Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI

Moccia, Marcello; Valsecchi, Nicola; Ciccarelli, Olga; Schijndel, Ronald A. van; Barkhof, Frederik; Prados, Ferrán

doi:10.1016/j.nicl.2020.102418

Cited by 18 publications

(13 citation statements)

References 44 publications

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“…at 3.0 T). This finding is in line with recent studies, 19,20 which showed reduced sample sizes when using registration-based methods of longitudinal atrophy measurement over serial CSA measurements. This supports the use of Reg in future clinical trials.…”

Section: Discussionsupporting

confidence: 92%

Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration‐Based Approach: Relevance for Clinical Studies

Valsasina

Horsfield²,

Meani

et al. 2021

Magnetic Resonance Imaging

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Background Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). Purpose To compare a new, registration‐based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. Study Type Retrospective. Subjects Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. Field Strength/Sequence 3D T1‐weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). Assessment Percentage cord area changes (PCACs) between baseline and follow‐up (cohort I: 2.34 years [interquartile range = 2.00–2.55 years], cohort II: 1.05 years [interquartile range = 1.01–1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow‐up straightened cord images, followed by AS‐based optimized cord segmentation. A subset of studies was analyzed twice by two observers. Statistical Tests Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed‐effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 − β = 0.80). Results Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was −1.12% (SE = 0.22) with Reg, −1.32% (SE = 0.30) with AS, and −1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was −0.83% (SE = 0.25) with Reg, −0.92% (SE = 0.32) with AS, and −1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra‐ and inter‐observer agreement range was 0.72–0.91 with AS, and it was >0.96 with Reg. Data Conclusion The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. Level of Evidence 3 Technical Efficacy Stage 2

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Section: Discussionsupporting

confidence: 92%

Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration‐Based Approach: Relevance for Clinical Studies

Valsasina

Horsfield²,

Meani

et al. 2021

Magnetic Resonance Imaging

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“…Moreover, Aymerich F et al [97] in a longitudinal study did not find a correlation between brain and cervical spinal cord atrophy in PPMS patients. These findings may indicate that in PPMS patients, brain and spinal cord pathologies evolve independently and measurements of brain and spinal cord atrophy can provide complementary information about the nature and extent of the disease in PPMS patients [95,[97][98][99]]. An interesting result concerning spinal cord atrophy in different MS clinical phenotypes come from study by Eden et al [100].…”

Section: Spinal Cord Atrophymentioning

confidence: 96%

“…It was reported that spinal cord atrophy in PPMS occurs in a very early phase of the disease and progresses more rapidly than in RRMS patients (1-5% vs. 2-3% per year) [89,95,96]. It is also important that the progression of spinal cord atrophy, especially spinal cord grey matter in PPMS patients, strongly correlates with an increase in neurological disability [97,98]. Moreover, Aymerich F et al [97] in a longitudinal study did not find a correlation between brain and cervical spinal cord atrophy in PPMS patients.…”

Section: Spinal Cord Atrophymentioning

confidence: 99%

Magnetic Resonance Imaging in Primary Progressive Multiple Sclerosis Patients

Siger

2022

Clin Neuroradiol

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The recently developed effective treatment of primary progressive multiple sclerosis (PPMS) requires the accurate diagnosis of patients with this type of disease. Currently, the diagnosis of PPMS is based on the 2017 McDonald criteria, although the contribution of magnetic resonance imaging (MRI) to this process is fundamental. PPMS, one of the clinical types of MS, represents 10%–15% of all MS patients. Compared to relapsing–remitting MS (RRMS), PPMS differs in terms of pathology, clinical presentation and MRI features. Regarding conventional MRI, focal lesions on T2-weighted images and acute inflammatory lesions with contrast enhancement are less common in PPMS than in RRMS. On the other hand, MRI features of chronic inflammation, such as slowly evolving/expanding lesions (SELs) and leptomeningeal enhancement (LME), and brain and spinal cord atrophy are more common MRI characteristics in PPMS than RRMS. Nonconventional MRI also shows differences in subtle white and grey matter damage between PPMS and other clinical types of disease. In this review, we present separate diagnostic criteria, conventional and nonconventional MRI specificity for PPMS, which may support and simplify the diagnosis of this type of MS in daily clinical practice.

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“…Furthermore, a large-scale study on primary progressive MS (PPMS) patients showed that measures obtained at different spinal cord segments had comparable clinical correlates. Incorporating brain MRI scans to acquire upper cervical measures appeared more effortless and accurate than utilizing spinal MRI scans, given the lower variability of the surrounding cerebrospinal fluid (CSF) signals in the former [ 29 ]. On this matter, when choosing the most reliable level of the spinal cord to measure, the width of CSF at that level (to maximize the CSF/spinal cord contrast), variations in the cross-sectional area of the spinal cord (to ensure the reliability of the measurements), and prevalence of disc protrusions are important.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Magnetic Resonance Imaging Analysis of Early Markers of Upper Cervical Cord Atrophy in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Adibi

Najafi

Merajifar

et al. 2021

Multiple Sclerosis International

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Purpose. To quantitatively analyze the C2/C3 segments of the spinal cord on magnetic resonance imaging (MRI) scans of neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) patients in their first five years of the disease and to investigate the intergroup differences regarding markers of spinal cord atrophy and their correlations with expanded disability status scale (EDSS). Materials and Methods. Twenty NMOSD patients and twenty RRMS patients, within their first five years of the disease, were enrolled in this cross-sectional study. All patients underwent spinal cord MR imaging using 1.5 Tesla systems, and C2/C3 portions of the spinal cord were segmented in the obtained scans. C2/C3 anteroposterior diameter (C2/C3 SC-APD), transversal diameter (C2/C3 SC-TD), and cross-sectional area (C2/C3 SC-CSA) were quantitatively measured using Spinal Cord Toolbox v.4.3. Results. Three NMOSD patients were seropositive for anti-AQP4 IgG. The mean C2/C3 SC-CSA in NMOSD patients was significantly lower than in RRMS patients. NMOSD patients had significantly lower C2/C3 SC-TDs than RRMS patients. With the three anti-AQP4+ patients excluded from the analysis, C2/C3 SC-TD was negatively correlated with EDSS. Conclusion. In the early stages of the disease, quantitative evaluation of C2/C3 spinal cord parameters, including cross-sectional area and transversal diameter in NMOSD patients, appears to be of potential diagnostic and prognostic value.

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Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI

Abstract: Highlights The GBSI provided clinically meaningful measurements of spinal cord atrophy, with low sample size. Deriving spinal cord atrophy from brain MRI using the GBSI is easier than spinal cord MRI. Spinal cord atrophy on GBSI could be used as a secondary outcome measure.

Cited by 18 publications

References 44 publications

Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration‐Based Approach: Relevance for Clinical Studies

Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration‐Based Approach: Relevance for Clinical Studies

Magnetic Resonance Imaging in Primary Progressive Multiple Sclerosis Patients

Quantitative Magnetic Resonance Imaging Analysis of Early Markers of Upper Cervical Cord Atrophy in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

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