The spatio-temporal relationship between white matter lesion volume changes and brain atrophy in clinically isolated syndrome and early multiple sclerosis

Mattiesing, Rozemarijn M; Gentile, Giordano; Brouwer, Iman; Schijndel, Ronald A. van; Uitdehaag, Bernard M. J.; Twisk, Jos W. R.; Kappos, Ludwig; Freedman, Mark S.; Comi, Giancarlo; Jack, Dominic; Stefano, Nicola De; Barkhof, Frederik; Battaglini, Marco; Vrenken, Hugo

doi:10.1016/j.nicl.2022.103220

Cited by 5 publications

(6 citation statements)

References 30 publications

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“…Future studies should focus not only on the correlations within the same time interval but should also investigate the relationships between WM lesion changes and subsequent brain atrophy and vice versa. This has been addressed in a separate paper for the present dataset ( Mattiesing et al, 2022 ).…”

Section: Discussionmentioning

confidence: 89%

The spatio-temporal relationship between concurrent lesion and brain atrophy changes in early multiple sclerosis: A post-hoc analysis of the REFLEXION study

Gentile

Mattiesing

Brouwer

et al. 2023

NeuroImage: Clinical

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Section: Discussionmentioning

confidence: 89%

The spatio-temporal relationship between concurrent lesion and brain atrophy changes in early multiple sclerosis: A post-hoc analysis of the REFLEXION study

Gentile

Mattiesing

Brouwer

et al. 2023

NeuroImage: Clinical

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“…Data availability and quality 11 allowed the quantification of atrophy in 169 patients, that is global atrophy (PBVC m24–m60 : −1.009 ± 0.967%) and central atrophy (PVVC m24–m60 : 7.511 ± 9.117%) from month 24 to month 60. Results of the stepwise forward linear regressions for models 1 and 2 are shown in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

“…The REFLEX/REFLEXION studies lasted from 16 November 2006 until 30 August 2013. 12 Only those patients who started treatment immediately at the beginning of REFLEX ( N = 262), 11 the early treatment group, were included in this study. This was chosen due to the study design, as patients in the delayed treatment group started treatment immediately after conversion to clinically definite multiple sclerosis (CDMS), resulting in lowered probabilities of progression in this subgroup over time.…”

Section: Methodsmentioning

confidence: 99%

“…As described in the work by Mattiesing et al 11 the yearly percentage brain volume change (PBVC) as a measure of global atrophy and percentage ventricular volume change (PVVC) as a measure of central atrophy were calculated using SIENA 17 and VIENA, 19 respectively. A more negative value for PBVC and more positive value for PVVC are indicative of faster atrophy.…”

Section: Methodsmentioning

confidence: 99%

“…We used data from the REFLEX/REFLEXION studies, including patients that started early subcutaneous interferon beta-1a treatment, as we have shown the presence of pseudo-atrophy in the first year in this data set. 11 We now hypothesized that brain and lesion volume (LV) changes in the pseudo-atrophy period have different predictive value for disease progression compared with the period after the resolution of edema.…”

Section: Introductionmentioning

confidence: 99%

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Disease progression in the first 5 years of treatment in multiple sclerosis: Predictive value of early brain and lesion volume changes

Mattiesing,

Kramer,

Strijbis

et al. 2023

Mult Scler

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Background: Whether the degree of inflammation (and its resolution) and neurodegeneration after treatment initiation predicts disease progression in multiple sclerosis (MS) remains unclear. Objectives: To assess the predictive value of magnetic resonance imaging (MRI)-derived brain and lesion volume (LV) changes in years 1 and 2 of treatment for disease progression. Methods: Patients receiving early interferon beta-1a treatment in REFLEX/REFLEXION ( N = 262) were included. Predictive regression models included new/enlarging LV (positive activity), disappearing/shrinking LV (negative activity), and global/central atrophy during years 1 and 2. Results: Faster global atrophy and/or pseudo-atrophy and positive lesion activity in years 1 and 2 related to an increased probability and faster conversion to clinically definite multiple sclerosis (CDMS). Negative lesion activity in year 1 and slower central atrophy in year 2 were predictive of confirmed disability progression (9-Hole Peg Test). Positive lesion activity in year 2 was predictive of faster global atrophy, while positive lesion activity in years 1 and 2 was predictive of faster central atrophy. Conclusions: A higher degree of global atrophy and/or pseudo-atrophy in year 1 was predictive of CDMS. Positive lesion activity in any year was related to CDMS and neurodegeneration. Disability was related to negative lesion activity in year 1 and slower central atrophy in year 2.

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Changes of brain parenchyma free water fraction reflect tissue damage and impaired processing speed in multiple sclerosis

Caporale,

Chiarelli,

Biondetti

et al. 2024

Human Brain Mapping

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Free water fraction (FWF) represents the amount of water per unit volume of brain parenchyma, which is not bound to macromolecules. Its excess in multiple sclerosis (MS) is related to increased tissue loss. The use of mcDESPOT (multicomponent driven single pulse observation of T1 and T2), a 3D imaging method which exploits both the T1 and T2 contrasts, allows FWF to be derived in clinically feasible times. However, this method has not been used to quantify changes of FWF and their potential clinical impact in MS. The aim of this study is to investigate the changes in FWF in MS patients and their relationship with tissue damage and cognition, under the hypothesis that FWF is a proxy of clinically meaningful tissue loss. To this aim, we tested the relationship between FWF, MS lesion burden and information processing speed, evaluated via the Symbol Digit Modalities Test (SDMT). In addition to standard sequences, used for T1‐ and T2‐weighted lesion delineation, the mcDESPOT sequence with 1.7 mm isotropic resolution and a diffusion weighted imaging protocol (b = 0, 1200 s/mm2, 40 diffusion directions) were employed at 3 T. The fractional anisotropy map derived from diffusion data was used to define a subject‐specific white matter (WM) atlas. Brain parenchyma segmentation returned masks of gray matter (GM) and WM, and normal‐appearing WM (NAWM), in addition to the T1 and T2 lesion masks (T1L and T2L, respectively). Ninety‐nine relapsing–remitting MS patients (age = 43.3 ± 9.9 years, disease duration 12.3 ± 7.7 years) were studied, together with twenty‐five healthy controls (HC, age = 38.8 ± 11.0 years). FWF was higher in GM and NAWM of MS patients, compared to GM and WM of HC (both p < .001). In MS patients, FWF was the highest in the T1L and GM, followed by T2L and NAWM, respectively. FWF increased significantly with T1L and T2L volume (ρ ranging from 0.40 to 0.58, p < .001). FWF in T2L was strongly related to both T1L volume and the volume ratio T1L/T2L (ρ = 0.73, p < .001). MS patients performed worse than HC in the processing speed test (mean ± SD: 54.1 ± 10.3 for MS, 63.8 ± 10.8 for HC). FWF in GM, T2L, perilesional tissue and NAWM increased with SDMT score reduction (ρ = −0.30, −0.29, −0.33 respectively and r = −.30 for T2L, all with p < .005). A regional analysis, conducted to determine which NAWM regions were of particular importance to explain the relationship between FWF and cognitive impairment, revealed that FWF spatial variance was negatively related to SDMT score in the corpus callosum and the superior longitudinal fasciculus, WM structures known to be associated with cognitive impairment, in addition to the left corticospinal tract, the sagittal stratum, the right anterior limb of internal capsule. In conclusion, we found excess free water in brain parenchyma of MS patients, an alteration that involved not only MS lesions, but also the GM and NAWM, impinging on brain function and negatively associated with cognitive processing speed. We suggest that the FWF metric, derived from noninvasive, rapid MRI acquisitions and bearing good biological interpretability, may prove valuable as an MRI biomarker of tissue damage and associated cognitive impairment in MS.

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The spatio-temporal relationship between white matter lesion volume changes and brain atrophy in clinically isolated syndrome and early multiple sclerosis

Cited by 5 publications

References 30 publications

The spatio-temporal relationship between concurrent lesion and brain atrophy changes in early multiple sclerosis: A post-hoc analysis of the REFLEXION study

The spatio-temporal relationship between concurrent lesion and brain atrophy changes in early multiple sclerosis: A post-hoc analysis of the REFLEXION study

Disease progression in the first 5 years of treatment in multiple sclerosis: Predictive value of early brain and lesion volume changes

Changes of brain parenchyma free water fraction reflect tissue damage and impaired processing speed in multiple sclerosis

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