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Open Access 01-12-2021 | Encephalopathy | Case report

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

Authors: S. M. Stoyell, B. S. Baxter, J. McLaren, H. Kwon, D. M. Chinappen, L. Ostrowski, L. Zhu, J. A. Grieco, M. A. Kramer, A. K. Morgan, B. C. Emerton, D. S. Manoach, C. J. Chu

Published in: BMC Neurology | Issue 1/2021

Abstract

Background

Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies.

Case presentation

We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient’s disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry.

Conclusions

Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

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Title: Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy
Authors: S. M. Stoyell
B. S. Baxter
J. McLaren
H. Kwon
D. M. Chinappen
L. Ostrowski
L. Zhu
J. A. Grieco
M. A. Kramer
A. K. Morgan
B. C. Emerton
D. S. Manoach
C. J. Chu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Encephalopathy
Diazepam
Published in: BMC Neurology / Issue 1/2021
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-021-02376-5

2024 ASCO Annual Meeting

Springer Medicine

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy

Abstract

Background

Case presentation

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Case presentation

Conclusions

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