects were separated into two different groups based on their EDSS: (G1: 1≤EDSS2Y≤3.5 (N=26) and G2: 3.5