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Gadolinium enhanced magnetic resonance imaging detects focal blood-brain barrier breakdown in new inflammatory multiple sclerosis lesions, but such lesions do not correlate with disease progression. To explore whether the latter might relate to subtle but widespread blood-brain barrier (BBB) breakdown with low grade inflammation mediating tissue damage, quantitative techniques were used to detect subtle gadolinium enhancement within otherwise normal-appearing white matter and within lesions not showing visible enhancement. T1-weighted imaging was performed prior to and at 5, 20 and 40 min following injection of 0.3 mmol/kg gadopentate dimeglumine in 33 patients with multiple sclerosis and five healthy control subjects. In healthy controls, a significant increase in white matter signal 5 min following contrast injection was observed (1.8%, P < 0.0005); the signal returned to baseline values by 20 min. In multiple sclerosis patients, a non-significant trend was noted for signal to remain elevated in normal-appearing white matter at the 20 and 40 min post-contrast time points; this was most apparent in primary progressive multiple sclerosis. Significant increases in signal intensity were noted at all time points post contrast in apparent non-enhancing lesions. The transient post contrast signal increase in controls is likely due to intravascular gadopentate dimeglumine. The persistent increases in signal intensity in non-enhancing lesions suggest more widespread abnormalities in BBB than is visually apparent, but substantiation of BBB leakage in normal appearing white matter will require further study using more sensitive methods.
Silver et al. (Sun,) studied this question.