Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis

Davies, G.; Ramió-Torrentà, Lluı́s; Hadjiprocopis, Andreas; Chard, Declan; Griffin, Colette; Rashid, Waqar; Barker, Gareth J.; Kapoor, Raju; Thompson, Alan J.; Miller, David H.

doi:10.1136/jnnp.2003.021915

Cited by 65 publications

(79 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This study extends the recent observation that NAWM and NAGM MTR are both abnormal in clinically early RRMS [8], by showing that the MTR abnormalities in both regions progressively increase over two years of follow-up. In addition, backward extrapolation of the rates of change -assuming linearity -suggests that NAWM MTR abnormality is present prior to the onset of symptoms and precedes NAGM MTR abnormality.…”

Section: ■ Mtr Findings In Nawm and Nagmsupporting

confidence: 68%

“…Quantitative MR measures are being obtained at regular intervals to investigate lesions, NAWM and NAGM. We have recently studied the entry MTR characteristics of this patient cohort and reported a significant decrease in both NAWM and NAGM MTR compared with healthy controls [8]. In the present study we investigated serial NAWM and NAGM MTR changes in patients followed with yearly scans for two years in order to address the following questions: (i) are longitudinal changes occurring in NAWM, NAGM or in both regions?…”

mentioning

confidence: 97%

See 1 more Smart Citation

Increasing normal–appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing–remitting multiple sclerosis

et al. 2005

View full text Add to dashboard Cite

Abnormalities within normal-appearing grey and white matter (NAGM and NAWM) occur early in the clinical course of multiple sclerosis (MS) and can be detected in-vivo using the magnetisation transfer ratio (MTR). To better characterize the rates of change in both tissues and to ascertain when such changes begin, we serially studied a cohort of minimally disabled, early relapsing-remitting MS patients, using NAGM and NAWM MTR histograms. Twenty-three patients with clinically definite early relapsing-remitting MS (mean disease duration at baseline 1.9 years), and 19 healthy controls were studied. A magnetisation transfer imaging sequence was acquired yearly for two years. Twenty-one patients and 10 controls completed followup. NAWM and NAGM MTR histograms were derived and mean MTR calculated. A hierarchical regression analysis, adjusting for brain parenchymal fraction,was used to assess MTR change over time. MS NAWM and NAGM MTR were significantly reduced in comparison with controls at baseline and, in patients, both measures decreased further during follow-up: (-0.10 pu/year, p=0.001 and -0.18 pu/year, p<0.001 respectively). The rate of MTR decrease was significantly greater in NAGM than NAWM (p=0.004). Under the assumption that such changes are linear, backward extrapolation of the observed rates of change suggested that NAWM abnormality began before symptom onset. We conclude that increasing MTR abnormalities in NAWM and NAGM are observed early in the course of relapsing-remitting MS. It is now important to investigate whether these measures are predictive of future disability, and consequently, whether MTR could be used as a surrogate marker in therapeutic trials.

show abstract

Section: ■ Mtr Findings In Nawm and Nagmsupporting

confidence: 68%

mentioning

confidence: 97%

Increasing normal–appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing–remitting multiple sclerosis

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Recent magnetic resonance imaging (MRI) studies have shown that although detectable in all CDMS forms, GM damage seems to be more frequent and prominent in patients with secondary progressive MS [5] and primary progressive MS [5][6][7], compared to patients with less-advanced or less-disabling forms of disease [8]. However, GM involvement has also been found in patients with relapsing-remitting (RR) MS in studies using parametric MR-based methods, such as T 1 relaxivity, magnetic resonance spectroscopy (MRS), cortical atrophy measurements [9][10][11][12][13][14][15] or magnetization transfer ratio (MTR) imaging [6]. Although MTR appears particularly sensitive in detecting early GM abnormalities [8,16,17], it suffers from a lack of specificity to characterize the physiopathological processes implied in such GM damage.…”

Section: Introductionmentioning

confidence: 98%

Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MS

et al. 2007

View full text Add to dashboard Cite

Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) was used to study metabolic abnormalities inside the gray matter (GM) during or distant to white matter (WM) inflammatory processes reflected by T(1) gadolinium-enhancing lesions in patients at the very early stage of multiple sclerosis (MS). The spectroscopic examination was performed in the axial plane using a home-designed acquisition-weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms). Bilateral thalami and the medial occipital cortex were explored in 35 patients (15 with and 20 without T(1)-Gd enhancing lesions) with clinically isolated syndrome suggestive of MS and in 30 controls. The mean duration since the first presenting symptom was 9.1 (+/-6.7) months. The two groups of patients (with or without T(1) Gd-enhancing lesions) did not differ in terms of time elapsed since the first clinical onset and T(2) lesion load. The spatial contamination of surrounding WM tissues was obtained in each GM region by determining the tissue component in the ROI from GM and WM probability maps smoothed with the point spread function of the MRSI acquisition. Contribution of WM signal was important (60%) inside thalami while the region centered on the medial occipital cortex was well representative of GM metabolism (>70%). Comparisons of relative metabolite levels (ratios of each metabolite over the sum of all metabolites) between all patients and controls showed significant decrease in relative N-acetyl aspartate (NAA) levels, increase in relative choline-containing compounds (Cho) levels and no change in relative creatine/phosphocreatine levels inside the three ROIs. Decrease in relative NAA levels and increase in relative Cho levels were found in patients with inflammatory activity, while no metabolic alterations were present in patients without T(1) Gd-enhancing lesions. These results suggest that abnormalities in GM metabolism observed in patients at the very early stage of MS are mainly related to neuronal dysfunction occurring during acute inflammatory processes.

show abstract

“…A number of diffusion-weighted or tensor, 11,46 magnetization transfer, [46][47][48][49] and magnetic resonance spectroscopy 7,50,51 imaging studies have investigated the extent of thalamic damage in patients with MS with various disease types (table). All suggested that there may be a common mechanism for WM axonal loss and thalamic neuronal injury related to thalamocortical pathways.…”

Section: Neuroimaging Characteristics Of Thalamicmentioning

confidence: 99%

The thalamus and multiple sclerosis

Minagar¹,

Barnett²,

Benedict³

et al. 2013

Neurology

303

222

View full text Add to dashboard Cite

The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. Neurology â 2013;80:210-219 GLOSSARY CIS 5 clinically isolated inflammatory demyelinating syndrome; DIR 5 double inversion recovery; DTI 5 diffusion tensor imaging; EDSS 5 Expanded Disability Status Scale; GM 5 gray matter; LGN 5 lateral geniculate nucleus; MS 5 multiple sclerosis; NAGM 5 normal-appearing gray matter; NAWM 5 normal-appearing white matter; SWI 5 susceptibility-weighted imaging; WM 5 white matter.Multiple sclerosis (MS) is a progressive inflammatory and degenerative disease of the human CNS that leads to demyelination and neuronal/axonal loss. Both the etiology and cure for MS remain elusive, and for many years scientific research into the pathogenesis of MS has heavily focused on a disease principally affecting CNS white matter (WM).Notwithstanding the traditional focus upon WM as the predominant target of the disease mechanisms in MS, recent findings, which indicate significant gray matter (GM) involvement, are an important and substantial refinement in our understanding of the pathobiological underpinnings of the disease process in MS, of particular relevance to cognitive decline as well as overall disease worsening.1,2 Neuropathologic data implicate significant cortical demyelination and neuro-axonal and synaptic loss in both the early and late phases of the disease process.2-5 Both cortical 3 and subcortical demyelination are observed during the course of MS, targeting a landscape of GM-rich struct...

show abstract

Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis

Cited by 65 publications

References 28 publications

Increasing normal–appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing–remitting multiple sclerosis

Increasing normal–appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing–remitting multiple sclerosis

Relationships between gray matter metabolic abnormalities and white matter inflammation in patients at the very early stage of MS

The thalamus and multiple sclerosis

Contact Info

Product

Resources

About