Adenotonsillectomy for sleep-disordered breathing in children with syndromic craniosynostosis.

Syndromic craniosynostosis (SCS) is known to be associated with sleep-disordered breathing (SDB) in childhood. Problems can occur at various levels, but midface hypoplasia is a major factor in affected infants.Adenotonsillectomy (AT) has been proven to be efficacious as a first-line treatment of SDB in healthy children. However, its role in the treatment of this issue in those with SCS has not been evaluated. Owing to the multiple possible levels of obstruction in such individuals, AT may have no benefit. This study therefore aimed to evaluate the effectiveness of AT in this group of patients.Twenty-six children with SCS with moderate to severe obstructive sleep apnea (OSA) were treated with AT. The mean age at surgery was 4.5 years (range, 1.6-13.9 y). Seven had severe OSA, 11 had moderate OSA, and 7 had mild OSA preoperatively. Of 25 children, 15 (60%) demonstrated an improvement in sleep severity scores postoperatively.Overall, there was a significant improvement in the mean number of saturation dips greater than 4%/h and in the mean nadir of dips in saturation after the operation. There was no significant difference in mean oxygen saturation, number of pulse rate rises per hour, or percentage time spent less than 90% SaO2.Clinically, there is thought to be some benefit in performing AT in these groups of patients. In children with SCS, in whom the cause of obstruction might be at multiple levels, AT should still to be considered as first-line treatment in the management of OSA/SDB.We acknowledge that some children may still go on to require further airway intervention. Further multicenter trials would be useful to examine more closely the significance of the effects of AT in children with craniofacial disorders experiencing SDB.

Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase).

OBJECTIVE: Our objective was to evaluate the safety, pharmacokinetics, and efficacy of laronidase in young, severely affected children with mucopolysaccharidosis I. METHODS: This was a prospective, open-label, multinational study of 20 patients who had mucopolysaccharidosis I and were <5 years old (16 with Hurler syndrome, 4 with Hurler-Scheie syndrome) and were scheduled to receive intravenous laronidase at 100 U/kg (0.58 mg/kg) weekly for 52 weeks. Four patients underwent dosage increases to 200 U/kg for the last 26 weeks because of elevated urinary glycosaminoglycan levels at week 22. RESULTS: Laronidase was well tolerated at both dosages. Investigators reported improved clinical status in 94% of patients at week 52. The mean urinary glycosaminoglycan level declined by approximately 50% at week 13 and was sustained thereafter. A more robust decrease in urinary glycosaminoglycan was observed in patients with low antibody levels and those who were receiving the 200 U/kg dosage. On examination, the liver edge was reduced by 69.5% in patients with a palpable liver at baseline and week 52 (n = 10). The proportion of patients with left ventricular hypertrophy decreased from 53% to 17%. Global assessment of sleep studies showed improvement or stabilization in 67% of patients, and the apnea/hypopnea index decreased by 5.8 events per hour (-8.5%) in those with abnormal baseline values. The younger patients with Hurler syndrome (<2.5 years) and all 4 patients with Hurler-Scheie syndrome showed normal mental development trajectories during the 1-year treatment period. CONCLUSIONS: Laronidase seems to be well tolerated and to provide clinical benefit in patients who have severe mucopolysaccharidosis I and are <5 years old. Enzyme replacement therapy is not curative and may not improve all affected organs and systems in individuals when irreversible changes have developed. The long-term clinical outcome and effects of antibodies and laronidase dosing on glycosaminoglycan reduction warrant additional investigation.

An exploratory study of physiological correlates of neurodevelopmental delay in infants with sickle cell anaemia.

This study aimed to investigate whether infants with sickle cell anaemia (SCA) are at risk of neurodevelopmental delay, and whether any delay is associated with SCA pathology. Twenty-eight infants (14 SCA; 14 age- and ethnic-similar controls) were assessed longitudinally with the Bayley Infant Neurodevelopmental Screener (BINS) at 3, 9 and 12 months. Transcranial Doppler (TCD) and pulse oximetry (SpO2) measures were recorded longitudinally in SCA infants, and a subgroup of controls. Haemoglobin values were obtained from SCA infants. At each age, SCA infants obtained BINS scores indicative of greater risk of neurodevelopmental delay compared with controls. The number of moderate-high BINS risk scores increased significantly between 3 and 9 months. At 9 months BINS raw scores correlated negatively with TCD velocity and positively with haemoglobin. This exploratory study suggests that SCA infants may be at greater risk of neurodevelopmental delay than previously considered, and may provide the impetus for further research into the very early precursors of cognitive impairment.

Sickle cell disease: ischemia and seizures.

Although the prevalence of seizures in children with sickle cell disease (SCD) is 10 times that of the general population, there are few prospectively collected data on mechanism. With transcranial Doppler and magnetic resonance imaging (MRI) and angiography, we evaluated 76 patients with sickle cell disease, 29 asymptomatic and 47 with neurological complications (seizures, stroke, transient ischemic attack, learning difficulty, headaches, or abnormal transcranial Doppler), who also underwent bolus-tracking perfusion MRI. The six patients with recent seizures also had electroencephalography. Group comparisons (seizure, nonseizure, and asymptomatic) indicated that abnormal transcranial Doppler was more common in the seizure (4/6; 67%) and nonseizure (26/41; 63%) groups than in the asymptomatic (10/29; 34%) group (chi2; p = 0.045), but abnormal structural MRI (chi2; p = 0.7) or magnetic resonance angiography (chi2; p = 0.2) were not. Relative decreased cerebral perfusion was found in all seizure patients and in 16 of 32 of the remaining patients with successful perfusion MRI (p = 0.03). In the seizure patients, the perfusion abnormalities in five were ipsilateral to electroencephalographic abnormalities; one had normal electroencephalogram results. These findings suggest that vasculopathy and focal hypoperfusion may be factors in the development of sickle cell disease-associated seizures.