 RRMS and PPMS patients also show differences on the retinal layers yields examined under OCT.Some authors have proposed a dual classification of PPMS, according to the shape of edges of the scars, in MS-like and ADEM-like Proteomic analysis have shown that two proteins, Secretogranin II and Protein 7B2, in CSF can be used to separate RRMS from PPMS

Recently, the hypothesis of PPMS being apart from RRMS/SPMS is taken further credibility due that it was shown that CSF from PPMS patients can carry the disease to other animals, producing neurodegeneration in mice and that Normal Appearing White Matter (NAWM) structure is also different

The predominant lesions in PPMS are slowly expanding lesions with T cells, microglial, and macrophage-associated demyelination in close similar to pattern I demyelination

As of 2019 it has been found that the profile of T-cells is different in PPMS and SPMS

MS can be considered among the acquired demyelinating syndromes with a multiphasic instead of monophasic behaviour.Multiple sclerosis has a prodromal stage in which an unknown underlying condition, able to damage the brain, is present, but no lesion has still developed.