title: Heightened Delta Power during Slow-Wave-Sleep in Patients with Rett Syndrome Associated with Poor Sleep Efficiency.
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.
authors.affiliation: Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America; Department of Biomedical Engineering, Whiting School of Engineering,Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Simon
authors.initials: S
authors.lastname: Ammanuel
authors.affiliation: Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America; Department of Biomedical Engineering, Whiting School of Engineering,Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Chan
authors.affiliation: Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America; Department of Biomedical Engineering, Whiting School of Engineering,Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Adler
authors.affiliation: Department of Neurology and Developmental Medicine, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America.
authors.forename: Balaji M
authors.initials: BM
authors.lastname: Lakshamanan
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Siddharth S
authors.initials: SS
authors.lastname: Gupta
authors.affiliation: Department of Neurology and Developmental Medicine, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Ewen
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Johnston
authors.affiliation: Sleep Center, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Marcus
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Sakkubai
authors.initials: S
authors.lastname: Naidu
authors.affiliation: Neuroscience Laboratory, Hugo Moser Research Institute at Kennedy Krieger, Baltimore, Maryland, United States of America; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Shilpa D
authors.initials: SD
authors.lastname: Kadam
mesh_terms: D015415:Biomarkers / Q000032:analysis; D058256:Brain Waves / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D005260:Female; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D017286:Polysomnography; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000235:genetics* / Q000473:pathology; D020919:Sleep Disorders, Intrinsic / Q000235:genetics / Q000503:physiopathology*; D012894:Sleep Stages / Q000502:physiology*
chemical_list: D015415:Biomarkers; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2