Global N-acetylaspartate declines even in benign multiple sclerosis

BACKGROUND AND PURPOSE: Neuro-axonal damage is a well known sequelae of MS pathogeneses. Consequently, our aim was to test whether the ̃20% of patients with MS exhibiting a clinically benign disease course also have minimal neural dysfunction as reflected by the global concentration of their MR imaging marker NAA. MATERIALS AND METHODS: Q _NAA was obtained with nonlocalizing whole-head ¹H-MR spectroscopy in 43 patients with benign RRMS (30 women, 13 men; mean age, 44.7 ± 7.3 years of age) with 21.0 ± 4.4 years (range, 15-35 years) of disease duration from the first symptom and an EDSS score of 1.9 (range, 0-3). Q _NAA was by divided by the brain volume (from MR imaging segmentation) to normalize it into WBNAA. All participants gave institutional review board approved written informed consent, and the study was HIPAA compliant., RESULTS: The patients' lesion load was 12.2 ± 7.7 cm ³. Their 8.3 ± 1.8 mmol/L WBNAA was 35% lower than that in controls (P <.001). Individual average loss rates (absolute loss compared with controls divided by disease duration) clustered around 0.22 ± 0.09 mmol/L/year (1.7%/year, assuming monotonic decline). This rate could be extrapolated from that already reported for patients with RRMS of much shorter disease duration. WBNAA did not correlate with lesion load or EDSS. CONCLUSIONS: Normal WBNAA is not characteristic of benign MS and is not an early predictor of its course. These patients, therefore, probably benefit from successful compensation and sparing of eloquent regions. Because they may ultimately have a rapid decline once their brain plasticity is exhausted, they may benefit from treatment options offered to more affected patients.