Genetic Diversity and Evolutionary Kinetics of Influenza A Virus H3N2 Subtypes Circulating in Riyadh, Saudi Arabia.

Presence of a large foreign workforce and the annual gathering of people for pilgrimage from around the globe have significantly contributed to the emergence and diversity of respiratory viruses in Saudi Arabia. Here, we report the sequence and phylogenetic analysis of the H3N2 subtype of influenza A virus (IAV) in clinical samples collected from Riyadh, Saudi Arabia. Based on RT-PCR, IAV was found in 88 (28.3%) of the 311 samples screened. Of the 88-IAV positive samples, 43 (48.8%) were H1N1 subtype while the remaining 45 (51.2%) were found to be of the H3N2 subtype. Complete sequencing of HA and NA genes of H3N2 revealed, twelve and nine amino acid (AA) substitutions respectively, and importantly, these variations are absent in the current vaccine strains. Based on the phylogenetic analysis, the majority of H3N2 strains were grouped in the same clades as the vaccine strains. Importantly, the N-glycosylation sites at AA 135(NSS) were found to be unique to 6 strains in the investigated HA1 protein and were absent in the current vaccine strains. These data may have significant clinical implications in designing novel and population-based vaccines for IAV and underscore the need for regular monitoring of efficacy of vaccines due to emerging variants.

ON-1 and BA-IX Are the Dominant Sub-Genotypes of Human Orthopneumovirus A&B in Riyadh, Saudi Arabia.

Human orthopneumovirus (HOPV) is the major viral pathogen responsible for lower respiratory tract infections (LRTIs) in infants and young children in Riyadh, Saudi Arabia. Yet, predominant HOPV subtypes circulating in this region and their molecular and epidemiological characteristics are not fully ascertained. A total of 300 clinical samples involving nasopharyngeal aspirates (NPAs), throat swabs, and sputum were collected during winter seasons of 2019/2020 and 2021/2022 for HOPV subtyping and genotyping. Of the 300 samples, HOPV was identified in 55 samples (18.3%) with a distinct predominance of type A viruses (81.8%) compared to type B viruses (18.2%). Importantly, the ON1 strain of HOPV-A and BA-IX strain of HOPV-B groups were found to be responsible for all the infections. Sequence analysis revealed a duplication region within 2nd HVR of G protein gene of ON1 and BA-IX strains. This nucleotide duplication exerted a profound effect on protein length and affinity towards cell receptors. Further, these modifications may aid the HOPV in immune evasion and recurrent infections. Data from this study showed that ON-1 genotype of HOPV-A and BA-IX genotype of HOPV-B were dominant in Riyadh, Saudi Arabia. Further, a duplication of sequence within 2nd HVR of G protein gene was found.

Severe asthma in children: An official statement from Saudi Pediatric Pulmonology Association.

In Saudi Arabia, the prevalence of pediatric asthma ranges between 8% and 25%. However, there are no sufficient data regarding severe asthma in childhood in Saudi Arabia. Therefore, a task force has been formed by the Saudi Pediatric Pulmonology Association which is a subsidiary group of the Saudi Thoracic Society and consists of Saudi experts with well-respected academic and clinical backgrounds in the fields of pediatric asthma as well as other respiratory diseases to write a consensus on definitions, phenotypes, and pathophysiology, evaluation, and management. To achieve this, the subject was divided into various sections, each of which was assigned to at least 2 experts. Without a central literature review, the authors searched the literature using their own strategies. To reach an agreement, the entire panel reviewed and voted on proposed findings and recommendations.

Application of aerosol therapy in respiratory diseases in children: A Saudi expert consensus.

The Saudi Pediatric Pulmonology Association (SPPA) is a subsidiary of the Saudi Thoracic Society (STS), which consists of a group of Saudi experts with well-respected academic and clinical backgrounds in the fields of asthma and other respiratory diseases. The SPPA Expert Panel realized the need to draw up a clear, simple to understand, and easy to use guidance regarding the application of different aerosol therapies in respiratory diseases in children, due to the high prevalence and high economic burden of these diseases in Saudi Arabia. This statement was developed based on the available literature, new evidence, and experts' practice to come up with such consensuses about the usage of different aerosol therapies for the management of respiratory diseases in children (asthma and nonasthma) in different patient settings, including outpatient, emergency room, intensive care unit, and inpatient settings. For this purpose, SPPA has initiated and formed a national committee which consists of experts from concerned specialties (pediatric pulmonology, pediatric emergency, clinical pharmacology, pediatric respiratory therapy, as well as pediatric and neonatal intensive care). These committee members are from different healthcare sectors in Saudi Arabia (Ministry of Health, Ministry of Defence, Ministry of Education, and private healthcare sector). In addition to that, this committee is representing different regions in Saudi Arabia (Eastern, Central, and Western region). The subject was divided into several topics which were then assigned to at least two experts. The authors searched the literature according to their own strategies without central literature review. To achieve consensus, draft reports and recommendations were reviewed and voted on by the whole panel.

Sleep quality and insomnia during the COVID-19 lockdown among the Saudi public: A cross-sectional study.

OBJECTIVES: To measure the Saudi population's sleep quality during the lockdown of COVID-19. METHODS: An internet-based questionnaire that was performed during the lockdown of the COVID-19 pandemic among the Saudi population over 2 weeks from April 1 to April 15, 2020. We used the instant messaging application WhatsApp and Twitter to reach the targeted population. Saudi citizens and non-Saudi residents who can read and understand the questionnaire were recruited. Data were analyzed using Stata and SPSS. RESULTS: A total of 790 responses were included. The majority of participants were the Saudi population 735 (92.9%). The prevalence of insomnia and poor sleep quality were 54.4% and 55.5%, respectively. Saudi citizenship was associated with longer sleep duration (p=0.031). Female gender and being married were associated with worse global PSQI, sleep quality, sleep distribution, sleep latency, and daytime dysfunction. CONCLUSION: Our findings showed that during the COVID-19 pandemic, the Saudi population had a high prevalence of insomnia and poor sleep quality. Routine monitoring of the psychological impact of life-threatening outbreaks and the adoption of effective early mental health actions should be considered.

Parental attitude and knowledge towards asthma care measures for their children in Saudi Arabia.

BACKGROUND: Appropriate asthma management in children reduces emergency department visits, hospitalization, and improves the quality of life. We aim to assess the level of children asthma control and its association with parental knowledge. METHODS: A prospective study conducted to measure childhood asthma control with a validated childhood asthma control test (C-ACT), and to assess asthma knowledge among the parents of children aged 4-11 years and their parents upon asthma clinic visits. C-ACT score ≤ 19 is considered as uncontrolled child asthma. RESULTS: We have invited 238 parents to participate in the study; 177 (74.4%) completed the survey. The mean age of the parents and their children were 38.8 ± 7.6 and 7.8 ± 2.7 years, respectively; 28.2% of parents were smokers, and 46.3% of them were college graduated. Nearly 61.6% of the parents and children scored ≤ 19 on C-ACT; 54.2% and 37.9% of parents knew how inhaled salbutamol and corticosteroids work, respectively. A quarter of the parents received an asthma action plan. Multinomial logistic regression analysis showed that parents who did not know their children's medications name (OR, 6.1; 95% CI, 2.15-17.29), and when to use inhaled corticosteroid (OR, 2.1; 95% CI, 1.32-3.45) were independent factors predicting uncontrolled asthma in children with score ≤ 19. CONCLUSIONS: The study indicated that there is an association between poor asthma control (scored ≤ 19 on C-ACT) and parental knowledge of asthma medications. The parents should be educated thoroughly on asthma care, including medications used to minimize asthma exacerbations in their children.

Screening for obesity in the offspring of first-cousin consanguineous couples: A Phase-I study in Saudi Arabia.

Consanguineous or cousin marriages are very common in Saudi Arabia. However, owing to limited studies and insufficient knowledge about genetic diseases/disorders, many couples are unaware of the increased health risks for their offspring. Among the inherited and complex diseases from parents' consanguinity, obesity is common; therefore, we examined the prevalence of obesity in the offspring of first-cousin consanguineous couples in Saudi Arabia. In this questionnaire-based study, 657 individuals (mean age = 18.7 ±â€¯10.2 years; age range = 2-65 years) who were residing in Riyadh, Saudi Arabia participated. Among them, almost 90% were native Saudis. Participants mean body mass index (BMI) was 24.5 ±â€¯9.1 kg/m2. Sex- stratified demographic details confirmed a significant association between age and BMI (p < .001). We confirmed that adolescents and adults were more prone to develop obesity. Adults and non-Saudi participants were three times more likely to develop obesity if they had first-cousin consanguineous parents than those who did not. Of the 30% of participants who were obese, 100 will be selected for Phase II, in which we plan to perform exome sequencing.

Vaccine hesitancy among Saudi parents and its determinants. Result from the WHO SAGE working group on vaccine hesitancy survey tool.

OBJECTIVES: To assess the prevalence of vaccine hesitancy and its determinants among Saudi parents. In addition, we explored the relationship between vaccine hesitancy and child's immunization status. Methods: A cross-sectional study was conducted using interviews with parents visiting outpatient clinics at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, between July 2017 and October 2018. The strategic advisory group of experts on immunization vaccine hesitancy survey was used. Results: A total of 500 parents were interviewed. Twenty percent of parents were hesitant to get their child vaccinated. Parents with higher educational levels were more vaccine hesitant (p less than 0.001). Among parents who reported hesitancy toward vaccination, 36% of children were not vaccinated fully for their age. Concerns related to vaccine safety were the most frequent reason (53%) reported by vaccine-hesitant parents. Negative beliefs toward vaccination seemed to be associated with increase hesitancy and incomplete vaccination status of children. In multivariate analyses, the main factors associated with both parents' hesitancy and incomplete vaccination status were believing that vaccines are ineffective (adjusted odds ratio [AOR]=28, 95% confidence interval [CI]: 7.9-102.3) and believing that vaccines are not important (AOR=27, 95% CI: 5.8-126). Conclusion: Vaccine hesitancy among parents in Kingdom of Saudi Arabia is a concern and is likely to influence the vaccination status of their children. Countering vaccine related concerns must be tailored, particularly in higher-educated groups.

Narcolepsy in Saudi patients before and after the 2009 H1N1 vaccination. The experience of 2 referral centers.

OBJECTIVES: To assess the number of Saudi patients diagnosed with narcolepsy in 2 tertiary centers before and after the introduction of the 2009 A(H1N1)pdm09 vaccine.  Methods: We started collecting data after the first international report of an association between the A(H1N1)pdm09 vaccine and narcolepsy between January 2010 and December 2016. All patients diagnosed with narcolepsy after 2009 were included and data were collected for 7 years to account for any possible delays in the diagnosis of narcolepsy.  Results: One-hundred and seventy-three patients with narcolepsy were identified. The majority (144 patients, 83%) had symptom onset before June 2009. Only 29 patients (17%) had symptom onset after 2009. No difference in the annual number of narcolepsy cases was found  before and after 2009. Conclusion: Based on data obtained from 2 tertiary care sleep disorders center, there was no increase in the number of cases of narcolepsy among Saudis following the introduction of the influenza A(H1N1)pdm09 vaccination.

Mycoplasma pneumoniae-associated mucositis syndrome: A rare and clinically challenging disease in a Saudi child.

Mycoplasma pneumoniae-associated mucositis (MPAM) is an extra-pulmonary manifestation of M. pneumoniae infection and may present as isolated mucosal lesions (e.g., ocular, oral, and urogenital) or as a combination of mucosal and minimal cutaneous lesions. MPAM is a rare entity that lies on the spectrum of erythema multiform (EM) major and Stevens-Johnson syndrome (SJS). We present a 12-year-old boy who presented with classical clinical manifestations of MPAM and strongly positive M. pneumoniae PCR results. The patient was treated with antimicrobial therapy and had an uneventful recovery. Physicians should be aware of this rare entity and manage patients accordingly.

Epidemiology of 11 respiratory RNA viruses in a cohort of hospitalized children in Riyadh, Saudi Arabia.

Respiratory tract infections are a principal cause of illness and mortality in children worldwide and mostly caused by viruses. In this study, the epidemiology of 11 respiratory RNA viruses was investigated in a cohort of hospitalized children at a tertiary referral center in Riyadh from February 2008 to March 2009 using conventional and real-time monoplex RT-PCR assays. Among 174 nasopharyngeal aspirates, respiratory syncytial virus (RSV) was detected in 39 samples (22.41%), influenza A virus in 34 (19.54%), metapneumovirus (MPV) in 19 (10.92%), coronaviruses in 14 (8.05%), and parainfluenza viruses (PIVs) in 11 (6.32%). RSV, PIVs and coronaviruses were most prevalent in infants less than 6 months old, whereas MPV and influenza A virus were more prominent in children aged 7-24 and 25-60 months, respectively. The majority of the viruses were identified during winter with two peaks observed in March 2008 and January 2009. The presented data warrants further investigation to understand the epidemiology of respiratory viruses in Saudi Arabia on spatial and temporal basis.

Proxy molecular diagnosis from whole-exome sequencing reveals Papillon-Lefevre syndrome caused by a missense mutation in CTSC.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D)) was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal.

Nonsense mutation in coiled-coil domain containing 151 gene (CCDC151) causes primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder characterized by impaired ciliary function that leads to subsequent clinical phenotypes such as chronic sinopulmonary disease. PCD is also a genetically heterogeneous disorder with many single gene mutations leading to similar clinical phenotypes. Here, we present a novel PCD causal gene, coiled-coil domain containing 151 (CCDC151), which has been shown to be essential in motile cilia of many animals and other vertebrates but its effects in humans was not observed until currently. We observed a novel nonsense mutation in a homozygous state in the CCDC151 gene (NM_145045.4:c.925G>T:p.[E309*]) in a clinically diagnosed PCD patient from a consanguineous family of Arabic ancestry. The variant was absent in 238 randomly selected individuals indicating that the variant is rare and likely not to be a founder mutation. Our finding also shows that given prior knowledge from model organisms, even a single whole-exome sequence can be sufficient to discover a novel causal gene.

Determinants of asthma control among children in Saudi Arabia.

OBJECTIVE: Asthma is the most common chronic disease among children. Uncontrolled asthma may considerably decrease the quality of life for patients and their families. Our objective was to identify possible risk factors for poor asthma control in children. METHODS: A cross-sectional study was conducted among children with asthma aged 4-11 years who attended a pediatric clinic for follow-up visits at one of the major teaching hospitals in Riyadh, Saudi Arabia. Asthma control status was measured by the childhood asthma control test. Multiple logistic regression analysis was performed to explore the relationships between the outcome and exposure variables. RESULTS: Uncontrolled asthma was present in 89 out of 158 children (59.3%). Asthma control improved with the number of siblings. Control improved by 69% with two or three siblings (OR = 0.31, 95% CI = 0.10-0.96) and by 87% with four or more siblings (OR = 0.13, 95% CI = 0.04-0.48). Similarly, asthma control improved with an increased asthma knowledge of the caregiver (OR = 0.87, 95% CI = 0.81-0.93). Household incomes less than SAR 15 000 and sharing a bedroom increased the odds of having uncontrolled asthma by 2.30 (95% CI = 1.02-5.21) and 3.33 (95% CI = 1.33-8.35), respectively. CONCLUSIONS: In addition to knowledge, socioeconomic factors, such as family income, household crowding, and the number of siblings are associated with asthma control among children in Saudi Arabia. Further research is needed to investigate the role of these factors.

Introducing integrated laboratory classes in a PBL curriculum: impact on student's learning and satisfaction.

BACKGROUND: With the introduction of integrated problem-based learning (PBL) program in the medical curriculum, there is a need to create laboratory classes that suit students' learning needs and the changes introduced to the curriculum. This paper outlines the development and implementation of four integrated laboratory classes (ILCs) at King Saud University College of Medicine. It also examines whether core concepts addressed in these classes were learned and retained and how the students perceived the ILCs. METHODS: ILCs are based on enhancing enquiry-based learning, and encouraging students to work on tasks in small groups (apply and integrate knowledge from biochemistry, pathology and microbiology) and conduct a laboratory procedure (practical part). In two of these ILCs, a pretest comprising 15 multiple-choice questions were administrated at the start of the class and an identical posttest was administrated at the end of these classes. Performance of the students in the Objective Structured Practical Examination (OSPE) at the end of the blocks was also evaluated. Students' perceptions were evaluated using a questionnaire completed at the end of each class. RESULTS: A total of 247, 252, 238, and 244 students participated in practical classes covering cerebrospinal fluid infection, small intestine, liver function tests and adrenal gland function, respectively. Students got higher scores in posttests compared to pre-test scores in two classes (12.68 ± 2.03 vs 6.58 ± 3.39 and 13.02 ± 2.03 vs 7.43 ± 2.68, respectively). Paired t-test showed that the difference was significant (P < 0.001) in both tests. The mean scores of students in stations dealing with ILCs at the end of the block examinations were not significantly different from the mean scores for other stations not related to ILCs. The questionnaire indicated that most students expressed positive attitude towards working on tasks and applying knowledge learnt. Students also felt that conducting laboratory procedures and interpreting laboratory findings were valuable to their learning. CONCLUSIONS: Given the increase in the posttest scores (short-term retention) and the satisfactory performance of students at the end of block examinations (long-term retention) together with the students' satisfaction, the study suggests that the core concepts addressed in these classes were learned and retained.

Significance of fractional exhaled nitric oxide measurements in detecting primary ciliary dyskinesia in Saudi children.

OBJECTIVE: To examine the usefulness of fractional exhaled nitric oxide (FENO) measurements in detecting primary ciliary dyskinesia (PCD) in children. METHODS: This observational study was conducted at the Department of Pediatrics and Physiology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia from January 2011 to December 2011. The study population consisted of 22 children with symptoms suggestive of PCD and the diagnosis was confirmed by ciliary biopsy. Using the American Thoracic Society guidelines, measurements of FENO were performed in 22 subjects with proven PCD biopsies and in 11 healthy age-matched subjects. RESULTS: No significant differences were found on the basis of age or ventilatory function tests between the PCD patients and control groups. Fractional exhaled nitric oxide values were significantly lower in children with PCD (6.19+/-1.43) compared to control group (17.00+/-6.30) (CI: -14.854 to -5.927, p<0.0001). Rhinorrhea was seen in 7 (31.8%), recurrent acute otitis media in 16 (72.7%), chronic otitis media in 5 (22.7%), recurrent sinusitis in 5 (22.7%), chronic productive cough in 8 (36.4%), bronchospasm in 11 (50%), and dextrocardia in 3 (13.6%) subjects. There was no correlation between age, FENO, and ventilatory function parameters. CONCLUSION: The measurement of FENO appears to be a useful tool for screening children for PCD. It can complement other tests such as nasal biopsy and electron microscopy studies.

Sleep-disordered breathing in children with craniosynostosis.

BACKGROUND: Syndromic craniosynostosis (SC) is associated with a high prevalence of sleep-disordered breathing (SDB). However, it remains unclear whether non-syndromic craniosynostosis (NSC) is associated with an increased risk for SDB. SETTING: This study was conducted at a tertiary referral pediatric medical center. METHODS: A prospective polysomnographic (PSG) evaluation was conducted of all children diagnosed with craniosynostosis over a 3-year period and who had not undergone previous PSG for SDB-related symptoms. RESULTS: Among 14 children fulfilling inclusion criteria, 10 had NSC and 4 were diagnosed with SC (Crouzon syndrome). SDB was present in 50 % of the NSC and in 75 % of SC. No associations emerged between the number of sutures affected and the presence of SDB. CONCLUSIONS: SDB is highly prevalent not only in SC but also among asymptomatic children with NSC. The diagnosis of NSC should prompt a diagnostic PSG as a routine component of the clinical evaluation, and PSG findings may aid in the formulation of decisions regarding timing and need for surgical interventions.

Effects of inhaled fluticasone on intraocular pressure and central corneal thickness in asthmatic children without a family history of glaucoma.

PURPOSE: The aim of this study is to report the effects of fluticasone-inhaled corticosteroid on intraocular pressure (IOP) and central corneal thickness (CCT) of asthmatic children without a family history of glaucoma. MATERIALS AND METHODS: In this prospective study, 93 children were divided into two groups: 69 asthmatic children with no family history of glaucoma who were taking inhaled fluticasone propionate 250 µg daily for at least 6 months (Group 1) and 24 age-matched control subjects without asthma (Group 2). Three measurements each, of IOP and CCT, were performed with a hand-held noncontact tonometer and a noncontact specular microscope, respectively, over a 12-week period. The order of IOP and CCT measured were randomized at each visit. Between-group comparison and the relationship between CCT and IOP measurements were investigated. P < 0.05 was statistically significant. RESULTS: The mean age was 8 ± 2.4 years (range, 5-15 years) and 9 ± 2.9 years (range, 5-15 years) for Groups 1 and 2, respectively (P = 0.1337). The mean IOP was 14 ± 3.3 mmHg (range, 10-24 mmHg) and 14 ± 2.9 mmHg (range, 11-22 mmHg) for Groups 1 and 2, respectively (P = 0.3626). The mean CCT was 531 ± 30.1 µm (range, 467-601 µm) and 519 ± 47.0 µm (range, 415589 µm) for Groups 1 and 2, respectively (P = 0.1625). There was a weak but statistically significant correlation between IOP and CCT in Group 1 (Pearson's R = 0.3580, P = 0.0025). CONCLUSIONS: Inhaled fluticasone at the regular dose used in this study over a short period (6-24 months) was not associated with a significant effect on CCT and IOP measured with noncontact devices in asthmatic children between 5 and 15 years, without a family history of glaucoma. A weak correlation between IOP and CCT values in asthmatic children did exist.

Experience and attitude of interns to pelvic and sensitive area examinations during their undergraduate medical course.

OBJECTIVE: To explore the experience of interns in sensitive area examination during their undergraduate medical course and identify factors interfering with such examinations. METHODS: A cross sectional study was carried out from May to June 2010. Interns (n=315) at King Saud University College of Medicine were invited via email to complete a web-based questionnaire developed using surveymonkey.com. RESULTS: Out of 315 interns, 211 completed the questionnaire; 60% males and 40% females. The mean percentage of interns who never performed any of these examinations was 28.9% for digital rectal examination, 17.5% for breast, 43.1% for female pelvic examination, 13.3% for inguinal (hernia), and 34.6% for male external genitalia. Compared to females, male students conducted more rectal examinations (87 versus 63, p<0.005), and male external genitalia examinations (112 versus 26, p<0.001). On the other hand, compared to male students, females conducted more pelvic examination (68 versus 52, p=0.03) and breast examinations (92 versus 82, p=0.27). The most common reasons for not performing sensitive area examinations included patient's refusal (33.1%), and examining patients of opposite gender (27.6%). Confidence in performance of these examinations was correlated to increased frequency of the examination. CONCLUSION: This study highlights that most common factors interfering with the students' conducting sensitive area examinations are patient's refusal and examining patients of the opposite sex. There is a strong correlation between increased frequency of conducting an examination and student's confidence in performance.

Sleep-disordered breathing in children with Chiari malformation type II and myelomeningocele.

BACKGROUND: The prevalence of sleep-disordered breathing (SDB) in children with Chiari malformation type II (CM-II), a known association of neural tube defects (NTD), has not been well documented. The aim of the present study was to assess the prevalence and possible predictive factors of SDB in patients with CM-II. METHODS: The study included all patients with documented CM-II who were routinely referred from the Neurosurgery Clinic to the University Sleep Disorders Centre at King Khalid University Hospital, Riyadh, Saudi Arabia, between January 2002 and July 2009. Overnight full polysomnography (PSG) was performed in all patients. Polysomnographic data were analyzed using descriptive statistics. RESULTS: Sixteen children (11 boys, five girls) were included in the study; their mean age was 4.7 years (range, 0.8-10 years) and their mean body mass index was 18.05 kg/m(2) (range, 15.4-25.4 kg/m(2) ). For the whole group, the mean apnea-hypopnea index (AHI) was 6.3/h (range, 0.2-24.5/h), with AHI recorded as >5/h in five patients (31.3%) and ≥ 10/h in three patients (18.8%). The mean central apnea-hypopnea index was 5.9/h (range, 0-24.5/h) and the mean obstructive apnea-hypopnea index was 0.4/h (range, 0-2.9/h). The mean arousal index was 15.1/h (range, 5-34/h). CONCLUSION: The major assumption linking CM-II and NTD with potential brainstem compression and respiratory dysfunction during sleep was confirmed. Indeed, SDB is highly prevalent, and clearly underreported and undertreated in patients with CM-II associated with NTD.