1. 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

2. 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

5. 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)