Localized 1 H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis

Sarchielli, Paola; Presciutti, O.; Tarducci, R.; Gobbi, G.; Alberti, Andrea; Pelliccioli, G.P.; Chiarini, P; Gallai, Virgilio

doi:10.1007/s00415-002-0758-5

Cited by 76 publications

(52 citation statements)

References 44 publications

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“…It is note worthy that the two groups of CIS 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. Few MRS studies have reported reduction in NAA inside GM in early RRMS patients [13,18], while other studies reported no differences [19][20][21]. The same contradictory results were shown in patients at the very early stage of MS, with no NAA changes in the WM observed in two studies [37,38] and a widespread NAA decrease observed in another study using non-localized MRS technique [39].…”

Section: Discussion J Technical Aspectsmentioning

confidence: 41%

“…Better knowledge of the characteristics of GM changes at the early stage of MS may offer useful new perspectives on the pathogenesis of GM injury in MS, and in this regard -MR spectroscopic imaging (MRSI) may be of value. Few MRS studies have been performed in early RRMS patients [13,[18][19][20][21] and have provided inconsistent results that may be related to the existence of neuronal dysfunction related to acute inflammation without any significant irreversible neuronal loss.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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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.

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Section: Discussion J Technical Aspectsmentioning

confidence: 41%

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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“…In people with multiple sclerosis (MS), changes in metabolite concentrations have been observed using 1 H-MRS in lesions, normal appearing white matter (NAWM) and cortical grey matter (CGM). A metabolite of particular interest has been N-acetyl-aspartate (NAA), which is found almost exclusively within neurons and neuronal processes in the mature brain in vivo [5], and which has been found to be reduced in lesions [1,13,28], NAWM [8,16,22,35], and CGM [8,25,36] in subjects with MS. It has been suggested that such decreases may reflect both irreversible axonal loss [4] and reversible structural or metabolic injury [12].…”

Section: Introductionmentioning

confidence: 99%

Metabolite changes in early relapsing–remitting multiple sclerosis

Tiberio

Chard²,

et al. 2005

J Neurol

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Previous in vivo proton magnetic resonance spectroscopic imaging ((1)H-MRSI) studies have found reduced levels of N-acetyl-aspartate (NAA) in multiple sclerosis (MS) lesions, the surrounding normal-appearing white matter (NAWM) and cortical grey matter (CGM), suggesting neuronal and axonal dysfunction and loss. Other metabolites, such as myoinositol (Ins), creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx), can also be quantified by (1)H-MRSI, and studies have indicated that concentrations of these metabolites may also be altered in MS. Relatively little is known about the time course of such metabolite changes. This preliminary study aimed to characterise changes in total NAA (tNAA, the sum of NAA and N-acetyl-aspartyl-glutamate), Cr, Cho, Ins and Glx concentrations in NAWM and in CGM, and their relationship with clinical outcome, in subjects with clinically early relapsing-remitting MS (RRMS). Twenty RRMS subjects and 10 healthy control subjects underwent (1)H-MRSI examinations yearly for two years. Using the LCModel, tNAA, Cr, Cho, Ins and Glx concentrations were estimated both in NAWM and CGM. At baseline, the concentration of tNAA was significantly reduced in the NAWM of the MS patients compared to the control group (-7%, p = 0.003), as well as in the CGM (-8.7%, p = 0.009). NAWM tNAA concentrations tended to recover from baseline, but otherwise tissue metabolite profiles did not significantly change in the MS subjects, or relatively between MS and healthy control subjects. While neuronal and axonal damage is apparent from the early clinical stages of MS, this study suggests that initially it may be partly reversible. Compared with other MR imaging measures, serial (1)H-MRSI may be relatively less sensitive to progressive pathological tissue changes in early RRMS.

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“…In the initial disease presentation (RRMS), there seems no (or slight) reduction in NAA levels, however, a prominent reduction in NAA levels can be captured during progressive MS [47,49]. In accordance with progressive MS, changes in NAA levels within cortical grey matter were correlated with EDSS, auditive selective attention and cognitive performance [48,50,51].…”

Section: Current Imaging Techniquesmentioning

confidence: 72%

“…However, these imaging techniques have also been used to study cortical adaptive functions in patients with RRMS, SPMS and PPMS [47,48]. In the initial disease presentation (RRMS), there seems no (or slight) reduction in NAA levels, however, a prominent reduction in NAA levels can be captured during progressive MS [47,49].…”

Section: Current Imaging Techniquesmentioning

confidence: 99%

Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?

Lee

Taghian

Petratos

2014

Acta Neuropathol Commun

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Axonal degeneration is a major determinant of permanent neurological impairment during multiple sclerosis (MS). Due to the variable course of clinical disease and the heterogeneity of MS lesions, the mechanisms governing axonal degeneration may differ between disease stages. While the etiology of MS remains elusive, there now exist potential prognostic biomarkers that can predict the conversion to clinically definite MS. Specialized imaging techniques identifying axonal injury and drop-out are becoming established in clinical practice as a predictive measure of MS progression, such as optical coherence tomography (OCT) or diffusion tensor imaging (DTI). However, these imaging techniques are still being debated as predictive biomarkers since controversy surrounds their lesion-specific association with expanded disability status scale (EDSS). A more promising diagnostic measure of axonal degeneration has been argued for the detection of reduced N-acetyl aspartate (NAA) and Creatine ratios via magnetic resonance spectroscopic (MRS) imaging, but again fail with its specificity for predicting actual axonal degeneration. Greater accuracy of predictive biomarkers is therefore warranted and may include CSF neurofilament light chain (NF-L) and neurofilament heavy chain (NF-H) levels, for progressive MS. Furthermore, defining the molecular mechanisms that occur during the neurodegenerative changes in the various subgroups of MS may in fact prove vital for the future development of efficacious neuroprotective therapies. The clinical translation of a combined Na + and Ca 2+ channel blocker may lead to the establishment of a bona fide neuroprotective agent for the treatment of progressive MS. However, more specific therapeutic targets to limit axonal damage in MS need investigation and may include such integral axonal proteins such as the collapsin response mediator protein-2 (CRMP-2), a molecule which upon post-translational modification may propagate axonal degeneration in MS. In this review, we discuss the current clinical determinants of axonal damage in MS and consider the cellular and molecular mechanisms that may initiate these neurodegenerative changes. In particular we highlight the therapeutic candidates that may formulate novel therapeutic strategies to limit axonal degeneration and EDSS during progressive MS.

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Localized 1 H magnetic resonance spectroscopy in mainly cortical gray matter of patients with multiple sclerosis

Cited by 76 publications

References 44 publications

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

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

Metabolite changes in early relapsing–remitting multiple sclerosis

Axonal degeneration in multiple sclerosis: can we predict and prevent permanent disability?

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