Sleep and Epilepsy Link by Plasticity

Abstract

We aimed to explore the link between NREM sleep and epilepsy. Based on human and experimental data we propose that a sleep-related epileptic transformation of normal neurological networks underlies epileptogenesis. Major childhood epilepsies as medial temporal lobe epilepsy (MTLE), absence epilepsy (AE) and human perisylvian network (PN) epilepsies - made us good models to study. These conditions come from an epileptic transformation of the affected functional systems. This approach allows a system-based taxonomy instead of the outworn generalized-focal classification. MTLE links to the memory-system, where epileptic transformation results in a switch of normal sharp wave-ripples to epileptic spikes and pathological high frequency oscillations, compromising sleep-related memory consolidation. Absence epilepsy (AE) and juvenile myoclonic epilepsy (JME) belong to the corticothalamic system. The burst-firing mode of NREM sleep normally producing sleep-spindles turns to an epileptic working mode ejecting bilateral synchronous spike-waves. There seems to be a progressive transition from AE to JME. Shared absences and similar bilateral synchronous discharges show the belonging of the two conditions, while the continuous age windows - AE affecting schoolchildren, JME the adolescents - and the increased excitability in JME compared to AE supports the notion of progression. In perisylvian network epilepsies - idiopathic focal childhood epilepsies and electrical status epilepticus in sleep including Landau-Kleffner syndrome - centrotemporal spikes turn epileptic, with the potential to cause cognitive impairment. Postinjury epilepsies modeled by the isolated cortex model highlight the shared way of epileptogenesis suggesting the derailment of NREM sleep-related homeostatic plasticity as a common step. NREM sleep provides templates for plasticity derailing to epileptic variants under proper conditions. This sleep-origin explains epileptiform discharges' link and similarity with NREM sleep slow oscillations, spindles and ripples. Normal synaptic plasticity erroneously overgrowing homeostatic processes may derail toward an epileptic working-mode manifesting the involved system's features. The impact of NREM sleep is unclear in epileptogenesis occurring in adolescence and adulthood, when plasticity is lower. The epileptic process interferes with homeostatic synaptic plasticity and may cause cognitive impairment. Its type and degree depends on the affected network's function. We hypothesize a vicious circle between sleep end epilepsy. The epileptic derailment of normal plasticity interferes with sleep cognitive functions. Sleep and epilepsy interconnect by the pathology of plasticity.

Commonalities and Differences in NREM Parasomnias and Sleep-Related Epilepsy: Is There a Continuum Between the Two Conditions?

“…Recently, a provocative paper highlighted the impressive parallelism between DoA and SHE based on the arousal system's hyperfunction and NREM sleep dissociation states (64). A brilliant conclusion on the dual nature of DoA and SHE is also available in The Philosophy of Sleep written almost 200 years ago.…”

From Physiology to Pathology of Cortico-Thalamo-Cortical Oscillations: Astroglia as a Target for Further Research

“…The cortico-thalamo-cortical network processes behaviourally relevant internal and external information and determines vigilance states as well as neuronal network oscillation during sleep (Figure 4A), thus playing a fundamental role in both physiology and pathology (25, [276][277][278][279][280][281]. Several lines of evidence suggest that epilepsy and sleep are strongly related (282). Notably, various forms of epilepsy display different incidences across the 24 h sleep/wake cycle and among different sleep stages, possibly due to specific seizure susceptibility dependent on brain excitability and network engagement (283)(284)(285).…”

“…SWDs largely arise in a specific critical vigilance window in correspondence with passive wakefulness, transitions to NREM slow-wave sleep as well as during transitions between internal substages of NREM sleep (stage I to III; N1: light sleep or passive wakefulness, N2: light slow-wave sleep and N3: deep slow-wave sleep, respectively) ( Figure 4E ). Moreover, SWDs are disrupted by arousing stimuli and do not transition to REM sleep directly ( 38 , 275 , 302 – 308 ), thus suggesting that absence seizures prefer low and shifting-vigilance periods during superficial slow-wave NREM sleep ( 282 ). With respect to the incidence of seizures across the 24 h cycle, the distribution of generalized SWDs is still under debate.…”

Sleep spindles, ripples, and interictal epileptiform discharges in the human anterior and mediodorsal thalamus

“…The aim of the current study was to assess the function of ANT and MD in sleep-related neural plasticity and intellectual ability (IQ) measured by the association between sleep spindles, thalamic ripples and IEDs during NREM sleep. It was proposed that sleep-related epileptic transformation of normal neurological networks, involving the hippocampus, thalamus and cortex, interfere with sleep-related synaptic homeostasis, neural plasticity, and cognitive functioning (for a recent review, see Halász & Szűcs, 2020). In this pathway, the role of the human ANT and MD is not clear.…”