Sleep Deprivation Exacerbates Seizures and Diminishes GABAergic Tonic Inhibition

Abstract

Patients with epilepsy report that sleep deprivation is a common trigger for breakthrough seizures. The basic mechanism of this phenomenon is unknown. In the Kv1.1−/− mouse model of epilepsy, daily sleep deprivation indeed exacerbated seizures though these effects were lost after the third day. Sleep deprivation also accelerated mortality in ~ 52% of Kv1.1−/− mice, not observed in controls. Voltage‐clamp experiments on the day after recovery from sleep deprivation showed reductions in GABAergic tonic inhibition in dentate granule cells in epileptic Kv1.1−/− mice. Our results suggest that sleep deprivation is detrimental to seizures and survival, possibly due to reductions in GABAergic tonic inhibition. ANN NEUROL 2021;90:840–844

Multimodal wearable sensors inform cycles of seizure risk

“…Furthermore, changes in sleep patterns and sleep deprivation may impact sympathetic arousal 63 and cortical excitability, 64 and sleep deprivation is a known seizure risk factor. 65 Some work suggests divergent mechanisms for the regulation of EDAp vs. EDAt, 62 and artifactual drift in the EDAt signal is a concern for long recording periods. 47 These factors may underpin differences in the EDAt and EDAp channels, with EDAp being the more meaningful feature for multiday seizure risk in this work.…”

To Not Sleep, Perchance to Seize

“… 8 These mutant mice also have disrupted sleep at baseline. 8 In this study, 7 the authors reduced sleep time in adult Kv1.1 −/− mice even further by keeping them awake (with “gentle” handling) 4 hours per day during a period of time when they ordinarily sleep, for 5 days in a row. EEG recordings showed that these sleep-deprived mice had significantly more electrographic seizures on the second, third, and fourth days of sleep deprivation, but this effect wore off and their seizure counts were not different from controls (Kv1.1 −/− mice without sleep deprivation) on the fifth day of sleep deprivation and returned to baseline levels after sleep deprivation was stopped.…”

“…Against this background, Konduru and colleagues 7 examined the effect of sleep deprivation in a genetic animal model of temporal lobe epilepsy, the Kv1.1 knockout mouse (Kv1.1 −/− ). These mice harbor a mutation in the alpha subunit of the voltage-gated delayed rectifier potassium channel Kcna1 , making them prone to spontaneous seizure generation as well as to sudden unexpected death (thus of relevance to understanding SUDEP, sudden unexpected death in epilepsy).…”

“…Konduru and colleagues 7 found that miniature GABA-mediated inhibitory postsynaptic currents (IPSCs) in hippocampal dentate gyrus neurons from sleep-deprived Kv1.1 knockout mice were reduced (both current magnitude and density) compared with nonsleep-deprived mutants. This reduction in tonic GABAergic inhibition may contribute to increased excitability already present in Kv1.1 null mice, leading to increased seizures as well as increased risk of SUDEP.…”

The role of sleep state and time of day in modulating breathing in epilepsy: implications for sudden unexpected death in epilepsy

“…Sleep deprivation caused by sleep disorders of frequent nocturnal seizures can result in sleep deprivation. Sleep deprivation itself can induce seizures and interictal spiking (Mattson et al, 1965 ; Pratt et al, 1968 ; Malow et al, 2000b ; Konduru et al, 2021 ). In amygdala kindled cats, acute sleep deprivation reduces seizure and after discharge threshold (Shouse and Sterman, 1982 ).…”