The role of ADC values within the normal-appearing brain in the prognosis of multiple sclerosis activity during interferon-\u03b2 therapy in the 3-year follow-up: a preliminary report

Anna Zacharzewska-Gondek,Joanna Bladowska,Sławomir Budrewicz,Marek Sąsiadek,Grzegorz Trybek,Anna Pokryszko-Dragan

doi:10.1038/s41598-020-69383-3

Abstract

Predictors of multiple sclerosis (MS) activity during disease-modifying treatment are being extensively investigated. The aim of this study was to assess the prognosis of NEDA (no evidence of disease activity) status during IFN-β (interferon-β) treatment, using apparent diffusion coefficient (ADC) measurements obtained at initial MRI (magnetic resonance imaging). In 87 MS patients treated with IFN-β, ADC values were calculated for 13 regions of normal-appearing white and grey matter (NAWM, NAGM) based on MRI performed with a 1.5 T magnet before (MS0, n = 45) or after one year of therapy (MS1, n = 42). Associations were evaluated between ADC, conventional MRI findings, demographic and clinical factors and NEDA status within the following 3 years using logistic, Cox and multinomial logistic regression models. NEDA rates in the MS0 group were 64.4%, 46.5% and 33.3% after the 1st, 2nd and 3rd year of treatment, respectively and in MS1 patients 71.4% and 48.7% for the periods 1st–2nd and 1st–3rd years of treatment, respectively. ADC values in the NAWM regions contributed to loss of NEDA and its clinical and radiological components, with a 1–3% increase in the risk of NEDA loss (p = 0.0001–0.0489) in both groups. ADC measurements may have an additional prognostic value with regard to NEDA status.

Highlights

Predictors of multiple sclerosis (MS) activity during disease-modifying treatment are being extensively investigated
Even subtle impairment of tissue architecture may result in facilitated diffusion, which is detectable as increased apparent diffusion coefficient (ADC) or mean diffusivity (MD) values, as well as decreased fractional anisotropy (FA) v alues[15,16,27]
It was reported in a radiologic-histopathologic study that facilitated diffusion in normal-appearing white and grey matter (NAWM, NAGM) beyond demyelinating plaques in MS patients is related to neurodegeneration, and such changes are missed on conventional MR images[28]

Summary

Introduction

Predictors of multiple sclerosis (MS) activity during disease-modifying treatment are being extensively investigated. Even subtle impairment of tissue architecture may result in facilitated diffusion, which is detectable as increased ADC or mean diffusivity (MD) values, as well as decreased fractional anisotropy (FA) v alues[15,16,27] It was reported in a radiologic-histopathologic study that facilitated diffusion in normal-appearing white and grey matter (NAWM, NAGM) beyond demyelinating plaques in MS patients is related to neurodegeneration, and such changes are missed on conventional MR images[28]. We designed a study aimed at investigating ADC measurements in selected regions of normal-appearing white and deep grey matter obtained during initial MRI with DWI in patients with relapsing–remitting MS as potential prognostic factors with regard to disease activity (NEDA status) during therapy with interferon-β in the 3-year follow-up, compared with conventional MRI data, demographic and clinical factors. Due to the lack of a control group of non-treated patients, we use the term “prognostic factors/indicators” of treatment response instead of “predictors”, according to S ormani[29]

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