Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI

Abstract

To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (–3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity.

Radiologically isolated syndrome should be treated with disease-modifying therapy – No

“…The first point refers to whether the benefit–risk ratios of current DMT would actually be favorable among RIS patients. Emerging data suggest that in RIS, the clinical and pathological damage of magnetic resonance imaging (MRI) lesions might be compensated by more efficient reparative mechanisms, 2–5 which is in accordance with current data showing that almost 7 out of 10 RIS patients do not develop clinical relapses within a 5-year period of follow-up. 1 Furthermore, it is not yet known whether most RIS patients will ever develop clinical relapses.…”

“…Recent MS studies provide evidence that treatment effects on new T2 MRI lesions can predict long-term effects on relapses. 7,8 However, given the aforementioned potential capacity of RIS to repair, 2–5 the validity of MRI metrics (new T2 lesions) as surrogates for clinical outcomes in RIS clinical trials is not established.…”

Quantifying the Metabolic Signature of Multiple Sclerosis by in vivo Proton Magnetic Resonance Spectroscopy: Current Challenges and Future Outlook in the Translation From Proton Signal to Diagnostic Biomarker

“…Finally, some in vivo proton spectroscopy work has examined the metabolic signatures of clinically isolated syndrome (CIS) (67, 180–183) and radiologically isolated syndrome (RIS) (184, 185), including to predict conversion of individuals with these often prodromal syndromes to clinically definite multiple sclerosis. A comprehensive or detailed treatment of the existing literature thereof stands outside the scope of the present review, which centers instead on studies of the disease phenotypes defined above.…”

Quantitative spinal cord MRI in radiologically isolated syndrome

“…Our findings of a lack of atrophy and minimal microstructural change in the SC in RIS based on quantitative MRI metrics are in contrast to previous studies in clinically definite MS, in which SC quantitative MRI measures, including both DTI- and MTI-derived metrics, as well as SC-CSA, GM, and WM were found to be significantly altered in both relapsing-remitting and progressive subtypes of MS. This suggests that there is clear microstructural damage in both early and late stages of MS. 11 , 12 , 22 – 27 Theoretically, a decrease in FA may indicate loss of axonal integrity, whereas an increase in λ ⊥ and decrease in MTR is suggestive of inflammation and/or demyelination. The one quantitative SC-MRI measure that showed a trend toward a difference in RIS vs HCs was that MTR was lower in RIS, suggesting that inflammation and demyelination may be one of the only microstructural changes detectable in the very earliest stage of MS, which is in keeping with known pathologic mechanisms in MS. 28 In addition, this finding suggests that inflammation and demyelination are the underlying pathologic substrates of visible lesions in the SC in RIS.…”