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Updated: Aug 19, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Immunological time-course of gadolinium-enhancing MRI lesions in patients with multiple sclerosis
G Giovannoni1, N C Silver, C D Good
1National Hospital for Neurology and Neurosurgery and Institute of Neurology, London, UK. G.Giovannoni@ion.ucl.ac.uk
Abstract:
In multiple sclerosis (MS) gadolinium (Gd)-enhanced MRI activity correlates weakly with immunological markers of disease activity. We, therefore, tested the hypothesis that the poor correlation could be partly explained by the temporal profile of Gd enhancement. We measured urinary neopterin:creatinine ratios (neopt.:creat.(urine)) in 5 patients with active MS undergoing weekly Gd-enhanced MRI studies of the brain. The neopt.:creat.(urine) associated with new Gd-enhancing lesions (<8 days) was significantly higher than the ratio not associated with new Gd-enhancing lesions [mean(geometric) neopt.: creat.(urine) = 413 micromol/mol (range = 207-521) vs. 250 micromol/mol (range = 132-492), p = 0.03]. Pro-inflammatory immunological markers, which are probably produced early on in the life cycle of an active MS lesion, should preferably be correlated with newly enhancing lesions (<8 days). Failure to do this may explain the poor and unpredictable correlations between immunological markers and Gd-enhanced MRI activity, which cannot be accurately aged in cross-sectional and serial monthly MRI studies.
Insights
In multiple sclerosis (MS), correlating MRI activity with immune markers is challenging. This study suggests that the timing of gadolinium enhancement in MS lesions may explain the weak correlation with immune markers.
Area of Science:
- Neuroimmunology
- Radiology
- Biomarker Research
Background:
- Gadolinium-enhanced MRI activity in multiple sclerosis (MS) shows weak correlation with immunological markers of disease activity.
- This discrepancy may stem from the temporal dynamics of gadolinium enhancement within MS lesions.
Purpose of the Study:
- To investigate if the temporal profile of gadolinium enhancement influences the correlation between MRI activity and immunological markers in MS.
- To determine if early-stage inflammatory markers correlate better with newly enhancing MS lesions.
Main Methods:
- Weekly brain MRI with gadolinium enhancement was performed on 5 patients with active MS.
- Urinary neopterin:creatinine ratios (neopt.:creat.(urine)), a marker of immune system activation, were measured.
- Correlation analysis was performed between neopt.:creat.(urine) levels and the presence/age of Gd-enhancing lesions.
Main Results:
- Urinary neopterin:creatinine ratios were significantly higher for newly enhancing lesions (<8 days) compared to lesions not associated with recent enhancement (mean 413 vs. 250 micromol/mol, p=0.03).
- Pro-inflammatory markers are likely produced early in the MS lesion lifecycle.
Conclusions:
- The temporal profile of gadolinium enhancement is crucial for understanding the relationship between MRI activity and immunological markers in MS.
- Correlating immunological markers with newly enhancing lesions (<8 days) may improve the predictability of MS disease activity.
- Failure to account for lesion age in MRI studies contributes to poor correlations with immunological markers.
