The increased incidence of seizures during the night has been known for a long time. Mechanisms associated with the generation of epileptic seizures during sleep are not fully understood. It has been suggested there are several mechanisms of pathological synchronization of brain bioelectrical activity, triggered by physiological stages of sleep (Gigli, 1992). The phases of sleep in which there is greatest risk of seizures include the phases associated with a higher probability of awakening - mainly phase I and II NREM sleep type. Phase of sleep associated with EEG desynchronization - REM is characterized by a lower risk of seizures. The probability of awakening during sleep increases the risk of seizure in the case of idiopathic generalized epilepsies (Bonakis, 2009). A similar mechanism was proposed in focal and secondarily generalized seizures (Manni, 2005). Also in these types of epilepsy light sleep phase (I and II NREM) may initiate abnormal synchronous epileptic discharges. The EEG patterns associated with arousal (K complexes) trigger pathological EEG hypersynchrony in the second phase of NREM sleep. Seizure during sleep is associated with the interruption of the continuity of sleep and disorder of its architecture. Seizure, both partial (Bateman, 2008) and generalized (Seyal, 2009), can cause apnea of central origin. It is probably due to the short-term disturbances of respiratory rhythmogenesis during sleep by hypersynchronic epileptic discharges. The effects of sleep-apnea during seizures, are prolonged hypoxia with a decrease in blood oxygen saturation to 58% and a significant hypercapnia and acidosis (Seyal, 2009). The mechanism of respiratory arrest, and neurogenic pulmonary edema associated with asystole are some of the hypothetical mechanisms of sudden unexpected death in epilepsy (SUDEP) (Nashef, 2007; So, 2008; Jehi, 2008; Pezzela, 2009). Descriptions of near SUDEP cases during polysomnographic studies indicate sleep apnea as an important part of the clinical picture (So, 2000; Trotti, 2009). The pathogenesis of SUDEP is probably associated with the diving reflex mechanisms, generated during apnea (So, 2008) followed by significant bradycardia to asystole and a significant increase in systemic blood pressure, which significantly increases the afterload and metabolic demands of myocardium. In literature there are two cases of patients in whom obstructive sleep apnea caused changes in the EEG and cerebral hypoxia, which in one case ended in death, and in the second with transient encephalopathy (Dyken, 2004). Animal model of SUDEP proves that central apnea and myocardial ischemic changes should be considered as the main patomechanisms of death in the course of a seizure (Johnston, 1997). The relationship between sleep-disordered breathing and epilepsy also revealed a higher incidence of obstructive sleep apneas in patients with epilepsy compared with the general population matched for age. In various studies, the incidence of sleep-disordered breathing is estimated between 5% and 63% in patients with epilepsy (Malow, 1997; Malow, 2000; Beran, 1999; Weatherwax, 2003; Malow, 2003, Hollinger, 2006). Higher incidence of obstructive apneas and hypopneas was found in patients with drug-resistant epilepsy (Malow, 2000). The co-existence of idiopathic epilepsy and obstructive sleep apneas was also observed in the elderly population (Chihorek, 2007). In the cited paper the authors suggest that the increase in the number of new cases of idiopathic epilepsy in the elderly is associated with an increased incidence of sleep-disordered breathing in these patients. A number of studies indicate the beneficial effect of treatment with CPAP method for reducing the number of seizures (Malow, 2000, Hollinger, 2006; Chihorek, 2007; Malow, 2008). Precise pathomechanisms linking apnea with seizure are unknown. There are several reasons that may come up for coexistence of the observed higher incidence of seizures with sleep-disordered breathing. Particularly interesting is the observation on the significantly higher prevalence of sleep apnea in patients with drug-resistant epilepsy (Malow, 2000). One of the pathomechanisms may be related to apnea hypoxia, which leads to decrease of the available pool of ATP in cortical neurons. It was shown that lack of ATP increases the excitability of neurons by the partial depolarization of the cell membrane (Somjen, 2001), which reduces the seizure threshold. Reducing the amount of ATP in neurons also causes increase in amplitude of the sodium ion current in neurons (Rola, 2004), which may accelerate neuron depolarization and action potential generation. Another possible pathomechanism, causing seizures during sleep apnea, is the increased number of awakenings and disturbed sleep architecture. Obstructive type of respiratory disorders are most common during light sleep (stage I and II NREM sleep), during the instability of the respiratory center. In these phases, there are also more awakenings. K complexes and sleep spindles which occur in II phase of NREM are associated with increased pathological hyper synchrony (Bonakis, 2009). Patients with sleep-disordered breathing have disturbed sleep architecture. There is an increased time of shallow sleep (stage I and II NREM) and the reduction or total absence of REM sleep stage. As mentioned above, the NREM sleep, I and Phase II contribute to the occurrence of seizures, while desynchronization of bioelectrical activity of the brain in REM stage prevents seizures (Seyal, 2009). A patient with severe sleep apneas and disturbed sleep architecture is staying longer in the NREM stages, exposed to the induction of seizures, and less in the REM stages of sleep associated with lower risk of seizure. Although the consequence of these pathomechanisms may be increased risk of seizures in patients with apneas, but thanks to the possible treatment a reduction in seizure frequency is observed. Case reports noted the reduction of symptoms of sleep-disordered breathing after surgical treatment of epilepsy (Foldvary-Schaefer, 2008) and the reverse effect of vagal stimulation (Holmes, 2003) which indicates a mutual relationship of these two disease entities.
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