**4.1 Generalized seizures**

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

module underlying alternations of sleep and awake cycle.

from reduction of K<sup>+</sup>

neuromodulators [9].

**3. Effect of sleep on epilepsy**

becomes accentuated during sleep.

seizures had nocturnal seizures [10].

the effect of sleep on specific epilepsy syndromes.

**4. Adult epilepsies, associated with sleep**

The existence of two antagonistic systems promoting wakefulness and sleep was assumed in 1930 by von Economo [3]. In the 1940s, the "ascending arousal system" concept in the brainstem of animal and human brain, maintaining wakefulness, became clearer and more accepted. Now this system is called activating reticular arousal system (ARAS) [4]. The ARAS consist of neuronal network, containing several neurotransmitters, including acetylcholine, noradrenalin, serotonin, catecholamine, histamine, and orexin that play a role in the arousal system [5, 6]. Saper discovered that the ventrolateral preoptic area (VPLO) was involved in inducing NREM sleep [7]. It contains GABA-ergic and galanin-ergic neurons which inhibit the activating brainstem ARAS harboring and keep it from firing throughout the entire NREM sleep, providing the substrate of the "sleep system" with opposite function to the "wake system" When VLPO neurons fire during sleep, they inhibit the arousal system cell groups, thus disinhibiting and reinforcing their own firing. Similarly, when arousal neurons fire at high rate during wakefulness, they inhibit the VLPO, thereby disinhibiting their own firing [7]. This concept is nowadays accepted as the basics of the hypothalamic "sleep switch"

The brainstem cholinergic system provokes fast rhythms on the EEG, while

Seizures and epilepsy syndromes are classified based on the time of occurrence of seizures regarding the sleep-wake cycle. Pure sleep epilepsies, arousal epilepsy, wakefulness epilepsy, and epilepsy occurring irrespective of time are the four main types of seizures [1, 2, 10]. Sleep accentuated epilepsy includes epilepsies with seizures occurring during both awake and asleep state, but epileptiform activity

Gowers noted that seizures happening during daytime cluster at certain times of the day, specifically upon awakening and late afternoon; and seizures occurring at night tend to occur mainly at bedtime and early morning hours before awakening [2] Janz observed that up to 45% of patients with primarily generalized tonic–clonic

In general, NREM sleep facilitates interictal epileptiform activity (IEA) and REM inhibits IEA and is protective against seizures. NREM sleep is a synchronized state that allows better conduction of electrical impulses rather than REM sleep that is an asynchronous state [11–14]. The hypothesis is that during NREM sleep more neurons are in a resting state making them more recruitable into discharges. Whereas during REM sleep there is more neuronal firing that makes neurons less available to generate IEA. Despite the fact that the generators of different sleep and arousal states exert some common effects on seizure disorders, the distinct pathways, seizure manifestations, and mechanisms involved also depend on the pathophysiology of the specific epileptic syndrome. This section will briefly discuss

Seizures are divided in generalized and focal. In generalized seizures, the epileptic activity starts in multiple brain regions simultaneously, while in focal

conductance by acetylcholine, norepinephrine, and other

abolishing thalamic spindle generation and delta oscillations [8]. Cortical neurons are depolarized by glutamate release, mainly from the thalamocortical fibers, but also by cortico-cortical axons once the activation has started and/or

**38**
