Effect of immunomodulatory medication on regional gray matter loss in relapsing–remitting multiple sclerosis—A longitudinal MRI study

Bendfeldt, Kerstin; Egger, Hanspeter; Nichols, Thomas E.; Loetscher, Patrick; Denier, Niklaus; Küster, Pascal; Traud, Stefan; Mueller-Lenke, Nicole; Naegelin, Yvonne; Gass, Achim; Kappos, Ludwig; Radue, Ernst‐Wilhelm; Borgwardt, Stefan

doi:10.1016/j.brainres.2010.02.035

Cited by 31 publications

(39 citation statements)

References 48 publications

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“…Nine studies included a healthy control arm [15,21,23,27,32,40,[48][49][50]. A majority of the studies (N = 20) recruited only relapsing-remitting (RR) MS patients [14,[16][17][18]20,23,[26][27][28]31,33,35,37,[39][40][41][42]47,48,51]. Sixteen studies recruited primary progressive (PP) MS and secondary progressive (SP) MS patients [15,21,22,24,25,29,30,32,34,36,38,[43][44][45][46]49].…”

Section: Overall Study Descriptionmentioning

confidence: 99%

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The natural history of brain volume loss among patients with multiple sclerosis: A systematic literature review and meta-analysis

Vollmer

Signorovitch

Huynh

et al. 2015

Journal of the Neurological Sciences

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Section: Overall Study Descriptionmentioning

confidence: 99%

“…Of the 38 articles, 8 were clinical trials [14,20,26,27,31,39,50,51] and 30 were observational studies [15][16][17][18][19][21][22][23][24][25][28][29][30][32][33][34][35][36][37][38][40][41][42][43][44][45][46][47][48][49]. Nine studies included a healthy control arm [15,21,23,27,32,40,[48][49][50].…”

Section: Overall Study Descriptionmentioning

confidence: 99%

The natural history of brain volume loss among patients with multiple sclerosis: A systematic literature review and meta-analysis

Vollmer

Signorovitch

Huynh

et al. 2015

Journal of the Neurological Sciences

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“…Indeed, VBM has been used extensively in the analysis of brain atrophy in MS (Battaglini et al., 2009; Bendfeldt et al., 2009, 2010; Ceccarelli et al., 2008; Raz et al., 2010). We have used VBM to demonstrate that there were distinct associations between voxelwise GM loss and specific clinical disabilities (MacKenzie‐Graham et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

et al. 2018

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IntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%–70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing–remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol‐treated compared to placebo‐treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty‐two estriol‐ and forty‐nine placebo‐treated RRMS patients underwent clinical evaluations and brain MRI. Voxel‐based morphometry (VBM) was used to evaluate voxelwise GM sparing from high‐resolution T1‐weighted scans.ResultsA region of treatment‐induced sparing (TIS) was defined as the areas where GM was spared in estriol‐ as compared to placebo‐treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability‐specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol‐treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability‐specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

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“…3 Accordingly, the effect of DMTs on MRI-derived estimates of brain atrophy is a common outcome in MS trials. [4][5][6][7] Recent studies reveal that retinal atrophy mirrors brain atrophy over time in MS. 8 However, it remains unclear whether various DMTs differentially affect retinal atrophy, similar to their varying effects upon brain atrophy. Optical coherence tomography (OCT) is a noninvasive, inexpensive, reliable, and reproducible imaging technique that generates high-resolution images of the retina, allowing most individual retinal layers to be discerned and quantified.…”

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confidence: 99%

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

et al. 2017

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Objective: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell 1 inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results: The effects of glatiramer acetate (GA; n 5 48), natalizumab (NAT; n 5 46), and interferonb-1a subcutaneously (IFN SC ; n 5 35) and intramuscularly (IFN IM ; n 5 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFN SC -and GAtreated patients exhibited 0.37 mm/y (p , 0.001) and 0.14 mm/y (p 5 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFN SC group, GCIP thinning was 1.53 mm/y faster during the first year of therapy vs during the time interval afterwards (p , 0.001).Conclusions: Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials. Neurology ® 2017;88:525-532 GLOSSARY AMT 5 average macular thickness; DMT 5 disease-modifying therapy; GA 5 glatiramer acetate; GCIP 5 ganglion cell 1 inner plexiform layer; HC 5 healthy control; IFN 5 interferon; IFN IM 5 intramuscular interferon-b-1a; IFN SC 5 subcutaneous interferon-b-1a; INL 5 inner nuclear layer; MME 5 microcystic macular edema; MS 5 multiple sclerosis; NAT 5 natalizumab; OCT 5 optical coherence tomography; ON 5 optic neuritis; ONL 5 outer nuclear layer; pRNFL 5 peripapillary retinal nerve fiber layer thickness; RRMS 5 relapsing-remitting multiple sclerosis.Although multiple sclerosis (MS) is conventionally regarded as an autoimmune, inflammatory, demyelinating disorder of the CNS, neurodegeneration resulting from these processes is recognized as the principal substrate of long-term disability.1,2 Currently available disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS) modulate or suppress the immune system, reducing the risk for future inflammation and associated neurodegeneration.3 Accordingly, the effect of DMTs on MRI-derived estimates of brain atrophy is a common outcome in MS trials. [4][5][6][7] Recent studies reveal that retinal atrophy mirrors brain atrophy over time in MS. 8 However, it remains unclear wh...

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Effect of immunomodulatory medication on regional gray matter loss in relapsing–remitting multiple sclerosis—A longitudinal MRI study

Cited by 31 publications

References 48 publications

The natural history of brain volume loss among patients with multiple sclerosis: A systematic literature review and meta-analysis

The natural history of brain volume loss among patients with multiple sclerosis: A systematic literature review and meta-analysis

Estriol‐mediated neuroprotection in multiple sclerosis localized by voxel‐based morphometry

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

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