Sleep disorders have an adverse impact on daily living for both children and their caregivers.1 Sleep disturbance and lack of restful sleep can masquerade as a myriad of clinical problems, including inattention, depression, headache, and seizures. While most neurological disorders are well characterized during the waking state, descriptions of pathophysiology, signs and comorbidities are frequently poorly described during sleep. Physiologic changes associated with sleep can cause an alteration of signs and function during both REM (rapid eye movement) and non-REM (NREM) sleep. These changes may include alterations in muscle tone, central control of autonomic functions, and changes in cortical neurotransmitter system interaction and balance.
Epilepsy is also a disorder that affects every aspect of a child’s cognitive, social, and emotional well-being. When these disorders coexist, they can be both challenging to identify and differentiate, and a burden to the young patient and their families.
This review is devoted to the relationships between epilepsy, sleep and its disorders. The effects of epilepsy on sleep architecture and the quality of children’s sleep are reviewed. How sleep may affect epilepsy and the role of circadian rhythms is discussed next. Evidence regarding the relation between epilepsy and both childhood sleep breathing disorders and restless legs syndrome (RLS) is summarized. Finally, a discussion highlighting differences between epilepsy and the most common sleep disorders during childhood is provided. An outline of evaluation and treatment of the epileptic child with a sleep disorder ends this review.
Epilepsy has important effects on sleep and the sleep–wake cycle.2 Alterations in total sleep, time sleep latency, and spontaneous awakenings have been demonstrated in epileptic children.3 Epilepsy may affect both the quantity and the architecture of sleep. The effects of epilepsy on sleep vary depending on seizure type. In patients with primary generalized tonic–clonic seizures, the amount of REM sleep is decreased by 50%, while in those suffering from secondarily generalized seizures, it may be as low as 41%.4,5 Infants with epileptic encephalopathies (hypsarrhythmia and Lennox–Gastaut syndrome)6 also have decreased REM sleep as well as a decrease in total sleep time in a 24-hour period.6,7,8 Prolonged sleep latency, an increase in the proportion of stages 1 and 2 NREM sleep, a decrease in the proportion of stages 3 and 4 NREM sleep, and an increase in the shifting between sleep stages have also been described.
Patients affected with childhood absence epilepsy and epilepsy with myoclonic absences do not show sleep disturbances.9 Among patients with complex partial seizures, only in those suffering from multiple nocturnal seizures, as in nocturnal frontal lobe epilepsy (NFLE), the proportion of REM sleep significantly lowered.10 Children with focal drug-resistant epilepsy studied with all-night polysomnography evidence a reduction of total sleep time, reduction of stage 2 and REM stage percentage and increase in first REM latency.11,12 REM stage can also be reduced by 18%–12% in patients with daytime temporal lobe seizures.13 Interestingly, patients with benign rolandic epilepsy have no associated sleep disorders.14,15 Likewise, children with continuous slow spike waves of sleep have no associated sleep disorders.
Sleep, on average, covers one third of the life span of a human being. Sleep tends to activate the EEG as delineated in Table 44–1. The relationship between sleep stages and ictal or interictal epileptiform discharges is well known,16,17 the modulation of epileptiform paroxysms during sleep depending on the type of epilepsy and the different electrophysiological status characterizing NREM and REM stages. During drowsiness and the first stages of NREM sleep, EEG activity becomes more synchronized, thus facilitating the propagation of epileptiform discharges; muscular tone is diminished but preserved, permitting the clinical manifestation of the seizures. On the contrary, in REM sleep, when EEG activity is desynchronized and postural tone inhibited, the paroxysmal activity is inhibited. Interictal discharges of localization-related epilepsies tend to propagate during NREM sleep and become topographically restricted in REM stages. The thalamocortical volleys that physiologically evoke the K-complexes and spindles in NREM stages, drive burst-pause firing in cortical neurons, facilitating the occurrence of generalized discharges in primary generalized epilepsy.
Interictal epileptiform activity in the EEG occurs more frequently during NREM sleep than during wakefulness, and tends to be suppressed by REM sleep.18
Representative samples of sleep are very important in the evaluation of the pediatric epilepsy patient. In a significant percentage of children, epileptiform activity appears in the EEG recording only while the patient sleeps. Conversely, epileptiform activity in the EEG recording is rarely isolated to wakefulness.19 Sleep deprivation is commonly used to increase the likelihood of obtaining a significant EEG recording in children. However, it is unclear whether this is best achieved by natural sleep, sedated sleep, or sleep deprivation20 The existing literature supports a role for sleep deprivation, separate from the induction of sleep with a hypnotic agent, in activating epileptiform discharges.20 A sleep-deprived patient is more likely to provide an adequate sleep tracking with activation of epileptiform discharges. Interestingly, it has been shown that sleep deprivation can increase the occurrence of epileptiform abnormalities in the waking portion of the EEG in a child who previously had a normal awake EEG.21
Both sleep and arousals may activate epileptiform discharges and facilitate seizures, and in several seizure disorders the occurrence of seizures is clearly state dependent.
Children with epilepsy have more sleep problems than siblings or healthy controls. In addition, children with active seizure disorders have more complaints than epileptic children who are seizure free. Children with idiopathic epilepsy have a greater incidence of parasomnias, bedtime difficulties, sleep fragmentation, and daytime drowsiness. Age is also a factor with younger children having more sleep problems than older children.22 Zaiwalla and Stores23,24 found that parents describe their children’s sleep as “unrefreshing.” The unrefreshing quality was associated with frequent physiologic arousals, daytime sleepiness, and lethargy. They also found increased incidence of parasomnias and sleep fragmentation in these children.23 Rosen et al2 observed a correlation between nighttime awakening and daytime problems in learning and behavior in children with epilepsy. Stores24 examined 79 children with epilepsy and 73 age-matched controls. Epileptic children aged 5–16 years were found to have more frequent sleep disturbances than matched controls. These disturbances included poor sleep quality and anxiety about sleeping. There was also a correlation between seizure frequency and anxiety about sleeping. In younger children between the ages of 5 and 11 years, poor sleep quality was associated with daytime inattention. This correlation was not noted in the older group. For instance, Hunt and Stores25 found significant sleep disruption in younger children with tuberous sclerosis and active epilepsy. Problems with daytime inattention were seen more frequently in children who were experiencing frequent nocturnal seizures.
Epilepsy can alter also circadian rhythms, in fact Fauteck et al26 have demonstrated lack of melatonin variation in children with epilepsy and poor sleep and other studies have demonstrated improved sleep in developmentally disabled children with the use of melatonin.27
On the other hand, sleep fragmentation and the associated daytime sleepiness in children may cause an increase in seizure frequency and can produce difficulty in obtaining seizure control. Fountain et al28 report an independent effect of sleep deprivation on epileptiform discharges from the activation observed during sleep. Patients with obstructive sleep apnea syndrome (OSAS) or restless leg syndrome may exhibit increased difficulty with seizure control secondary to sleep fragmentation produced by their sleep disorder. Patients with altered sleep patterns may also experience increased seizures. These sleep alterations may be secondary to behavioral problems associated with sleep onset. Central nervous system abnormalities that alter or interrupt circadian pathways may also affect sleep and seizure control.
Children with epilepsy underperform in achievement testing when compared with age and IQ-matched controls. It is hypothesized that underachievement in some children may in part be secondary to poor daytime alertness resulting from sleep fragmentation. Daytime sleepiness persisted in nine preadolescent children after discontinuation of anticonvulsant therapy despite seizure control. The persistence of daytime sleepiness in these children raises the question of an underlying increased sleep tendency in patients with epilepsy or the persistent effect of drugs on behavior after washout.
Anticonvulsants can improve sleep abnormalities by improving seizures decreasing microarousals and sleep fragmentation. Anticonvulsants can control seizures, which in turn may restore circadian rhythms and normalize sleep. Seizures cause change in circadian rhythms by means of propagation of discharges through the limbic system via the hypothalamus, producing alterations in melatonin, and/or direct effects on the suprachiasmatic nucleus. In addition, anticonvulsants may have a direct effect on sleep.
The most common epileptic disorders related to sleep are discussed later.
Epilepsy with grand mal (GTC) seizures on awakening is a particular form of generalized idiopathic epilepsy (GIE)29 characterized by a frequent genetic trait, onset in late childhood, adolescence, and young adulthood. GTC seizures appear exclusively or predominantly after awakening or while relaxing.30 After sleep deprivation and during early sleep stages or soon after awakening, the EEG may be diagnostic in revealing generalized spike-wave discharges.
In patients with myoclonic astatic epilepsy (Doose syndrome), tonic seizures, which present with 10–15 Hz spike series, occur almost exclusively during sleep.31
Infantile spasms also occur more frequently in the period that just precedes or follows from sleep, rarely occur during NREM sleep, and never during REM. The brief, generalized tonic seizures associated with Lennox–Gastaut syndrome occur more frequently in clusters upon awakening and during NREM sleep.32
Children with infantile spasms exhibit a hypsarrhythmia (West syndrome) in the awake EEG tracing. NREM sleep can alter this pattern with bursts of more diffuse polyspike-waves and more synchronous slow spike and waves. Spindles may be superimposed on a generalized low-amplitude tracing between bursts. Periods of bursts and low-amplitude activity may alternate, resembling burst-suppression pattern.33 The hypsarrhythmic pattern may be completely suppressed in REM sleep, paradoxically normalizing the EEG.
Recently Kohyama et al34 reported that, seizure control in children with infantile spasms could be predicted by an increase in the number of spontaneous horizontal eye movements associated with phasic chin muscle activity during REM sleep. Patients with a good response to valproate, clonazepam, and/or zonisamide had significantly fewer simultaneous phasic events than poor responders who subsequently required hormonal therapy.34 In patients with good response to treatment, REM phasic activity was similar to controls. It was postulated that an increase in REM phasic activity suggests loss of inhibition from the pons to the motor neurons controlling REM muscle atonia. During wakefulness, children with Lennox–Gastaut syndrome show a typical 2–2.5 Hz slow spike-wave pattern. However, during NREM sleep, frontally dominant bilateral rhythmic discharges with a frequency of about 10 Hz occur that are considered to be an essential feature of this syndrome, and which are sometimes, but not always accompanied by tonic seizures.
Juvenile Myoclonic Epilepsy (JME)35 is another GIE in which the myoclonic jerks usually occur after awakening and are often precipitated by sleep deprivation. Interictal EEG tracings show generalized bursts of spike- and polyspike-and-wave complexes at 3–6 Hz that are facilitated by sleep deprivation, intermittent light stimulation, and awakening,36 but usually disappear during both REM and NREM sleep.
Seizures in benign epilepsy of childhood with centrotemporal spikes (BECT) and idiopathic (with age-related onset), localization-related epilepsies are strongly activated by sleep. Typical EEG pictures show diphasic high-amplitude spikes followed by a slow wave localized on the centrotemporal areas. Activation of EEG abnormalities in drowsiness and sleep is typical and in about 30% of patients spikes appear only during sleep.37,38 Spikes can remain unilateral but in about half of the cases they are bilateral synchronous or asynchronous, often shifting location in subsequent EEG recordings. Other uncommon EEG aspects are the coexistence of occipital spikes or generalized spike-and-wave discharges.
Seventy-five percent of children with Rolandic epilepsy have seizures exclusively during either daytime or nighttime sleep; while approximately 15% have seizures whether they are awake or asleep, and 10%–20% only experience seizures when awake. Not only are Rolandic seizures more likely to occur during sleep, but when nocturnal, are also typically longer and more likely to secondarily generalize.33 Epilepsies with seizures occurring primarily during the day are rare and can be seen in young patients with benign epilepsy of childhood with occipital paroxysms.
The Landau–Kleffner syndrome (LKS),39,40,41 a disorder characterized by an acquired speech disturbance (aphasia and auditory agnosia) occurring in previously age-appropriate children, is characterized on sleep EEG by almost continuous bitemporal paroxysmal activity. Disrupted executive and cognitive functions, more than language, leading to severe cognitive and behavioral disturbances are characteristic of Continuous Spike and Waves during Sleep (CSWS)9,42 in which EEG paroxysmal activity accounts for at least 85% of sleep and predominates on both frontal areas. The EEG features of LKS and CSWS differ from those recorded in Lennox–Gastaut syndrome, in which sleep EEGs usually show polyspike-and-wave activity and bursts of low-amplitude fast activity related or not to tonic fits.
Localization-related seizures in lesional or cryptogeneic partial epilepsy may have a random occurrence. In some patients, irrespective of the clinical form, seizures may acquire a more regular circadian rhythm during the illness and appear preferentially or almost only during sleep and seizures can be induced by relative sleep deprivation in some patients with temporal lobe epilepsy.43
However, there is a peculiar form of partial epilepsy, NFLE, in which seizures appear almost exclusively during sleep.44
HOT SPOTS IN THE DIFFERENTIAL DIAGNOSIS BETWEEN EPILEPSY AND SLEEP DISORDERS
Sleep disorders or sleep-related physiological events frequently coexist in patients with epilepsy and may mimic epileptic seizures. Prompt recognition of phenomena mimicking epilepsy is vital to prevent patients undergoing unnecessary and costly investigations, and clinicians instigating potentially harmful therapeutic regimens (Table 44–2). Furthermore, it is important to recognize these cases because treatment of the sleep disorder may contribute to seizure control by decreasing sleep disruption.14,45
|Sleep-related breathing disorders|
|Hypersomnias of central origin|
|Circadian rhythm sleep disorders|
|Parasomnias: disorders of arousal (from NREM sleep); parasomnias usually associated with REM sleep; other parasomnias|
|Sleep-related movement disorders: restless legs syndrome; periodic limb movement disorder; sleep-related leg cramps; sleep-related bruxism; sleep-related rhythmic movement disorder; sleep-related movement disorder, unspecified; sleep-related movement disorder due to drug or substance; sleep-related movement disorder due to medical condition|
|Isolated symptoms, apparently normal variants, and unresolved issues: long sleeper; short sleeper; snoring; sleep talking; sleep starts (hypnic jerks); benign sleep myoclonus of infancy; propriospinal myoclonus at sleep onset; excessive fragmentary myoclonus|
|Other sleep disorders|
|Appendix A: sleep disorders associated with conditions classifiable elsewhere: fibromyalgia; sleep-related epilepsy; sleep-related headaches; sleep-related gastroesophageal reflux disease; sleep-related abnormal swallowing, choking, and laryngospasm|
Sleep-disordered breathing problems represent an important category of pediatric sleep problems and encompass a wide spectrum of respiratory disorders occurring during sleep, ranging from primary snoring to OSAS. OSAS is characterized by repetitive episodes of upper airway obstruction or cessation of breathing during sleep, associated with blood oxygen saturation reduction and consequent arousals and sleep disruption.46 The prevalence of pediatric OSAS is estimated at 1%–4% for children between the ages of 2 and 18. The symptoms of obstructive sleep apnea (OSA) in children differ from those seen in adults. Although daytime sleepiness and fatigue are reported in children, behavioral problems, hyperactivity, and neurocognitive deficits are much more common in children with sleep apnea compared to normal controls. Children with severe sleep-disordered breathing often have multiple respiratory obstructive episodes; when chronic, this pattern leads to sleep deprivation and excessive daytime sleepiness (EDS).47 Pediatric OSAS can be confirmed with polysomnography. The severity of OSAS has been defined by use of apnea/hypopnea index (AHI) criteria alone. The criteria differ from adults, with an apnea index of more than one per hour considered abnormal.
Awakenings with feeling of suffocation and fear due to sleep apnea are common, with intense distress and may be mistaken for a nightmare, sleep terror, seizure, or panic attack, but obstructive apneas occur repeatedly during the night, compared to the typical single occurrence per night for nocturnal panic (a waking from sleep in a state of panic, defined as an abrupt and discrete period of intense fear or discomfort, accompanied by tachycardia, sweating, shortness of breath, chest pressure, and so on.).48
The typical cause of OSAS in children is enlarged tonsils and adenoids and for 70% of children symptoms of OSAS are alleviated by tonsillectomy and/or adenoidectomy.49 For children who are overweight, weight loss is the recommended treatment. Craniofacial surgeries are also an option in selected children with anatomic abnormalities.
Finally, in children in whom tonsillectomy or adenoidectomy is contraindicated or unsuccessful, nasal continuous positive airway pressure (CPAP) may be appropriate.
Narcolepsy is a chronic neurologic disorder occurring in approximately 1 in 2000 persons that peak in the second decade of life. There is no significant gender difference but a significant ethnic difference as the disorder is more frequent in Japan. Symptoms include EDS with or without cataplexy (a bilateral loss of muscle tone, triggered by strong emotion such as laughter or crying with consciousness usually unaffected), hypnagogic hallucinations, sleep paralysis, and fragmented nighttime sleep.46
As sleepiness may be the only symptom in children, the diagnosis of narcolepsy may be more difficult in children and adolescents.50 Narcolepsy is likely an under-recognized disorder in pediatric practice; 30% of adults report symptom onset before 15 years, perhaps 16% before 10 years of age, and possibly 4% before the age of 5.51
The symptoms of narcolepsy are frequently misdiagnosed as neurologic, psychiatric, or behavioral.52,53,54 Diagnostic confusion arises because a lack of responsiveness due to excessive sleepiness is mistaken for epileptic absences and cataplexy is confused with a variety of seizures types. In young children, recognition of excessive sleepiness can be confounded by the occurrence of daytime naps in normal children. However, these should normally cease by the age of 3–4 years after which the reappearance of repeated napping is significant. The variety in the degree and distribution of loss of tone in cataplexy can therefore be mistaken for different types of focal and generalized epileptic seizures. A lack of responsiveness associated with tiredness can be confused with facial myoclonia associated with absences.
The identification of triggers for cataplexy (usually strong emotions such as laughter or crying) is important in differentiating these paroxysmal events. Home-video recording of events by parents can be more use than attempting to capture events in unfamiliar environments such as hospitals because a degree of familiarity with surroundings and a relatively relaxed state is often required for cataplexy to occur. The relative frequency of attacks, their relation to emotional experience, and preservation of consciousness are useful guides to genuine cataplexy. Polysomnography with a multiple sleep latency test (MSLT) may provide clear evidence of narcolepsy, but results are not always conclusive in children, and repeat studies might be necessary. Monozygotic twins are discordant for narcolepsy. Eighty-six percent of narcoleptics with definite cataplexy have HLA DQB1–0602 on chromosome 6, but greater than 99% of patients with these haplotypes are normal.
The recent findings of reduced or absent cerebrospinal fluid hypocretin in most cases of narcolepsy with cataplexy, mean that estimation of this neuropeptide may aid diagnosis.55
The current treatment recommendations for narcolepsy in children include education (with the family and the other individuals with whom the child interacts), sleep hygiene (appropriate sleep scheduling and daily naps), and pharmacological interventions. Modafinil (Provigil), a pro-alerting drug that is FDA approved for the treatment of narcolepsy in adults, can dramatically improve daytime sleepiness. If Modafinil proves ineffective, traditional stimulants such as methylphenidate, and dextroamphetamine may also be of benefit; anticholinergic drugs are useful to treat cataplexy.56
Parasomnias are considered benign phenomena, especially in children, and do not usually have a serious impact on sleep quality and quantity. They include disorders of arousal (arising from NREM sleep), parasomnias usually associated with REM sleep and other parasomnias.46
Disorders of arousal are common pediatric sleep disorders that tend to cease with development.57 The three basic types of arousal disorders recognized in the ICSD-2 are confusional arousals, sleep terrors, and sleepwalking.
Confusional arousals, affecting up to 20% of children, are characterized by mental confusion and disorientation, relative unresponsiveness to environmental stimuli, and difficulty awakening the subject58 (Fig. 44–1). These events present a difficult diagnostic problem since the confusion can resemble postictal confusion in a patient with seizures. They are sometimes associated with incontinence. Sleep terrors, affecting 1%–7% of children, are “arousals from slow-wave sleep accompanied by a cry or piercing scream and autonomic nervous system and behavioural manifestations of intense fear” generally lasting 1–5 minutes46 (Fig. 44–2). Although appearing alert, the child typically does not respond when spoken to, and more forceful attempts to intervene may meet with resistance and increased agitation.
Sleepwalking, peaking by age 8–12 years,57 is defined as “a series of complex behaviours (such as changes in bodily position, turning and resting on one’s hand, playing with the sheets, sitting up in bed, resting on knees, etc.) that are usually initiated during arousals from slow-wave sleep and culminate in walking around with an altered state of consciousness and impaired judgment.”46
During disorders of arousal, although children are asleep, they may appear awake (eyes open), but they may not recognize their parents and resist attempts to be comforted or soothed, with attempts to wake the child often prolonging the event. Typical parasomnias resolve spontaneously with children rapidly returning to sleep, with no recollection of the event in the morning.
Disorders of arousal may be triggered by a variety of factors including sleep deprivation, a disruption to the sleep environment or sleep schedule, stress, febrile illness, medications, alcohol, emotional stress in susceptible individuals, or the presence of sleep-disordered breathing.59 Disorders of arousal tend to occur in the first part of the night when NREM stages 3 and 4 predominate. Polysomnography during the events reveals a rhythmic, delta activity pattern, associated with a marked increase in muscle tone, and changes in respiratory and heart rates.
Parasomnias may mimic epileptic seizures, although historical features are very useful in distinguishing these disorders. Features that suggest a NREM parasomnia rather than seizures are a low rate of same-night recurrence of the episodes, long duration, appearance within the first few hours of sleep, (seizures may occur throughout the night) and the characteristic motor pattern (parasomnias are not stereotypical and complex and repetitive behavior with abnormal movements, such as dystonic and dyskinetic postures, are absent).60 Moreover, the clinical picture of arousal disorders (early age at onset, decrease in frequency, or disappearance after puberty) differs from NFLE that first occurs between ages 10 and 20 years, often persists into adulthood, and manifests with daytime complaints such as sleepiness (Fig. 44–3). Sleep terrors are also distinguished from nocturnal panic attacks by being followed by a quick return to sleep without recall of the event.48
Many parasomnias can be diagnosed on the basis of history-taking. Patients should be considered for video-EEG monitoring if events are stereotypic or repetitive, occur frequently (minimum one event per week), have not responded to medications, and the history is suggestive of potentially epileptic events.61 Prompting the patient to make audio–video recordings at home with subsequent data analysis and comparison with the episodes recorded at the sleep laboratory may facilitate the diagnosis of arousal parasomnia.
Management includes reassuring parents that these episodes are a developmental phenomenon, harmless and they should not awaken their child who should be gently redirected back to bed without awakening. Every effort should be made to avoid any predisposing and triggering factors identified by a careful general medical and sleep history and polysomnography. Medications are rarely used to treat these sleep disorders but may be indicated if episodes are very frequent or when the child or others in the home are in danger of the behavior. In these cases imipramine or clonazepam at bedtime are beneficial in some patients.
Nightmares are “disturbing mental experiences that generally occur during REM sleep and often result in awakening.”46 They are common in young children, peaking at ages 3–6 years62 and their frequency decreases with age. A careful sleep history that focuses on the time of night of fearful awakenings helps to distinguish REM-related nightmares from disorders of arousals: the distinctive features of a nightmare are the recall of a long, frightening dream, and clear orientation on awakening. The major distinction between nightmares and nocturnal panic is the stage of sleep: a panic attack is a NREM event usually occurring from stages NREM 2 to 3.48
The lack of motor behavior during the episodes and the absence of confusion on awakening, as well as the availability of detailed dream reports helps distinguish nightmares from nocturnal frontal lobe seizures.60 In doubtful cases, video-polysomnography is indicated.
Sporadic nightmares are not worrisome, and require reassurance only, but recurrent nightmares or those with disturbing content may indicate excessive daytime stress.63 Once the basis for the nightmares is discerned, measures should be taken to eliminate or reduce the child’s exposure to the causative factor.
Recurrent isolated sleep paralysis is “an inability to perform voluntary movements at sleep onset or on awaking from sleep in the absence of a diagnosis of narcolepsy.46 Each episode lasts from seconds to a few minutes and is usually accompanied by intense anxiety. Sleep paralysis should be differentiated from atonic seizures that occur during wakefulness and nocturnal panic attacks usually not associated with paralysis (patients typically sit up and/or get out of bed).48 Reassurance and education are the most useful treatment in isolated cases. If the frequency of sleep paralysis is bothersome to patients, there is a suggestion that SSRIs may be of some benefit, likely because of their REM-suppressing properties.64
Sleep enuresis is “characterized by recurrent involuntary voiding during sleep.” In primary sleep enuresis, recurrent involuntary voiding occurs at least twice weekly during sleep after age of 5 years.46 The prevalence of primary nocturnal enuresis is approximately 30% of 4-year olds and is more common in boys than girls at all ages.46 In secondary enuresis the patients, older than 5 years of age, have previously been consistently dry during sleep for at least 6 months. Epileptic seizures are excluded because in these cases enuresis is the only symptom and occurs without any motor phenomenon.
Primary nocturnal enuresis is a heterogeneous condition for which various causative factors have been identified, so the treatment could be a combination of noninvasive tools and only particular cases and motivated patients should receive a specific pharmacologic treatment.65
Sleep-related groaning (catathrenia) is an unusual sleep-related behavior characterized by an expiratory groaning noise occurring almost every night, mainly during REM sleep and in the second half of the night.66,67,68 The noise occurs without any respiratory distress or concomitant motor phenomena; patients are unaware of their groaning, and upon awakening in the morning, do not recall anything particular about the night and feel restored. Affected patients have no overt neurological or respiratory diseases and during the groaning arterial oxygen saturation remains normal. Its predominant or exclusive occurrence during REM sleep, its duration (groaning usually lasts few seconds, often repeated in clusters), and the absence of any concomitant motor phenomena distinguish this nocturnal sound from moaning occurring during epileptic seizures.
Therapy remains problematic as patients usually decline any treatment because they are unconcerned about the problem.