Disability in multiple sclerosis is related to normal appearing brain tissue                 MTR histogram abnormalities

Traboulsee, Anthony; Dehmeshki, Jamshid; Peters, Kevin R.; Griffin, Colette; Brex, Peter; Silver, N. C.; Ciccarrelli, O; Chard, Declan; Barker, Gareth J.; Thompson, Alan J.; Miller, David H.

doi:10.1191/1352458503ms958oa

Cited by 80 publications

(45 citation statements)

References 25 publications

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“…To have a comprehensive picture of the patients studied, we also investigated the possible structural correlates of fMRI abnormalities in these patients, by assessing global brain damage, in terms of T 2 -visible lesions, brain volume, NAWM and GM involvement, and regional damage of WM fiber bundles variously related with the cognitive tasks investigated. In agreement with previous studies [Brass et al, 2004;Davie et al, 1999;De Stefano et al, 2006;Droogan et al, 1999;Falini et al, 1998;Filippi et al, 1996;Horsfield et al, 1996;Traboulsee et al, 2003], we found a relatively high proportion of T 2 -visible lesions in these patients and widespread abnormalities in the NABTs. Consistent with previous studies reporting the Stroop effect on fMRI activations in healthy people [Bench et al, 1993;Carter et al, 1995;Mitchell, 2005;Pardo et al, 1990], both groups of subjects showed the activation of several areas located in the frontal (PFC, ACC, and IFG) and parietal lobes (IPL and postcentral gyrus), and the cerebellum during the interference and facilitation conditions.…”

Section: Discussionsupporting

confidence: 93%

“…On the contrary, magnetic resonance imaging (MRI) has provided combersome and controversial results. In detail, the majority of the studies showed that the load of T 2 -visible lesions is similar between patients with BMS and those with other disease phenotypes, whereas the extent of normal-appearing brain tissue (NABT) damage was found to be less pronounced in patients with BMS than in other forms of the disease in some studies [Davie et al, 1999;De Stefano et al, 2006;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000, but not in others [Brass et al, 2004;Droogan et al, 1999;Horsfield et al, 1996;Traboulsee et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

“…Such an approach was driven by two considerations: (a) to investigate cortical functional changes in patients with a ''real'' benign course (i.e., with no locomotor and cognitive impairment), and (b) to study the underlying functional cortical correlates of brain-mediated clinical aspects (contrary to cognition, locomotor ability is indeed likely to be associated to both brain and spinal cord integrity). Differently from previous studies based on an ''overall'' assessment of brain damage [Brass et al, 2004;Davie et al, 1999;De Stefano et al, 2006;Droogan et al, 1999;Falini et al, 1998;Filippi et al, 1996Filippi et al, , 1999Filippi et al, , 2000Horsfield et al, 1996;Traboulsee et al, 2003], we investigated the structural correlates of fMRI abnormalities, by using diffusion tensor (DT) tractography, since it is likely that damage of ''strategic'' white matter (WM) fiber bundles of the brain might be more strictly linked to functional cortical changes than ''overall'' NABT damage. DT MRI provides quantitative data on water molecular motion, a marker of tissue structure and organization.…”

Section: Introductionmentioning

confidence: 99%

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Structural and functional MRI correlates of Stroop control in benign MS

Rocca

Valsasina

Ceccarelli

et al. 2007

Human Brain Mapping

113

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The objective of this study was to assess the functional and structural substrates of cognitive network changes in patients with benign multiple sclerosis (BMS), using an analysis of effective connectivity and MR tractography. Using a 3-Tesla scanner, we acquired dual-echo, diffusion tensor (DT) and functional MRI during the performance of the Stroop task from 15 BMS patients and 19 healthy controls. DT MRI tractography was used to calculate DT derived metrics from several white matter (WM) fiber bundles, thought to be involved in cognitive performance. DT MRI metrics from WM fiber bundles not directly related with cognitive performance were also derived. Effective connectivity analysis was performed using statistical parametric mapping. MS patients had significantly abnormal DT MRI metrics in all the structures analyzed. Compared with controls, MS patients had more significant activations of several areas of the cognitive network involved in Stroop performance, bilaterally. Compared with controls, BMS patients also had increased connectivity strengths between several cortical areas of the sensorimotor network and the right (R) inferior frontal gyrus and the R cerebellum, as well as decreased connectivity strengths with the anterior cingulate cortex. Coefficients of altered connectivity were moderately correlated with structural MRI metrics of tissue damage within intra-and inter-hemispheric cognitiverelated WM fiber bundles, while no correlations were found with the remaining fiber bundles studied, suggesting that functional cortical changes in patients with BMS might represent an adaptive response driven by damage of specific WM structures. Hum Brain Mapp 30:276-290, 2009. V V C 2007 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural and functional MRI correlates of Stroop control in benign MS

Rocca

Valsasina

Ceccarelli

et al. 2007

Human Brain Mapping

113

View full text Add to dashboard Cite

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“…Such measures are sensitive in depicting subtle abnormalities in NAWM and NAGM and convincing evidence has emerged that increasing abnormality in these tissues is associated with clinical progression. 99,100 However, these subtle MR changes are pathologically nonspecific and could potentially represent the effects of inflammation, gliosis, or axonal loss, all of which occur in NAWM. 4,101 Although they may be valuable for monitoring clinically relevant disease progression they should not be considered as specific markers of neurodegeneration.…”

Section: Other Measuresmentioning

confidence: 99%

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Miller¹

2004

Neurotherapeutics

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Summary:Multiple sclerosis (MS) is a chronic disease of the CNS that most commonly affects young adults. It is usually characterized in the early years by acute relapses followed by partial or complete remission; in later years progressive and irreversible disability develops. Because of the protracted and unpredictable clinical course, biological surrogate markers are much needed to make clinical trials of potential disease-modifying treatments more efficient. Magnetic resonance (MR) outcome measures are now widely used to monitor treatment outcome in MS trials. Areas of multifocal inflammation are detected with a high sensitivity as new areas of gadolinium enhancement and T2 abnormality, and these may be considered as surrogate markers for clinical relapses. However, progressive disability is not clearly related to inflammatory lesions but rather to a progressive and diffuse process with increasing neuroaxonal loss. MR surrogate measures for neuroaxonal loss include atrophy (tissue loss in brain and spinal cord), N-acetyl aspartate, and T1 hypointense lesions. Diffuse abnormality in normal appearing brain tissue may also be monitored using magnetization transfer ratio and other quantitative MR measures. For treatment trials of new agents aimed at preventing disability, measures of neuroaxonal damage should be acquired, especially atrophy, which occurs at all stages of MS and which can be quantified in a sensitive and reproducible manner. Because the MR surrogates for neuroaxonal loss are not yet validated as predicting future disability, definitive trials should continue to monitor an appropriate disability endpoint.

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“…The application of non-conventional magnetic resonance imaging (MRI) techniques, such as magnetization transfer imaging, magnetic resonance spectroscopy, and diffusion tensor imaging, has led to only modest achievements in linking imaging data with clinical measures of disease severity for neurologic disorders in general and for multiple sclerosis (MS) in particular. Alternately, OCT has been incorporated with increasing frequency as an exploratory outcome in treatment trials, observational studies, and even clinical practice in order to achieve a greater understanding of the relationship between changes in retinal structure and patient reported outcomes of visual function [33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

et al. 2011

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Summary: Axonal and neuronal degeneration are important features of multiple sclerosis (MS) and other neurologic disorders that affect the anterior visual pathway. Optical coherence tomography (OCT) is a non-invasive technique that allows imaging of the retinal nerve fiber layer (RNFL), a structure which is principally composed of ganglion cell axons that form the optic nerves, chiasm, and optic tracts. Since retinal axons are nonmyelinated until they penetrate the lamina cribrosa, the RNFL is an ideal structure (no other central nervous system tract has this unique arrangement) for visualizing the processes of neurodegeneration, neuroprotection and, potentially, even neuro-repair. OCT is capable of providing high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and permits objective analysis of the RNFL (axons) as well as ganglion cells and other neurons in the macula. In a systematic OCT examination of multiple sclerosis (MS) patients, RNFL thickness and macular volumes are reduced when compared to disease-free controls.Conspicuously, these changes, which signify disorganization of retinal structural architecture, occur over time even in the absence of a history of acute demyelinating optic neuritis. RNFL axonal loss in MS is most severe in those eyes with a corresponding reduction in low-contrast letter acuity (a sensitive vision test involving the perception of gray letters on a white background) and in those patients who exhibit the greatest magnitude of brain atrophy, as measured by validated magnetic resonance imaging techniques. These unique structure-function correlations make the anterior visual pathway an ideal model for investigating the effects of standard and novel therapies that target axonal and neuronal degeneration. We provide an overview of the physics of OCT, its unique properties as a non-invasive imaging technique, and its potential applications toward understanding mechanisms of brain tissue injury in MS, other optic neuropathies, and neurologic disorders.

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Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities

Cited by 80 publications

References 25 publications

Structural and functional MRI correlates of Stroop control in benign MS

Structural and functional MRI correlates of Stroop control in benign MS

Biomarkers and surrogate outcomes in neurodegenerative disease: Lessons from multiple sclerosis

Optical Coherence Tomography (OCT): Imaging the Visual Pathway as a Model for Neurodegeneration

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