Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis

Liu, Clarence; Edwards, Simon; Gong, Qiyong; Roberts, Neil; Blumhardt, L D

doi:10.1136/jnnp.66.3.323

Cited by 164 publications

(143 citation statements)

References 51 publications

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“…Conversely, a study that investigated the UCCA in CIS showed significant baseline atrophy in patients with abnormal MRI scans compared to controls (14). Further, a study that measured cord volume showed a significant decrease in relapsing-remitting MS patients compared to controls (12). However, neither of these investigations performed gender correction between the cohorts, and the CIS analysis (14) did not adjust for TICV.…”

Section: Discussionmentioning

confidence: 97%

“…Progressive MS patients have consistently shown cord atrophy in comparison with normal controls (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The correlation between atrophy and clinical disability (EDSS) reported in some investigations (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)13), and the association between diffuse cord abnormalities and atrophy (4) suggest that findings of cord atrophy in clinical phenotypes of MS could be used as a surrogate marker of disease severity and prognosis, as well as in disease-modifying drug treatment trials.…”

Section: Discussionmentioning

confidence: 99%

“…Magnetic resonance imaging (MRI) offers a means of measuring atrophy resulting from this disorder in vivo, and a number of studies have revealed significant cord atrophy cross-sectionally in patients with progressive forms of MS (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Further, a strong correlation between cervical cord atrophy and disability was found in some studies (2,3,6,8).…”

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confidence: 99%

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Upper cervical cord area in early relapsing‐remitting multiple sclerosis: Cross‐sectional study of factors influencing cord size

Rashid

Davies

Chard

et al. 2006

Magnetic Resonance Imaging

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Purpose: To determine whether the upper cervical cord area (UCCA) is influenced by disease effect in early relapsing-remitting multiple sclerosis (MS), using statistical modeling to account for potential covariates. Materials and Methods:A cohort of 39 patients were studied cross-sectionally within three years of first symptom onset (median disease duration ϭ 1.6 years) and compared with 26 healthy controls. The UCCA was measured from axial reconstructions of three-dimensional T 1 -weighted scans with automated detection of the edge of the cord. Statistical analysis adjusted for factors such as total intracranial volume (TICV) and gender. Clinical correlations, in particular those thought likely to be related to cord pathology, were also investigated. Results:No significant disease effect was noted on UCCA (P ϭ 0.685), although there was borderline evidence of a lower UCCA in patients with symptoms of bowel or bladder disturbance (P ϭ 0.043). A strong association was noted between UCCA and TICV (r ϭ 0.558; P Յ 0.001), and there was a trend for females to have a smaller UCCA (P ϭ 0.062). The latter finding appeared to reflect a gender-related difference in TICV (P Յ 0.001). Conclusion:Atrophy of the upper cervical cord is not readily apparent in most patients early in the course of relapsing-remitting MS. In evaluations of disease-related changes in the UCCA in cross-sectional studies, TICV and gender should be considered as potentially confounding covariates.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Upper cervical cord area in early relapsing‐remitting multiple sclerosis: Cross‐sectional study of factors influencing cord size

Rashid

Davies

Chard

et al. 2006

Magnetic Resonance Imaging

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“…The relatively large number of both controls and patients in our study resulted in greater statistical power, and to improve this further we measured the total intracranial volume (TICV) and used it to eliminate some of the normal population variance in CSA. The TICV is not affected by MS, and was used for normalization purposes in several previous atrophy studies (9,15,16,23,24). We also estimated the statistical power of the study, and the increase in power due to the normalization.…”

mentioning

confidence: 99%

Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

Mann¹,

Constantinescu²,

Tench³

2007

Magnetic Resonance Imaging

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Purpose: To measure accurately the upper cervical cord cross-sectional area (CSA) in patients with relapsing remitting multiple sclerosis (RRMS), and normal control subjects, to address the paradox that longitudinal reduction in CSA has been detected in RRMS while reduction compared to controls has not. We hypothesized that a lack of statistical power and/or measurement sensitivity due to partial volume averaging in previous studies contributed to this paradox. Materials and Methods:Using a technique that corrects for partial volume averaging, we measured the CSA in 35 normal controls and 35 RRMS patients. We used the total intracranial volume (TICV) to normalize the CSA and therefore reduce the normal variance and improve the statistical power. Results:The mean TICV did not differ between groups. Statistical power analysis indicated that a 5% reduction in CSA in the patients could be detected with an estimated power of 0.74 before normalization and 0.9 after. The mean CSA in the patients was not reduced compared to controls after (P ϭ 0.928) or before (P ϭ 0.881) normalization. Conclusion:Using a sensitive analysis method, and apparently appropriate statistical power, we did not detect reduced CSA in RRMS patients. We hypothesize that this may be due to inflammation.

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“…Measurement of the size of CNS structures may provide an indication of the total amount of tissue damage that has occurred up to a given point in time. New computer-assisted methods have been developed to precisely and reliably quantify tissue loss in MRI, [5][6][7][8][9][10][11][12][13] and atrophy has been shown to occur even in the early stages of MS. 3,4,[6][7][8][9] However, previous longitudinal studies in MS 3,[6][7][8][9][14][15][16] have not shown very strong or consistent relations between brain atrophy and disability. These studies have been limited to relatively short follow-up periods of 6 months to 3 years.…”

mentioning

confidence: 67%

Spinal schwannoma mimicking lower limb SMA

Fischer¹,

Brunn²,

Schröder³

et al. 2002

Neurology

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Abstract-Objective:To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression. Methods: A follow-up study was conducted to reassess patients from a phase III trial of interferon ␤-1a (IFN␤-1a) 8 years after randomization. Clinical and MRI data from 172 patients followed over 2 years in the original trial were used as baseline data. Follow-up data were obtained on 160 patients, including 134 patients with follow-up MRI examinations. Brain atrophy was estimated by automated calculation of brain parenchymal fraction. The relation between atrophy during the original trial and disability status at follow-up was determined. Correlations were also determined between lesion measurements from the original trial and the brain parenchymal fraction at follow-up. Results: Brain atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up. Brain atrophy at follow-up was related to lesion volumes measured during the original trial. Conclusions: The relation between atrophy progression and subsequent neurologic disability status suggests that atrophy progression during RRMS is clinically relevant. Therefore, atrophy progression may be a useful marker for disease progression in clinical trials. The relation between lesions and subsequent atrophy indicates that brain atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to atrophy remain undefined. NEUROLOGY 2002;59:1412-1420 MRI has fallen short of expectations in terms of providing a surrogate marker in MS. The lack of robust correlations between conventional MRI measures of pathology and clinical measures of disability has been attributed to various shortcomings of both MRI and clinical assessments. At least part of the discrepancy may be due to the use of MRI measurements that include both reversible and irreversible components of MS pathology. Conventional MRI lesion measurements also neglect to account for diffuse abnormalities in normal-appearing tissue in MS. One of the alternative MRI measures that have been proposed to monitor MS progression is the estimation of CNS atrophy. [1][2][3][4][5][6][7][8][9][10][11] In contrast to MRI-visible lesions, CNS atrophy is believed to reflect the net effect of severe and potentially irreversible processes such as demyelination and axonal loss. Measurement of the size of CNS structures may provide an indication of the total amount of tissue damage that has occurred up to a given point in time. New computer-assisted methods have been developed to precisely and reliably quantify tissue loss in MRI, [5][6][7][8][9][10][11][12][13] and atrophy has been shown to occur even in the early stages of MS.3,4,6-9 However, previous longitudinal studies in MS 3,[...

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Three dimensional MRI estimates of brain and spinal cord atrophy in multiple sclerosis

Cited by 164 publications

References 51 publications

Upper cervical cord area in early relapsing‐remitting multiple sclerosis: Cross‐sectional study of factors influencing cord size

Upper cervical cord area in early relapsing‐remitting multiple sclerosis: Cross‐sectional study of factors influencing cord size

Upper cervical spinal cord cross‐sectional area in relapsing remitting multiple sclerosis: Application of a new technique for measuring cross‐sectional area on magnetic resonance images

Spinal schwannoma mimicking lower limb SMA

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