(1)H-MRSI evidence for cortical gray matter pathology that is independent of cerebral white matter lesion load in patients with secondary progressive multiple sclerosis

We examined: (i) neuro-axonal disturbance (as indicated by (1)H-MRSI NA/Cr values) in the cortical grey matter (cGM) of 10 untreated patients with relapsing-remitting (RR) and 10 with secondary-progressive (SP) multiple sclerosis (MS), and (ii) the relationships between cGM-NA/Cr values and the degree of EDSS-measured clinical disability and cerebral white-matter (WM) lesion load (LL) in these patients. Whereas mean and median cGM-NA/Cr values in our RR group were similar to those in 18 age-matched normal controls (NC), large statistically-significant decreases (between 14.3% and 18.5%) were found in our SP group relative to both our RR and NC groups. When data from all patients was combined, we found: (i) a large negative correlation between EDSS scores and cGM-NA/Cr values (r=-0.55); and (ii) a larger negative correlation of cGM-NA/Cr values with cerebral T1-hypointese WM-LL (T1-LL, r=-0.73) than with cerebral T2-hyperintense-LL (T2-LL, r=-0.63). Importantly, (i) correlations of WM-LL with cGM-NA/Cr were larger in the RR group than in the SP group (T1-LL: r=-0.79 vs. -0.54; T2-LL: r=-0.63 vs. -0.51), and (ii) cerebral WM-LL values could not fully account for the extent of the decrease in mean cGM-NA/Cr that was seen in our SP group relative to our NC group. Our observations are consistent with the possibilities that: (i) in patients with RR-MS, (1)H-MRSI-measured cGM neuro-axonal disturbances are strongly related to the effects of axonal transection that are associated with cerebral WM lesions; and (ii) in patients with SP-MS, such cGM neuro-axonal disturbances are more severe and are associated with a more-widespread degenerative process (which probably includes a considerable degree of cortical demyelination).