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Relapsing-remitting Multiple Sclerosis and Whole-Brain N-Acetylaspartate Measurement: Evidence for Different Clinical Cohorts—Initial Observations¹

¹ From the Department of Radiology, New York University School of Medicine, 560 First Ave, New York, NY 10016 (O.G., D.M.M., B.S.Y.L., J.S.B., J.H., R.I.G.); and Department of Neurology, University of Pennsylvania Medical Center, Philadelphia (J.L., D.J., C.E.M.). Received July 26, 2001; revision requested September 6; final revision received March 13, 2002; accepted March 25. Supported by NIH grants NS33385, NS37739, and NS29029. Address correspondence to R.I.G. (e-mail: robert.grossman@med.nyu.edu).

View larger version (23K): [in a new window]   Figure 1. (a) Dot plot of the individual patients’ () distribution as a function of their average rate of WBNAA decline per year of clinically definite disease duration (1i), as defined in Equations (1) and (4). (b) Expanded -3 to 5 mmol/L/y region of a. Vertical dotted lines at 1i = 0 and 1.7 mmol/L/y partition the group according to criteria defined in the Results section of the text. Note the continuous "normal" nature of the distribution of these rates.

View larger version (31K): [in a new window]   Figure 2. Individuals’ WBNAA levels as a function of their clinically definite disease duration: Y1 in Equation (1). Subgroupings of stable (), moderate ( [all patients indicated with shaded boxes in this subgroup were receiving medication at the time of measurement]), and rapid () were determined according to the Results section. Note that individual WBNAA levels fall naturally into distinct subgroups. Solid lines = regressions for each subgroup (Eqq [5]-[7]; dashed lines = their 95% CIs.

View larger version (14K): [in a new window]   Figure 3. Dot plot of individual patients’ distribution as a function of their average rate of WBNAA decline per year of disease duration from the first symptom (2i), as defined in Equations (2) and (4). Vertical dotted lines at 2i = 0 and at 1.7 mmol/L/y partition the group, as described in the Results section of the text. Note the continuous "normal" nature of the distribution of these rates, which is also narrower than that exhibited when using the shorter clinically definite duration shown in Figure 1.

View larger version (30K): [in a new window]   Figure 4. Individual patients’ distribution is the same as in Figure 2, except that disease duration (Y2) is defined according to Equation (2) (ie, from the first symptom). Subgroupings stable (), moderate ( [all patients indicated with shaded boxes in this subgroup were receiving medication at the time of measurement]), and rapid () were determined according to the Results section. Solid lines = regression for each group; Equations (8)-(10) and dashed lines = regressions’ 95% CIs. Note that individual WBNAA levels still fall into distinct subgroups; however, nearly half the subjects in the rapid subgroup moved into the moderate subgroup. Subjects in the moderate and stable subgroups were unaffected by the change of disease duration scale.