Deep Gray Matter Involvement on Brain MRI Scans Is Associated with Clinical Progression in Multiple Sclerosis

Assessing Abnormal Iron Content in the Deep Gray Matter of Patients with Multiple Sclerosis versus Healthy Controls

“…However, it is still unknown whether iron deposition is a cause or a consequence of the inflammatory demyelinating aspect in MS pathology. On the other hand, the work by Neema et al 9 showed the presence of deep GM T2 hypointensities and suggested that excessive iron deposition is associated with the progression of disease. The plots in Fig 3 show that SPMS and RRMS are well-separated with a dominance of RRMS for younger ages and a dominance of SPMS for older ages.…”

“…It is just these regions that have increased iron content as seen with SWI and with conventional MR imaging. 4,9 The recent work of Haacke et al 18 suggests that the iron increase seen in MR imaging occurs at the confluence of the small draining veins out of the structures of interest such as the PUT, GP, and CN. Given the previous evidence that MS is a perivenular disease and that iron builds up in the venule wall, 12,30 it may be that these increases in iron represent venous endothelial damage.…”

“…1 Thus, iron from any of the above-mentioned sources could lead to inflammation and a further buildup of iron, causing the system to be self-sustainable. 17 When iron is present, the result is a hypointense signal intensity on T2-or T2*-weighted images and a change in the phase for SWI, 9,18,19 which makes it possible to quantify iron changes in vivo. Different results have been reported in studying iron involvement in MS.…”

“…6,7 However, whether the starting point is in the GM or WM is still unclear. [7][8][9] Currently, there is an increased interest in studying how GM is affected 6,10,11 and particularly deep GM involvement in MS when iron deposition has been observed. 6,12,13 Brain iron accumulation in neurodegenerative diseases, including MS, is not new and has been shown histologically in the past.…”

In vivo iron quantification in collagenase‐induced microbleeds in rat brain

“…Thus, BMB represents a source of pathologic iron in the brain that is potentially cytotoxic (e.g., free radical production through the Fenton reaction). Oxidative damage, iron accumulation, and/or changes in iron metabolism have been implicated in neurodegenerative and cerebrovascular diseases (28)(29)(30)(31)(32)(33)(34)(35). In addition, because iron is deposited at the site of a BMB in proportion to the amount of extravasated blood, iron content in BMB can be considered a marker for the severity of underlying vessel disease (2).…”