Figure 1. Epileptic EEG abnormalities in patient U during the course of the disease. The EEG recordings marked by stars in Table 2 were used for the visualization. Figure 1. Epileptic EEG abnormalities in patient U during the course of the disease. The EEG recordings marked by stars in Table 2 were used for the visualization. Figure 2. (A) The examples of fast and slow waves of sensorimotor (µ) rhythm (Cz). The EEG recordings marked by stars in Table 2 were used for the visualization. (B) The visualization of frequency rate of sensorimotor rhythm (SM_FrR) calculations for the EEG recording of patient U registered on 21 August 2015, 18 January 2017 and 20 March 2021; red vertical line corresponds to the median PSD that divides PSD into high and low values, marked respectively by blue and orange boxes. The averages over these boxes were used to calculate SM_FrR. x—frequency bands, y—PSD. Figure 2. (A) The examples of fast and slow waves of sensorimotor (µ) rhythm (Cz). The EEG recordings marked by stars in Table 2 were used for the visualization. (B) The visualization of frequency rate of sensorimotor rhythm (SM_FrR) calculations for the EEG recording of patient U registered on 21 August 2015, 18 January 2017 and 20 March 2021; red vertical line corresponds to the median PSD that divides PSD into high and low values, marked respectively by blue and orange boxes. The averages over these boxes were used to calculate SM_FrR. x—frequency bands, y—PSD.

Figure 3. The mean difference between RTT and TD is shown in the above Gardner–Altman estimation plot for two parameters: (A) frequency rate of sensorimotor rhythm (SM_FrR); (B) amplitude of general slowing (GS_Amp). Both groups (children with Rett syndrome, RTT, and typically developed group, TD) are plotted on the left axes; the Hedges’ g effect size is plotted on floating axes on the right.

Figure 3. The mean difference between RTT and TD is shown in the above Gardner–Altman estimation plot for two parameters: (A) frequency rate of sensorimotor rhythm (SM_FrR); (B) amplitude of general slowing (GS_Amp). Both groups (children with Rett syndrome, RTT, and typically developed group, TD) are plotted on the left axes; the Hedges’ g effect size is plotted on floating axes on the right.

Figure 4. Scatterplots of RSS total scores against the frequency rate of sensorimotor rhythm frequency rate (SM_FrR, r = −0.61, p = 0.0002) and the amplitude of the general slowing of sensorimotor rhythm (GS_amp, r = 0.68, p < 0.0001) for RTT patients (Spearman’s correlation).

Figure 4. Scatterplots of RSS total scores against the frequency rate of sensorimotor rhythm frequency rate (SM_FrR, r = −0.61, p = 0.0002) and the amplitude of the general slowing of sensorimotor rhythm (GS_amp, r = 0.68, p < 0.0001) for RTT patients (Spearman’s correlation).

Table 1. Behavioral phenotype (Rett Syndrome Severity Subscales (RSSSs)) of patient U for corresponding EEG recordings. 0—no deficit, 3—severely affected with exact characteristics specific to particular subscale.

Table 1. Behavioral phenotype (Rett Syndrome Severity Subscales (RSSSs)) of patient U for corresponding EEG recordings. 0—no deficit, 3—severely affected with exact characteristics specific to particular subscale.

Age at EEG RegistrationMedicationsRett Syndrome Severity Subscales (Scores)RTT StagesTotalSeizuresBreathScoliosisWalkHand UseSpeechSleep1 y 1 m 80003131I1 y 7 m 80003131II2 y 6 m 120213231II3 y 5 m 120213231III3 y 10 m 120213231III4 y 4 m 120213231III4 y 9 mSarizotan or placebo120213231III5 y 2 mSarizotan open-label120213231III5 y 3 mSarizotan open-label120213231III5 y 4 mSarizotan open-label120213231III5 y 7 mSarizotan open-label120213231III6 y 1 m 120213231III6 y 8 m 131213231III6 y 11 mLamotrigine131213231III

Table 2. EEG data of patient U relevant for 14 EEG recordings for several parameters: general slowing (GS), sensorimotor rhythm (SM), beta rhythm (β) and epileptiform activity. Max—maximal, Min—minimal, Fr—frequency, FrR—frequency rate as the ratio between high-frequency and low-frequency waves, Amp—amplitude, Index—the percentage of EEG parameters to the whole analyzed EEG fragments.

Table 2. EEG data of patient U relevant for 14 EEG recordings for several parameters: general slowing (GS), sensorimotor rhythm (SM), beta rhythm (β) and epileptiform activity. Max—maximal, Min—minimal, Fr—frequency, FrR—frequency rate as the ratio between high-frequency and low-frequency waves, Amp—amplitude, Index—the percentage of EEG parameters to the whole analyzed EEG fragments.

EEG Parameters GSSM (µ)β (µ)EpileptiformAge at EEG RegistrationFrAmpAmpMinFrMaxFrIndexFrRAmpIndex1 y 1 m *1.3351405.28.663.91.172511.61 y 7 m *1.5301954.67.954.70.862025.72 y 6 m *1.5851853.98.746.80.372020.23 y 5m1.9901455.29.539.40.352032.13 y 10 m *2.395656.110.134.40.342038.54 y 4 m2.490705.510.535.250.422029.44 y 9 m2.385604.310.929.250.381521.55 y 2 m *2.1100684.411.833.80.661518.65 y 3 m1.990724.911.341.80.451514.95 y 4 m2.795886.811.844.50.551516.75 y 7 m2.495945.111.238.20.411519.96 y 1 m *2.2951126.611.436.10.381512.26 y 8 m *2.6125556.111.818.10.241562.56 y 11 m2.5130655.511.717.60.221244.1

Table 3. Descriptive statistics of demographic and medical RTT and TD groups. RSS scores are presented only for patients (0—no deficit, 3—severely affected with exact characteristics specific to particular subscale).

Table 3. Descriptive statistics of demographic and medical RTT and TD groups. RSS scores are presented only for patients (0—no deficit, 3—severely affected with exact characteristics specific to particular subscale).

Valid NMeanMedianStd. Dev.Std. ErrorAge TD419.1069.043.4570.54Age RTT328.468.084.150.73age of regression, RTT (month)3217.4517.55.61.19RSSSeizures310.8100.980.18Breath irregularities311.1911.050.19Scoliosis30111.050.19Walk311.9421.120.2Hand use321.9121.030.18Speech322.5330.510.09Sleep310.5800.760.14Total329.759.53.650.65

Table 4. EEG parameters in patients with Rett syndrome (RTT) and typically developed (TD) children. Following EEG parameters are presented: general slowing (GS), sensorimotor rhythm (SM), beta rhythm and EEG abnormalities. Max—maximal, Min—minimal, Fr—frequency, FrR—frequency rate as the ratio between high-frequency and low-frequency waves, Amp—amplitude, Index—the percentage of EEG parameters to the whole analyzed EEG fragments.

Table 4. EEG parameters in patients with Rett syndrome (RTT) and typically developed (TD) children. Following EEG parameters are presented: general slowing (GS), sensorimotor rhythm (SM), beta rhythm and EEG abnormalities. Max—maximal, Min—minimal, Fr—frequency, FrR—frequency rate as the ratio between high-frequency and low-frequency waves, Amp—amplitude, Index—the percentage of EEG parameters to the whole analyzed EEG fragments.

RTT (n = 32)TD (n = 41) Mean ± STDMedianMean ± STDMedianMann–Whitney U testGS_Fr2.55 ± 0.622.403.23 ± 0.653.2Z = −3.98, p = 0.0001Gs_Amp72.50 ± 38.3370.0035.24 ± 26.3130Z = 4.20, p = 0.0001SM_Amp108.81 ± 49.62107.5073.17 ± 24.5165Z = 3.346, p = 0.0007SM_MinFr3.16 ± 1.343.556.42 ± 1.396.3Z = −4.608, p < 0.0001SM_MaxFr9.89 ± 1.8610.2010.71 ± 1.1910.91Z = −2.37, p = 0.017SM_Index18.95 ± 20.069.8825.95 ± 14.4823.4Z = −2.69, p = 0.007SM_FrR0.41 ± 0.140.400.66 ± 0.140.665Z = −5.54, p < 0.0001Beta_Amp20.13 ± 7.8919.7516.63 ± 4.7415Z = 1.67, p = 0.084Epileptiform activity8.78 ± 13.535.130.86 ± 1.680.11Z = 5.63, p < 0.0001 Table 5. Partial correlation of age and RSS scales with mean amplitude of general slowing (GS_amp) and frequency rate of sensorimotor rhythm (SM_FrR). Comparison of correlations is estimated for dependent samples according to [31]; single-sided testing. Significant differences are presented in bold. Table 5. Partial correlation of age and RSS scales with mean amplitude of general slowing (GS_amp) and frequency rate of sensorimotor rhythm (SM_FrR). Comparison of correlations is estimated for dependent samples according to [31]; single-sided testing. Significant differences are presented in bold. RSS SubscalesPartial Correlation with
GS_ampPartial Correlation with
SM_FrRComparison of
GS and SM CorrelationsSeizuresr = 0.19, p = 0.3r = −0.41, p = 0.02p = 0.12Breath irregularitiesr = −0.09, p = 0.6r = −0.35, p = 0.05p = 0.04 Scoliosisr = 0.3, p = 0.09r = −0.19, p = 0.3p = 0.28Walkr = 0.47, p = 0.006r = −0.49, p = 0.005p = 0.45Hand user = 0.5, p = 0.003r = −0.4, p = 0.02p = 0.28Speechr = 0.45, p = 0.01r = −0.3, p = 0.1p = 0.21Sleepr = 0.35, p = 0.05r = −0.2, p = 0.2p = 0.21Totalr = 0.58, p = 0.0005r = −0.62, p = 0.0002p = 0.39