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Non-REM-sleep instability in recurrent sleepwalking in pre-pubertal children
Sleep Medicine 6 (2005) 515–521 www.elsevier.com/locate/sleep
Original article
Non-REM-sleep instability in recurrent sleepwalking in pre-pubertal children Christian Guilleminaulta,*, Ji Hyun Leea, Allison Chana, Maria-Cecilia Lopesa, Yu-shu Huanga, Agostinho da Rosab a
Stanford University Sleep Disorders Clinic, 401 Quarry Road, Suite 3301, Stanford, CA 94305, USA b Universidade Tecnica de Lisboa Biological Engineering Laboratory, Lisbon, Portugal Received 13 January 2005; received in revised form 24 February 2005; accepted 4 March 2005 Available online 1 July 2005
Abstract Background and purpose: We questioned whether or not the sleep of pre-pubertal children with recurrent sleepwalking was different from that recorded in normal children. Patients and methods: Twelve pre-pubertal chronic sleepwalkers were compared to age- and gender-matched normal children. All children had a clinical evaluation covering pediatric, sleep, neuropsychiatric and otolaryngological fields. Two standardized sleep questionnaires were administered, and a minimum of two successive polysomnograms were performed with monitoring of sleep electroencephalographic (EEG) and cardiorespiratory variables. The research investigations were performed on nights without sleepwalking to search for the presence of other sleep disorders, including upper airway resistance syndrome (UARS). Sleep was scored using standard atlases, but it was also evaluated for the cyclic alternating pattern (CAP) rate. Results: All sleepwalkers presented with either obstructive sleep apnea (nZ2) or UARS (nZ10). Compared to normal children, sleepwalkers had shorter total sleep time but no significant change in wake after sleep onset when considering all arousals O3 s. CAP analysis showed a significantly higher CAP rate than in controls. Conclusions: Chronic sleepwalkers have instability of non-rapid eye movement (NREM) sleep detectable only by the calculation of CAP rate. Instability of NREM sleep was seen even on nights without sleepwalking and is probably related to the presence of the associated sleep disorders. We hypothesize that chronic NREM-sleep instability is a risk factor for occurrence of sleepwalking when further sleep disruption is triggered by external events. q 2005 Elsevier B.V. All rights reserved. Keywords: Children; Chronic sleepwalking; Sleep-disordered breathing; Cyclic alternating pattern; NREM-sleep instability
1. Introduction Somnambulism (sleepwalking) is defined as an arousal parasomnia [1]. It consists of large movements in bed or walking during sleep. Oscillating between 2 and 14% in children, its prevalence is controversial [2–6]. Sleepwalking often decreases with onset of puberty, but at least 25% of children with chronic sleepwalking may continue to sleepwalk in adulthood [2–7]. It is thought to arise from slow
* Corresponding author. Tel.: C1 650 723 6601; fax: C1 650 725 8910. E-mail address: [email protected] (C. Guilleminault).
1389-9457/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2005.03.003
wave sleep (SWS), particularly stage 4 non-rapid eye movement (NREM) sleep. An occasional confusional arousal can be seen in 40–50% of children between 3 and 6 years of age [2]. Sleepwalking may be a recurrent event with risk of injury to oneself and others [8,9]. In our own subjects with chronic problems, injuries were seen in male teenagers (age 14–17 years). Injuries had occurred in five out of 120 of our cases of children having been referred for chronic sleepwalking. These teenagers had intermittent episodes of sleepwalking with events beginning between 4 and 6 years of age. The sleepwalking events were occasionally associated with frightening or terrifying visual hallucination; subjects reported a need to escape from dangerous situations, such as facing a snake in bed, fighting intruders, and running away from unknown but terrifying threats. Although
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the images and impressions were never clear, the marked feeling of terror or need to escape was a consistent factor. This current study investigated the sleep electroencephalogram (EEG) of 12 pre-pubertal children known to be chronic sleepwalkers. All had been symptomatic for several years and had a limited response to medication trials performed by private pediatricians for variable durations. Medications prescribed had included zolpidem 5 and 10 mg at bedtime; diazepam 2–5 mg at bedtime; and clonazepam 0.5 mg at bedtime [10]. Parents reported that they had not pursued medical treatment due to intermittent occurrence of events despite medications and reluctance to having their child continuously receive psychotropic drugs. The children were free of medication for a minimum of 3 months prior to the study.
2. Protocol Sleepwalkers were compared to age- and gendermatched normal children, who served as controls. All children underwent the same investigation. Parents of sleepwalkers and controls signed an informed consent before participating in the study. They permitted the usage of clinical and polygraphic recording data for research.
3. Clinical investigation All children had pediatric and sleep interviews as well as general pediatric, neurological and psychiatric clinical evaluations. The Pediatric Sleep Questionnaire [11] and the Sleep Disorders Questionnaire [12] were filled out by the children with the help of their parents. Every child had a sleep-deprived awake and asleep EEG to eliminate the presence of a seizure disorder. Past medical history and medical tests were obtained from private pediatricians. After the initial visit, parents were asked to maintain sleep diaries for 4 weeks. Specifically, they were asked to indicate the time of sleep onset and morning awakening, the presence of abnormal behavior events, the type and duration of daytime activity, and overall daytime behavior. During two of the 4 weeks, the children were asked to wear an actigraph on their non-dominant wrist. All children were seen in a multidisciplinary clinic. A pediatric sleep medicine specialist, otolaryngologist, maxillo-mandibular surgeon and pediatric orthodontist were simultaneously present for an evaluation of the upper airway and investigation of craniofacial development. Results were standardized using scales for the description of tonsil sizes [13]. The Mallampati scale was utilized to assess the proximity of the tip of uvula to the base of tongue [14]. The face was described based on its divisions into thirds. The presence of allergic rhinitis, a deviated septum, enlargement of nasal inferior turbinates and asymmetry of nares were noted. Class of occlusion was determined, and
any abnormality of bite was specified. Frontal and anterolateral photographs were obtained. Photos of abnormal noses, palates and mandibles were taken. 4. Polysomnography A minimum of two polysomnograms was obtained. The test encompassed EEG (C4/A1, C3/A2, Fp1/T3, T3/O1, Fp2/T4, T4/O2, Fp1/C3, Fp2/C4), electro-oculogram (EOG), chin and leg electromyogram (EMG), electrocardiogram (ECG) (modified V2 lead), and body position sensors. Respiration was monitored with a nasal cannula [15,16], pressure transducer, mouth thermistor, thoracoabdominal piezzo-electric bands, esophageal pressure (Pes), and finger pulse-oximetry. Neck circumference was measured. Subjects were videotaped during recording. On the second night, subjects were monitored with the same montage, but no Pes was used. 5. Control subjects Age-matched control subjects were recruited from the community for polysomnographic study of their sleep. Subjects had clinical interviews, evaluations and review of their medical files obtained from their private pediatrician. These children and their parents filled out the same questionnaires. Children underwent two nights of polysomnography as did the patients. 6. Data analysis Sleep/wake was scored following international criteria [17]. Short EEG arousals (O3, but !15 s) were also scored using the American Sleep Disorders Association (ASDA) criteria [18,19]. A hypopnea was defined as a 30% reduction in nasal airflow compared to prior normal breathing for at least 10 s. An apnea was defined as a decrease in nasal flow of at least 70% for at least 10 s. Either a drop in oxygen saturation (SaO2) O3% or an EEG arousal was required to score these events. An apnea–hypopnea index (AHI), the number of apneas and hypopneas per hour of sleep, was calculated. Both the presence of flow limitation (!30% flow) at the nasal cannula pressure transducer system [20] and increased respiratory effort with a more negative peak end inspiratory esophageal pressure (Pes) curve [21,22] were investigated. In association with a partial flow limitation, defined as a limited reduction of flow (!30% of prior nasal cannula curve amplitude) without a clear impact on SaO2, two Pes patterns were recognized: a “Pes crescendo” and; a “continuous sustained effort”. While they were both determined on at least 4 successive breaths, the Pes crescendo was associated with the presence of a more negative peak end inspiratory Pes with each breath [21]. The continuous sustained effort pattern was seen with an increased effort
C. Guilleminault et al. / Sleep Medicine 6 (2005) 515–521
with an associated peak inspiratory Pes reached in 1 or 2 breaths. Although there was no increase over time, effort was maintained with this pattern [22]. Termination of flow limitation was indicated either by ‘respiratory event related arousal’ (RERA) [23,24] or with an abrupt return to a normal effort (‘Pes reversal’ [21,22]) without alpha EEG arousal. Based on these events a ‘respiratory disturbance index’ (RDI) was calculated. The definitions used for restless legs syndrome, periodic limb movements or other sleep disorders were those outlined in the International Classification of Sleep Disorders [25] and in the ASDA Atlas [18].
7. Determination of cyclic alternating pattern (CAP) CAPs [20,21] are electrocortical events that recur at regular intervals in the range of seconds during NREM sleep. These events are clearly distinct from the background EEG rhythm; they are marked by abrupt frequency shifts or amplitude changes. Two phases (A and B) are present within a CAP cycle and recur within 2–60 s (Figs. 1 and 2). When none of the phases (A and B) are identifiable, sleep has reached a new stable state [26,27]. Phase A is identified by transient events typically observed in NREM sleep.
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It includes EEG patterns of higher voltage, slower frequency and faster, lower voltage than the background EEG (with an increase in amplitude by at least one-third compared to the background EEG). Following this, phase B is defined by an EEG pattern of lesser EEG amplitude with EEG figures of stages 1–2 NREM sleep. If there is difficulty reaching a new stable state during NREM sleep passing from wake to REM sleep, the CAP rate will increase. The greater the number of cycles (i.e. the greater the number of phases A and B or CAP rate), the greater is the instability of NREM sleep. CAP was scored in a blind protocol, so that the scorer had no knowledge of the child’s status (sleepwalker/control). This scorer also had a significant prior experience with CAP scoring. Due to prior in-laboratory tests and interscorer differences in the scoring of phases A2 and A3, it was decided to score phase A only, independent of its subdivision, and to consider only the total CAP rate.
8. Statistical analysis Mann–Whitney U test or paired t-test was used based on normality of distribution for statistical comparison between groups.
Fig. 1. CAP sequences in subject no. 4. Note the succession of phase A with high amplitude slow wave, followed by low amplitude wave segment, phase B (three EEG channels on top of figure). The child presents with flow limitation (‘cannula’ channel). The duration of the segment during stage 2 NREM sleep is 60 s.
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Fig. 2. Flow limitation with nasal cannula ‘flattening’ and CAP sequence in subject no. 5. The patient presents with moderate snoring (MIC-microphonechannel), associated with flattening of the signal from the nasal cannula/pressure transducer (underline). She also presents a succession of high amplitude waves and low amplitude segments, representing the phases A and B of CAP in her EEG channels. The flow limitation is seen even in the absence of noisy breathing, as shown on the right side of the figure. The time duration of the graph is 60 s.
9. Results Twelve sleepwalkers were recruited in this study, mean age 8.6G1.7 years. They were chronic sleepwalkers with evidence of these parasomnia events for a mean of 3G2 years. None had sustained any injuries during sleepwalking. The frequency of events was variable but occurred at least 50% of the time. Twelve control children were enrolled, mean age 8.7G1.8 years. None of them had any sleep disorder or chronic illness. All were in good health at the time of the study (Table 1), and none had a history of parasomnia. Controls and sleepwalkers were gendermatched. Questionnaires confirmed the presence of the abnormal behavior during sleep in all sleepwalkers. They also indicated the presence of chronic snoring in eight out of 12 sleepwalkers versus none in controls. A positive history for nocturnal enuresis until the age of 7 or 8 years old was also present in two of the older sleepwalkers. Six sleepwalkers had a history of chronic nasal allergy and were found to have bilateral enlargement of their inferior nasal turbinates. There was a positive history of repetitive upper airway infection during the first 3 years of life in four children and repetitive otitis media and earache
in two others. Ear, nose, and throat (ENT) investigation showed 4Ctonsils in one child, 3Ctonsils in seven children, and 2Ctonsils in the remaining four. Two children had a Mallampati scale of 4; six had a scale of 3. These scores were supportive of the presence of a small upper airway in nine out of 12 of the sleepwalkers. Only one child in the control group had 3Ctonsils.
10. Polysomnography All sleepwalkers had at least two recording nights. The CAP analysis was always performed on a recording night without confusional arousal and/or sleepwalking and without esophageal pressure monitoring. 10.1. Respiration during sleep All sleepwalkers presented evidence of abnormal breathing during sleep. Eight children were intermittent or regular snorers. Tabulation of apneas and hypopneas showed an elevated AHI in only two cases, with an AHI of three and four events per hour, respectively. The overall AHI for the 12 sleepwalkers was 0.8G1 events/h; that is, they were normal
C. Guilleminault et al. / Sleep Medicine 6 (2005) 515–521 Table 1 Characteristics and CAP rate of each group ID number Controls 1 2 3 4 5 6 7 8 9 10 11 12 MeanGSD Sleepwalkers 1 2 3 4 5 6 7 8 9 10 11 12 MeanGSD
Age
Gender
TST (min)
CAP rate (%)
10.3 4.8 11.0 7.0 9.0 10.5 9.0 8.0 10.0 7.0 8.0 10.0 8.7G1.8
M F F M F M M M F M M F 7(M)5(F)
440 517 507 522 483 514 509 497 479 509 520 461 496.5G25.8
58.0 24.6 63.0 37.0 57.0 61.0 59.0 49.0 60.0 34.0 45.0 57.0 50.3G12.5
10.0 5.0 11.0 7.1 9.0 10.2 8.8 8.0 9.5 7.0 8.0 10.0 8.6G1.7
M F F M F M M M F M M F 7(M)5(F)
40.0 469.0 478.5 490.0 519.5 505.8 527.0 469.0 460.0 457.5 499.0 433.6 475.8G0.5*
89.0 37.0 80.0 66.0 63.3 78.1 80.0 76.8 52.3 57.2 59.0 75.8 69.5G14.0*
TST, total sleep time; CAP rate, percentage of CAP time over sleep time; M, male gender, F, female gender. *P!0.01, Mann–Whitney U test.
values. However, usage of the nasal cannula pressure transducer and esophageal pressure (Pes) catheter demonstrated the presence of abnormal breathing. The mean RDI for sleepwalkers was 9.7G4 events/h with a mean lowest SaO2 of 94G1.3%. All subjects presented evidence of mouth-breathing during the recording. Controls had an AHI of 0.5G0.5 and an RDI of 0.8G0.9 (Mann–Whitney U test PZ0.0001). No regular snoring was recorded in controls, and the lowest SaO2 was 98G1% (c2 statistic PZ0.01). 10.2. Sleep analysis As mentioned, sleep analyses were performed on a night without Pes recording, but all other respiratory and polygraphic variables were monitored. No evidence of periodic limb movement was noted. As can be seen in Table 1, there was a significant difference in total sleep time between controls and sleepwalkers (PZ0.01 Mann–Whitney U test), despite the fact that no parent or child had reported symptoms or signs of daytime sleepiness. Total sleep time was shorter in sleepwalkers, but the percentage of REM sleep was not significantly different between sleepwalkers and controls (22G2.1% in sleepwalkers versus 21.8G2.7% in normals).
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This difference in total sleep time was noted despite the fact that the same time in bed was maintained in controls and sleepwalkers. As determined by the ASDA criteria, the presence of an EEG arousal that was 3 s or longer was not significantly different between groups. The wake after sleep onset (WASO) duration was 13G5 min in controls and 15G7 min in sleepwalkers. All subjects presented at least four NREM–REM sleep cycles. The fact that sleepwalkers had a slightly earlier awakening time at the end of the night than controls accounts for this difference in total sleep time, but there is no satisfactory explanation for this finding. 10.3. CAP analysis As shown in Table 1, there was a significant difference (Mann–Whitney U test, PZ0.01) in CAP rate between sleepwalkers and controls. The increase in CAP rate was seen despite an absence of confusional arousal or sleepwalking episode during the monitored night. 10.4. Respiratory effort and sleep A sub-analysis was performed to consider the presence of both a ‘Pes crescendo’ and ‘continuous sustained effort’. As previously reported [22], the presence of each type of pattern was associated more with sleep stages than with any other factor. Pes crescendos were noted predominantly during stages 1–2 NREM and REM sleep, while sustained continuous effort was more related to SWS. The number of children and parasomnia events were too few to derive any conclusion on the role of one type of event versus another in the occurrence of the parasomnia.
11. Discussion We have already reported that sleep-disordered breathing, more particularly what we have described as upper airway resistance syndrome (UARS) [28], can be associated with sleepwalking in children [29]. We have demonstrated that treatment of the sleep breathing disorder can eliminate the parasomnia. In a survey of children in the Tucson area, Goodwin et al. [30] identified a frequent association between sleep-disordered breathing and chronic sleepwalking in children. Finally, in their general population survey, Ohayon et al. [31] found that obstructive sleep apnea syndrome was the most common sleep disorder associated with sleepwalking in patients 15 to 24 years old. Similarly, in young adults, Guilleminault et al. [32] investigated violence with sleepwalking, reporting the presence of sleepdisordered breathing in sleepwalking as well as the subsequent control of the aggressive behavior upon treatment of the sleep-disordered breathing. Espa et al. [33] investigated 10 adult sleepwalkers and reported that sleep-disordered breathing may be associated with sleepwalking.
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The children who participated in the study were similar to all children referred to our clinic. They had recurrent episodes of sleepwalking. Most, but not all, children had received some type of medication (a benzodiazepine or Zolpidem) from their pediatrician; however, the results were incomplete, even if some improvement had been noted. In addition, parents were concerned that their children would need to take these medications on a chronic basis. For these two reasons, parents sought a more specialized consult. None of the parents or pediatricians were concerned about sleep-disordered breathing or any other sleep disorder. One of the interesting aspects of ours and Espa’s study [33] is the demonstration of an abnormal sleep pattern even on the nights without a sleepwalking event. The usual sleep scoring does not allow identification of sleep disruption in association with a parasomnia. This problem was clearly demonstrated by Zucconi et al. [34] in young adults, but determination of CAP rate clearly indicates that there is abnormal NREM sleep in children with chronic sleepwalking. Normative data on CAP rate have been recently studied in pre-pubertal children by two different groups, and the data of our normal controls are closely related to those reported [35,36]. We mentioned that sleepwalkers woke up earlier than controls, despite the fact that the total sleep time was maintained. Behaviorally, children usually asked to urinate when waking up, but they had no other requests. Neither control subjects nor sleepwalkers reported a dream/nightmare or a negative feeling at morning awakening. We were unable to identify any physiological factor that could explain this difference in wake-up time. Children sleepwalkers demonstrate instability of NREM sleep, even on nights without a sleepwalking event. The instability is most likely related to the UARS or other sleep disorders (such as periodic limb movement syndrome) that have been shown to be associated with chronic sleepwalking. NREM-sleep instability is insufficient to trigger sleepwalking; therefore, one has to consider the abnormal sleep as a background on which confusional arousal or sleep walking has a greater chance to occur. A further disruption of sleep related to daytime stress, migraine, alcohol intake, or worsening of abnormal breathing with acute allergic rhinitis, or other factors will lead to the confusional arousal and sleepwalking. The treatment of the sleep disorder responsible for NREM-sleep instability has been shown to eliminate sleepwalking, despite the fact that stress, alcohol intake, migraine and rhinitis still occur. Investigation of CAP during sleep allows clinicians to not only recognize NREM-sleep instability and its severity but also to follow the impact of treatment trials.
Acknowledgements This study was performed with the help of Compumedics TM that graciously provided the sleep monitoring system.
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Original article
Non-REM-sleep instability in recurrent sleepwalking in pre-pubertal children Christian Guilleminaulta,*, Ji Hyun Leea, Allison Chana, Maria-Cecilia Lopesa, Yu-shu Huanga, Agostinho da Rosab a
Stanford University Sleep Disorders Clinic, 401 Quarry Road, Suite 3301, Stanford, CA 94305, USA b Universidade Tecnica de Lisboa Biological Engineering Laboratory, Lisbon, Portugal Received 13 January 2005; received in revised form 24 February 2005; accepted 4 March 2005 Available online 1 July 2005
Abstract Background and purpose: We questioned whether or not the sleep of pre-pubertal children with recurrent sleepwalking was different from that recorded in normal children. Patients and methods: Twelve pre-pubertal chronic sleepwalkers were compared to age- and gender-matched normal children. All children had a clinical evaluation covering pediatric, sleep, neuropsychiatric and otolaryngological fields. Two standardized sleep questionnaires were administered, and a minimum of two successive polysomnograms were performed with monitoring of sleep electroencephalographic (EEG) and cardiorespiratory variables. The research investigations were performed on nights without sleepwalking to search for the presence of other sleep disorders, including upper airway resistance syndrome (UARS). Sleep was scored using standard atlases, but it was also evaluated for the cyclic alternating pattern (CAP) rate. Results: All sleepwalkers presented with either obstructive sleep apnea (nZ2) or UARS (nZ10). Compared to normal children, sleepwalkers had shorter total sleep time but no significant change in wake after sleep onset when considering all arousals O3 s. CAP analysis showed a significantly higher CAP rate than in controls. Conclusions: Chronic sleepwalkers have instability of non-rapid eye movement (NREM) sleep detectable only by the calculation of CAP rate. Instability of NREM sleep was seen even on nights without sleepwalking and is probably related to the presence of the associated sleep disorders. We hypothesize that chronic NREM-sleep instability is a risk factor for occurrence of sleepwalking when further sleep disruption is triggered by external events. q 2005 Elsevier B.V. All rights reserved. Keywords: Children; Chronic sleepwalking; Sleep-disordered breathing; Cyclic alternating pattern; NREM-sleep instability
1. Introduction Somnambulism (sleepwalking) is defined as an arousal parasomnia [1]. It consists of large movements in bed or walking during sleep. Oscillating between 2 and 14% in children, its prevalence is controversial [2–6]. Sleepwalking often decreases with onset of puberty, but at least 25% of children with chronic sleepwalking may continue to sleepwalk in adulthood [2–7]. It is thought to arise from slow
* Corresponding author. Tel.: C1 650 723 6601; fax: C1 650 725 8910. E-mail address: [email protected] (C. Guilleminault).
1389-9457/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2005.03.003
wave sleep (SWS), particularly stage 4 non-rapid eye movement (NREM) sleep. An occasional confusional arousal can be seen in 40–50% of children between 3 and 6 years of age [2]. Sleepwalking may be a recurrent event with risk of injury to oneself and others [8,9]. In our own subjects with chronic problems, injuries were seen in male teenagers (age 14–17 years). Injuries had occurred in five out of 120 of our cases of children having been referred for chronic sleepwalking. These teenagers had intermittent episodes of sleepwalking with events beginning between 4 and 6 years of age. The sleepwalking events were occasionally associated with frightening or terrifying visual hallucination; subjects reported a need to escape from dangerous situations, such as facing a snake in bed, fighting intruders, and running away from unknown but terrifying threats. Although
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the images and impressions were never clear, the marked feeling of terror or need to escape was a consistent factor. This current study investigated the sleep electroencephalogram (EEG) of 12 pre-pubertal children known to be chronic sleepwalkers. All had been symptomatic for several years and had a limited response to medication trials performed by private pediatricians for variable durations. Medications prescribed had included zolpidem 5 and 10 mg at bedtime; diazepam 2–5 mg at bedtime; and clonazepam 0.5 mg at bedtime [10]. Parents reported that they had not pursued medical treatment due to intermittent occurrence of events despite medications and reluctance to having their child continuously receive psychotropic drugs. The children were free of medication for a minimum of 3 months prior to the study.
2. Protocol Sleepwalkers were compared to age- and gendermatched normal children, who served as controls. All children underwent the same investigation. Parents of sleepwalkers and controls signed an informed consent before participating in the study. They permitted the usage of clinical and polygraphic recording data for research.
3. Clinical investigation All children had pediatric and sleep interviews as well as general pediatric, neurological and psychiatric clinical evaluations. The Pediatric Sleep Questionnaire [11] and the Sleep Disorders Questionnaire [12] were filled out by the children with the help of their parents. Every child had a sleep-deprived awake and asleep EEG to eliminate the presence of a seizure disorder. Past medical history and medical tests were obtained from private pediatricians. After the initial visit, parents were asked to maintain sleep diaries for 4 weeks. Specifically, they were asked to indicate the time of sleep onset and morning awakening, the presence of abnormal behavior events, the type and duration of daytime activity, and overall daytime behavior. During two of the 4 weeks, the children were asked to wear an actigraph on their non-dominant wrist. All children were seen in a multidisciplinary clinic. A pediatric sleep medicine specialist, otolaryngologist, maxillo-mandibular surgeon and pediatric orthodontist were simultaneously present for an evaluation of the upper airway and investigation of craniofacial development. Results were standardized using scales for the description of tonsil sizes [13]. The Mallampati scale was utilized to assess the proximity of the tip of uvula to the base of tongue [14]. The face was described based on its divisions into thirds. The presence of allergic rhinitis, a deviated septum, enlargement of nasal inferior turbinates and asymmetry of nares were noted. Class of occlusion was determined, and
any abnormality of bite was specified. Frontal and anterolateral photographs were obtained. Photos of abnormal noses, palates and mandibles were taken. 4. Polysomnography A minimum of two polysomnograms was obtained. The test encompassed EEG (C4/A1, C3/A2, Fp1/T3, T3/O1, Fp2/T4, T4/O2, Fp1/C3, Fp2/C4), electro-oculogram (EOG), chin and leg electromyogram (EMG), electrocardiogram (ECG) (modified V2 lead), and body position sensors. Respiration was monitored with a nasal cannula [15,16], pressure transducer, mouth thermistor, thoracoabdominal piezzo-electric bands, esophageal pressure (Pes), and finger pulse-oximetry. Neck circumference was measured. Subjects were videotaped during recording. On the second night, subjects were monitored with the same montage, but no Pes was used. 5. Control subjects Age-matched control subjects were recruited from the community for polysomnographic study of their sleep. Subjects had clinical interviews, evaluations and review of their medical files obtained from their private pediatrician. These children and their parents filled out the same questionnaires. Children underwent two nights of polysomnography as did the patients. 6. Data analysis Sleep/wake was scored following international criteria [17]. Short EEG arousals (O3, but !15 s) were also scored using the American Sleep Disorders Association (ASDA) criteria [18,19]. A hypopnea was defined as a 30% reduction in nasal airflow compared to prior normal breathing for at least 10 s. An apnea was defined as a decrease in nasal flow of at least 70% for at least 10 s. Either a drop in oxygen saturation (SaO2) O3% or an EEG arousal was required to score these events. An apnea–hypopnea index (AHI), the number of apneas and hypopneas per hour of sleep, was calculated. Both the presence of flow limitation (!30% flow) at the nasal cannula pressure transducer system [20] and increased respiratory effort with a more negative peak end inspiratory esophageal pressure (Pes) curve [21,22] were investigated. In association with a partial flow limitation, defined as a limited reduction of flow (!30% of prior nasal cannula curve amplitude) without a clear impact on SaO2, two Pes patterns were recognized: a “Pes crescendo” and; a “continuous sustained effort”. While they were both determined on at least 4 successive breaths, the Pes crescendo was associated with the presence of a more negative peak end inspiratory Pes with each breath [21]. The continuous sustained effort pattern was seen with an increased effort
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with an associated peak inspiratory Pes reached in 1 or 2 breaths. Although there was no increase over time, effort was maintained with this pattern [22]. Termination of flow limitation was indicated either by ‘respiratory event related arousal’ (RERA) [23,24] or with an abrupt return to a normal effort (‘Pes reversal’ [21,22]) without alpha EEG arousal. Based on these events a ‘respiratory disturbance index’ (RDI) was calculated. The definitions used for restless legs syndrome, periodic limb movements or other sleep disorders were those outlined in the International Classification of Sleep Disorders [25] and in the ASDA Atlas [18].
7. Determination of cyclic alternating pattern (CAP) CAPs [20,21] are electrocortical events that recur at regular intervals in the range of seconds during NREM sleep. These events are clearly distinct from the background EEG rhythm; they are marked by abrupt frequency shifts or amplitude changes. Two phases (A and B) are present within a CAP cycle and recur within 2–60 s (Figs. 1 and 2). When none of the phases (A and B) are identifiable, sleep has reached a new stable state [26,27]. Phase A is identified by transient events typically observed in NREM sleep.
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It includes EEG patterns of higher voltage, slower frequency and faster, lower voltage than the background EEG (with an increase in amplitude by at least one-third compared to the background EEG). Following this, phase B is defined by an EEG pattern of lesser EEG amplitude with EEG figures of stages 1–2 NREM sleep. If there is difficulty reaching a new stable state during NREM sleep passing from wake to REM sleep, the CAP rate will increase. The greater the number of cycles (i.e. the greater the number of phases A and B or CAP rate), the greater is the instability of NREM sleep. CAP was scored in a blind protocol, so that the scorer had no knowledge of the child’s status (sleepwalker/control). This scorer also had a significant prior experience with CAP scoring. Due to prior in-laboratory tests and interscorer differences in the scoring of phases A2 and A3, it was decided to score phase A only, independent of its subdivision, and to consider only the total CAP rate.
8. Statistical analysis Mann–Whitney U test or paired t-test was used based on normality of distribution for statistical comparison between groups.
Fig. 1. CAP sequences in subject no. 4. Note the succession of phase A with high amplitude slow wave, followed by low amplitude wave segment, phase B (three EEG channels on top of figure). The child presents with flow limitation (‘cannula’ channel). The duration of the segment during stage 2 NREM sleep is 60 s.
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Fig. 2. Flow limitation with nasal cannula ‘flattening’ and CAP sequence in subject no. 5. The patient presents with moderate snoring (MIC-microphonechannel), associated with flattening of the signal from the nasal cannula/pressure transducer (underline). She also presents a succession of high amplitude waves and low amplitude segments, representing the phases A and B of CAP in her EEG channels. The flow limitation is seen even in the absence of noisy breathing, as shown on the right side of the figure. The time duration of the graph is 60 s.
9. Results Twelve sleepwalkers were recruited in this study, mean age 8.6G1.7 years. They were chronic sleepwalkers with evidence of these parasomnia events for a mean of 3G2 years. None had sustained any injuries during sleepwalking. The frequency of events was variable but occurred at least 50% of the time. Twelve control children were enrolled, mean age 8.7G1.8 years. None of them had any sleep disorder or chronic illness. All were in good health at the time of the study (Table 1), and none had a history of parasomnia. Controls and sleepwalkers were gendermatched. Questionnaires confirmed the presence of the abnormal behavior during sleep in all sleepwalkers. They also indicated the presence of chronic snoring in eight out of 12 sleepwalkers versus none in controls. A positive history for nocturnal enuresis until the age of 7 or 8 years old was also present in two of the older sleepwalkers. Six sleepwalkers had a history of chronic nasal allergy and were found to have bilateral enlargement of their inferior nasal turbinates. There was a positive history of repetitive upper airway infection during the first 3 years of life in four children and repetitive otitis media and earache
in two others. Ear, nose, and throat (ENT) investigation showed 4Ctonsils in one child, 3Ctonsils in seven children, and 2Ctonsils in the remaining four. Two children had a Mallampati scale of 4; six had a scale of 3. These scores were supportive of the presence of a small upper airway in nine out of 12 of the sleepwalkers. Only one child in the control group had 3Ctonsils.
10. Polysomnography All sleepwalkers had at least two recording nights. The CAP analysis was always performed on a recording night without confusional arousal and/or sleepwalking and without esophageal pressure monitoring. 10.1. Respiration during sleep All sleepwalkers presented evidence of abnormal breathing during sleep. Eight children were intermittent or regular snorers. Tabulation of apneas and hypopneas showed an elevated AHI in only two cases, with an AHI of three and four events per hour, respectively. The overall AHI for the 12 sleepwalkers was 0.8G1 events/h; that is, they were normal
C. Guilleminault et al. / Sleep Medicine 6 (2005) 515–521 Table 1 Characteristics and CAP rate of each group ID number Controls 1 2 3 4 5 6 7 8 9 10 11 12 MeanGSD Sleepwalkers 1 2 3 4 5 6 7 8 9 10 11 12 MeanGSD
Age
Gender
TST (min)
CAP rate (%)
10.3 4.8 11.0 7.0 9.0 10.5 9.0 8.0 10.0 7.0 8.0 10.0 8.7G1.8
M F F M F M M M F M M F 7(M)5(F)
440 517 507 522 483 514 509 497 479 509 520 461 496.5G25.8
58.0 24.6 63.0 37.0 57.0 61.0 59.0 49.0 60.0 34.0 45.0 57.0 50.3G12.5
10.0 5.0 11.0 7.1 9.0 10.2 8.8 8.0 9.5 7.0 8.0 10.0 8.6G1.7
M F F M F M M M F M M F 7(M)5(F)
40.0 469.0 478.5 490.0 519.5 505.8 527.0 469.0 460.0 457.5 499.0 433.6 475.8G0.5*
89.0 37.0 80.0 66.0 63.3 78.1 80.0 76.8 52.3 57.2 59.0 75.8 69.5G14.0*
TST, total sleep time; CAP rate, percentage of CAP time over sleep time; M, male gender, F, female gender. *P!0.01, Mann–Whitney U test.
values. However, usage of the nasal cannula pressure transducer and esophageal pressure (Pes) catheter demonstrated the presence of abnormal breathing. The mean RDI for sleepwalkers was 9.7G4 events/h with a mean lowest SaO2 of 94G1.3%. All subjects presented evidence of mouth-breathing during the recording. Controls had an AHI of 0.5G0.5 and an RDI of 0.8G0.9 (Mann–Whitney U test PZ0.0001). No regular snoring was recorded in controls, and the lowest SaO2 was 98G1% (c2 statistic PZ0.01). 10.2. Sleep analysis As mentioned, sleep analyses were performed on a night without Pes recording, but all other respiratory and polygraphic variables were monitored. No evidence of periodic limb movement was noted. As can be seen in Table 1, there was a significant difference in total sleep time between controls and sleepwalkers (PZ0.01 Mann–Whitney U test), despite the fact that no parent or child had reported symptoms or signs of daytime sleepiness. Total sleep time was shorter in sleepwalkers, but the percentage of REM sleep was not significantly different between sleepwalkers and controls (22G2.1% in sleepwalkers versus 21.8G2.7% in normals).
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This difference in total sleep time was noted despite the fact that the same time in bed was maintained in controls and sleepwalkers. As determined by the ASDA criteria, the presence of an EEG arousal that was 3 s or longer was not significantly different between groups. The wake after sleep onset (WASO) duration was 13G5 min in controls and 15G7 min in sleepwalkers. All subjects presented at least four NREM–REM sleep cycles. The fact that sleepwalkers had a slightly earlier awakening time at the end of the night than controls accounts for this difference in total sleep time, but there is no satisfactory explanation for this finding. 10.3. CAP analysis As shown in Table 1, there was a significant difference (Mann–Whitney U test, PZ0.01) in CAP rate between sleepwalkers and controls. The increase in CAP rate was seen despite an absence of confusional arousal or sleepwalking episode during the monitored night. 10.4. Respiratory effort and sleep A sub-analysis was performed to consider the presence of both a ‘Pes crescendo’ and ‘continuous sustained effort’. As previously reported [22], the presence of each type of pattern was associated more with sleep stages than with any other factor. Pes crescendos were noted predominantly during stages 1–2 NREM and REM sleep, while sustained continuous effort was more related to SWS. The number of children and parasomnia events were too few to derive any conclusion on the role of one type of event versus another in the occurrence of the parasomnia.
11. Discussion We have already reported that sleep-disordered breathing, more particularly what we have described as upper airway resistance syndrome (UARS) [28], can be associated with sleepwalking in children [29]. We have demonstrated that treatment of the sleep breathing disorder can eliminate the parasomnia. In a survey of children in the Tucson area, Goodwin et al. [30] identified a frequent association between sleep-disordered breathing and chronic sleepwalking in children. Finally, in their general population survey, Ohayon et al. [31] found that obstructive sleep apnea syndrome was the most common sleep disorder associated with sleepwalking in patients 15 to 24 years old. Similarly, in young adults, Guilleminault et al. [32] investigated violence with sleepwalking, reporting the presence of sleepdisordered breathing in sleepwalking as well as the subsequent control of the aggressive behavior upon treatment of the sleep-disordered breathing. Espa et al. [33] investigated 10 adult sleepwalkers and reported that sleep-disordered breathing may be associated with sleepwalking.
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The children who participated in the study were similar to all children referred to our clinic. They had recurrent episodes of sleepwalking. Most, but not all, children had received some type of medication (a benzodiazepine or Zolpidem) from their pediatrician; however, the results were incomplete, even if some improvement had been noted. In addition, parents were concerned that their children would need to take these medications on a chronic basis. For these two reasons, parents sought a more specialized consult. None of the parents or pediatricians were concerned about sleep-disordered breathing or any other sleep disorder. One of the interesting aspects of ours and Espa’s study [33] is the demonstration of an abnormal sleep pattern even on the nights without a sleepwalking event. The usual sleep scoring does not allow identification of sleep disruption in association with a parasomnia. This problem was clearly demonstrated by Zucconi et al. [34] in young adults, but determination of CAP rate clearly indicates that there is abnormal NREM sleep in children with chronic sleepwalking. Normative data on CAP rate have been recently studied in pre-pubertal children by two different groups, and the data of our normal controls are closely related to those reported [35,36]. We mentioned that sleepwalkers woke up earlier than controls, despite the fact that the total sleep time was maintained. Behaviorally, children usually asked to urinate when waking up, but they had no other requests. Neither control subjects nor sleepwalkers reported a dream/nightmare or a negative feeling at morning awakening. We were unable to identify any physiological factor that could explain this difference in wake-up time. Children sleepwalkers demonstrate instability of NREM sleep, even on nights without a sleepwalking event. The instability is most likely related to the UARS or other sleep disorders (such as periodic limb movement syndrome) that have been shown to be associated with chronic sleepwalking. NREM-sleep instability is insufficient to trigger sleepwalking; therefore, one has to consider the abnormal sleep as a background on which confusional arousal or sleep walking has a greater chance to occur. A further disruption of sleep related to daytime stress, migraine, alcohol intake, or worsening of abnormal breathing with acute allergic rhinitis, or other factors will lead to the confusional arousal and sleepwalking. The treatment of the sleep disorder responsible for NREM-sleep instability has been shown to eliminate sleepwalking, despite the fact that stress, alcohol intake, migraine and rhinitis still occur. Investigation of CAP during sleep allows clinicians to not only recognize NREM-sleep instability and its severity but also to follow the impact of treatment trials.
Acknowledgements This study was performed with the help of Compumedics TM that graciously provided the sleep monitoring system.
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