Paroxysmal Microarousals in Amygdala‐Kindled Kittens: Could They Be Subclinical Seizures?

Abstract

Amygdala-kindled kittens exhibit frequent epileptiform EEG transients, often in conjunction with phasic arousal events of sleep [k-complexes, pontogeniculo-occipital (PGO) waves, and/or sleep spindles]. In this study, paroxysmal microarousals occurred throughout the sleep-wake cycle after kindling, but were most frequent during seizure-prone states of slow-wave sleep (SWS) and the transition into rapid-eye-movement sleep (REM). Their incidence correlated with interictal sleep fragmentation as well as onset of spontaneous convulsions. Results could reflect transsynaptic kindling effects on brainstem and forebrain arousal mechanisms with which amygdala is reciprocally connected. Increased discharge rates of neural generators for normal EEG and behavioral arousal could disrupt sleep at some times and recruit epileptic neurons in the kindled focus to precipitate seizures at others. Alternatively, epileptiform EEG paroxysms were accompanied by subtle behavioral stereotypes (a head nod, limb elevation, eye twitch, lip smack, or a combination of these). Behavioral correlates were elements of partial kindled seizures, suggesting that paroxysmal microarousals may be subclinical seizures. Whether or not the microarousals are true seizures, our findings may link ictal onset and interictal sleep disorders to a subclinical paroxysmal arousal disorder and suggest a common epileptic mechanism.

Sleep and arousal mechanisms in experimental epilepsy: Epileptic components of NREM and antiepileptic components of REM sleep

“…However, spontaneous phasic activity and highly localized multifocal EEG discharge persist at this time in the spontaneously epileptic kindled cat and may be evoked by photic stimulation (although there is no clinical accompaniment). Figure 1 shows that 20-Hz photic stimulation can not only evoke epileptiform phasic events in these cats but also precipitate GTCs during the transition from SWS to REM [Shouse et al, 1995]. These findings suggest that phasic activity can provoke epileptiform discharges in any sleep state.…”

“…Amygdala kindling, in contrast, provides a model of a localization-related epilepsy (TLE) that is the prototypic pure sleep epilepsy with respect to convulsions in humans [Janz, 1962]. Repetitive electrical stimulation of amygdala in 2.5-to 6.5-month-old kittens creates spontaneous sleep epilepsy that can persist to adulthood [e.g., Shouse et al, 1990Shouse et al, , 1995. EEG seizure discharge propagation and GTCs occur most often in SWS and the transition into REM.…”

“…Amygdala-kindled kittens and LKS display multiple abnormal EEG foci (including but not limited to centrotemporal areas) and multiple seizure types (e.g., partial, atonic, atypical absence, tonic-clonic, and subclinical). IIDs spread during NREM sleep, when most clinically evident seizures occur [Shouse et al, 1995[Shouse et al, , 2000Stephanatos et al, 2002]. Shared sleep disorders include delayed sleep onset, increased wakefulness after sleep onset, and abbreviated sleep time [Richdale and Prior, 1995;see Malow, this issue].…”

The relationship between sleep and epilepsy: Evidence from clinical trials and animal models

“…Clinical and experimental evidence points to the effects that sleep can have on subsequent epileptic episodes, by either facilitating or inhibiting the episodes, depending on whether the sleep phase is NREM or REM, respectively [36][37][38][39][40]. Generalized synchrony present in the NREM phase could enhance the propagation of post-synaptic responses (including epileptogenic discharges), concomitant with the muscular tonus that would facilitate the stereotypical movement that is observed during most seizures.…”

Cyclic Alternating Pattern as a Provocative Factor in Nocturnal Paroxysmal Dystonia

“…Sequences of EEG arousals recurring at brief intervals are actually associated with a condition of sleep instability, which is a favorable background not only for physiological motor events (13-16), but also for abnormal movements (7,(17)(18)(19) and for epileptic seizures (20)(21)(22)(23) . From the standpoint of motor activity during sleep, phase A of CAP is considered a facilitatory condition for occurrence of the motor patterns and the B phase exerts an inhibitory action that limits the movement duration and counteracts transition toward complete wakefulness (19).…”