Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)‐induced experimental demyelinating lesion model

Degaonkar, Mahaveer; Khubchandhani, M.; Dhawan, Jyoti; Jayasundar, Rama; Jagannathan, Naranamangalam R.

doi:10.1002/nbm.771

Cited by 31 publications

(20 citation statements)

References 32 publications

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“…While this result should be interpreted prudently (there was no longitudinal relative change in the MS subjects compared with controls), it would appear consistent with previous work noting recovery in lesion NAA concentrations [1,13,15]. This could be explained by transient axonal metabolic dysfunction, perhaps mirroring demyelination and remyelination [19], associated with sub-lethal axonal injury. Resolution of inflammation-associated cerebral oedema may also contribute towards this finding, particularly in the NAWM [24,30].…”

Section: Discussionsupporting

confidence: 83%

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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Section: Discussionsupporting

confidence: 83%

Metabolite changes in early relapsing–remitting multiple sclerosis

Tiberio

Chard²,

et al. 2005

J Neurol

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“…The finding that in the normal appearing white matter of ppMS patients and in controls the Cho level as well as the NAA level relate similarly to the ADC and the FA and thus to the presence of neuronal structures suggests a constructive role of Cho in the preservation of neuronal structures in ppMS. This appears to be at odds with previous reports in which Cho increases observed in a demyelinating lesion model [21] and in normal appearing white matter of MS patients [22] were associated with demyelination and the subsequent breakdown of neurons.…”

Section: Discussioncontrasting

confidence: 79%

Analysis of the human brain in primary progressive multiple sclerosis with mapping of the spatial distributions using 1H MR spectroscopy and diffusion tensor imaging

et al. 2005

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Primary progressive multiple sclerosis (ppMS; n=4) patients and controls (n=4) were examined by 1H magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in order to map choline (Cho), creatine and N-acetylaspartate (NAA), the fractional anisotropy (FA) and the apparent diffusion constant (ADC). After chemical shift imaging (point-resolved spectroscopy, repetition time/echo time 1,500 ms/135 ms) of a supraventricular volume of interest of 8x8x2 cm3 (64 voxels) MRS peak areas were matched to the results of DTI for the corresponding volume elements. Mean FA and NAA values were reduced in the ppMS patients (P<0.01, both) and the ADC increased (P<0.02). The spatial distribution of NAA showed strong correlation to ADC in both ppMS patients and controls (r =-0.74 and r= -0.70; P<0.00001, both), and weaker correlations to FA (r=0.49 and r=0.41; P<0.00001, all). FA and ADC also correlated significantly with Cho in patients and controls (P<0.00001, all). The relationship of Cho and NAA to the ADC and the FA and thus to the content of neuronal structures suggests that these metabolite signals essentially originate from axons (NAA) and the myelin sheath (Cho). This is of interest in view of previous reports in which Cho increases were associated with demyelination and the subsequent breakdown of neurons.

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“…12 The role of MR spectroscopy in the diagnostic work-up of patients with HCC remains to be fully appreciated. There is evidence, however, that the MR spectroscopy pattern grossly correlates with the stage of the disease, in that young patients showed features of ongoing myelin breakdown with elevated mIns/Cr and Cho/Cr as well as increased lipid resonances, which are known to occur during active demyelination phases, 13 whereas older patients showed alterations that may reflect a condition of neuroaxonal damage and gliosis consistent with the burnt-out stage of the disease.…”

Section: Resultsmentioning

confidence: 99%