title: Impaired slow wave sleep downscaling in patients with infantile spasms.
abstract: BACKGROUND
  West syndrome is a severe epileptic encephalopathy of infancy, characterized by infantile spasms, global retardation, and a severely abnormal electroencephalogram (EEG) pattern known as hypsarrhythmia, which is most prominent during slow waves sleep. The restorative function of slow wave sleep has been linked to downscaling, a neuronal process ensuring a balance of global synaptic strength, which is important for normal cortical functioning and development. A key electrophysiological marker for this downscaling is the reduction of the slope of slow waves across the night.
  
  
  METHODS
  We retrospectively compared the slope of slow waves between 14 untreated patients with infantile spasms and healthy age and gender matched controls. Patients were examined in one all-night sleep EEG before treatment, and in two follow-up nap recordings, under and after treatment with corticosteroids.
  
  
  RESULTS
  In patients with infantile spasms the overnight reduction in the slope of slow waves was significantly diminished compared to controls (p = 0.009). Moreover, untreated patients revealed overall steeper slopes. During corticosteroid treatment the slope was reduced compared to controls (p = 0.001). After successful treatment the slope was similar between patients and controls.
  
  
  CONCLUSIONS
  Our results provide evidence for reduced downscaling in patients with infantile spasms. Moreover, the marked reduction of the slope during corticosteroid treatment may reflect a loss of synaptic connections due to the effect of glucocorticoids. This altered sleep dependent regulation of synaptic strength in infantile spasms may contribute the underlying pathomechanism of the developmental regression. Furthermore the normalization of synaptic strength due to corticosteroids might provide a potential mechanistic explanation for this treatment strategy.
authors.affiliation: Pediatric Sleep Disorders Center, University Children's Hospital Zurich, Switzerland; Division of Clinical Neurophysiology, University Children's Hospital Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Switzerland; Child Development Center, University Children's Hospital Zurich, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Fattinger
authors.affiliation: Pediatric Sleep Disorders Center, University Children's Hospital Zurich, Switzerland; Division of Clinical Neurophysiology, University Children's Hospital Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmitt
authors.affiliation: Pediatric Sleep Disorders Center, University Children's Hospital Zurich, Switzerland; Division of Clinical Neurophysiology, University Children's Hospital Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Switzerland.
authors.forename: Bigna K
authors.initials: BK
authors.lastname: Bölsterli Heinzle
authors.affiliation: Pediatric Sleep Disorders Center, University Children's Hospital Zurich, Switzerland; Division of Clinical Neurophysiology, University Children's Hospital Zurich, Switzerland.
authors.forename: Hanne
authors.initials: H
authors.lastname: Critelli
authors.affiliation: Pediatric Sleep Disorders Center, University Children's Hospital Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Switzerland; Child Development Center, University Children's Hospital Zurich, Switzerland.
authors.forename: Oskar G
authors.initials: OG
authors.lastname: Jenni
authors.affiliation: Pediatric Sleep Disorders Center, University Children's Hospital Zurich, Switzerland; Children's Research Center, University Children's Hospital Zurich, Switzerland; Child Development Center, University Children's Hospital Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), University of Zurich, Switzerland. Electronic address: reto.huber@kispi.uzh.ch.
authors.forename: Reto
authors.initials: R
authors.lastname: Huber
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D013036:Spasms, Infantile / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D000305:Adrenal Cortex Hormones
keywords: Corticosteroids; Hypsarrhythmia; Infantile spasms; NREM sleep; Slope of sleep slow waves