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Sleep-related disordered breathing in children with syndromic craniosynostosis
Journal of Cranio-Maxillo-Facial Surgery 39 (2011) 153e157
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Sleep-related disordered breathing in children with syndromic craniosynostosis Suhail Al-Saleh a, c, Andrea Riekstins a, c, Christopher R. Forrest b, c, John H. Philips b, c, Jeremy Gibbons a, Indra Narang a, c, * a
Division of Respiratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada Division of Plastic Surgery, Center for Craniofacial Care or Research, Hospital for Sick Children, Toronto, Ontario, Canada c University of Toronto, Toronto, Ontario, Canada b
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 18 December 2009 Accepted 23 April 2010
Background: Syndromic craniosynostosis patients are at risk for sleep-related disordered breathing (SRDB) but the role of polysomnography (PSG) in assessing these patients has not been fully explored. Our aim was to evaluate the prevalence or severity of SRDB in children with syndromic craniosynostosis or the impact of treatments on their SRDB. Methods: We conducted a retrospective review of all patients with syndromic craniosynostosis referred between 1996 or 2008 for an initial PSG to rule out SRDB. For those with SRDB, we reviewed the interventions post PSG. Results: 35 patients (18 females) were included. Specific diagnoses were Crouzon’s (n ¼ 18), Apert’s (n ¼ 14), Pfeiffer (n ¼ 2) or Saethre-Chotzen (n ¼ 1) syndromes. Their mean age was 4.5 years or their mean body mass index (BMI) was 16.9 kg/m2. Of these patients, 26/35 (74%) had evidence of SRDB. The median obstructive apnoea index was 6.6/h (range 0.5e36.4/h) or median central apnoea index was 1.0/h (range 0.0e66.4/h). A total of 16 children had interventions to treat SRDB, of which 14/16 had a follow up PSG or only 10/14 (x%) had a significant improvement of their SRDB. Conclusion: This review confirms a high prevalence SRDB in this referred population. Despite various interventions, complete resolution of SRDB could not be achieved. Ó 2010 European Association for Cranio-Maxillo-Facial Surgery.
Keywords: syndromic craniosynostosis sleep-related disordered breathing central sleep apnoea obstructive sleep apnoea paediatrics or polysomnography
1. Introduction Syndromic craniosynostosis is a group of craniofacial malformations which includes Crouzon’s, Apert’s, Pfeiffer or SaethreChotzen syndromes. These syndromes are associated with premature fusion of one or more cranial sutures, or other craniofacial manifestations including maxillary hypoplasia, cleft lip or palate, choanal atresia, Chiari malformation, hydrocephalus, tracheoe bronchial malformations, or/or other skeletal or respiratory anomalies (Jones, 2006). The genetic basis of these craniosynostosis syndromes includes mutations in the Fibroblast growth factor receptor 1, 2 or 3 genes with an autosomal dominant inheritance fashion (Jones, 2006; Kimonis et al., 2007). Syndromic craniosynostosis can be associated with central nervous system and/or airway complications including restriction of brain growth, visual disturbance, increased intracranial pressure or airway obstruction.
* Corresponding author. Division of Respiratory Medicine, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. Tel.: þ1 416 813 6346; fax: þ1 416 813 6246. E-mail address: [email protected] (I. Narang).
The pathophysiology of upper airway obstruction is related to distortion and displacement of craniofacial bones which can compromise both nasopharyngeal and oropharyngeal spaces. These anomalies may include reduction of the pharyngeal height, width and depth, increased length and thickness of the velum, decreased length of the hard palate, marked reduction of the posterior cranial base with a lesser degree reduction of the anterior cranial base, choanal stenosis or atresia, midnasal stenosis, tracheal cartilaginous sleeve, maxillary hypoplasia and other airway anomalies (Mixter et al., 1990; Cohen and Kreiborg, 1992; Sirotnak et al., 1995; Noorily et al., 1999). These changes are present in infancy and tend to be more pronounced with craniofacial growth specifically increased pharyngeal length, increased soft palate thickness, decreased hard palate length, decreased pharyngeal height, and depth and shortened cranial base with increasing age from infancy to teenage period (Peterson-Falzone et al., 1981). Sleep-related disordered breathing (SRDB) is a group of respiratory disorders specific to sleep or exacerbated by sleep. These disorders include obstructive sleep apnoea (OSA), central sleep apnoea (CSA), periodic breathing and hypoventilation. The commonest sleep disorder seen in children is OSA. OSA is a disorder of breathing during sleep characterized by prolonged partial upper
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airway obstruction (obstructive hypopnoea) and/or intermittent complete obstruction (obstructive apnoea) that disrupts normal ventilation during sleep and normal sleep patterns (Loughlin et al., 1996). The reported prevalence of OSA is around 2e4% (O’Brien et al., 2003; Montgomery-Downs et al., 2004; LofstrandTidestrom and Hultcrantz, 2007; Lumeng and Chervin, 2008). Adenotonsillar hypertrophy is the most common cause of OSA in healthy children with no underlying co-morbidities; adenotonsillectomy improves OSA and related symptoms in most of these cases (Stradling et al., 1990; Suen et al., 1995). However, if OSA is left untreated, serious complications can occur including failure to thrive, pulmonary hypertension, cardiac dysfunction, poor daytime performance and behavioural problems (Brouillette et al., 1982; Tal et al., 1988; Gozal, 1998; Amin et al., 2002; Chervin et al., 2002; O’Brien et al., 2004; Amin et al., 2005; Bonuck et al., 2006). In children with syndromic craniosynostosis with significant upper airway obstruction and/or OSA, additional complications such as increased intracranial pressure, and sudden cardiopulmonary arrest and death have been described (Schafer, 1982; Mixter et al., 1990; Sirotnak et al., 1995; Lauritzen et al., 1998; Mitsukawa et al., 2004; Hayward and Gonsalez, 2005; Witherow et al., 2008). Central apnoeas, periodic breathing or central hypoventilation are less common than OSA. They can be primary as in congenital central hypoventilation syndrome or secondary due to trauma, infection or ArnoldeChiari malformations (Marcus, 2001). In children with craniosynostosis, OSA has been described in several case reports and series (Peterson-Falzone et al.,1981; Schafer, 1982; Mixter et al., 1990; Cohen and Kreiborg, 1992; Edwards et al., 1992; Moore, 1993; Sirotnak et al., 1995; Gonsalez et al., 1996; Jarund and Lauritzen, 1996; Gonsalez et al., 1997; Perkins et al., 1997; Gonsalez et al., 1998; Lauritzen et al., 1998; Sculerati et al., 1998; Jarund et al., 1999; Noorily et al., 1999; Hoeve et al., 2003; Mitsukawa et al., 2004; Pijpers et al., 2004; Fearon, 2005; Hayward and Gonsalez, 2005; Phillips et al., 2006; Ahmed et al., 2008; Nelson et al., 2008; Witherow et al., 2008; Amonoo-Kuofi et al., 2009). CSA also has been reported in cases with hindbrain herniation (Gonsalez et al., 1998). However, most of these studies relied on clinical assessment and/or parents’ questionnaires. Reported treatment options for OSA in this population include choanal dilatation (Mixter et al., 1990; Jarund et al., 1999), continuous Positive Airway Pressure (CPAP) (Gonsalez et al., 1996; Jarund et al., 1999; Hoeve et al., 2003), nasopharyngeal airways (Gonsalez et al., 1996; Perkins et al., 1997; Ahmed et al., 2008), palatal surgery (Mixter et al., 1990; Edwards et al., 1992; Moore, 1993), adenotonsillectomy (Edwards et al., 1992; Moore, 1993; Perkins et al., 1997; Lauritzen et al., 1998; Hoeve et al., 2003; Amonoo-Kuofi et al., 2009), midface advancement surgeries (Edwards et al., 1992; Jarund and Lauritzen, 1996; Fearon, 2005; Phillips et al., 2006) or tracheostomy (Mixter et al., 1990; Moore, 1993; Sirotnak et al., 1995; Jarund and Lauritzen, 1996; Perkins et al., 1997; Lauritzen et al., 1998; Sculerati et al., 1998; Hoeve et al., 2003). These treatment modalities were instituted dependent on individual clinical criteria as there is no unified pathway or approach in assessing and managing children with syndromic craniosynostosis who have evidence of OSA. Only one study with 10 patients reported the use of a full PSG for evaluation of OSA pre- and post-LeFort III surgery in a selected population of syndromic craniosynostosis (Nelson et al., 2008). To our current knowledge, there are no studies that have used full PSG as a primary tool for evaluating children with craniosynostosis for SRDB and the various medical and surgical treatment outcomes for OSA. The objective of this study is to not only analyze the prevalence of SRDB in children with syndromic craniosynostosis who have been referred for an full overnight PSG for suspected SRDB but also to evaluate the impact of various treatments to relieve upper airway obstruction and/or brainstem compression in this population.
2. Methods 2.1. Study subjects At the Hospital for Sick Children, Toronto, Canada, the Centre for craniofacial care and research database was used to identify all patients with syndromic craniosynostosis. All patients who were referred to the sleep laboratory between January 1996 and December 2008 for an initial baseline PSG were included in the analysis. The primary indication for referral was suspected OSA. Exclusion criteria were: (1) patients with previous or current history of tracheostomy, (2) patients known to have SRDB from previous sleep studies, (3) patients who never had a full baseline PSG due to a medical intervention such as oxygen or CPAP therapy for the treatment of SRDB (termed spilt night study), and (4) patients who had their first baseline PSG before 1996 as the detailed polysomnographic raw data for the studies performed before 1996 could not be retrieved. The demographic data collected included type of syndromic craniosynostosis, any additional medical diagnoses, history of snoring, age at the time of PSG, gender, height, weight, and body mass index (BMI). Additional data including surgical or medical interventions prior to the PSG and within 2 years after the PSG were also documented. 2.2. Polysomnographic assessment Patients underwent a standard overnight PSG using XLTEC (Oakville, Canada) and Nicolet (Viasys, Madison, WI) data acquisition and analysis systems. PSG measurements included electroencephalogram (EEG), electro-oculogram (EOG), submental electromyogram (EMG) and bilateral anterior tibialis EMG. Respiratory measurements included chest wall and abdominal movement using chest wall and abdominal belts; nasal airflow measurements using nasal air pressure transducer and/or oronasal thermal sensor, oxygen saturation (SaO2), trans-cutaneous carbon dioxide (TcCO2) and end-tidal carbon dioxide (etCO2). Video and audio recordings were obtained for each study as well as body position, which was documented manually by a registered polysomnographic technician. Sleep architecture was assessed by standard techniques (Rechtschaffen, 1968). Information obtained from PSG included sleep onset latency and rapid eye movement (REM) onset latency, total sleep time (TST), sleep efficiency, time spent in each sleep stage (minutes and percentage), number and classification of arousals, number of independent leg movements and snoring. Recorded respiratory data included counts and indexes of the following events: OSA, CSA, hypopnoea and mixed apnoeas in nonrapid eye movement (NREM) sleep, REM sleep and total sleep. All events were scored according to the current American Academy of Sleep Medicine (AASM) scoring guidelines (Iber et al., 2007) by a registered polysomnographic technician. If a study was obtained prior to May 2007 when new scoring guidelines were introduced to our institution, these studies were rescored according to the current guidelines. An obstructive apnoea event was scored when airflow dropped at least 90% from baseline with chest and/or abdominal motion throughout the entire event; the duration of which was at least a minimum of two baseline breaths. A hypopnoea event was scored when airflow dropped at least 50% from baseline, the duration of which was at least a minimum of two baseline breaths. The hypopnoea event must have been accompanied by either (i) a minimum 3% drop in oxygen desaturation, (ii) an arousal, or (iii) an awakening (Iber et al., 2007). A central apnoea was defined as a cessation of airflow with an absence of respiratory and abdominal effort for a minimum of 20 s or of the duration of
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two prior baseline breaths in which case the event must be accompanied by (i) a minimum 3% drop in oxygen desaturation, (ii) an arousal, or (iii) an awakening. OSA severity was graded according to the obstructive apnoeaehypopnoea index (OAHI), the number of obstructive apnoeas and obstructive hypopnoeas per hour during sleep. OAHI of <1.5 was considered normal, OAHI from 1.5 to <5 was mild OSA; OAHI from 5 to <10 was moderate OSA and OAHI 10 was considered severe OSA. The central apnoea index (CAI) was defined as the number of central apnoeas per hour during sleep. The CSA diagnosis was considered when the CAI was >5 events/hour sleep. Follow up PSGs performed within 2 years from the baseline PSGs were analyzed and if not already done so, scored according to the current paediatric AASM scoring guidelines. Because there are no guidelines or data regarding criteria for re-assessment of the follow up PSGs with regards to what is considered a significant change in OAHI and/or, we defined a follow up PSG as improved if OAHI and/or CAI decreased in the follow up sleep study by 50%; deteriorated if OAHI and/or CAI increased in the follow up sleep study by 50% and not improved if it did not meet the above mentioned criteria as is our current clinical practise. 2.3. Statistical analysis The analyses involved descriptive statistics and included frequencies, percentages, mean, median and/or range values which were obtained for all baseline and PSG data. Maximum and minimum values were recorded for both SaO2 and TcCO2. A standard statistical package was used (SAS, version 9.2, Cary, NC, USA). 3. Results Out of 84 patients with syndromic craniosynostosis identified from the centre for craniofacial care and research database at the Hospital for Sick Children, 54 children were referred for overnight PSG. 19 patients were excluded due to: (1) previous or current history of tracheostomy at the time of the baseline PSG (n ¼ 11), (2) incomplete baseline PSG (n ¼ 3), (3) first baseline PSG before 1996 (n ¼ 3), (4) formal diagnosis of OSA from other centres (n ¼ 1) and (5) unavailability of PSG raw data for the rescoring according to the current AASM paediatric guidelines (n ¼ 1). A total of 35 patients were included in the final analysis. The baseline characteristics of those patients at the time of the baseline study are listed in Table 1. Twenty-three patients had at least one surgical intervention prior to the PSG, the majority of which were craniofacial surgery. Details of these interventions are listed in Table 2. PSG data are displayed in Table 3. Twenty-six of 35 children (74%) had abnormal PSG results. Of these, 7/26 had evidence of mild OSA, 7/26 had moderate OSA, 10/26 had severe OSA, and two patients had CSA in addition to moderate to severe OSA. Overall 16 out of 26 patients who had evidence of SRDB had one or more intervention within 2 years of the PSG specifically to treat SRDB. The remaining 10 children did not have any intervention to treat for SRDB within 2 years of the baseline PSG as: six had mild OSA and therefore no intervention was taken, two patients with moderate OSA were lost to follow up and two patients with severe OSA are awaiting maxillofacial surgical intervention. Of the 16 patients who did undergo the intervention(s), a follow up PSG was done in 14 children. Of these, 10/14 demonstrated a significant improvement but the remaining 4/14 children had either no improvement or worsening in their SRDB post intervention. Summary results of 16 children who had intervention(s) for SRDB are shown in Table 4.
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Table 1 Baseline characteristics of children with craniosynostosis. Patients (n ¼ 35)
Results
Age, years, mean (range) Male: Female Weight, kg, mean (range) Height, cm, mean (range) BMI kg/m2, mean (range) Crouzon’s syndrome, no. (%) Apert’s syndrome, no. (%) Pfeiffer syndrome, no. (%) Saethre-Chotzen syndrome, no. (%) Chiari malformations, no. (%) History of increased ICP, no. (%) Cleft lip/palate, no. (%) History of snoring, no. (%)
4.5 (0.13e15.1) 17:18 20.6 (4.7e79.5) 103.8 (42.0e182.0) 16.9 (11.2e29.1) 18 (51%) 14 (40%) 2 (6%) 1 (3%) 10 (29%) 11 (31%) 7 (20%) 32 (91%)
Abbreviations: BMI, body mass index; ICP, intracranial pressure.
Table 2 Summary of surgical procedures prior to sleep study. Previous interventions (n ¼ 23)
Number (%)
Patients who had more than one intervention Tonsilloadenoidectomy Craniofacial surgery (cranial vault reconstruction, cranio-orbital reshaping, Lefort I, LeFort III) Cleft lip/palate repair V-P shunt insertion Others (nasal stent, choanal atresia relief)
12 (52%) 1 (4%) 20 (87%) 4 (17%) 8 (35%) 3 (9%)
Abbreviations: V-P, ventriculo-peritoneal.
Table 3 Sleep study results of 35 children with syndromic craniosynostosis. Results
Median (range)
Sleep latency, min Sleep efficiency, % TST, min REM latency, min Sleep Stage 1 (% of TST) Sleep Stage 2 (% of TST) Sleep Stage Slow wave (% of TST) Sleep REM Stage (% of TST) Mean SaO2, % Minimum SaO2, % Highest CO2, mmHg OAHI CAI
1.5 91.8 429.0 73.0 5.0 47.4 26.6 26.0 97.8 85.3 52.0 6.6 1.0
(0.0e51.0) (73.2e99.2) (343.5e513.5) (0.0e211.8) (0.2e11.6) (18.3e91.0) (7.7e51.2) (0.0e46.2) (94.9e99.7) (58.0e96.0) (39.2e68.0) (0.5e36.4) (0.0e66.4)
Abbreviations: CAI, central apnoea index; CO2, carbon dioxide; OAHI, obstructive apnoeaehypopnoea index; REM, rapid eye movement; SaO2, oxygen saturation; TST, total sleep time.
4. Discussion To our knowledge, to date this is the largest review of syndromic craniosynostosis population evaluated for SRDB and treatment outcomes with formal full PSG using the current paediatric scoring guidelines (Iber et al., 2007). In children with syndromic craniosynostosis referred for formal PSG evaluation, we found a high proportion with SRDB (74%) which is in keeping with the estimated high prevalence (40e85%) quoted in other studies that had not utilized formal PSG (Moore, 1993; Sirotnak et al., 1995; Gonsalez et al., 1997; Perkins et al., 1997; Sculerati et al., 1998). However, we suspect that the prevalence is under-estimated in this selected population as we excluded children with history of tracheostomy. Of significant note, the majority of the patients with SRDB (73%) were classified in the moderate to severe OSA and most of these children with SRDB (n ¼ 23) were less
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Table 4 Summary of surgical and medical procedures post sleep study to treat SRDB. Patients (n ¼ 16)
Diagnosis
Intervention
1
Crouzon’s syndrome
2 3 4 5 6
Apert’s syndrome Crouzon’s syndrome Apert’s syndrome Crouzon’s syndrome Apert’s syndrome
Continued BIPAP with oxygen even after Cranial vault surgery and ArnoldeChiari decompression Adenotonsillectomy Cranio-orbital surgery, V-P shunt insertion Adenotonsillectomy CPAP Oxygen
7 8 9 10 11 12 13
Crouzon’s syndrome Crouzon’s syndrome Crouzon’s syndrome Apert’s syndrome Crouzon’s syndrome Crouzon’s syndrome Crouzon’s syndrome
Adenotonsillectomy LeFort III surgery Adenotonsillectomy Palatal release Adenotonsillectomy CPAP followed by Adenotonsillectomy Cranial vault reconstruction
14 15 16
Apert’s syndrome Apert’s syndrome Pfeiffer’s syndrome
Adenotonsillectomy LeFort III CPAP
Age at baseline PSG (years) 2.7 3 2.7 4 1.4 1.1 4.4 4.9 3.8 10.3 8.4 1.3 0.25 5.7 6.3 0.8
Baseline PSG OAHI/CAI
Follow up PSG results OAHI/CAI
Follow up PSG time from 1st test
10.6 CAI ¼ 66.4 30 2.4 7.5 13.7 7.2 CAI ¼ 3.8 19.2 13 6.6 9 16.7 15.7 8.1 CAI ¼ 11.8 36.4 8.1 19.2
5.1 CAI ¼ 4.5 14.4 3.3 2.8 17.4 2.5 CAI ¼ 0.7 Not done Not done 76.9 2.0 0.4 5.7 3.6 CAI ¼ 6.2 18 15.3 1.4
8 months 2 1 2 1 2
years year years year months
1 year 2 years 4 months 1.5 years 1.5 years 1 year 1.5 years 1.5 years
Abbreviations: BIPAP, Bi-level intermittent positive airway pressure; CAI, central apnoea index; CPAP, continuous positive airway pressure; OAHI, obstructive apnoeaehypopnoea index; PSG, polysomnography; V-P, ventriculo-peritoneal.
than 10 years of age, highlighting that SRDB is likely due to a combination of adenotonsillar hypertrophy and structural bony growth (Peterson-Falzone et al., 1981). Despite an improvement in the majority of children in SRDB post surgical intervention, complete resolution of SRDB as per PSG criteria was achieved only in minority of them which underscores the multifactorial nature of the aetiology of and treatment of SRDB in this population. There were apparent limitations in this study. First this was a referred sample and the conclusions are applicable only to patients with syndromic craniosynostosis who were referred for suspected SRDB although our included population represents around half of the total syndromic craniosynostosis population in our centre. Future baseline studies attempting to screen all children with syndromic craniosynostosis for SRDB, perhaps prior to any surgical intervention to accurately determine the true prevalence of SRDB are needed. Second, there was a potential for selection bias; being a retrospective chart review, it was not possible to completely standardize patient screening, questionnaires or determine if there was a significant improvement in clinical symptoms post surgical intervention for SRDB. Further limitations include no systematic assessment of the upper airways by an otolaryngologist although this was done on an individual basis as determined clinically. The impact of SRDB on cardiopulmonary and neurocognitive function was not assessed although this is clearly an important area for future research. Other limitations were that treatments for SRDB could not be standardized due to the complexity of the upper airway in these children, which should allow for cautious interpretation of the treatment outcomes as determined by the PSG findings. The lack of standardization of the surgical procedures in this population is an issue that have been addressed previously (Nada et al., 2009). Finally, although 26/35 children had imaging of the head, either Magnetic Resonance imaging (n ¼ 8) or computerized tomography (CT) (n ¼ 18); this was done for pre-operative purposes and was not intended to specify upper airway obstruction or soft tissue enlargement in those with OSA, clearly another important area for future research. In one small study by Hoeve et al. reviewed 72 patients with craniosynostosis but only 10 patients had a formal overnight PSG. PSG was used to screen 10 children with syndromic craniosynostosis. Of these 5/10 (50%) had evidence of OSA (Hoeve et al., 2003; Pijpers et al., 2004). However, they screened only 16% of their total syndromic craniosynostosis population. Furthermore, OSA was likely under-estimated as they defined OSA for OAHI >5 events/h.
The study was limited due to lack of data on treatments and their outcomes in that population using follow up PSG data. In one small study (n ¼ 10) which did evaluate SRDB using PSG data pre and post a standardized surgical procedure (LeFort III surgery), there was a significant improvement in OSA but not complete resolution (Nelson et al., 2008). However, they also included 6 tracheotomized patients and 9 of the 10 patients were on CPAP or Bi-Level Positive Airway Pressure (BIPAP) therapy, thus there were no baseline PSG data available on these patients to quantitatively assess upper airway obstruction prior to the surgery. The authors also excluded patients with CSA which could contribute to significant morbidity in these children. Finally a recent small study evaluated children (n ¼ 20) who underwent LeFort III surgery, although only nine patients had baseline PSG for suspected SRDB (Flores et al., 2009). This study showed that 8/9 had severe OSA. However, follow up data with PSG was limited to three patients only post intervention limiting the applicability of the study. The findings of our study highlight the importance of screening children with syndromic craniosynostosis who were suspected to have SRDB using full formal PSG, the gold standard test to diagnose SRDB (Loughlin et al., 1996; Marcus et al., 2002; Kushida et al., 2005). Furthermore, the above findings confirm the need for ongoing evaluation with a PSG post surgical intervention. 5. Conclusion This retrospective review confirms a high prevalence of moderate to severe OSA in this population of children referred for suspected SRDB. Although an improvement was observed in SRDB, complete resolution of SRDB in most children with syndromic craniosynostosis was not achieved despite various surgical and/or medical interventions. Since the impact of residual SRDB in this population is unknown, further research is urgently needed to longitudinally evaluate cardiopulmonary and neurocognitive function in those children with ongoing SRDB in those who did and did not have an intervention to treat underlying SRDB. Conflicts of interest disclosure The authors Dr. Suhail Al-Saleh, Andrea Riekstins, Dr. Christopher R. Forrest, Dr. John H. Philips, Jeremy Gibbons, Dr. Indra Narang have no conflicts of interest to disclose.
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Abbreviations AASM BIPAP CSA CAI CPAP EEG EMG EOG etCO2 NREM OSA OAHI SaO2 PSG REM SRDB TcCO2 TST
American academy of sleep medicine bi-level positive airway pressure central sleep apnoea central apnoea index continuous positive airway pressure electroencephalogram electromyogram Electro-oculogram end-tidal carbon dioxide non-rapid eye movement obstructive sleep apnoea obstructive apnoeaehypopnoea index oxygen saturation polysomnography rapid eye movement sleep-related disordered breathing trans-cutaneous carbon dioxide total sleep time
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Cleft Palate J 18: 237e250, 1981 Phillips JH, George AK, Tompson B: Le Fort III osteotomy or distraction osteogenesis imperfecta: your choice. Plast Reconstr Surg 117: 1255e1260, 2006 Pijpers M, Poels PJ, Vaandrager JM, de Hoog M, van den Berg S, Hoeve HJ, et al: Undiagnosed obstructive sleep apnoea syndrome in children with syndromal craniofacial synostosis. J Craniofac Surg 15: 670e674, 2004 Rechtschaffen AKA: A manual of standardized terminology: techniques and scoring system for sleep stages of human subjects. Los Angeles, CA: UCLA Brain Information Service/Brain Research Institute, 1968 Schafer ME: Upper airway obstruction and sleep disorders in children with craniofacial anomalies. Clin Plast Surg 9: 555e567, 1982 Sculerati N, Gottlieb MD, Zimbler MS, Chibbaro PD, McCarthy JG: Airway management in children with major craniofacial anomalies. 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Sleep-related disordered breathing in children with syndromic craniosynostosis Suhail Al-Saleh a, c, Andrea Riekstins a, c, Christopher R. Forrest b, c, John H. Philips b, c, Jeremy Gibbons a, Indra Narang a, c, * a
Division of Respiratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada Division of Plastic Surgery, Center for Craniofacial Care or Research, Hospital for Sick Children, Toronto, Ontario, Canada c University of Toronto, Toronto, Ontario, Canada b
a r t i c l e i n f o
a b s t r a c t
Article history: Paper received 18 December 2009 Accepted 23 April 2010
Background: Syndromic craniosynostosis patients are at risk for sleep-related disordered breathing (SRDB) but the role of polysomnography (PSG) in assessing these patients has not been fully explored. Our aim was to evaluate the prevalence or severity of SRDB in children with syndromic craniosynostosis or the impact of treatments on their SRDB. Methods: We conducted a retrospective review of all patients with syndromic craniosynostosis referred between 1996 or 2008 for an initial PSG to rule out SRDB. For those with SRDB, we reviewed the interventions post PSG. Results: 35 patients (18 females) were included. Specific diagnoses were Crouzon’s (n ¼ 18), Apert’s (n ¼ 14), Pfeiffer (n ¼ 2) or Saethre-Chotzen (n ¼ 1) syndromes. Their mean age was 4.5 years or their mean body mass index (BMI) was 16.9 kg/m2. Of these patients, 26/35 (74%) had evidence of SRDB. The median obstructive apnoea index was 6.6/h (range 0.5e36.4/h) or median central apnoea index was 1.0/h (range 0.0e66.4/h). A total of 16 children had interventions to treat SRDB, of which 14/16 had a follow up PSG or only 10/14 (x%) had a significant improvement of their SRDB. Conclusion: This review confirms a high prevalence SRDB in this referred population. Despite various interventions, complete resolution of SRDB could not be achieved. Ó 2010 European Association for Cranio-Maxillo-Facial Surgery.
Keywords: syndromic craniosynostosis sleep-related disordered breathing central sleep apnoea obstructive sleep apnoea paediatrics or polysomnography
1. Introduction Syndromic craniosynostosis is a group of craniofacial malformations which includes Crouzon’s, Apert’s, Pfeiffer or SaethreChotzen syndromes. These syndromes are associated with premature fusion of one or more cranial sutures, or other craniofacial manifestations including maxillary hypoplasia, cleft lip or palate, choanal atresia, Chiari malformation, hydrocephalus, tracheoe bronchial malformations, or/or other skeletal or respiratory anomalies (Jones, 2006). The genetic basis of these craniosynostosis syndromes includes mutations in the Fibroblast growth factor receptor 1, 2 or 3 genes with an autosomal dominant inheritance fashion (Jones, 2006; Kimonis et al., 2007). Syndromic craniosynostosis can be associated with central nervous system and/or airway complications including restriction of brain growth, visual disturbance, increased intracranial pressure or airway obstruction.
* Corresponding author. Division of Respiratory Medicine, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. Tel.: þ1 416 813 6346; fax: þ1 416 813 6246. E-mail address: [email protected] (I. Narang).
The pathophysiology of upper airway obstruction is related to distortion and displacement of craniofacial bones which can compromise both nasopharyngeal and oropharyngeal spaces. These anomalies may include reduction of the pharyngeal height, width and depth, increased length and thickness of the velum, decreased length of the hard palate, marked reduction of the posterior cranial base with a lesser degree reduction of the anterior cranial base, choanal stenosis or atresia, midnasal stenosis, tracheal cartilaginous sleeve, maxillary hypoplasia and other airway anomalies (Mixter et al., 1990; Cohen and Kreiborg, 1992; Sirotnak et al., 1995; Noorily et al., 1999). These changes are present in infancy and tend to be more pronounced with craniofacial growth specifically increased pharyngeal length, increased soft palate thickness, decreased hard palate length, decreased pharyngeal height, and depth and shortened cranial base with increasing age from infancy to teenage period (Peterson-Falzone et al., 1981). Sleep-related disordered breathing (SRDB) is a group of respiratory disorders specific to sleep or exacerbated by sleep. These disorders include obstructive sleep apnoea (OSA), central sleep apnoea (CSA), periodic breathing and hypoventilation. The commonest sleep disorder seen in children is OSA. OSA is a disorder of breathing during sleep characterized by prolonged partial upper
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airway obstruction (obstructive hypopnoea) and/or intermittent complete obstruction (obstructive apnoea) that disrupts normal ventilation during sleep and normal sleep patterns (Loughlin et al., 1996). The reported prevalence of OSA is around 2e4% (O’Brien et al., 2003; Montgomery-Downs et al., 2004; LofstrandTidestrom and Hultcrantz, 2007; Lumeng and Chervin, 2008). Adenotonsillar hypertrophy is the most common cause of OSA in healthy children with no underlying co-morbidities; adenotonsillectomy improves OSA and related symptoms in most of these cases (Stradling et al., 1990; Suen et al., 1995). However, if OSA is left untreated, serious complications can occur including failure to thrive, pulmonary hypertension, cardiac dysfunction, poor daytime performance and behavioural problems (Brouillette et al., 1982; Tal et al., 1988; Gozal, 1998; Amin et al., 2002; Chervin et al., 2002; O’Brien et al., 2004; Amin et al., 2005; Bonuck et al., 2006). In children with syndromic craniosynostosis with significant upper airway obstruction and/or OSA, additional complications such as increased intracranial pressure, and sudden cardiopulmonary arrest and death have been described (Schafer, 1982; Mixter et al., 1990; Sirotnak et al., 1995; Lauritzen et al., 1998; Mitsukawa et al., 2004; Hayward and Gonsalez, 2005; Witherow et al., 2008). Central apnoeas, periodic breathing or central hypoventilation are less common than OSA. They can be primary as in congenital central hypoventilation syndrome or secondary due to trauma, infection or ArnoldeChiari malformations (Marcus, 2001). In children with craniosynostosis, OSA has been described in several case reports and series (Peterson-Falzone et al.,1981; Schafer, 1982; Mixter et al., 1990; Cohen and Kreiborg, 1992; Edwards et al., 1992; Moore, 1993; Sirotnak et al., 1995; Gonsalez et al., 1996; Jarund and Lauritzen, 1996; Gonsalez et al., 1997; Perkins et al., 1997; Gonsalez et al., 1998; Lauritzen et al., 1998; Sculerati et al., 1998; Jarund et al., 1999; Noorily et al., 1999; Hoeve et al., 2003; Mitsukawa et al., 2004; Pijpers et al., 2004; Fearon, 2005; Hayward and Gonsalez, 2005; Phillips et al., 2006; Ahmed et al., 2008; Nelson et al., 2008; Witherow et al., 2008; Amonoo-Kuofi et al., 2009). CSA also has been reported in cases with hindbrain herniation (Gonsalez et al., 1998). However, most of these studies relied on clinical assessment and/or parents’ questionnaires. Reported treatment options for OSA in this population include choanal dilatation (Mixter et al., 1990; Jarund et al., 1999), continuous Positive Airway Pressure (CPAP) (Gonsalez et al., 1996; Jarund et al., 1999; Hoeve et al., 2003), nasopharyngeal airways (Gonsalez et al., 1996; Perkins et al., 1997; Ahmed et al., 2008), palatal surgery (Mixter et al., 1990; Edwards et al., 1992; Moore, 1993), adenotonsillectomy (Edwards et al., 1992; Moore, 1993; Perkins et al., 1997; Lauritzen et al., 1998; Hoeve et al., 2003; Amonoo-Kuofi et al., 2009), midface advancement surgeries (Edwards et al., 1992; Jarund and Lauritzen, 1996; Fearon, 2005; Phillips et al., 2006) or tracheostomy (Mixter et al., 1990; Moore, 1993; Sirotnak et al., 1995; Jarund and Lauritzen, 1996; Perkins et al., 1997; Lauritzen et al., 1998; Sculerati et al., 1998; Hoeve et al., 2003). These treatment modalities were instituted dependent on individual clinical criteria as there is no unified pathway or approach in assessing and managing children with syndromic craniosynostosis who have evidence of OSA. Only one study with 10 patients reported the use of a full PSG for evaluation of OSA pre- and post-LeFort III surgery in a selected population of syndromic craniosynostosis (Nelson et al., 2008). To our current knowledge, there are no studies that have used full PSG as a primary tool for evaluating children with craniosynostosis for SRDB and the various medical and surgical treatment outcomes for OSA. The objective of this study is to not only analyze the prevalence of SRDB in children with syndromic craniosynostosis who have been referred for an full overnight PSG for suspected SRDB but also to evaluate the impact of various treatments to relieve upper airway obstruction and/or brainstem compression in this population.
2. Methods 2.1. Study subjects At the Hospital for Sick Children, Toronto, Canada, the Centre for craniofacial care and research database was used to identify all patients with syndromic craniosynostosis. All patients who were referred to the sleep laboratory between January 1996 and December 2008 for an initial baseline PSG were included in the analysis. The primary indication for referral was suspected OSA. Exclusion criteria were: (1) patients with previous or current history of tracheostomy, (2) patients known to have SRDB from previous sleep studies, (3) patients who never had a full baseline PSG due to a medical intervention such as oxygen or CPAP therapy for the treatment of SRDB (termed spilt night study), and (4) patients who had their first baseline PSG before 1996 as the detailed polysomnographic raw data for the studies performed before 1996 could not be retrieved. The demographic data collected included type of syndromic craniosynostosis, any additional medical diagnoses, history of snoring, age at the time of PSG, gender, height, weight, and body mass index (BMI). Additional data including surgical or medical interventions prior to the PSG and within 2 years after the PSG were also documented. 2.2. Polysomnographic assessment Patients underwent a standard overnight PSG using XLTEC (Oakville, Canada) and Nicolet (Viasys, Madison, WI) data acquisition and analysis systems. PSG measurements included electroencephalogram (EEG), electro-oculogram (EOG), submental electromyogram (EMG) and bilateral anterior tibialis EMG. Respiratory measurements included chest wall and abdominal movement using chest wall and abdominal belts; nasal airflow measurements using nasal air pressure transducer and/or oronasal thermal sensor, oxygen saturation (SaO2), trans-cutaneous carbon dioxide (TcCO2) and end-tidal carbon dioxide (etCO2). Video and audio recordings were obtained for each study as well as body position, which was documented manually by a registered polysomnographic technician. Sleep architecture was assessed by standard techniques (Rechtschaffen, 1968). Information obtained from PSG included sleep onset latency and rapid eye movement (REM) onset latency, total sleep time (TST), sleep efficiency, time spent in each sleep stage (minutes and percentage), number and classification of arousals, number of independent leg movements and snoring. Recorded respiratory data included counts and indexes of the following events: OSA, CSA, hypopnoea and mixed apnoeas in nonrapid eye movement (NREM) sleep, REM sleep and total sleep. All events were scored according to the current American Academy of Sleep Medicine (AASM) scoring guidelines (Iber et al., 2007) by a registered polysomnographic technician. If a study was obtained prior to May 2007 when new scoring guidelines were introduced to our institution, these studies were rescored according to the current guidelines. An obstructive apnoea event was scored when airflow dropped at least 90% from baseline with chest and/or abdominal motion throughout the entire event; the duration of which was at least a minimum of two baseline breaths. A hypopnoea event was scored when airflow dropped at least 50% from baseline, the duration of which was at least a minimum of two baseline breaths. The hypopnoea event must have been accompanied by either (i) a minimum 3% drop in oxygen desaturation, (ii) an arousal, or (iii) an awakening (Iber et al., 2007). A central apnoea was defined as a cessation of airflow with an absence of respiratory and abdominal effort for a minimum of 20 s or of the duration of
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two prior baseline breaths in which case the event must be accompanied by (i) a minimum 3% drop in oxygen desaturation, (ii) an arousal, or (iii) an awakening. OSA severity was graded according to the obstructive apnoeaehypopnoea index (OAHI), the number of obstructive apnoeas and obstructive hypopnoeas per hour during sleep. OAHI of <1.5 was considered normal, OAHI from 1.5 to <5 was mild OSA; OAHI from 5 to <10 was moderate OSA and OAHI 10 was considered severe OSA. The central apnoea index (CAI) was defined as the number of central apnoeas per hour during sleep. The CSA diagnosis was considered when the CAI was >5 events/hour sleep. Follow up PSGs performed within 2 years from the baseline PSGs were analyzed and if not already done so, scored according to the current paediatric AASM scoring guidelines. Because there are no guidelines or data regarding criteria for re-assessment of the follow up PSGs with regards to what is considered a significant change in OAHI and/or, we defined a follow up PSG as improved if OAHI and/or CAI decreased in the follow up sleep study by 50%; deteriorated if OAHI and/or CAI increased in the follow up sleep study by 50% and not improved if it did not meet the above mentioned criteria as is our current clinical practise. 2.3. Statistical analysis The analyses involved descriptive statistics and included frequencies, percentages, mean, median and/or range values which were obtained for all baseline and PSG data. Maximum and minimum values were recorded for both SaO2 and TcCO2. A standard statistical package was used (SAS, version 9.2, Cary, NC, USA). 3. Results Out of 84 patients with syndromic craniosynostosis identified from the centre for craniofacial care and research database at the Hospital for Sick Children, 54 children were referred for overnight PSG. 19 patients were excluded due to: (1) previous or current history of tracheostomy at the time of the baseline PSG (n ¼ 11), (2) incomplete baseline PSG (n ¼ 3), (3) first baseline PSG before 1996 (n ¼ 3), (4) formal diagnosis of OSA from other centres (n ¼ 1) and (5) unavailability of PSG raw data for the rescoring according to the current AASM paediatric guidelines (n ¼ 1). A total of 35 patients were included in the final analysis. The baseline characteristics of those patients at the time of the baseline study are listed in Table 1. Twenty-three patients had at least one surgical intervention prior to the PSG, the majority of which were craniofacial surgery. Details of these interventions are listed in Table 2. PSG data are displayed in Table 3. Twenty-six of 35 children (74%) had abnormal PSG results. Of these, 7/26 had evidence of mild OSA, 7/26 had moderate OSA, 10/26 had severe OSA, and two patients had CSA in addition to moderate to severe OSA. Overall 16 out of 26 patients who had evidence of SRDB had one or more intervention within 2 years of the PSG specifically to treat SRDB. The remaining 10 children did not have any intervention to treat for SRDB within 2 years of the baseline PSG as: six had mild OSA and therefore no intervention was taken, two patients with moderate OSA were lost to follow up and two patients with severe OSA are awaiting maxillofacial surgical intervention. Of the 16 patients who did undergo the intervention(s), a follow up PSG was done in 14 children. Of these, 10/14 demonstrated a significant improvement but the remaining 4/14 children had either no improvement or worsening in their SRDB post intervention. Summary results of 16 children who had intervention(s) for SRDB are shown in Table 4.
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Table 1 Baseline characteristics of children with craniosynostosis. Patients (n ¼ 35)
Results
Age, years, mean (range) Male: Female Weight, kg, mean (range) Height, cm, mean (range) BMI kg/m2, mean (range) Crouzon’s syndrome, no. (%) Apert’s syndrome, no. (%) Pfeiffer syndrome, no. (%) Saethre-Chotzen syndrome, no. (%) Chiari malformations, no. (%) History of increased ICP, no. (%) Cleft lip/palate, no. (%) History of snoring, no. (%)
4.5 (0.13e15.1) 17:18 20.6 (4.7e79.5) 103.8 (42.0e182.0) 16.9 (11.2e29.1) 18 (51%) 14 (40%) 2 (6%) 1 (3%) 10 (29%) 11 (31%) 7 (20%) 32 (91%)
Abbreviations: BMI, body mass index; ICP, intracranial pressure.
Table 2 Summary of surgical procedures prior to sleep study. Previous interventions (n ¼ 23)
Number (%)
Patients who had more than one intervention Tonsilloadenoidectomy Craniofacial surgery (cranial vault reconstruction, cranio-orbital reshaping, Lefort I, LeFort III) Cleft lip/palate repair V-P shunt insertion Others (nasal stent, choanal atresia relief)
12 (52%) 1 (4%) 20 (87%) 4 (17%) 8 (35%) 3 (9%)
Abbreviations: V-P, ventriculo-peritoneal.
Table 3 Sleep study results of 35 children with syndromic craniosynostosis. Results
Median (range)
Sleep latency, min Sleep efficiency, % TST, min REM latency, min Sleep Stage 1 (% of TST) Sleep Stage 2 (% of TST) Sleep Stage Slow wave (% of TST) Sleep REM Stage (% of TST) Mean SaO2, % Minimum SaO2, % Highest CO2, mmHg OAHI CAI
1.5 91.8 429.0 73.0 5.0 47.4 26.6 26.0 97.8 85.3 52.0 6.6 1.0
(0.0e51.0) (73.2e99.2) (343.5e513.5) (0.0e211.8) (0.2e11.6) (18.3e91.0) (7.7e51.2) (0.0e46.2) (94.9e99.7) (58.0e96.0) (39.2e68.0) (0.5e36.4) (0.0e66.4)
Abbreviations: CAI, central apnoea index; CO2, carbon dioxide; OAHI, obstructive apnoeaehypopnoea index; REM, rapid eye movement; SaO2, oxygen saturation; TST, total sleep time.
4. Discussion To our knowledge, to date this is the largest review of syndromic craniosynostosis population evaluated for SRDB and treatment outcomes with formal full PSG using the current paediatric scoring guidelines (Iber et al., 2007). In children with syndromic craniosynostosis referred for formal PSG evaluation, we found a high proportion with SRDB (74%) which is in keeping with the estimated high prevalence (40e85%) quoted in other studies that had not utilized formal PSG (Moore, 1993; Sirotnak et al., 1995; Gonsalez et al., 1997; Perkins et al., 1997; Sculerati et al., 1998). However, we suspect that the prevalence is under-estimated in this selected population as we excluded children with history of tracheostomy. Of significant note, the majority of the patients with SRDB (73%) were classified in the moderate to severe OSA and most of these children with SRDB (n ¼ 23) were less
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Table 4 Summary of surgical and medical procedures post sleep study to treat SRDB. Patients (n ¼ 16)
Diagnosis
Intervention
1
Crouzon’s syndrome
2 3 4 5 6
Apert’s syndrome Crouzon’s syndrome Apert’s syndrome Crouzon’s syndrome Apert’s syndrome
Continued BIPAP with oxygen even after Cranial vault surgery and ArnoldeChiari decompression Adenotonsillectomy Cranio-orbital surgery, V-P shunt insertion Adenotonsillectomy CPAP Oxygen
7 8 9 10 11 12 13
Crouzon’s syndrome Crouzon’s syndrome Crouzon’s syndrome Apert’s syndrome Crouzon’s syndrome Crouzon’s syndrome Crouzon’s syndrome
Adenotonsillectomy LeFort III surgery Adenotonsillectomy Palatal release Adenotonsillectomy CPAP followed by Adenotonsillectomy Cranial vault reconstruction
14 15 16
Apert’s syndrome Apert’s syndrome Pfeiffer’s syndrome
Adenotonsillectomy LeFort III CPAP
Age at baseline PSG (years) 2.7 3 2.7 4 1.4 1.1 4.4 4.9 3.8 10.3 8.4 1.3 0.25 5.7 6.3 0.8
Baseline PSG OAHI/CAI
Follow up PSG results OAHI/CAI
Follow up PSG time from 1st test
10.6 CAI ¼ 66.4 30 2.4 7.5 13.7 7.2 CAI ¼ 3.8 19.2 13 6.6 9 16.7 15.7 8.1 CAI ¼ 11.8 36.4 8.1 19.2
5.1 CAI ¼ 4.5 14.4 3.3 2.8 17.4 2.5 CAI ¼ 0.7 Not done Not done 76.9 2.0 0.4 5.7 3.6 CAI ¼ 6.2 18 15.3 1.4
8 months 2 1 2 1 2
years year years year months
1 year 2 years 4 months 1.5 years 1.5 years 1 year 1.5 years 1.5 years
Abbreviations: BIPAP, Bi-level intermittent positive airway pressure; CAI, central apnoea index; CPAP, continuous positive airway pressure; OAHI, obstructive apnoeaehypopnoea index; PSG, polysomnography; V-P, ventriculo-peritoneal.
than 10 years of age, highlighting that SRDB is likely due to a combination of adenotonsillar hypertrophy and structural bony growth (Peterson-Falzone et al., 1981). Despite an improvement in the majority of children in SRDB post surgical intervention, complete resolution of SRDB as per PSG criteria was achieved only in minority of them which underscores the multifactorial nature of the aetiology of and treatment of SRDB in this population. There were apparent limitations in this study. First this was a referred sample and the conclusions are applicable only to patients with syndromic craniosynostosis who were referred for suspected SRDB although our included population represents around half of the total syndromic craniosynostosis population in our centre. Future baseline studies attempting to screen all children with syndromic craniosynostosis for SRDB, perhaps prior to any surgical intervention to accurately determine the true prevalence of SRDB are needed. Second, there was a potential for selection bias; being a retrospective chart review, it was not possible to completely standardize patient screening, questionnaires or determine if there was a significant improvement in clinical symptoms post surgical intervention for SRDB. Further limitations include no systematic assessment of the upper airways by an otolaryngologist although this was done on an individual basis as determined clinically. The impact of SRDB on cardiopulmonary and neurocognitive function was not assessed although this is clearly an important area for future research. Other limitations were that treatments for SRDB could not be standardized due to the complexity of the upper airway in these children, which should allow for cautious interpretation of the treatment outcomes as determined by the PSG findings. The lack of standardization of the surgical procedures in this population is an issue that have been addressed previously (Nada et al., 2009). Finally, although 26/35 children had imaging of the head, either Magnetic Resonance imaging (n ¼ 8) or computerized tomography (CT) (n ¼ 18); this was done for pre-operative purposes and was not intended to specify upper airway obstruction or soft tissue enlargement in those with OSA, clearly another important area for future research. In one small study by Hoeve et al. reviewed 72 patients with craniosynostosis but only 10 patients had a formal overnight PSG. PSG was used to screen 10 children with syndromic craniosynostosis. Of these 5/10 (50%) had evidence of OSA (Hoeve et al., 2003; Pijpers et al., 2004). However, they screened only 16% of their total syndromic craniosynostosis population. Furthermore, OSA was likely under-estimated as they defined OSA for OAHI >5 events/h.
The study was limited due to lack of data on treatments and their outcomes in that population using follow up PSG data. In one small study (n ¼ 10) which did evaluate SRDB using PSG data pre and post a standardized surgical procedure (LeFort III surgery), there was a significant improvement in OSA but not complete resolution (Nelson et al., 2008). However, they also included 6 tracheotomized patients and 9 of the 10 patients were on CPAP or Bi-Level Positive Airway Pressure (BIPAP) therapy, thus there were no baseline PSG data available on these patients to quantitatively assess upper airway obstruction prior to the surgery. The authors also excluded patients with CSA which could contribute to significant morbidity in these children. Finally a recent small study evaluated children (n ¼ 20) who underwent LeFort III surgery, although only nine patients had baseline PSG for suspected SRDB (Flores et al., 2009). This study showed that 8/9 had severe OSA. However, follow up data with PSG was limited to three patients only post intervention limiting the applicability of the study. The findings of our study highlight the importance of screening children with syndromic craniosynostosis who were suspected to have SRDB using full formal PSG, the gold standard test to diagnose SRDB (Loughlin et al., 1996; Marcus et al., 2002; Kushida et al., 2005). Furthermore, the above findings confirm the need for ongoing evaluation with a PSG post surgical intervention. 5. Conclusion This retrospective review confirms a high prevalence of moderate to severe OSA in this population of children referred for suspected SRDB. Although an improvement was observed in SRDB, complete resolution of SRDB in most children with syndromic craniosynostosis was not achieved despite various surgical and/or medical interventions. Since the impact of residual SRDB in this population is unknown, further research is urgently needed to longitudinally evaluate cardiopulmonary and neurocognitive function in those children with ongoing SRDB in those who did and did not have an intervention to treat underlying SRDB. Conflicts of interest disclosure The authors Dr. Suhail Al-Saleh, Andrea Riekstins, Dr. Christopher R. Forrest, Dr. John H. Philips, Jeremy Gibbons, Dr. Indra Narang have no conflicts of interest to disclose.
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Abbreviations AASM BIPAP CSA CAI CPAP EEG EMG EOG etCO2 NREM OSA OAHI SaO2 PSG REM SRDB TcCO2 TST
American academy of sleep medicine bi-level positive airway pressure central sleep apnoea central apnoea index continuous positive airway pressure electroencephalogram electromyogram Electro-oculogram end-tidal carbon dioxide non-rapid eye movement obstructive sleep apnoea obstructive apnoeaehypopnoea index oxygen saturation polysomnography rapid eye movement sleep-related disordered breathing trans-cutaneous carbon dioxide total sleep time
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