**2. Electrophysiology of sleep**

The human states are divided into wakefulness, Non-REM (NREM) sleep, and REM sleep, REM being rapid eye movements. Sleep non-REM are subdivided in N1, N2, and N3. N1 and N2 are superficial sleep stages, where patient may be easily aroused and N3 is a deep sleep, where arousal is difficult. The characterization of each of those three stages is based on the EEG recording, in conjunction with eye and muscle activity recording. N2 is characterized by the presence of spindles and K-complexes and N3 - by the presence of high voltage slow delta waves.

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" module underlying alternations of sleep and awake cycle.

The brainstem cholinergic system provokes fast rhythms on the EEG, while 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 from reduction of K<sup>+</sup> conductance by acetylcholine, norepinephrine, and other neuromodulators [9].

#### **3. Effect of sleep on epilepsy**

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 becomes accentuated during sleep.

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 seizures had nocturnal seizures [10].

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 the effect of sleep on specific epilepsy syndromes.

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

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

**39**

**4.2 Focal seizures**

*4.2.1 Temporal lobe epilepsy*

*Sleep Disorders and Epilepsy*

of consciousness.

in 41% [10].

*4.1.2 Juvenile myoclonic epilepsy*

permissible the conduction of epileptic discharges.

fully weaned from therapy long-term in later adulthood.

of convulsions, but without myoclonic seizures.

**4.1 Generalized seizures**

*DOI: http://dx.doi.org/10.5772/intechopen.93989*

*4.1.1 Primary generalized tonic-clonic seizures*

seizures, the epileptic discharges originate in one area of brain that may or may not spread to other regions of the brain. Seizures occurring with loss of consciousness are known as focal dyscognitive seizure or focal seizure with loss of consciousness, formerly known as complex partial seizures. Seizures occurring without change in awareness are called focal simple seizures where there is no loss

Gowers first noted that patients with primary generalized tonic-clonic seizures have their seizures in two peaks during sleep: the first - two hours after sleep onset and at the end of the sleep cycle [1]. There are two peaks of sleep-related seizures occurred between 9-11 pm and 3-5 am respectively [10]. Further studies showed that generalized tonic-clonic epilepsy occurs mainly during NREM sleep [15, 16]. Generalized interictal epileptiform activity (IEA) increases in NREM sleep [17]. In arousal epilepsies or epilepsies occurring during awake and sleep states, IEA can occur at any time. Meanwhile, in pure sleep epilepsy, IEA have been described during REM sleep and/or on awakening in 9% of the patients and restricted to NREM sleep

Juvenile myoclonic epilepsy [JME] is a syndrome characterized by the combination of myoclonic, absence, and generalized tonic-clonic seizures that especially occur in the morning in the first one to two hours after awakening, that is a hallmark of this syndrome. Seizures are often triggered by externally provoked arousals in the morning after a sleepless night associated with alcohol consumption. JME is an agerelated, genetic, and generalized epilepsy syndrome that typically begins in early adolescence [10, 18]. Seizures can also occur on awakening from a nap, but rarely at other times during the day [18]. The classic EEG shows generalized spike-wave complexes at 4-6 Hz as well as polypiles. The discharges increase markedly at sleep onset and awakening, but are less frequent in NREM sleep, REM sleep, and wakefulness. The arousal period is apparently a hyper-synchronous state that makes more

Valproic acid or other newer broad-spectrum antiepileptics [AEDs] such as levetiracetam, lamotrigine, topiramate, zonisamide and perampanel may lead to excellent seizure control in patients who adhere to rigid compliance and avoid seizure precipitant such as sleep deprivation and alcohol binges. Medication requirement typically endures throughout life, with seldom patients being success-

A closely related primary generalized epilepsy syndrome called generalized tonic-clonic seizures upon awakening (GTCOA) has a similar pattern of occurrence

Sleep related complex partial seizures originating in the temporal lobe are frequent and represent around 33% of all temporal lobe seizures [19]. Nocturnal temporal lobe epilepsy (NTLE) is a subtype of medically refractory temporal lobe epilepsy, usually presenting during adolescence with seizures nearly exclusively

#### *Sleep Disorders and Epilepsy DOI: http://dx.doi.org/10.5772/intechopen.93989*

seizures, the epileptic discharges originate in one area of brain that may or may not spread to other regions of the brain. Seizures occurring with loss of consciousness are known as focal dyscognitive seizure or focal seizure with loss of consciousness, formerly known as complex partial seizures. Seizures occurring without change in awareness are called focal simple seizures where there is no loss of consciousness.
