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. Author manuscript; available in PMC: 2025 Aug 25.
Published in final edited form as: J Neurol. 2025 Aug 12;272(9):569. doi: 10.1007/s00415-025-13295-7

Table 3.

Multi-modal findings in relation to hypotheses H1 to H6

A. Longitudinal change from Visit 1 to Visit 2
Marker Region Sample size (n) Difference (%) Effect size (dz)a p
Cho Frontal Lobe 15 4.84 −0.86 0.02*
Parietal Lobe 15 4.35 −0.81 0.01*
Temporal Lobe 15 6.21 −0.44 0.12
Occipital Lobe 15 4.81 −0.59 0.08
Cr Frontal Lobe 15 3.35 −0.55 0.08
Parietal Lobe 15 2.52 −0.41 0.10
Temporal Lobe 15 6.21 −0.68 0.02*
Occipital Lobe 15 2.36 −0.40 0.15
aTSC Global GM 17 9.98 1.20 <0.01*
Global WM 17 3.77 0.50 0.11
B. Rate of change relationships from Visit 1 to Visit 2
Marker Region Outcome Sample size (n) r p
Cho Frontal Lobe RPQ 15 0.52 0.05
Parietal Lobe 15 0.68 <0.01*
Temporal Lobe 15 0.50 0.06
Occipital Lobe 15 0.75 <0.01*
Frontal Lobe BTACT 13 −0.33 0.27
Parietal Lobe 13 −0.49 0.09
Temporal Lobe 13 −0.48 0.10
Occipital Lobe 13 −0.26 0.38
Cr Frontal Lobe RPQ 15 0.55 0.03*
Parietal Lobe 15 0.52 0.05
Temporal Lobe 15 0.65 <0.01*
Occipital Lobe 15 0.43 0.11
Frontal Lobe BTACT 13 −0.46 0.11
Parietal Lobe 13 −0.36 0.23
Temporal Lobe 13 −0.45 0.12
Occipital Lobe 13 −0.30 0.32
aTSC Global GM RPQ 17 0.45 0.07
Global WM 17 0.36 0.12
Global GM BTACT 15 −0.60 0.02*
Global WM 15 0.10 0.74
T2 Body CC RPQ 13 −0.61 0.03*
FA Corona radiata RPQ 17 0.79 <0.01*
BTACT 15 −0.65 0.01*
C. Group differences at Visit 2
Marker Region Sample size (n) Difference (%) Effect size (d)b p
Cho Frontal Lobe 16 patients / 23 controls 1.77 −0.13 0.66
Parietal Lobe 0.85 −0.06 0.97
Temporal Lobe 1.79 −0.11 0.92
Occipital Lobe 0.83 −0.05 0.88
Cr Frontal Lobe 1.50 0.20 0.66
Parietal Lobe 2.62 0.29 0.50
Temporal Lobe 1.85 −0.15 0.56
Occipital Lobe 0.96 0.12 0.80
aTSC Global GM 17 patients / 23 controls 1.36 −0.24 0.51
Global WM 0.67 −0.08 0.77
D. Cross-sectional relationships at Visit 2
Marker Region Outcome Sample size (n) r p
Cho Frontal Lobe RPQ 16 0.41 0.11
Parietal Lobe 16 0.27 0.31
Temporal Lobe 16 0.53 0.03*
Occipital Lobe 16 0.42 0.11
Frontal Lobe BTACT 16 0.14 0.59
Parietal Lobe 16 0.11 0.68
Temporal Lobe 16 0.17 0.52
Occipital Lobe 16 0.04 0.90
Cr Frontal Lobe RPQ 16 0.45 0.08
Parietal Lobe 16 0.02 0.94
Temporal Lobe 16 0.56 0.03*
Occipital Lobe 16 0.09 0.75
Frontal Lobe BTACT 16 −0.10 0.72
Parietal Lobe 16 −0.06 0.84
Temporal Lobe 16 0.17 0.52
Occipital Lobe 16 0.50 0.05
aTSC Global GM RPQ 17 −0.15 0.56
Global WM 17 0.42 0.10
Global GM BTACT 17 −0.01 0.96
Global WM 17 0.11 0.68
T1 Corona radiata RPQ 16 0.70 <0.01*
Body CC 16 0.51 0.04*
Genu CC 16 0.66 <0.01*
Splenium CC 16 0.58 0.02*
Frontal WM 16 0.56 0.03*
T2 Genu CC RPQ 16 0.58 0.02*
ADC Corona radiata RPQ 17 0.64 <0.01*
FA Frontal WM RPQ 17 −0.56 0.02*
E. Predictive relationships with Visit 2 symptomatic and cognitive outcomes
Marker Region Outcome Sample size (n) r p
Cho Frontal Lobe RPQ 18 0.18 0.48
Parietal Lobe 18 0.23 0.37
Temporal Lobe 18 0.29 0.24
Occipital Lobe 18 0.22 0.38
Frontal Lobe BTACT 18 0.08 0.75
Parietal Lobe 18 0.11 0.65
Temporal Lobe 18 0.30 0.23
Occipital Lobe 18 −0.02 0.93
Cr Frontal Lobe RPQ 18 −0.16 0.51
Parietal Lobe 18 0.20 0.43
Temporal Lobe 18 0.24 0.35
Occipital Lobe 18 −0.04 0.87
Frontal Lobe BTACT 18 0.32 0.20
Parietal Lobe 18 0.30 0.23
Temporal Lobe 18 0.25 0.32
Occipital Lobe 18 0.32 0.19
aTSC Global GM RPQ 19 −0.13 0.60
Global WM 19 0.02 0.94
Global GM BTACT 19 0.39 0.10
Global WM 19 0.15 0.54
T1 Corona radiata BTACT 15 0.58 0.02*
Body CC 15 0.57 0.03*
Genu CC 15 0.82 <0.01*
Splenium CC 15 0.57 0.03*
Global WM 15 0.58 0.03**
ADC Corona radiata RPQ 19 0.51 0.02*
Splenium CC BTACT 19 0.48 0.04*
FA Frontal WM RPQ 19 −0.53 0.02*
F. Predictive relationships with Visit 3 symptomatic and cognitive outcomes
Marker Region Outcome Sample size (n) r p
Cho Frontal Lobe RPQ 14 0.31 0.28
Parietal Lobe 14 0.36 0.21
Temporal Lobe 14 0.24 0.41
Occipital Lobe 14 0.23 0.43
Frontal Lobe BTACT 12 0.59 0.04*
Parietal Lobe 12 0.56 0.06
Temporal Lobe 12 0.76 <0.01*
Occipital Lobe 12 0.61 0.04*
Cr Frontal Lobe RPQ 14 −0.17 0.55
Parietal Lobe 14 0.11 0.71
Temporal Lobe 14 0.20 0.50
Occipital Lobe 14 0.13 0.66
Frontal Lobe BTACT 12 0.45 0.14
Parietal Lobe 12 0.46 0.13
Temporal Lobe 12 0.57 0.05
Occipital Lobe 12 0.85 <0.01*
aTSC Global GM RPQ 15 −0.30 0.29
Global WM 15 0.01 0.98
Global GM BTACT 13 0.19 0.52
Global WM 13 0.61 0.03*
T1 Genu CC BTACT 10 0.71 0.03*
ADC Genu CC BTACT 13 0.63 0.02*
Splenium CC 13 0.64 0.02*
G. Predictive relationships with Visit 2 functional outcome
Marker Region Estimate SE Odds Ratio (95% Confidence Interval) p AUC
Cho Frontal Lobe −1.14 0.74 0.32 (0.08, 1.34) 0.12 0.65
Parietal Lobe −1.51 0.85 0.22 (0.04, 1.17) 0.08 0.72
Temporal Lobe −0.84 0.69 0.43 (0.11, 1.68) 0.22 0.67
Occipital Lobe −0.07 0.61 0.94 (0.28, 3.10) 0.91 0.54
Cr Frontal Lobe −0.20 0.34 0.82 (0.43, 1.58) 0.55 0.59
Parietal Lobe −0.16 0.31 0.85 (0.46, 1.58) 0.61 0.58
Temporal Lobe 0.12 0.25 1.13 (0.69, 1.86) 0.63 0.53
Occipital Lobe −0.04 0.27 0.96 (0.57, 1.64) 0.89 0.55
aTSC Global GM −0.13 0.22 0.88 (0.58, 1.34) 0.56 0.56
Global WM 0.11 0.15 1.12 (0.83, 1.51) 0.46 0.54
a

dz < 0 denotes decrease (Visit 1 to Visit 2)

b

d < 0, denotes lower values in patients vs. controls

CC = corpus callosum; SE = standard error; AUC = area under the curve

Note. Markers were predominately measured within WM with the exception of aTSC. For brevity, only the statistically significant (*p < 0.05) findings involving 23Na MRI, MRF, and DTI markers are presented (see Table S3 for overlap with prior publications and Table S6 for NAA and mI). (A) The Wilcoxon signed-rank test (WSRT) was used to evaluate whether markers from Visit 1 were significantly different from those at Visit 2, following H1. (B) Spearman correlations were used to evaluate whether rates of change in markers were associated with rates of change in symptomatic and cognitive outcomes, from Visit 1 to Visit 2, following H2. (C) The Mann-Whitney U (MWU) test was used to evaluate whether markers from Visit 2 were significantly different in patients compared to controls, following H3. (D) Spearman correlations were used to evaluate whether markers at Visit 2 cross-sectionally correlated with symptomatic and cognitive outcomes at Visit 2, following H4. (E) Spearman correlations were used to evaluate whether markers at Visit 1 serially correlated with symptomatic and cognitive outcomes at Visit 2 or (F) Visit 3, following H5. (G) Logistic regression was used to evaluate whether markers at Visit 1 were significantly associated with functional outcome at Visit 2, following H6. Additionally, receiver operating characteristic curve analysis assessed the overall discriminative ability of the logistic regression models for predicting functional outcome at Visit 2.