Multimodal MRI Response to Fingolimod in Multiple Sclerosis: A Nonrandomized, Single Arm, Observational Study

Bernitsas, Evanthia; Kopinsky, Hannah; Lichtman-Mikol, Samuel; Razmjou, Sarah; Santiago-Martinez, Carla; Yarraguntla, Kalyan; Bao, Fen

doi:10.1111/jon.12824

Cited by 5 publications

(17 citation statements)

References 54 publications

(121 reference statements)

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“…Fifteen studies examined the longitudinal evolution of NAWM MTR 7). 39,40,81,[91][92][93]107 In studies which reported a significant change over time, and in line with a previous report, 111 absolute change in NAWM MTR was small (<1.5% up to 36 months) with reported estimates of an annual decline of 0.1% in early RRMS, possibly preceding clinical onset by years. 54 However, others found no change in NAWM MTR over two years in an early MS cohort with minimal disability, after controlling for age and gender.…”

Section: Longitudinal Change In Nawm Mtrsupporting

confidence: 86%

“…Intra-study and inter-study heterogeneity were apparent in treatment with DMTs and steroids (Table 3 and Supplementary Table 4 for summaries; Supplementary Table 3 for detailed descriptions). Homogeneous DMTs were prescribed across the cohort in eleven studies (Supplementary Table 4); comprising fingolimod, 40 dimethyl fumarate, 32,104 subcutaneous interferon (IfN)-β1a, 39,88 or IfN-β1b, 31,77,101 intramuscular IfN-β1a, 107,109 and subcutaneous glatiramer acetate. 87 Patients in four further studies were either untreated or received homogeneous DMTs which were IfN-α 98 IfN-β, 53,54 and glatiramer acetate.…”

Section: Disease Modifying Therapies (Dmts) and Steroid-usagementioning

confidence: 99%

“…The radiofrequency pulse shape was generally Gaussian (k=28), 40,45,61,94,95,98 Sinc-Gaussian (k=5), 35,59,74,82 Fermi (k=4), 57,58,84,90 1-2-1 binomial (k=2), 80,91 and hyperbolic secant pulses (k=1) 71 were also used. Forty studies did not specify pulse shape.…”

Section: Shape Of Mt Pulsementioning

confidence: 99%

“…A linear mixed-model showed that lesion MTR did not change significantly longitudinally (β=0.375 [-0.56 to 1.30], t-value=0.82, p=0.42, Supplementary Table 8). 36,40,81,87,[91][92][93]96,107,111 However, MTR longitudinal evolution depends on lesion characteristics 43 and may be subtle 88 (Supplementary Figure 1 and 2). MTR of active CELs varies from month-to-month before and after enhancement, 62,[91][92][93]101,112 while MTR of GM lesions, 43 'slowly expanding' lesions, 99 T1-weighted hypointense, 87 and T2-weighted hyperintense 87,96 lesions may remain relatively stable over several years, irrespective of relapses.…”

Section: Longitudinal Change In Lesion Mtrmentioning

confidence: 99%

“…MTR increases may be seen with treatment (e.g. fingolimod 40 over two years) although not always (e.g. laquinomod 114 ).…”

Section: Longitudinal Change In Lesion Mtrmentioning

confidence: 99%

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Quantitative magnetisation transfer imaging in relapsing-remitting multiple sclerosis: a systematic review and meta-analysis

York

Thrippleton

Meijboom

et al. 2021

Preprint

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Myelin-sensitive MRI such as magnetisation transfer imaging has been widely used in the clinical context of multiple sclerosis. The influence of methodology and differences in disease subtype on imaging findings is, however, not well established. Here, we aim to review systematically the use of quantitative magnetisation transfer imaging in the brain in relapsing-remitting multiple sclerosis. We examine how methodological differences, disease effects and their interaction influence magnetisation transfer imaging measures. Articles published before 06/01/2021 were retrieved from online databases (PubMed, EMBASE and Web of Science) with search terms including "magnetisation transfer" and "brain" for systematic review. Only studies which used human in vivo quantitative magnetisation transfer imaging in adults with relapsing-remitting multiple sclerosis (with or without healthy controls) were included. Data including sample size, magnetic field strength, MRI acquisition protocol parameters, treatments and clinical findings were extracted. Where possible, effect sizes were calculated for meta-analyses to determine magnetisation transfer (1) differences between patients and healthy controls; (2) longitudinal change; and, (3) relationships with clinical disability in relapsing-remitting multiple sclerosis. Eighty-six studies met the inclusion/exclusion criteria. MRI acquisition parameters varied widely, and were also underreported. The majority of studies examined MTR (magnetisation transfer ratio) in white matter, but magnetisation transfer metrics, brain regions and results were heterogeneous. Analysis demonstrated a risk of bias due to selective reporting and small sample sizes. A random-effects meta-analysis revealed MTR was 1.1 percent units [95% CI -1.47pu to -0.73pu] lower in relapsing-remitting multiple sclerosis than healthy controls (z-value: -6.04, p<0.001, n=23). Linear mixed-model analysis did not show a significant longitudinal change in MTR across all brain regions (β=-0.14 [-0.9 to 0.61], t-value=-0.38, p=0.71, n=13) or normal-appearing white matter alone (β=-0.082 [-0.13 to -0.29], t-value=0.78, p=0.44, n=7). There was a significant negative association between MTR and clinical disability, as assessed by the Expanded Disability Status Scale (r=-0.30 [95% CI -0.48 to -0.08]; z-value=-2.91, p=0.01, n=8). Evidence suggests that magnetisation transfer imaging is sensitive to pathological changes in relapsing-remitting multiple sclerosis, although the effect of relapsing-remitting multiple sclerosis on magnetisation transfer metrics in different brain tissue types was small in comparison to the inter-study variability. Recommended improvements include: the use of techniques such as MTsat (magnetisation transfer saturation) or ihMTR (inhomogeneous MTR) which provide more robust and specific microstructural measures within clinically feasible acquisition times; detailed methodological reporting standards; and larger, demographically diverse cohorts for comparison, including healthy controls.

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