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. 2015 Oct 7;10(10):e0138113.
doi: 10.1371/journal.pone.0138113. eCollection 2015.

Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency

Simon Ammanuel  1 , Wesley C Chan  1 , Daniel A Adler  1 , Balaji M Lakshamanan  2 , Siddharth S Gupta  3 , Joshua B Ewen  4 , Michael V Johnston  3 , Carole L Marcus  5 , Sakkubai Naidu  3 , Shilpa D Kadam  6
Affiliations

Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency

Simon Ammanuel et al. PLoS One. .

Abstract

Sleep problems are commonly reported in Rett syndrome (RTT); however the electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly understood. The aim of this study was to analyze the temporal evolution of quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2-9 yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this study, EEG spectral analysis identified high delta power cycles representing slow wave sleep (SWS) in 8-9h overnight sleep EEGs from the frontal, central and occipital leads (AP axis), comparing age-matched girls with and without RTT. Automated algorithms quantitated the area under the curve (AUC) within identified SWS cycles for each spectral frequency wave form. Both age-matched RTT and control EEGs showed similar increasing trends for recorded delta wave power in the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also significantly lower in RTT. In contrast, the AUC for delta power within each SWS cycle was significantly heightened in RTT and remained heightened over consecutive cycles unlike control EEGs that showed an overnight decrement of delta power in consecutive cycles. Gamma wave power associated with these SWS cycles was similar to controls. However, the negative correlation of gamma power with age (r = -.59; p<0.01) detected in controls (2-5 yrs. vs. 6-9 yrs.) was lost in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by the younger age-group. Incidence of seizures in RTT was associated with significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in RTT evolved temporally and correlated significantly with clinical severity.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Boxplot of EEG spectral analysis and sleep structure analysis (A). Comparison of duration of overnight recordings in control EEGs with RTT EEGs revealed no significant differences. (B) Patients with RTT spent significantly less time during sleep in SWS (i.e.; high delta cycles) compared to the control group. (C) Patients with RTT had significantly fewer number of total SWS cycles compared to controls. (D) Therefore patients with RTT had significantly lower SWS percent.
Fig 2
Fig 2. Comparison of control EEGs’ and RTT EEGs’ delta power.
(A) Representative 8.5 hour EEG traces were scored as high delta power (black) and low delta power (grey). Comparison of RTT EEG with control EEGs revealed significantly higher delta power as well as fewer cycles. (B) RTT EEGs had significantly greater delta power in all three lead positions (frontal, central, occipital). (C) Patients with RTT had no significant difference in gamma power but revealed a trend of greater power reading in all three lead positions compared to control group.
Fig 3
Fig 3. Age-dependent evolution.
Because occipital lead displayed the greater difference between genotypes, occipital line graphs were used to display age related comparison. (A) Comparison of delta power revealed no significant difference between ages. Difference in delta power between Control EEGs and RTT EEGs seems to be driven by 2–5 year age group. (B) Gamma power in control group had a significant decrease from age group 2–5 year to 6–9 year group. The sharp decrease in gamma power is lost in patients with RTT as age increases.
Fig 4
Fig 4. SWS percent in Age Group.
Patients with RTT have significantly lower SWS percent compared to control group. Significance is driven in the age group 2–5 year old. The significance in SWS percent is lost in 6–9 years ago. Comparison of SWS percent reveals an increasing tread in SWS percent for patients with RTT instead of the decreasing trend in the control group.
Fig 5
Fig 5. Seizures correlates with high delta power.
Clinical severity of patients with RTT were recorded and documented. Seizures are a characteristic of RTT. Patients with RTT were separated into two groups: patients who showed no seizures and patients who experienced seizures (A) Patients with RTT who experienced seizures correlated negatively with lower SWS percent. (B) In addition patients with RTT who experienced seizures correlated negatively with lower cycles during sleep.
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