Wen-Chin Weng

Body weight status and obstructive sleep apnea in children

Objective:The relationship between weight status, adenotonsillar hypertrophy and obstructive sleep apnea (OSA) in children has not yet been well studied. As the sleep parameters may show a disparity in different weight statuses, this study examined the relationship between the data of over-night polysomnography and different weight statuses, as well as the impact of adenotonsillar hypertrophy on children with OSA.Methods:Children with sleep disturbances were recruited from our clinics. Standard physical examinations, history taking, lateral neck roentgenography, and full-night polysomnography were obtained. Children were divided into four groups based on the age- and gender-corrected body mass index (BMI): underweight, normal weight, overweight and obese. An adenoidal/nasopharyngeal ratio of more than 0.67 was considered adenoidal hypertrophy. Tonsillar hypertrophy was defined as having Grade III tonsils or above.Results:From July 2006 to January 2009, 197 children were included in this study. Obese children had a significantly higher apnea–hypopnea index (AHI), obstructive apnea index and lower minimum oxygen saturation (MinSaO2) than those of the other groups. Underweight children had the second highest AHI. A negative correlation was also found between BMI z scores and MinSaO2 (r=−0.194; P=0.007). Children with tonsillar hypertrophy (P=0.001) were associated with a higher risk of having OSA. The risk of having OSA was significantly higher in obese children (P=0.001) and underweight children (P=0.043) than in those with a normal weight.Conclusion:Obesity, underweight status and tonsillar hypertrophy are associated with children having OSA, and obese children have a significantly higher risk than children with underweight status.

Associations between Adenotonsillar Hypertrophy, Age, and Obesity in Children with Obstructive Sleep Apnea

Objective To investigate the contributions of adenoid and tonsil size to childhood obstructive sleep apnea (OSA) and the interactions between adenotonsillar hypertrophy, age, and obesity in children with OSA. Methods In total, 495 symptomatic patients were recruited. The patients were assigned to four groups according to age：toddler (age 1-3, n=42), preschool (age 3-6, n=164), school (age 6-12, n=200), and adolescence (age 12-18, n=89). All subjects had tonsil size graded by otolaryngologists, adenoid size determined on lateral radiographs (Fujioka method), and a full-night polysomnography. The apnea-hypopnea index (AHI), adenoid size, and tonsil size were compared in obese and non-obese children in the four age groups. Adjusted odds ratios (ORs) and 95% confidence interval (CI) of adenotonsillar hypertrophy and OSA risk were estimated by multi-logistic regression. Results The AHI was positively related to tonsil grade (r=0.33, p <0.001) and adenoid size (r=0.24, p <0.01) in all patients. Tonsil grade was positively related to AHI in all four age groups. Adenoid size was positively related to AHI in the toddler, preschool, school groups, but not in the adolescent group (r=0.11, p=0.37). Tonsil grade and adenoid size were both positively related to AHI in obese and non-obese children. In the regression model, obesity (OR=2.89; 95% CI 1.47-5.68), tonsillar hypertrophy (OR=3.15; 95% CI 2.04-4.88), and adenoidal hypertrophy (OR=1.89; 95% CI 1.19-3.00) significantly increased OSA risk. Conclusions Adenotonsillar hypertrophy and obesity are the major determinants of OSA in children. However, the influence of adenoid size decreases in adolescence.

Impacts of body weight after surgery for obstructive sleep apnea in children

Objective:To investigate the impacts of body weight status on surgical outcomes and shifts of body weight status after adenotonsillectomy(T&A) in children with obstructive sleep apnea (OSA).Methods:From 2009 to 2011, 161 children (mean age, 7.0±3.4 years; 78% boys) were included. All the children had clinical symptoms and preoperative polysomnographic evaluations diagnosis of OSA. Children were divided into four weight status groups (underweight, normal weight, overweight and obese), based on age and gender corrected body mass index (BMI).Results:Following T&A, the four different weight status groups significantly improved in apnea/hypopnea index (AHI) and minimum oxygen saturation. However, 49.1% of the children (79/161) had residual OSA (AHI ⩾1). The incidence of residual OSA (AHI ⩾1) in the obese group was 75%, which was significantly higher than the other three groups (P<0.01). Weight status changes after T&A were documented, and 54% (13/24) of the underweight children shifted to normal weight status within 6 months after surgery.Conclusion:Although sleep parameters improved in all weight statuses, obese children had a higher incidence of residual OSA postoperatively. About half of the underweight children shifted to normal weight status after T&A.

Functional Roles of Calreticulin in Cancer Biology

Calreticulin is a highly conserved endoplasmic reticulum chaperone protein which participates in various cellular processes. It was first identified as a Ca2+-binding protein in 1974. Accumulated evidences indicate that calreticulin has great impacts for the development of different cancers and the effect of calreticulin on tumor formation and progression may depend on cell types and clinical stages. Cell surface calreticulin is considered as an “eat-me” signal and promotes phagocytic uptake of cancer cells by immune system. Moreover, several reports reveal that manipulation of calreticulin levels profoundly affects cancer cell proliferation and angiogenesis as well as differentiation. In addition to immunogenicity and tumorigenesis, interactions between calreticulin and integrins have been described during cell adhesion, which is an essential process for cancer metastasis. Integrins are heterodimeric transmembrane receptors which connect extracellular matrix and intracellular cytoskeleton and trigger inside-out or outside-in signaling transduction. More and more evidences reveal that proteins binding to integrins might affect integrin-cytoskeleton interaction and therefore influence ability of cell adhesion. Here, we reviewed the biological roles of calreticulin and summarized the potential mechanisms of calreticulin in regulating mRNA stability and therefore contributed to cancer metastasis.

Levetiracetam in Continuous Spike Waves During Slow-Wave Sleep Syndrome

We investigated the clinical characteristics of children with continuous spike waves during slow-wave sleep syndrome and their treatment response to levetiracetam. Five boys and one girl, diagnosed with epilepsy with continuous spike waves during slow-wave sleep syndrome, were enrolled. Their clinical characteristics, including neuroimaging findings, were reviewed. The signs related to continuous spike waves during slow-wave sleep included increased seizure frequency (6/6), impaired responsiveness (3/6), and psychomotor regression (2/6). Magnetic resonance imaging disclosed lissencephaly in one patient, and porencephaly of the left hemisphere in another. The number of antiepileptic drugs before the use of levetiracetam was 0-4 (mean +/- SD, 2.3 +/- 1.5). Five of 6 children demonstrated a good response to levetiracetam, whereas 2 (40%) underwent a relapse of electrical status epilepticus during sleep pattern on electroencephalograms 4 and 5 months after clinical improvement. Both were 5 years old. The most common presenting sign in children with continuous spike waves during slow-wave sleep syndrome is increasing seizure frequency. Levetiracetam is effective in treating children with continuous spike waves during slow-wave sleep syndrome. However, the relapse rate of continuous spike waves during slow-wave sleep syndrome remains high in young children.

Quality of life after adenotonsillectomy for children with sleep-disordered breathing: A linear mixed model analysis

OBJECTIVE To study changes in quality of life (QoL) after adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB), and to elucidate discrepancies in QoL improvements after T&A in children of different gender, age, adiposity status, and disease severity. MATERIALS AND METHODS Children aged 2-18 years were recruited. All children had SDB-related symptoms and underwent preoperative full-night polysomnography (PSG). Caregivers completed the first obstructive sleep apnea 18-items questionnaire (OSA-18) prior to T&A and the second OSA-18 survey within 3 months after surgery. Disease severity was defined as primary snoring (apnea/hypopnea index, AHI < 1), mild obstructive sleep apnea (OSA) (5 > AHI ≥ 1), and moderate-to-severe OSA (AHI ≥ 5). Discrepancies in OSA-18 score changes after T&A for different groups were assessed using the linear mixed model. RESULTS In total, 144 children were enrolled (mean age, 7.0 ± 3.6 years; 76% boy). The OSA-18 total score changes after surgery were not significantly different by gender (boys vs. girls), age group (≥ 6 years vs. < 6 years), or adiposity (obese vs. non-obese). The OSA-18 total score changes after surgery differed by disease severity (primary snoring vs. moderate-to-severe OSA, P = 0.004; mild OSA vs. moderate-to-severe OSA, P = 0.003). Children with moderate-to-severe OSA had greater improvement in OSA-18 total score after surgery than those with mild OSA or primary snoring. CONCLUSIONS Children with SDB had QoL improvement after T&A, as documented by OSA-18 score changes. The QoL improvement after T&A for SDB children increased as disease severity increased, and the improvement was not affected by gender, age, or adiposity.

Mutation of Mitochondrial DNA G13513A Presenting with Leigh Syndrome, Wolff-Parkinson-White Syndrome and Cardiomyopathy

Mutation of mitochondrial DNA (mtDNA) G13513A, encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and Leigh syndrome. Wolff-Parkinson-White (WPW) syndrome and optic atrophy were reported in a high proportion of patients with this mutation. We report an 18-month-old girl, with an 11-month history of psychomotor regression who was diagnosed with WPW syndrome and hypertrophic cardiomyopathy, in association with Leigh syndrome. Supplementation with coenzyme Q10, thiamine and carnitine prevented further regression in gross motor function but the patients heart function deteriorated and dilated cardiomyopathy developed 11 months later. She was found to have a mutation of mtDNA G13513A. We suggest that mtDNA G13513A mutation is an important factor in patients with Leigh syndrome associated with WPW syndrome and/or optic atrophy, and serial heart function monitoring by echocardiography is recommended in this group of patients.

Quality of life after adenotonsillectomy in children with obstructive sleep apnea: Short-term and long-term results

OBJECTIVE To assess short-term and long-term changes in quality of life after adenotonsillectomy (T&A) in children with obstructive sleep apnea (OSA). MATERIALS AND METHODS Children aged 2-18 years old were enrolled. All subjects had clinical symptoms, overnight polysomnography diagnosis of OSA, and received T&A as treatment. Caregivers were asked to complete the OSA-18 survey before surgery, within 6 months after surgery (short-term), and more than 6 months after surgery (long-term). RESULTS A total of 114 children were included (mean age, 7.0±3.5 years; 75% boys). The mean OSA-18 total score was 71.5±16.0 before surgery. After surgery, the mean OSA-18 total score was significantly decreased in both the short-term (40.3±12.2, p<0.001) and the long-term (42.0±13.7, p<0.001). All five OSA-18 domains were also significantly decreased during short-term and long-term postoperative follow up (p<0.001). Short-term and long-term outcomes were compared. Mean OSA-18 total scores, sleep disturbance score, emotional distress score, daytime function score, and caregiver concerns score did not differ significantly between the short-term and long-term periods, while the physical symptom score was slightly higher in the long-term than the short-term period (9.7±3.3 vs. 8.7±3.0, p=0.02). Additionally, the physical symptoms score was higher in the long-term period in the female (p=0.01), older age (>6 years) (p=0.03), and non-obese (p=0.04) subgroups. CONCLUSION T&A improves short-term and long-term quality of life in children with OSA. Nevertheless, caregivers observed children with aggravation of physical symptoms of quality of life during long-term follow up, especially in the female, older, and non-obese subgroups.

Discrepancy between Objective and Subjective Outcomes after Adenotonsillectomy in Children with Obstructive Sleep Apnea Syndrome

Objective Adenotonsillectomy (T&A) is the first line therapy for pediatric obstructive sleep apnea (OSA); however, inconsistency between objective and subjective outcomes perplexes physicians. This study investigates changes of objective and subjective outcomes in children with OSA after T&A, in particular, to elucidate correlations and discrepancies between these 2 measures. Study Design Case series with record review. Setting Tertiary referral medical center. Subjects and Methods Symptomatic children with polysomnographic diagnosis of OSA (apnea-hypopnea index [AHI] > 1) were included. All children underwent T&A to treat OSA, along with completely objective (polysomnography) and subjective (Obstructive Sleep Apnea 18-Item Quality-of-Life Questionnaire [OSA-18]) measures before and 3 months after surgery. Results One hundred nineteen children were included (mean age, 6.9 ± 3.3 years; 76% boys). Adenotonsillectomy significantly reduced AHI from 15.4 ± 21.2 per hour to 1.6 ± 2.5 per hour (P < .001). The OSA-18 scores were significantly improved after surgery (P < .001). A weak but statistically significant positive correlation was found between AHI and OSA-18 scores preoperatively (ρ = 0.22, P = .016) but not postoperatively (ρ = 0.04, P = .677). Among those cases with residual OSA after surgery, only 6% (3/54) had a residual effect on quality of life (OSA-18 score > 60). Conclusion Adenotonsillectomy improves both objective and subjective outcomes. After surgery, quality of life significantly improved subjectively, despite an incomplete resolution of OSA objectively, leading to a better correlation between objective and subjective measures before as opposed to after surgery. Discrepancy between the 2 measures warrants an evaluation of a child both objectively and subjectively when treating OSA.

Early-Onset Seizures Are Correlated With Late-Onset Seizures in Children With Arterial Ischemic Stroke

Background and Purpose— Early-onset seizures are common in children with arterial ischemic stroke, but the clinical features and effects on the outcome of early-onset seizures have been less studied in children. Methods— Children aged 1 month to 18 years presenting with first-time and image-confirmed arterial ischemic stroke were identified for analysis. Results— A total of 78 survivors of arterial ischemic stroke were enrolled. Twenty (25.6%) had early-onset seizures, and 90% were initial presentation. Younger children (mean, 3.4±3.9 versus 9.0±6.2 years; P<0.001) and cortical involvement (5% versus 63.8%; P=0.01) are more likely to have early-onset seizures. Thirteen of 20 survivors with early-onset seizures had late-onset seizures after the acute stage, and 12 of them were diagnosed as poststroke epilepsy. Conclusions— Early-onset seizures occurred in 25.6% of children with arterial ischemic stroke. Younger age and cortical involvement were risk factors for early-onset seizures. Sixty-five percent of children with early-onset seizures had late-onset seizures after the acute stage.