Two-year serial whole-brain N-acetyl-l-aspartate in patients with relapsing-remitting multiple sclerosis
Rigotti DJ et al. – Whole–brain concentration of the neural marker N–acetyl–l–aspartate (WBNAA) of patients with relapsing–remitting multiple sclerosis (RR–MS) declined significantly at both the group and individual levels over a 2–year time period common in clinical trials. Because of the small sample sizes required to establish power, WBNAA can be incorporated into future studies.Methods
- Nineteen patients (5 men and 14 women) with clinically definite RR–MS, who were 33 ± 5 years old (mean ± SD), had a disease duration of 47 ± 28 months, and had a median Expanded Disability Status Scale (EDSS) score of 1.0 (range 0–5.5), underwent MRI and proton magnetic resonance spectroscopy (1H–MRS) semiannually for 2 years (5 time points).
- Eight matched control subjects underwent the protocol annually (3 time points).
- Their global N–acetyl–l–aspartate 1H–MRS signal was converted into absolute amounts by phantom replacement and into WBNAA by dividing with the brain parenchymal volume, VB, from MRI segmentation.
- The baseline WBNAA of the patients (10.5 ± 1.7 mM) was significantly lower than that of the controls (12.3 ± 1.3 mM; p < 0.002) and declined significantly (5%/year, p<0.002) vs that for the controls who did not show a decline (0.4%/year, p>0.7).
- Likewise, VB values of the patients also declined significantly (0.5%/year, p<0.0001), whereas those of the controls did not (0.2%/year, p=0.08).
- The mean EDSS score of the patients increased insignificantly from 1.0 to 1.5 (range 0–6.0) and did not correlate with VB or WBNAA.