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Brain metabolic changes suggestive of axonal damage in radiologically isolated syndrome
Maria Laura Stromillo1, Antonio Giorgio, Francesca Rossi
1Department of Neurological and Behavioral Sciences, University of Siena, Siena, Italy.
Background:
The MRI incidental finding in asymptomatic subjects of brain white matter (WM) changes meeting the Barkhof criteria for the diagnosis of multiple sclerosis (MS) has been recently characterized as the radiologically isolated syndrome (RIS). This entity needs to be more specifically defined to allow risk stratification of these subjects. We used brain proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess metabolic changes in an RIS population.
Methods:
Twenty-three RIS subjects who were classified according to the Okuda Criteria underwent 1H-MRSI examination with a central brain (CB) volume of interest (VOI) to measure levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr) in the whole CB-VOI, in lesional/perilesional and normal-appearing WM regions, and in the cortical gray matter (CGM). The 1H-MRSI data were compared with those of 20 demographically matched healthy controls (HC).
Results:
NAA/Cr levels were significantly lower in RIS than in HC in all regions (p < 0.005 for all). No differences in Cho/Cr levels were found in either brain region. A single-subject analysis showed that NAA/Cr levels were at least 2 SDs below the HC mean in the 44% of RIS in the normal-appearing WM and in the 61% of RIS in the CGM.
Conclusion:
Decreased brain NAA/Cr levels in a group of RIS subjects indicates that brain metabolic abnormalities suggestive of axonal damage can be significant even at this early disease stage. This information could be useful for stratifying RIS individuals with a high risk of progression to MS.
Insights
Radiologically isolated syndrome (RIS) patients show decreased brain N-acetylaspartate (NAA) levels, indicating axonal damage. This finding aids in identifying individuals at high risk for multiple sclerosis (MS) progression.
Area of Science:
- Neuroimaging
- Neurology
- Biochemistry
Background:
- Radiologically isolated syndrome (RIS) involves white matter (WM) changes on MRI in asymptomatic individuals, meeting criteria for multiple sclerosis (MS).
- RIS requires further definition for accurate risk stratification of affected subjects.
- Brain proton magnetic resonance spectroscopic imaging (1H-MRSI) was employed to investigate metabolic alterations in RIS.
Purpose of the Study:
- To assess metabolic changes in the brain of individuals with radiologically isolated syndrome (RIS) using 1H-MRSI.
- To compare metabolic profiles of RIS subjects with healthy controls (HC).
Main Methods:
- Twenty-three RIS subjects (Okuda Criteria) and 20 healthy controls (HC) underwent 1H-MRSI.
- N-acetylaspartate (NAA) and choline (Cho) levels, normalized to creatine (Cr), were measured in various brain regions (whole central brain (CB)-VOI, lesional/perilesional WM, normal-appearing WM, cortical gray matter (CGM)).
Main Results:
- RIS subjects exhibited significantly lower NAA/Cr levels compared to HC across all measured brain regions (p < 0.005).
- No significant differences in Cho/Cr levels were observed between RIS and HC groups.
- Individual analysis revealed that 44% of RIS subjects had NAA/Cr levels at least 2 standard deviations below the HC mean in normal-appearing WM, and 61% in CGM.
Conclusions:
- Reduced NAA/Cr levels in RIS subjects suggest significant metabolic abnormalities indicative of axonal damage, even in early stages.
- These metabolic findings can assist in stratifying RIS individuals based on their risk of progressing to MS.
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