Key questions and summary conclusions
(1) Is there any MRI feature that can support PPMS and SPMS diagnosis?
PPMS	Diffuse signal abnormalities in the spinal cord Spinal cord lesions involving the GM and ≥2 WM columns (axial plane) Atrophy of the lower portion of the cervical cord
SPMS	Spinal cord lesions involving the GM and ≥2 WM columns (axial plane) Atrophy of the lower portion of the cervical cord Cord GM atrophy
(2) Are there specific MRI features at disease onset able to predict disability and a progressive course?
PPMS	Gd-enhancing lesions at baseline Spinal cord lesions at baseline
SPMS	Number and volume of baseline brain T2-hyperintense lesions Increase of brain T2-hyperintense lesion volume during the first 5 years ≥2 Gd-enhancing lesions at baseline ≥1 spinal cord lesion at baseline ≥1 infratentorial lesion at baseline ≥1 cortical lesion at baseline ≥1 spinal cord lesion within 1 or 3 years ≥1 infratentorial lesion within 1 or 3 years ≥1 deep WM lesion within 1 year
(3) Are there MRI markers able to identify disability progression? In relapse-onset MS, are there MRI markers able to identify evolution to SPMS?
PPMS	New T1-hypointense lesions Cortical lesion number and volume Baseline GM damage Rate of brain atrophy
SPMS	T2 lesion volume Increase of T1-hypointense lesion volume Cortical lesion number and volume Conversion of dirty-appearing WM into focal WM lesions GM volume Rate of brain GM and deep GM atrophy
(4) Are there distinguishing MRI features between PPMS and SPMS?
None
(5) Are there candidate MRI biomarkers promising to identify MS progression?
≥4 paramagnetic rim lesions Subpial demyelination

Abbreviations: Gd=gadolinium; GM=gray matter; MRI=magnetic resonance imaging; MS=multiple sclerosis; P=progressive; PP=primary progressive; SP=secondary progressive; WM=white matter.