Supplementary Figure 1. Graphic representation of the differences in volumes (y axis) between ESES patients, healthy controls and refractory epilepsy controls (x axis). A. Left thalamic volume. B. Right thalamic volume. C. Total brain volume. The horizontal line represents the median, the limit of the box the interquartile range, and the whiskers the 5th and 95th percentiles respectively. In pairwise comparisons, left thalamic volume was smaller in ESES patients than in healthy controls (medians: 7.35 versus 7.74 cm3, Wilcoxon rank-sum test p=0.0055), and in refractory epilepsy controls than in healthy controls (7.09 versus 7.74 cm3, p=0.0001), but was not different between ESES patients and refractory epilepsy controls (7.35 versus 7.09 cm3, p=0.358) (Supplementary Figure 1A). The volume of the thalamus was different between the groups (Kruskal-Wallis test, p=0.0002) (Supplementary Figure 1B). In pairwise comparisons, right thalamic volume was smaller in ESES patients than in healthy controls (7.63 versus 7.99 cm3, Wilcoxon rank-sum test p=0.0049), and in refractory epilepsy controls than in healthy controls (7.52 versus 7.99 cm3, p=0.0002), but was not different between ESES patients and refractory epilepsy controls (medians: 7.63 versus 7.52 cm3, p=0.4837). The total brain volume was different between the groups (Kruskal-Wallis test, p=0.0001) (Supplementary Figure 1C). In pairwise comparisons, total brain volume was smaller in ESES patients than in healthy controls (1242.79 versus 1312.79, Wilcoxon rank-sum test p=0.025), and in refractory epilepsy controls than in healthy controls (1168.17 versus 1312.79, p<0.00001), but was larger in ESES patients than in refractory epilepsy controls (medians: 1242.79 versus 1168.17, p=0.0151).
Total brain volume ESES patients versus refractory epilepsy controls Intercept Group [0 ESES patients, 1 refractory epilepsy] Age [years] 1097.77 (971.75-1223.79) -72.64 (-143.19- -2.10) 15.61 (3.08-28.13) <0.0005 0.044 0.016 Total brain volume Refractory epilepsy controls versus healthy controls Intercept Group [0 refractory, 1 healthy control] Age [years] 1019.31 (923.09-1115.53) 121.41 (61.91-180.91) 16.28 (6.50-26.06) <0.0005 <0.0005 0.001 Supplementary Figure 2. Graphic representation of volumes (y axis) over age (x axis). A. Left thalamic volume. B. Right thalamic volume. C. Total brain volume. Individual observations are represented as circles with their respective best fit curves. Green: ESES patients. Blue: Healthy controls. Red: Refractory epilepsy controls. ABSOLUTE THALAMIC VOLUMES CORRECTING FOR AGE AND BRAIN VOLUME IN THE REGRESSION MODEL The main comparison was performed correcting for total brain volume using the relative thalamic volume (Table 2 and Figure 2). Correcting for total brain volume using it as a regressor in the regression model yielded similar results. Correcting for total brain volume using it as a
epilepsy controls Absolute right thalamic volume Refractory epilepsy controls versus healthy controls Intercept Group [0 refractory, 1 healthy control] Age [years] Total brain volume 0.48 (0.53-0.68) -0.09 (-0.5-0.12) 0.0002 (-0.001-0.006) 0.011 (0.003-0.018) <0.0005 0.472 0.947 0.038 Legend: CI: Confidence interval. ESES: Electrical status epilepticus in sleep. CORRECTION FOR AGE AND GENDER Linear regressions comparing the absolute thalamic and brain volumes between the groups correcting for age and gender. Element in the linear regression model Coefficient with 95%CI p-value LEFT THALAMUS Left thalamus ESES patients versus healthy controls Intercept Group [0 ESES patients, 1 healthy controls] Age [years] Gender [0=female, 1=male] 6.26 (5.53 - 6.99) 0.62 (0.20 - 1.04) 0.07 (0.008 - 0.14 0.50 (0.13 - 0.87) <0.0005 0.005 0.029 0.009 Left thalamus ESES patients versus refractory epilepsy controls Intercept Group [0 ESES patients, 1 refractory epilepsy] Age [years] Gender [0=female, 1=male] 5.77 (4.89 - 6.64) -0.07 (-0.50 - 0.37) 0.13 (0.06 - 0.21) 0.42 (-0.02 - 0.85) <0.0005 0.762 0.001 0.060 Left thalamus Refractory epilepsy controls versus healthy controls Intercept Group [0 refractory, 1 healthy control] Age [years] Gender [0=female, 1=male] 5.97 (5.40 - 6.54) 0.66 (0.32 - 0.9987) 0.10 (0.05 - 0.16) 0.40 (0.08 - 0.72) <0.0005 <0.0005 <0.0005 0.016 RIGHT THALAMUS
Linear regressions comparing the relative thalamic volumes between the groups correcting for age and gender. Element in the linear regression model Coefficient with 95%CI p-value RELATIVE LEFT THALAMIC VOLUME Relative left thalamic volume ESES patients versus healthy controls Intercept Group [0 ESES patients, 1 healthy controls] Age [years] Gender [0=female, 1=male] 0.59 (0.55 - 0.63) 0.02 (-0.003 - 0.05) -0.0003 (-0.004 - 0.004) -0.0002 (-0.02- 0.02) <0.0005 0.082 0.889 0.987 Relative left thalamic volume ESES patients versus refractory epilepsy controls Intercept Group [0 ESES patients, 1 refractory epilepsy] Age [years] Gender [0=female, 1=male] 0.59 (0.53 - 0.64) 0.02 (-0.004 - 0.05) 0.001 (-0.004 - 0.006) -0.02 (-0.05- 0.008) <0.0005 0.091 0.565 0.160 Relative left thalamic volume Refractory epilepsy controls versus healthy controls Intercept Group [0 refractory, 1 healthy control] Age Gender [0=female, 1=male] 0.62 (0.58 - 0.65) -0.006 (-0.03- 0.01) 0.0004 (-0.003- 0.004) -0.01 (-0.03 -0.005) <0.0005 0.559 0.783 0.148 RELATIVE RIGHT THALAMIC VOLUME Relative right thalamic volume Intercept Group [0 ESES patients, 1 healthy controls] Age [years] 0.60 (0.56 - 0.64) 0.03 (0.0008 - 0.05) -0.0004 (-0.004- 0.003) <0.0005 0.043 0.826
ESES patients versus healthy controls Gender [0=female, 1=male] 0.004 (-0.02 - 0.03) 0.713 Relative right thalamic volume ESES patients versus refractory epilepsy controls Intercept Group [0 ESES patients, 1 refractory epilepsy] Age [years] Gender [0=female, 1=male] 0.59 (0.53 - 0.65) 0.03 (0.0001 - 0.06) 0.002 (-0.004 - 0.007) -0.01 (-0.04 - 0 .02) <0.0005 0.049 0.574 0.386 Relative right thalamic volume Refractory epilepsy controls versus healthy controls Intercept Group [0 refractory, 1 healthy control] Age Gender [0=female, 1=male] 0.63 (0.60 - 0.66) -0.008 (-0.03- 0.01) 0.0003 (-0.003 - 0 .004) -0.007 (-0.03- 0.01) <0.0005 0.436 0.836 0.450 ANALYSIS OF THE THALAMIC VOLUME AS LEFT+RIGHT THALAMIC VOLUME Absolute thalamic volumes (Supplementary Figure 3). The volume of the left+right thalami was different between the groups (Kruskal-Wallis test, p=0.0001). In pairwise comparisons, left+right thalamic volume was smaller in ESES patients than in healthy controls (medians: 14.99 versus 15.97 cm3, Wilcoxon rank-sum test p=0.0047), and in refractory epilepsy controls than in healthy controls (14.35 versus 15.97 cm3, p=0.0001), but was not different between ESES patients and refractory epilepsy controls (14.67 versus 14.35 cm3, p=0.4181). Absolute volumes of the left + thalami