RIS CIS CDMS SPMS Long-term disability progression

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RIS CIS CDMS SPMS Long-term disability progression T2 and T1 lesion volume Whole brain / GM volume changes Cortical lesion volume / number Measures obtained using other advanced imaging techniques (MTI, MR spectroscopy)?  needs confirmation in large studies Time Disability Inflammation From RIS to first relapse Younger age Male sex Spinal cord lesions Degeneration RIS CIS CDMS SPMS From CIS to CDMS T2 lesion volume / number GdE lesion number Presence of cortical lesions Short-term disability progression Early relapse frequency Inter-relapse interval T2 lesion volume / number

Early relapses and late disease evolution Time from EDSS 3/4 to EDSS 6/7 not affected by early relapses High early relapses EDSS Time (years) 1 2 3 4 5 6 Int. early relapses Low early relapses 7 Late disease evolution not influenced by focal inflammation Early relapses and late disease evolution Early relapses do not affect late disease evolution Confavreux et al. 2003 Lyon database London Ontario database Scalfari et al. 2010 Rennes database Leray et al. 2010

Escalation therapy Induction therapy Bone marrow transplantation? Mitoxantrone Alemtuzumab (Ocrelizumab) NTZ (JCV- or low idx) Alemtuzumab (JCV+ or high idx) Fingolimod (combinations?) - Daclizumab Mild-moderate: Teriflunomide - DMF - (Laquinimod) IFN (pegylated?) or GA (40 mg tiw?) Severe: NTZ (JCV- or low idx) - Fingolimod (JCV+ or high idx)