Toward Precision Phenotyping of Multiple Sclerosis

Abstract

The classification of multiple sclerosis (MS) has been established by Lublin in 1996 and revised in 2013. The revision includes clinically isolated syndrome, relapsing-remitting, primary progressive and secondary progressive MS, and has added activity (i.e., formation of white matter lesions or clinical relapses) as a qualifier. This allows for the distinction between active and nonactive progression, which has been shown to be of clinical importance. We propose that a logical extension of this classification is the incorporation of additional key pathological processes, such as chronic perilesional inflammation, neuroaxonal degeneration, and remyelination. This will distinguish MS phenotypes that may present as clinically identical but are driven by different combinations of pathological processes. A more precise description of MS phenotypes will improve prognostication and personalized care as well as clinical trial design. Thus, our proposal provides an expanded framework for conceptualizing MS and for guiding development of biomarkers for monitoring activity along the main pathological axes in MS.

Phenotyping variants of tumefactive demyelinating lesions according to clinical and radiological features—A case series

“…Finally, characterizing specific groups of patients with tumefactive demyelinating lesions may facilitate a search for biomarkers and pathomechanisms similar to the successes recently realized in autoimmune encephalitis (53,54) and Myelin Oligodendrocyte Glycoprotein Antibody Disease (55, 56). Our clinical and treatment data imply GDLs are mediated, at least in part, by humoral mechanisms and further efforts should be made in this field to facilitate precision phenotyping and accurate treatment (57).…”

Reshaping neuroimmunology: diagnosis and treatment in the era of precision medicine

“…4 An early step towards this was the introduction of the so-called phenotype modifiers (active versus not active, and with versus without progression) in the 2013 revision, acknowledging the coexistence of relapsing activity and progression and incorporating the use of biomarkers to define disease activitygadolinium-enhancing lesions or new or unequivocally enlarging T2 lesions on magnetic resonance imaging (MRI). 2 It is not unrealistic to suppose that, in the future, further phenotype modifiers based on biomarkers for chronic perilesional inflammation, neuroaxonal degeneration, and remyelination (see section "Novel Biomarkers") could be incorporated to allow improved subtyping of MS. 4 For instance, serum neurofilament light chain (sNfl) could also contribute to the classification of MS as active or not active, whereas measurement of brain atrophy on MRI and retinal nerve fiber layer thickness on optical coherence tomography could contribute to identify ongoing progression. 2,4 Such refinements in MS Box 1 Comparison of the conventional approach with the emerging, precision-based approach to the management of neuroimmunological conditions based on three illustrative cases.…”

Personalized Treatment for Multiple Sclerosis: The Role of Precision Medicine

“…Another promising direction of precision medicine in MS is the development of combination therapies that target multiple immune pathways involved in MS pathogenesis (45). Combination therapies may have higher efficacy than singletarget therapies and may reduce the risk of treatment resistance or adverse effects.…”