H-1 Magnetic resonance spectroscopy of normal appearing white matter in primary progressive multiple sclerosis

Recent magnetic resonance imaging (MRI) and pathological studies have indic ated that axonal loss is a major contributor to disease progression in mult iple sclerosis. H-1 magnetic resonance spectroscopy (MRS), through measurem ent of N-acetyl aspartate (NAA), a neuronal marker, provides a unique tool to investigate this. Patients with primary progressive multiple sclerosis h ave few lesions on conventional MRI, suggesting that changes in normal appe aring white matter (NAWM), such as axonal loss, may be particularly relevan t to disease progression in this group. To test this hypothesis NAWM was st udied with MRS, measuring the concentration of N-acetyl derived groups (NA, the sum of NAA and N-acetyl aspartyl glutamate). Single-voxel MRS using a water-suppressed PRESS sequence was carried out in 24 patients with primary progressive multiple sclerosis and in 16 age-matched controls. Ratios of m etabolite to creatine concentration (Cr) were calculated in all subjects, a nd absolute concentrations were measured in 18 patients and all controls. N A/Cr (median 1.40, range 0.86-1.91) was significantly lower in NAWM in pati ents than in controls (median 1.70, range 1.27-2.14; P = 0.006), as was the absolute concentration of NA (patients, median 6.90 mM, range 4.62-10.38 m M; controls, median 7.77 mM, range 6.60-9.71 mM; P = 0.032). There was no s ignificant difference in the absolute concentration of creatine between the groups. This study supports the hypothesis that axonal loss occurs in NAWM in primary progressive multiple sclerosis and may well be a mechanism for disease progression in this group.