1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS

To compare brain metabolite levels in patients with primary progressive (PP) and relapsing remitting (RR) MS and controls. Hypotheses: (1) creatine (Cr), a putative marker of gliosis, is elevated and N-acetylospartate (NAA), a putative marker of axonal density and functional integrity, is reduced in PPMS lesions and normal appearing white matter (NAWM) compared to control white matter; (2) The pattern of metobolite change in PPMS is different than in RRMS. Methods: MRI and proton magnetic resonance spectroscopic imaging (H-1 MRSI) were collected from 15 PPMS patients, 13 RRMS patients, and 20 controls. Results: Cr was increased in PPMS NAWM compared to controls (P=0.035), and compared to RRMS NAWM (P=0.038). Cr was increased in focal MRI lesions from PPMS compared to lesions from RRMS (P=0.044) and compared to control white matter (P=0.041). NAA was similarly reduced in PPMS and RRMS NAWM compared to control. NAA was similarly reduced in PPMS and RRMS lesions, compared to control white matter. Conclusions: Creatine is higher in PPMS than RRMS NAWM and focal lesions. This observation is consistent with the notion that progressive disability in PPMS reflects increased gliosis and axonal loss whereas disability in RRMS reflects the cumulative effects of acute inflammatory lesions and axonal loss.