Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis

Lundell, Henrik; Svolgaard, Olivia; Dogonowski, Anne Marie; Christensen, Jeppe Romme; Selleberg, Finn; Sørensen, Per Soelberg; Blinkenberg, Morten; Siebner, Hartwig R.; Garde, Ellen

doi:10.1111/ane.12729

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…39 Previous studies in the spinal cord injured population have demonstrated parallel changes in both cord CSA and somatosensory regions 7,40,41 between CSA and hand grip strengths, 18 and between LRW and motor score, 35 whereas APW correlated with sensory scores. 35 In patients with MS, atrophy of the upper cervical cord is evident in APW but not LRW, 42 whereas studies on ALS have only reported on CSA. 3 We did not observe any relationships between motor function and cord metrics in the present large, young, and healthy cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Several large imaging studies in MS have demonstrated extensive cord atrophy. [42][43][44] We also know from longitudinal neuroimaging studies that brain volume decreases with aging and in neurodegenerative disorders such as Alzheimer and Parkinson disease. Whether the CSA of the spinal cord changes over time in healthy individuals is inconclusive.…”

Section: Discussionmentioning

confidence: 99%

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Heritability of cervical spinal cord structure

2020

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ObjectiveMeasures of spinal cord structure can be a useful phenotype to track disease severity and development; this observational study measures the hereditability of cervical spinal cord anatomy and its correlates in healthy human beings.MethodsTwin data from the Human Connectome Project were analyzed with semiautomated spinal cord segmentation, evaluating test-retest reliability and broad-sense heritability with an AE model. Relationships between spinal cord metrics, general physical measures, regional brain structural measures, and motor function were assessed.ResultsWe found that the spinal cord C2 cross-sectional area (CSA), left-right width (LRW), and anterior-posterior width (APW) are highly heritable (85%–91%). All measures were highly correlated with the brain volume, and CSA only was positively correlated with thalamic volumes (p = 0.005) but negatively correlated with the occipital cortex area (p = 0.001). LRW was correlated with the participant's height (p = 0.00027). The subjects' sex significantly influenced these metrics. Analyses of a test-retest data set confirmed validity of the approach.ConclusionsThis study provides the evidence of genetic influence on spinal cord structure. MRI metrics of cervical spinal cord anatomy are robust and not easily influenced by nonpathological environmental factors, providing a useful metric for monitoring normal development and progression of neurodegenerative disorders affecting the spinal cord, including—but not limited to—spinal cord injury and MS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Heritability of cervical spinal cord structure

2020

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“…1,[10][11][12] Spinal cord gray matter atrophy has been described at disease onset in patients with clinically isolated syndrome, a harbinger of MS, and is more pronounced in primary progressive compared to relapsing MS patients. [13][14][15][16] Several studies have highlighted the correlation between physical disability and cord and brain atrophy, 10,17,18 and recently a strong relationship between disability and SC gray matter (GM) atrophy has been shown. 12,19 Spinal cord atrophy has also been proposed as a prognostic biomarker for clinical outcomes in patients with traumatic spinal cord injury.…”

Section: Introductionmentioning

confidence: 99%

Intersubject Variability and Normalization Strategies for Spinal Cord Total Cross‐Sectional and Gray Matter Areas

Papinutto

Asteggiano

Bischof

et al. 2019

Journal of Neuroimaging

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Background and Purpose-The quantification of spinal cord (SC) atrophy by MRI has assumed an important role in assessment of neuroinflammatory/neurodegenerative diseases and traumatic SC injury. Recent technical advances make possible the quantification of gray matter (GM) and white matter tissues in clinical settings. However, the goal of a reliable diagnostic, prognostic or predictive marker is still elusive, in part due to large inter-subject variability of SC areas. Here, we investigated the sources of this variability and explored effective strategies to reduce it.Methods-129 healthy subjects (mean age: 41.0±15.9) underwent MRI on a Siemens 3T Skyra scanner. 2D PSIR at the C2-C3 vertebral level and a sagittal 1mm 3 3D T1-weighted brain acquisition extended to the upper cervical cord were acquired. Total cross-sectional area and GM area were measured at C2-C3, as well as measures of the vertebra, spinal canal and the skull. Correlations between the different metrics were explored using Pearson product-moment coefficients. The most promising metrics were used to normalize cord areas using multiple regression analyses.Results-The most effective normalization metrics were the V-scale (from SienaX) and the product of the C2-C3 spinal canal diameters. Normalization methods based on these metrics reduced the inter-subject variability of cord areas of up to 17.74%. The measured cord areas had a statistically significant sex difference, while the effect of age was moderate.Conclusions-The present work explored in a large cohort of healthy subjects the source of inter-subject variability of SC areas and proposes effective normalization methods for its reduction.

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“…A recent study has confirmed that SPMS and RRMS patients differ in cervical spinal cord average CSA (p = 0.03) as well as in C7 area (p = 0.002) (125). Atrophy of the upper cervical cord is most evident in the antero-posterior direction, and attains a cranio-caudal pattern with the progression of the disease (126,127). It presents a sensitive biomarker, especially as the estimated annual rate of SCA is greater when compared to the rate of brain atrophy in patients with MS (−1.78 vs. −0.5%) (123,128).…”

Section: Spinal Cord Atrophymentioning

confidence: 79%

Clinical and Paraclinical Biomarkers and the Hitches to Assess Conversion to Secondary Progressive Multiple Sclerosis: A Systematic Review

2021

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Conversion to secondary progressive (SP) course is the decisive factor for long-term prognosis in relapsing multiple sclerosis (MS), generally considered the clinical equivalent of progressive MS-associated neuroaxonal degeneration. Evidence is accumulating that both inflammation and neurodegeneration are present along a continuum of pathologic processes in all phases of MS. While inflammation is the prominent feature in early stages, its quality changes and relative importance to disease course decreases while neurodegenerative processes prevail with ongoing disease. Consequently, anti-inflammatory disease-modifying therapies successfully used in relapsing MS are ineffective in SPMS, whereas specific treatment for the latter is increasingly a focus of MS research. Therefore, the prevention, but also the (anticipatory) diagnosis of SPMS, is of crucial importance. The problem is that currently SPMS diagnosis is exclusively based on retrospectively assessing the increase of overt physical disability usually over the past 6–12 months. This inevitably results in a delay of diagnosis of up to 3 years resulting in periods of uncertainty and, thus, making early therapy adaptation to prevent SPMS conversion impossible. Hence, there is an urgent need for reliable and objective biomarkers to prospectively predict and define SPMS conversion. Here, we review current evidence on clinical parameters, magnetic resonance imaging and optical coherence tomography measures, and serum and cerebrospinal fluid biomarkers in the context of MS-associated neurodegeneration and SPMS conversion. Ultimately, we discuss the necessity of multimodal approaches in order to approach objective definition and prediction of conversion to SPMS.

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Spinal cord atrophy in anterior-posterior direction reflects impairment in multiple sclerosis

Cited by 8 publications

References 37 publications

Heritability of cervical spinal cord structure

Heritability of cervical spinal cord structure

Intersubject Variability and Normalization Strategies for Spinal Cord Total Cross‐Sectional and Gray Matter Areas

Clinical and Paraclinical Biomarkers and the Hitches to Assess Conversion to Secondary Progressive Multiple Sclerosis: A Systematic Review

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