White Matter Diffusion Changes during the First Year of Natalizumab Treatment in Relapsing-Remitting Multiple Sclerosis

Abstract

BACKGROUND AND PURPOSE: Natalizumab treatment strongly affects relapsing-remitting multiple sclerosis, possibly by restraining white matter damage. This study investigated changes in white matter diffusivity in patients with relapsing-remitting multiple sclerosis during their first year of natalizumab treatment by using diffusion tensor imaging.

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

“…In a comparative study, Wiebenga and colleagues found improvement in DTI parameters in patients treated with natalizumab during the first year of treatment, while this improvement was not observed in patients treated with interferon-beta or glatiramer acetate. 47 A recent study in 2019 by Vavasour and colleagues, in MS patients treated with alemtuzumab over 24 months, showed stabilization of myelin water fraction, a measure of myelin content, and DTI markers. 48 In 1-year 3T study, Gurevich and colleagues showed an increase in FA and a decrease in Radial Diffusivity (RD) of the pyramidal tracts, inferior and superior cerebellar peduncles in fingolimod-treated patients compared to patients on interferon beta-1b.…”

“…Only a small number of studies examined the effect of disease‐modifying agents on the advanced imaging metrics and the results are nonconclusive. In a comparative study, Wiebenga and colleagues found improvement in DTI parameters in patients treated with natalizumab during the first year of treatment, while this improvement was not observed in patients treated with interferon‐beta or glatiramer acetate 47 . A recent study in 2019 by Vavasour and colleagues, in MS patients treated with alemtuzumab over 24 months, showed stabilization of myelin water fraction, a measure of myelin content, and DTI markers 48 .…”

Grey matter atrophy is associated with disability increase in natalizumab-treated patients

“…Whether the observed stabilization of GM damage is due to a neuroprotective effect of natalizumab deserves further investigation in appropriately designed studies. Some studies have already pointed to this hypothesis using MRI 32,33 , with recent studies using spectroscopy showing that natalizumab increases the levels of N-acetylaspartate, creatine and phosphocreatine, maybe indicating an enhanced axonal metabolism in natalizumabtreated patients 34 and reduction of WM damage during the first year of treatment using diffusion tensor imaging 35 . Finally, body fluid biomarkers in a progressive MS study with patients treated with natalizumab also showed a reduction in intrathecal inflammation (decreased levels of osteopontin) accompanied by decreases in other markers of neurodegeneration (neurofilament light chain) and tissue damage (increases in MTR in cortical GM and normal-appearing WM) 36 .…”

The Role of Advanced Magnetic Resonance Imaging Techniques in Multiple Sclerosis Clinical Trials

“…A short observational study of 4 patients followed on fingolimod for 4 months with DTI noted widespread increase in MD in NAWM and FLAIR lesions without any clinical manifestations [58]. A 1-year longitudinal study noted the differential effect on FA when comparing natalizumab, interferon (IFN)-β, and glatiramer acetate [59]. These findings supported decreased severity of damage with natalizumab, which correlated with cognitive performance [59].…”

“…A 1-year longitudinal study noted the differential effect on FA when comparing natalizumab, interferon (IFN)-β, and glatiramer acetate [59]. These findings supported decreased severity of damage with natalizumab, which correlated with cognitive performance [59]. In an open-label phase IIA study of patients with progressive MS with oral methylprednisolone 1.5 g monthly, decreases in MD in NAWM and NAGM were found after 15 months [60].…”