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. 2018 Jan 29;8:1828. doi: 10.1038/s41598-018-19938-2

Table 3.

Factors associated with disease progression outcomes.

Survival Total ALSFRS-r Bulbar ALSFRS-r Slow Vital Capacity
HR (95%CI) p-value Interaction coefficient β3 (SD) (#) p-value Interaction coefficient β3 (SD) (#) p-value Interaction coefficient β3 (SD) (#) p-value
At baseline
Bilateral pre-central and central (motor) cortex
 R2* 0.97 (0.76 to 1.22) 0.77 −0.02 (0.11) 0.84
 Volume 0.73 (0.46 to 1.17) 0.19 0.42 (1.79) 0.81
 Naa 0.96 (0.78 to 1.19) 0.73 0.29 (1.07) 0.79
Bilateral PLIC
 FA 0.95 (0.89 to 1.01) 0.086 5.93 (2.88) 0.045
 MD+ 2.32 (1.03 to 5.23) 0.043 −0.77 (0.36) 0.036
Medulla oblongata
 R2* 1.02 (0.89 to 1.18) 0.78 0.005 (0.06) 0.93 0.01 (0.02) 0.61
 Volume 1.11 (0.97 to 1.26) 0.14 −5.55 (5.30) 0.30 −2.89 (1.86) 0.13
 FA 0.91 (0.49 to 1.71) 0.77 −0.54 (2.98) 0.86 0.03 (1.04) 0.98
 MD+ 1.15 (0.98 to 1.34) 0.085 0.05 (0.09) 0.57 0.04 (0.03) 0.021
Cervical spinal cord
 R2* 1.02 (0.97 to 1.07) 0.50 0.02 (0.02) 0.44 0.08 (0.07) 0.27
 Volume (¤) 0.87 (0.44 to 1.71) 0.68 −0.27 (0.34) 0.43 −0.88 (1.15) 0.45
 Corrected Volume (Δ) 0.93 (0.43 to 2.00) 0.85 −0.44 (0.37) 0.23 −1.29 (1.25) 0.31
Variations between inclusion and 3 months
Bilateral pre-central and central (motor) cortex
 R2* difference (t3 − t0) 1.02 (0.71 to 1.46) 0.91 −0.10 (0.08) 0.20
 Volume difference (t0 − t3) 0.53 (0.16 to 1.72) 0.29 4.36 (2.60) 0.10
 Naa difference (t0 − t3) 1.13 (0.80 to 1.60) 0.49 0.33 (0.78) 0.68
Bilateral PLIC
 FA difference (t3 − t0) 1.23 (0.22 to 6.75) 0.81 −0.01 (4.54) 0.99
 MD difference (t0 − t3) + 2.15 (0.37 to 12.36) 0.39 −0.22 (0.62) 0.73
Medulla oblongata
 R2* difference (t3 − t0) 0.96 (0.84 to 1.09) 0.51 −0.04 (0.04) 0.39 −0.02 (0.02) 0.46
 Volume difference (t0 − t3) 0.98 (0.72 to 1.33) 0.89 8.70 (8.02) 0.29 1.87 (4.72) 0.18
 FA difference (t3 − t0) 0.88 (0.29 to 2.64) 0.81 −1.62 (2.52) 0.53 0.04 (0.74) 0.96
 MD difference (t0 − t3) + 1.08 (0.78 to 1.50) 0.63 0.03 (0.09) 0.69 0.01 (0.02) 0.53
Cervical spinal cord
 R2* difference (t3-t0) 0.98 (0.88 to 1.09) 0.67 0.007 (0.02) 0.73 0.07 (0.08) 0.43
 Volume difference (t0 − t3) (¤) 8.72 (0.80 to 95.07) 0.07 −0.85 (0.49) 0.095 −4.56 (1.48) 0.005
 Corrected Volume (t0 − t3)(∆) 1.19 (0.54 to 2.61) 0.65 −0.28 (0.24) 0.26 −3.37 (1.27) 0.013

Volume (as a percentage of the intracranial volume and in mm3 for spinal cord); R2* values (in s−1); diffusivity; magnetic resonance spectrometry

HR = hazard ratio calculated with Cox proportional hazards. Volume (as a percentage of the intracranial volume and in mm3 for the spinal cord); R2* mean values (1/T2*) (in s−1). The volume of the cervical spinal cord is determined from the middle of the 3rd vertebra to the middle of the 5th vertebra. The corrected volume is the normalization of this volume by the cord length from C1 to C7.

Quantitative variables were expressed as the mean (standard deviation) if normally distributed or the median [interquartile range] if not. Categorical variables were expressed as the number (percentage). The normality of distribution was assessed using histograms and the Shapiro-Wilk test.

ALSFRS-r: Amyotrophic Lateral Sclerosis Rating Scale - Revised Version; CI: confidence interval; PLIC: posterior limb of internal capsule; FA: fractional anisotropy; MD: mean diffusivity; NAA: N-acetyl aspartate; SD = standard deviation; (#) Coefficient β_3 of a mixed model with the outcomes (global ALSFRS-r score or bulbar ALSFRS-r score or SVC) as the dependent variable. 〖At baseline: N = 40 patients.ALSFRS-r〗_ij = β_0 + β_1 t_ij + β_2 R2_i + β_3 R2_i*t_ij + γ_0i + γ_1i t_ij + ε_ij. tij = for any subject i, time in months elapsed from baseline to the current measure j of parameters. Variations between inclusion and 3 months: N = 26 patients. 〖ALSFRS-r〗_ij = β_0 + β_1 t_ij + β_2 R〖2(t3 − t0)〗_i + β_3 R〖2(t3 − t0)〗_i*t_ij + γ_0i + γ_1i t_ij + ε_ij. tij = for any subject i, time in months elapsed from 3 months to the current measure j of parameters. p-values for interactions tagged in bold are significant at p < 0.05. +In units × 10000. (¤) in units/1000.

Data not shown: there were no differences for the Glx, mI and Cho peaks.