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Impaired slow wave sleep downscaling in patients with infantile spasms


Fattinger, Sara; Schmitt, Bernhard; Bölsterli Heinzle, Bigna K; Critelli, Hanne; Jenni, Oskar G; Huber, Reto (2015). Impaired slow wave sleep downscaling in patients with infantile spasms. European Journal of Paediatric Neurology, 19(2):134-142.

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.
CONCLUSION: 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.

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.
CONCLUSION: 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.

Citations

3 citations in Web of Science®
3 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:22 Jan 2015 12:41
Last Modified:05 Apr 2016 18:47
Publisher:Elsevier
ISSN:1090-3798
Publisher DOI:https://doi.org/10.1016/j.ejpn.2014.11.002
PubMed ID:25530030

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