Spinal Cord Atrophy in Multiple Sclerosis: A Systematic Review and Meta‐Analysis

Casserly, Courtney; Seyman, Estelle; Alcaide‐Leon, Paula; Guenette, Melanie; Lyons, Carrie; Sankar, Stephanie; Svendrovski, Anton; Baral, Stefan; Oh, Jiwon

doi:10.1111/jon.12553

Cited by 88 publications

(88 citation statements)

References 102 publications

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“…39 However, we have a priori set our study duration at 1 year to obtain estimates for clinical trials and short-term observational studies; of note, we obtained annualized atrophy rates in line with pooled estimates from 94 studies (1.78%/year), 13 and the number of participants per arm was consistent with that obtained by other similar studies. Previous studies have shown that spinal cord atrophy predicts disease progression and conversion from CIS to RRMS over a long followup period.…”

Section: Discussionsupporting

confidence: 75%

“…Sample size to detect 60% treatment effect on spinal cord atrophy over 1 year was lower for GBSI than CSA (CIS: 106 vs 830; RRMS: 95 vs 335; PMS: 44 vs 215; power = 80%; alpha = 5%). 5,12,13 It is crucial to obtain an accurate and precise longitudinal measurement of spinal cord atrophy, because it could be used to monitor disease progression and become a primary outcome measure in phase 2 clinical trials with neuroprotective therapies, not only in MS, but also in other neurodegenerative disorders. ANN NEUROL 2019;86:704-713 S pinal cord atrophy on magnetic resonance imaging (MRI) is a marker of neurodegeneration in multiple sclerosis (MS), 1,2 and is one of the main substrates of longterm disease progression.…”

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confidence: 99%

“…[3][4][5][6][7][8][9][10][11] Spinal cord atrophy progresses faster than brain atrophy (1.7%/year vs 0.4-0.6%/year), is greater in progressive MS than in the relapsing forms of MS, and predicts disability. 5,12,13 It is crucial to obtain an accurate and precise longitudinal measurement of spinal cord atrophy, because it could be used to monitor disease progression and become a primary outcome measure in phase 2 clinical trials with neuroprotective therapies, not only in MS, but also in other neurodegenerative disorders. [14][15][16][17] Spinal cord atrophy is conventionally estimated with segmentation-based methods (eg, cervical cord cross-sectional area [CSA]), applied to volumetric spinal cord images, 18 that measure cord characteristics at each time point; indirect longitudinal atrophy measurements are obtained by numerical subtraction, with relatively low reproducibility and responsiveness to change.…”

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confidence: 99%

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Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral

Moccia

Prados

Filippi

et al. 2019

Annals of Neurology

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Objective: Spinal cord atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on magnetic resonance imaging using segmentation-based methods suffer from measurement variability, especially in multicenter studies. We compared the generalized boundary shift integral (GBSI), a registration-based method, with a standard segmentation-based method. Methods: Baseline and 1-year spinal cord 3-dimensional T1-weighted images (1mm isotropic) were obtained from 282 patients (52 clinically isolated syndrome [CIS], 196 relapsing-remitting MS [RRMS], 34 progressive MS [PMS]), and 82 controls from 8 MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) sites on multimanufacturer and multi-field-strength scans. Spinal Cord Toolbox was used for C2-5 segmentation and cross-sectional area (CSA) calculation. After cord straightening and registration, GBSI measured atrophy based on the probabilistic boundary-shift region of interest. CSA and GBSI percentage annual volume change was calculated. Results: GBSI provided similar rates of atrophy, but reduced measurement variability compared to CSA in all MS subtypes (CIS: −0.95 AE 2.11% vs −1.19 AE 3.67%; RRMS: −1.74 AE 2.57% vs −1.74 AE 4.02%; PMS: −2.29 AE 2.40% vs −1.29 AE 3.20%) and healthy controls (0.02 AE 2.39% vs −0.56 AE 3.77%). GBSI performed better than CSA in differentiating healthy controls from CIS (area under the curve [AUC] = 0.66 vs 0.53; p = 0.03), RRMS (AUC = 0.73 vs 0.59; p < 0.001), PMS (AUC = 0.77 vs 0.53; p < 0.001), and patients with disability progression from patients without View this article online at wileyonlinelibrary.com.

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Section: Discussionsupporting

confidence: 75%

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confidence: 99%

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confidence: 99%

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Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral

Moccia

Prados

Filippi

et al. 2019

Annals of Neurology

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“…27 One large metadata study found, on average, that patients with multiple sclerosis lose 1.78%/year of their cervical SC area. 16 We do not need to assume that SC atrophy during 1 year in HP would be zero; however, a large study with .1200 asymptomatic participants spanning 20-80 years in age found that in both men and women the C2/C3 intervertebral level cross-sectional area had a minimum decrease of about 1% and a maximum decrease of roughly 4.5% spanning several decades. 32 Thus, we can be fairly certain that during the course of a 1-year follow-up, normal SC atrophy would, most likely, not surpass 1.5%.…”

Section: Discussionmentioning

confidence: 98%

“…Most studies of MR imaging-based SC atrophy comparisons of diseased with healthy SC measures have relied on interindividual variability calculated from crosssectional data. 16 Intraindividual variability in healthy participants (HP) is often ignored or assumed to be equivalent to the mean change (or SD) in SC atrophy measures. 9 The utility of using cerebral 3D MRIs, including the upper cervical cord (UCC), as a source of MUCCA calculations is based on the availability of this sequence in most patients.…”

Section: Discussionmentioning

confidence: 99%

Considerations for Mean Upper Cervical Cord Area Implementation in a Longitudinal MRI Setting: Methods, Interrater Reliability, and MRI Quality Control

Chien

Juenger

Scheel³

et al. 2020

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Spinal cord atrophy is commonly measured from cerebral MRIs, including the upper cervical cord. However, rescan intraparticipant measures have not been investigated in healthy cohorts. This study investigated technical and rescan variability in the mean upper cervical cord area calculated from T1-weighted cerebral MRIs. MATERIALS AND METHODS: In this retrospective study, 8 healthy participants were scanned and rescanned with non-distortionand distortion-corrected MPRAGE sequences (11-50 sessions in 6-8 months), and 50 participants were scanned once with distortion-corrected MPRAGE sequences in the Day2day daily variability study. From another real-world observational cohort, we collected non-distortion-corrected MPRAGE scans from 27 healthy participants (annually for 2-4 years) and cross-sectionally from 77 participants. Statistical analyses included coefficient of variation, smallest real difference, intraclass correlation coefficient, Bland-Altman limits of agreement, and paired t tests.

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Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective

et al. 2021

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agnetic resonance imaging (MRI) is central in the diagnostic workup of patients with suspected multiple sclerosis (MS) given its high sensitivity to detect disease dissemination in space and over time and its substantial, albeit imperfect, ability to exclude other mimics of MS. From 2001 until 2017, great effort was expended providing successive iterations of the McDonald criteria to define imaging features typical of MS in patients presenting with clinically isolated syndrome (CIS). 1 However, diagnosis of primary progressive (PP) MS remains challenging and is only possible retrospectively based on clinical assessment.Identification of imaging features associated with PPMS and features that predict evolution from relapsing-remitting (RR) MS to secondary progressive (SP) MS is an important unmet need. Given the advent of effective therapies for RRMS that may reduce development of SPMS and limit disability worsening in progressive MS (PMS), 2 the need for such imaging indicators is all the greater.Diagnosis of PMS is limited by difficulties in distinguishing accumulating disability due to inflammatory disease activity from that attributable to degenerative processes associated with SPMS. Moreover, there are no accepted clinical criteria for diagnosing SPMS. 3,4 This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of PMS. MethodsIn this review, we report the conclusions of the "Diagnosis of Progressive MS: The Imaging Perspective" workshop held in Milan,

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Spinal Cord Atrophy in Multiple Sclerosis: A Systematic Review and Meta‐Analysis

Cited by 88 publications

References 102 publications

Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral

Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral

Considerations for Mean Upper Cervical Cord Area Implementation in a Longitudinal MRI Setting: Methods, Interrater Reliability, and MRI Quality Control

Diagnosis of Progressive Multiple Sclerosis From the Imaging Perspective

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