Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS

Rudick, Richard A.; Lee, Jar Chi; Nakamura, Kunio; Fisher, Elizabeth

doi:10.1016/j.jns.2008.11.018

Cited by 119 publications

(114 citation statements)

References 35 publications

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“…In the cerebral cortex of chronic MS patients, axonal and neuronal degeneration occurs in the absence of parenchymal inflammatory infiltrating lymphocytes (7,62), and it strongly correlates with clinical disability (63,64). However, the mechanisms of neuronal loss in MS are not yet defined, although a possible role is played by a "dying back" mechanism consisting of a retrograde degeneration of neuronal soma following axonal injury (8,46,65).…”

Section: Discussionmentioning

confidence: 99%

Granule-Derived Granzyme B Mediates the Vulnerability of Human Neurons to T Cell-Induced Neurotoxicity

Haile

Simmen

Pasichnyk

et al. 2011

The Journal of Immunology

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Multiple sclerosis (MS) is considered an autoimmune disease of the CNS and is characterized by inflammatory cells infiltrating the CNS and inducing demyelination, axonal loss, and neuronal death. Recent evidence strongly suggests that axonal and neuronal degeneration underlie the progression of permanent disability in MS. In this study, we report that human neurons are selectively susceptible to the serine-protease granzyme B (GrB) isolated from cytotoxic T cell granules. In vitro, purified human GrB induced neuronal death to the same extent as the whole activated T cell population. On the contrary, activated T cells isolated from GrB knockout mice failed to induce neuronal injury. We found that following internalization through various parts of neurons, GrB accumulated in the neuronal soma. Within the cell body, GrB diffused out of endosomes possibly through a perforin-independent mechanism and induced subsequent activation of caspases and cleavage of α-tubulin. Inhibition of caspase-3, a well-known substrate for GrB, significantly reduced GrB-mediated neurotoxicity. We demonstrated that treatment of neurons with mannose-6-phosphate prevented GrB entry and inhibited GrB-mediated neuronal death, suggesting mannose-6-phosphate receptor-dependent endocytosis. Together, our data unveil a novel mechanism by which GrB induces selective neuronal injury and suggest potential new targets for the treatment of inflammatory-mediated neurodegeneration in diseases such as MS.

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Section: Discussionmentioning

confidence: 99%

Granule-Derived Granzyme B Mediates the Vulnerability of Human Neurons to T Cell-Induced Neurotoxicity

Haile

Simmen

Pasichnyk

et al. 2011

The Journal of Immunology

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“…The differences in the acquisition protocol may cause the observed differences in the lesion intensity profile compared with previous works. 8,10 Our study shows that such an intensity profile introduces variations in GM and WM tissue distributions.…”

Section: Discussionmentioning

confidence: 70%

“…On images with a high lesion load, the observed differences in GM volume outside lesion regions reach values that are equivalent to the yearly expected GM atrophy. 9,10 Following these assumptions, SPM8, FANTASM, and SPM5 are the methods with the lowest reported incidence of WML on brain tissue volume measurements, especially on images with a high lesion load. The present study is not free of limitations.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, various studies have also analyzed the correlation between brain tissue atrophy and MS disability progression. 9,10 These studies showed a brain atrophy decrease rate between 0.3% and 0.5% of change in brain parenchyma per year in patients with MS, 9,10 with a decrease in GM and WM volume of up to 0.4% and 0.2% per year, respectively. 10 This statement along…”

mentioning

confidence: 95%

“…In contrast to other similar studies, [4][5][6] our analysis extended the number of segmentation methods involved, offering a comparative evaluation of the effects of WMLs on the volume measurements of 6 segmentation methods. Furthermore, given the reported correlation between brain atrophy rates and disability progression, 9,10 it can be clinically relevant for the MS community to extend the analysis of the effects of simulated WML to real data of patients with MS; hence, our analysis was focused exclusively on data from the T1-weighted images from patients with clinically confirmed MS.…”

mentioning

confidence: 99%

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Evaluating the Effects of White Matter Multiple Sclerosis Lesions on the Volume Estimation of 6 Brain Tissue Segmentation Methods

Valverde

Oliver

Diéz

et al. 2015

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:The accuracy of automatic tissue segmentation methods can be affected by the presence of hypointense white matter lesions during the tissue segmentation process. Our aim was to evaluate the impact of MS white matter lesions on the brain tissue measurements of 6 well-known segmentation techniques. These include straightforward techniques such as Artificial Neural Network and fuzzy C-means as well as more advanced techniques such as the Fuzzy And Noise Tolerant Adaptive Segmentation Method, fMRI of the Brain Automated Segmentation Tool, SPM5, and SPM8.

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Macular Volume Determined by Optical Coherence Tomography as a Measure of Neuronal Loss in Multiple Sclerosis

Burkholder

Osborne²,

Loguidice³

et al. 2009

Arch Neurol

177

128

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Background: Inner (area adjacent to the fovea) and outer regions of the macula differ with respect to relative thicknesses of the ganglion cell layer (neurons) vs retinal nerve fiber layer (RNFL; axons). Objective: To determine how inner vs outer macular volumes relate to peripapillary RNFL thickness and visual function in multiple sclerosis (MS) and to examine how these patterns differ among eyes with vs without a history of acute optic neuritis (ON). Design: Study using cross-sectional optical coherence tomography. Setting: Three academic tertiary care MS centers. Participants: Patients with MS, diagnosed by standard criteria, and disease-free control participants. Main Outcome Measures: Optical coherence tomography was used to measure macular volumes and RNFL thickness. Visual function was assessed using lowcontrast letter acuity and high-contrast visual acuity (Early Treatment Diabetic Retinopathy Study charts). Results: Among eyes of patients with MS (n=1058 eyes of 530 patients), reduced macular volumes were associated with peripapillary RNFL thinning; 10-µm differences in RNFL thickness (9.6% of thickness in control participants without disease) corresponded to 0.20mm 3 reductions in total macular volume (2.9% of vol

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Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS

Cited by 119 publications

References 35 publications

Granule-Derived Granzyme B Mediates the Vulnerability of Human Neurons to T Cell-Induced Neurotoxicity

Granule-Derived Granzyme B Mediates the Vulnerability of Human Neurons to T Cell-Induced Neurotoxicity

Evaluating the Effects of White Matter Multiple Sclerosis Lesions on the Volume Estimation of 6 Brain Tissue Segmentation Methods

Macular Volume Determined by Optical Coherence Tomography as a Measure of Neuronal Loss in Multiple Sclerosis

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