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Mainieri, G.; Loddo, G.; Provini, F.; Nobili, L.; Manconi, M.; Castelnovo, A. Diagnosis of NREM Sleep Parasomnias. Encyclopedia. Available online: https://encyclopedia.pub/entry/43795 (accessed on 27 July 2024).
Mainieri G, Loddo G, Provini F, Nobili L, Manconi M, Castelnovo A. Diagnosis of NREM Sleep Parasomnias. Encyclopedia. Available at: https://encyclopedia.pub/entry/43795. Accessed July 27, 2024.
Mainieri, Greta, Giuseppe Loddo, Federica Provini, Lino Nobili, Mauro Manconi, Anna Castelnovo. "Diagnosis of NREM Sleep Parasomnias" Encyclopedia, https://encyclopedia.pub/entry/43795 (accessed July 27, 2024).
Mainieri, G., Loddo, G., Provini, F., Nobili, L., Manconi, M., & Castelnovo, A. (2023, May 04). Diagnosis of NREM Sleep Parasomnias. In Encyclopedia. https://encyclopedia.pub/entry/43795
Mainieri, Greta, et al. "Diagnosis of NREM Sleep Parasomnias." Encyclopedia. Web. 04 May, 2023.
Diagnosis of NREM Sleep Parasomnias
Edit
This entry is adapted from the peer-reviewed paper 10.3390/diagnostics13071261

Non-rapid eye movement (NREM) sleep parasomnias mainly include confusional arousals (CA), sleep terrors (ST), and sleepwalking (SW), three clinical entities lumped together under the name of disorders of arousal (DoA).

NREM sleep parasomnias disorders of arousal sleepwalking confusional arousal

1. Clinical Interview

An accurate clinical interview is theoretically sufficient to confirm a diagnosis of disorders of arousal (DoA) according to standard international criteria [1][2]. However, limiting the diagnosis to clinical criteria may present limitations related to the age of occurrence of the episodes and the possibility to collect an accurate description of the episodes from the patients and their relatives/bed partners.
The presence of recurrent incomplete awakenings (criteria A, ICSD-3) associated with an inappropriate or absent responsiveness to the external environment (criteria B in ICSD-3) represents the very core of the definition of DoA [1]. During CA, patients may sit up in bed, stare straight ahead or look around the room with a perplexed or blunt expression, may vocalize intelligible or unintelligible words, and may often return back to sleep soon after. ST usually begins abruptly, with an intense autonomic activation (tachycardia, tachypnea, diaphoresis, mydriasis). Patients may rise screaming and appear scared and unresponsive to external attempts to interact or calm them down. During SW, patients leap out of bed and wander about the room or the house, or more rarely, may even walk outside. SW patients may perform routine activities like dressing, washing, preparing for school, urinating (sometimes at inappropriate locations), but can also engage in more dangerous actions like moving the furniture, manipulating sharp objects, or jumping out a window [1][3][4][5][6][7]. Prolonged cases associated with sleep driving have been described [8]. Notably, the arousal threshold is higher than wakefulness, and pain processing seems to be altered [9], further exposing these patients to potential dangers.
The ICSD-3 recognizes some other common features in DoA, meaning a limited or absent cognition or dream imagery during the episodes (criteria C in ICSD-3 and criteria B in DSM-5) and partial-to-complete amnesia for the episodes (criteria D in ICSD-3 and C in DSM-5) [1]. Frequent amnesia significantly undermines history taking and makes critical the presence of caregivers or bedpartners who witnessed the episodes during the clinical interview. Interestingly, the view of DoA as automatic behaviors performed in the absence of any conscious experience has been significantly challenged in the last two decades. In fact, different retrospective studies have shown various degrees of mental/oneiric recall associated with DoA episodes (above 70% of patients across their life span) [10][11][12]. Mental experiences during DoA episodes seem not only limited to single visual scenes or simple mental fragments, and even complex, vivid and long dream-like/hallucinatory experiences may not rule out a diagnosis of DoA [13]. In the only case series where patients with ST were interviewed immediately after their episodes, mental imagery was present in ~ 60% of the cases [14]. The degree of recall may depend on several factors, including the time distance between the clinical interview and the episode’s occurrence, as well as the individual mnesic ability (usually more developed in adults). Of note, the recall rate seems to differ between children and adults, in line with the hypotheses of more immature sleep mechanisms in children (and lower dream recall rate), and with an easier arousability in adults (that may facilitate the incorporation of the dream experience in long-term memory) [12][15]. Thus, it's suggested that criteria C and D should be considered optional supportive criteria (especially in children) but not mandatory criteria (see Table 1). Of note, in adults, mental content may also have a discriminatory value against RBD. Indeed, while negative emotions and violent behaviors are as frequent in DoA as in RBD [11], high levels of apprehension associated with misfortune (meaning any threat over which the subject does not have control) is more strictly associated with DoA than RBD. Self-defense or fleeing behaviors are more typical of DoA and direct fighting/aggressive behaviors (where the patient acts the first move) or aggressions by either humans or animals are more frequent in RBD [10][11]. Moreover, the occurrence in at-home settings (and not in a virtual dreaming scenario as in RBD) seems to be very specific for DoA [16].
Table 1. Suggestions for new DoA diagnostic criteria.
  Definition
Clinical Manifestation
  • Recurrent episodes of incomplete awakening from sleep.
  • Inappropriate or absent responsiveness to efforts of others to intervene or redirect the person during the episode.
  • Supportive features:
    • The events usually occur during the first third of the major sleep episode.
    • The individual may continue to appear confused and disoriented for several minutes or longer following the episode.
    • Limited (e.g., a single visual scene) or no associated cognition or dream imagery (especially in children).
    • Partial or complete amnesia for the episodes (especially in children).
Distress/Disability
D.
The disturbance causes clinically significant distress or impairment in mental, physical, social, occupational, educational, or other important areas of functioning, as indicated by the report of at least one:
  • Daytime sleepiness.
  • Disturbed sleep (of the patient or the bedpartner).
  • Self-injuries.
  • Injuries to others.
  • Psychological issues (e.g., feeling of shame, anxiety, fear to go to bed).
Exclusion
E.
The disturbance is not better explained by another sleep disorder, mental disorder, medical condition, medication, or substance abuse.
Levels of certainty
  • Possible: the diagnosis is based only on clinical interview (witness or self-report description).
  • Probable: the diagnosis is based only on clinical interview (witness or self-report description) and:
    −
    Home video recordings document typical behavioral episode(s) consistent with the clinical characteristics retrieved from the patient’s or witness’s interview.
    −
    The video-polysomnography documents minor episode(s) that does not fully correspond to the clinical description retrieved from the patient’s or witness’s interview.
  • Definite: video-polysomnography documents typical behavioral episode(s) out of NREM sleep.
CA, ST, and SW should be interpreted as a diagnostic continuum on the basis of clinical, epidemiological, physiological, and genetic evidence [17]. Indeed, patients usually display more than one clinical subtype (CA, ST or SW) throughout their lifespan and may even switch from one manifestation to the other within the same episode. Of note, the presence in the same subject of different semiological manifestations across episodes and a lack of stereotypy within the episodes, together with partial interactions with the surroundings (e.g., environment exploration and apparently purposeful object manipulation) seem to be specific for DoA. These elements support the differential diagnosis with sleep-related hyper-motor epilepsy (SHE)—the condition that poses more challenging issues in terms of differential diagnosis, especially in the presence of short episodes [3][18][19]. Contrary to REM sleep behavior disorder (RBD), eyes during DoA episodes are wide open [20], even during minor episodes, and movements more often involve the trunk [21].
The timing and the evolution of episodes are other essential features to consider. Indeed, DoA episodes more frequently—although not exclusively—occur during the first third of the night (when slow wave sleep (SWS) predominates), while RBD more typically occurs in the second half of the night (when REM sleep predominates); SHE tends to manifest more equally across the entire night [22]. Last but not least, DoA episodes usually occur in clusters across the life span, with a frequency of episodes that fluctuates over time, possibly in relation to sleep deprivation and stress [4].
Another fundamental part in DoA clinical history is the identification of predisposing, priming, and precipitating factors like the familiar history [23], the presence of symptoms or signs suggestive for other sleep disorders known to fragment sleep (like sleep apneas or periodic limb movements), an unusual sleep environment, sleep deprivation, sensory stimuli, or medications [24][25].

2. Questionnaires

Few questionnaires have been validated for screening patients with a clinical suspect of non-rapid eye movement (NREM) sleep parasomnias and/or quantify their severity. These scales have been validated mainly in adult populations.
The Munich Parasomnia Screening (MUPS) questionnaire [26] is a self-rating instrument composed of 21 items and provides a quick overview on the occurrence and frequency of parasomnias and other nocturnal behaviors in adults. However, the protocol of validation did not include a video-polysomnography (VPSG) to confirm the diagnosis, as this questionnaire was meant more for screening than for diagnostic purposes [26][27].
The Paris Arousal Disorders Severity Scale (PADSS) [28] is a useful instrument for monitoring DoA clinical symptoms and severity. It is composed by a self-rated scale assessing the occurrence of 17 parasomnia behaviors, their frequency, and consequences. Of note, neither MUPS or PADSS were validated against patients with SHE [29].
To this extent, the Frontal Lobe Epilepsy and Parasomnias (FLEP) Scale was developed to differentiate SHE from parasomnias, especially DoA [30]. However, not all the patients in this research had a diagnosis confirmed by VPSG. A successive Italian validation of the same scale [31], in which the diagnoses were confirmed by in-lab VPSG, did not confirm these encouraging results. The scale gave an incorrect diagnosis in 5.6% of cases, which included patients with SHE seizures characterized by nocturnal wandering (mistaken for SW), while around one-third of cases had uncertain diagnostic indications, due to items associated with a risk of misdiagnosis (mainly “recall” and “clustering” of the events, increasing the chance of mistaking RBD for seizures) [31].
The Arousal Disorders Questionnaire (ADQ) was recently validated to screen adults with DoA according to ICSD-3 criteria [32]. The questionnaire includes two parts: the first part is specific for each subtype (CA, ST, SW), while the second part assesses general DoA criteria. This questionnaire has a good interobserver reliability [33], an acceptable sensitivity and a high specificity for the diagnosis of DoA. Excluding the items regarding consciousness and episode recall (ICSD-3 criteria C and D, see Table 2), the sensitivity increased without major changes in specificity, highlighting that these criteria might not be always appropriate for adult cases of DoA.
Overall, the use of validated questionnaires might support the screening of DoA in non-specialized settings, improve DoA diagnostic accuracy in clinical and research sleep settings, assess the severity of DoA over time, before and after treatment, and guide further diagnostic assessments in case of atypical scenarios or comorbidities.
Table 2. Scales available for NREM sleep parasomnias screening, diagnosis, or follow-up.
  Validation Sample Sensitivity Specificity Utility
MUPS [26] 65 adult psychiatric patients
50 adult patients with sleep disorders
65 adult HC		 ST: 100%
CA: 100%
SW: 83%		 ST: 89%
CA: 97%
SW: 100%		 Screening of parasomnias, sleep-related movement disorders or normal variants
PADSS [28] 73 adult and adolescent active SW/ST
45 adult and adolescent patients with sleep disorders (26 former DoA, 19 RBD)
53 adult and adolescent HC		 DoA: 84% DoA: 88% DoA severity and follow-up
FLEP [30] 62 adult and children/adolescent patients (31 with SHE, 29 with DoA, 2 with RBD) SHE: 100% SHE: 90% Differentiate SHE from parasomnias
FLEP [31] 71 adult patients (11 DoA, 14 SHE and 46 RBD) SHE: 71% SHE: 100% Differentiate SHE from parasomnias
ADQ [32] 47 adult and adolescent DoA
103 adult and adolescent patients with sleep disorders (56 RBD, 39 SHE, 6 NES, 2 with drug-induced DoA)		 DoA: 72%
(83% without criteria C and D)		 DoA: 96%
(93% without criteria C and D)		 DoA diagnosis
DoA, Disorders of Arousal; RBD, REM behavior Disorder; SHE, Sleep-related hypermotor epilepsy; NES, Night Eating Syndrome; ST, Sleep Terror; CA, Confusional Arousal; SW, Sleepwalking; HC, healthy control subjects.

3. Video-Polysomnography

VPSG is usually performed when evaluating patients with atypical NREM sleep parasomnias, meaning cases with red flags, such as (1) adult onset; (2) stereotypical, repetitive, abnormal unnatural postures, ballistic movements or focal motor patterns; (3) high episode frequency; (4) episodes of brief duration; (5) episodes recurring in any part of the night; (6) other suspected sleep disorders; and (7) presence of dissociative symptoms [34] during daytime/other major psychiatric comorbidities [35] (see Figure 1).
Figure 1. Proposed levels of certainty in DoA diagnosis.
VPSG assumes an important role in the differential diagnosis between DoA and SHE [29], RBD or parasomnia overlap disorder [36], as well as in sleep-related (psychogenic) dissociative disorders [37]. Furthermore, VPSG traces can give important information regarding other potential sleep disorders triggering DoA, such as obstructive sleep apneas and periodic limb movements (PLM) (up to 33% of the cases in adults) [38].
Moreover, in the assessment of DoA, video synchronized with EEG adds critical information. The probability of catching a typical episode during VPSG is approximately 30–60% [38][39][40][41]. This percentage largely depends on the frequency/severity of parasomnia episodes, the life period when the recording is performed, the patient’s age, and the sensibility of the scorer to minor/brief nocturnal episodes [38][39][40][41], which represent the majority of episodes captured in-laboratory.

4. Home-Video-Recordings

Despite being the current gold standard for the assessment of complex nocturnal sleep behavior, supervised VPSG is expensive, time consuming, and often implies long waiting lists. Furthermore, as highlighted in the previous section, the probability of catching at least one parasomnia episode during a single-night VPSG assessment is far from being satisfactory. This percentage largely depends on the frequency/severity of parasomnia episodes, the patient’s age, and the sensibility of the scorer to minor/brief nocturnal episodes [38][39][40][41], which represent the majority of episodes captured in-laboratory. Indeed, the differential diagnosis of brief nocturnal episodes by both video and EEG is often extremely difficult [3]. In this perspective, the analysis of homemade video recordings of nocturnal episodes may be an important supportive diagnostic tool for DoA [42]. It offers multiple advantages: wide availability, low-costs, the possibility of recording patients in their usual sleep environment and of repeated recordings, increasing the chances of capturing multiple and possibly longer and more complex episodes compared to the standard in-laboratory setting.
Even in the case of partial recordings by parents/bed partners, when the onset of the episode is missed, video-recordings could be a useful tool for the differential diagnosis of nocturnal events, as it is not the onset of the episodes but the evolution and the offset of the events that has a discrimination value between DoA and SHE [42]. Furthermore, repeated home videos using professional high-quality infra-red motion-detector cameras can now record and store consecutive episodes from several nights.
Up to now, 2 single case reports highlighted the usefulness of monitoring nocturnal behaviors in adults with NREM sleep parasomnias with an infrared camera in the home environment for 5 and 2 weeks, respectively [13][43]. More recently, a study of 20 adults with frequent DoA episodes, recorded for at least 5 consecutive nights, confirmed a good feasibility, acceptability, and clinical value of home-video recordings in DoA [44]. An average of at least 3 nights was required to capture at least 1 event and events were usually more complex than those recorded during VPSG.

5. Differential Diagnoses

DoA must be differentiated by a number of other sleep disorders [45] (see Table 3): REM-related parasomnias, like nightmare disorder, RBD, and parasomnia overlap disorder [46]. SHE and sleep related psychogenic dissociative disorder (SRDD) are probably the trickiest conditions that might simulate DoA [34][37], in the absence of objective findings. Nocturnal panic attacks may also simulate ST [47][48][49]. Medication- or substance-induced nocturnal confusion must be always ruled out before considering a DoA diagnosis.
Table 3. DoA differential diagnoses.
  DoA RBD SHE SRDD Nightmare Disorder Nocturnal Panic Attacks
Age at onset Infancy >50 years, rare in children/adolescent (mostly Narcolepsy patients) Any age Variable Children>adults Variable—adults
Gender M = F M in sleep clinics, equal in general population M > F F > M M = F F in DP/NP, M in isolated NP
Predisposing or
priming conditions		 Family history, stressful situations, sleep deprivation - - Traumatic events/abuse/major psychopathology Traumatic events Mostly DP attacks
Triggers + - +/− + + +
Occurrence during the night Usually, first third Second part of the night Any time W close to bedtime Second part of the night First third
Sleep stage N3 REM sleep N1, N2 Prolonged W REM sleep Transition N2–N3
Frequency (number of episodes/
night)		 One major, possible multiple minor Variable, from one to several Several From one to several Usually, one Usually one, occasionally > one
Episodes
duration		 1–10 min Variable, seconds to several minutes Seconds to 3 min >1 h 3–30 min 2–8 min
Stereotypy - - + - - -
Mental
content		 Short scenes involving misfortune or threat Complex scenarios, variable content from aggression to positive - - Nightmare, intense fear -
Consciousness at the end of the
episodes		 Impaired Preserved Variable Preserved Preserved Preserved
Recall Rare in children, > in adults Frequent Inconstant Inconstant Present Vivid recall of fearful sensations, not related to dream scenario
Clinical
consequences		 Sleepiness, injuries, daytime impairment Injuries Injuries, daytime impairment Self-inflicted injuries Mood disturbance, daytime impairment, bedtime anxiety Daytime disfunction
M, males; F, females; DoA: disorders of arousal; DP, diurnal panic; NP, nocturnal panic; PTSD, post-traumatic stress disorder; SHE: sleep-related hypermotor epilepsy; RBD: REM-sleep behavior disorder; SRDD: sleep-related dissociative disorder; W, wake; N1: sleep stage 1, N2: sleep stage 2; N3: sleep stage 3.

6. Therapy

Current evidence on both pharmacological and non-pharmacological interventions in NREM sleep parasomnias is hampered by: (1) the relative low number of patients that reach specialistic attention; (2) the lack of agreement between specialized sleep centers; (3) the lack of animal models and of a clear understanding of neural circuits implied in NREM sleep parasomnias; and (4) the fact that treatment efficacy is particularly insidious to test, given the frequent episode-related amnesia and the consequent relatively low reliability of subjective reports. Only one study using an objective outcome (number of episodes captured with home-video recordings) has been conducted to date. This study suggested a reduction in the frequency of episodes in eight DoA patients treated with Clonazepam [44]. Treatment strategies currently available for DoA has been extensively reviewed elsewhere [50][51][52][53][54]. The researchers will briefly summarize them below and in Table 4.
Table 4. Treatment approaches available for DoA.
Non-Specific Interventions
Reassurance
Parents/bedpartners education
Sleep hygiene
Environmental safety
Treatment of other sleep disorders
Removal of triggering medications
Pharmacological interventions
  Age group Efficacy Type of evidence
Clonazepam Adults >70% Large case series
Case reports/small case series
Other benzodiazepines Adults Insufficient/
contradictory results		 Case reports/small case series
Antidepressants Adults Insufficient/
contradictory results		 Case reports/small case series
5-L-OH-Tryptophane Children >80% Open clinical trial (ST only)
Melatonin Adults -
Children		 Insufficient/
contradictory results		 Small retrospective case series/case reports
Non-pharmacological interventions
  Age group Efficacy Type of evidence
Scheduled awakenings Children Insufficient results Small case series
Hypnosis Adults -
Children		 Positive results Rater-blind trial/Case series
Integrated CBT protocols Adults Positive results Retrospective case series
Randomized control trial
Other specific non-pharmacological approaches Adults -
Children		 Insufficient results Case reports/Case series

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Subjects: Neurosciences
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Greta Mainieri
,
Giuseppe Loddo
,
Federica Provini
,
Lino Nobili
,
Mauro Manconi
,
Anna Castelnovo
View Times: 301
Revisions: 3 times (View History)
Update Date: 05 May 2023
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