The establishment of normal pediatric polysomnographic parameters is important for both clinical and research interests. Our objectives were to describe respiratory events, paradoxical breathing, periodic limb movements, and sleep architecture of children at the age of peak incidence of obstructive sleep apnea syndrome. We performed a retrospective cross-sectional analysis of a prospective cohort study of 66 children, 2-9 years old, at the Sleep Disorders Center at the Children's Hospital of Philadelphia. Subjects screened by questionnaire underwent a standard polysomnogram. The percent of total sleep time spent in sleep stages 1, 2, 3, 4, and rapid eye movement (REM) were 4 +/- 3%, 44 +/- 10%, 10 +/- 6%, 22 +/- 8%, and 21 +/- 6%, respectively. The arousal and awakening index was 11.2 +/- 4.3/hr. Respiratory events included a central apnea index of 0.08 +/- 0.14/hr, obstructive apnea index of 0.01 +/- 0.03/hr, and obstructive hypopnea index of 0.3 +/- 0.5/hr. The baseline arterial oxygen saturation (SpO2) was 97 +/- 1%, with a nadir of 92 +/- 3%. The index of periodic limb movements in sleep (PLMS) was 1.3 +/- 2.2/hr. Paradoxical breathing appeared significantly more frequent with piezo crystal effort belts (40 +/- 24% of epochs) than with respiratory inductive plethysmography (1.5 +/- 3% of epochs). We describe the occurrence of hypopneas during sleep, arousals and awakenings, and PLMS. We illustrate how different technologies can vary the apparent amount of paradoxical breathing. We also confirm previous data on the frequency distribution of sleep stages, SpO2, and relative rarity of respiratory events in this age group.

SummarySilent infarcts have been reported most commonly in school-aged children with homozygous sickle cell disease (SCD-SS) and are associated with neurocognitive deficits. However, the prevalence of silent infarcts in younger children with SCD-SS is not well defined. In this retrospective study, brain magnetic resonance imaging and angiography (MRI/A) studies performed before 6 years of age in a cohort of children with SCD-SS were analysed and the prevalence of abnormalities was calculated. Clinical and laboratory parameters were compared between the groups with and without silent infarcts. Sixty-eight of 96 children in the cohort had brain MRI/A performed prior to age 6 years. Of the 65 who were neurologically asymptomatic, 18 (27AE7%, 95% CI 17AE3-40AE2%) had silent infarcts (mean age 3AE7 ± 1AE1 years, range 1AE3-5AE9 years). Factors associated with silent infarcts included cerebral vessel stensosis by magnetic resonance angiography, lower rates of vasoocclusive pain and acute chest syndrome and lower haemoglobin levels. The prevalence of silent infarcts in young children with SCD-SS is similar to that of older children and anaemia and severe vasculopathy may be risk factors.

We evaluated the relationship between clinical features and hypoxic-ischemic injury (HII) shown by diffusion-weighted MRI (DWI) in young children with head trauma, comparing inflicted trauma (IT) to accidental trauma (AT). This single-center consecutive cohort study included children age birth to 36 months admitted for head injury July 2001 to December 2004 with brain magnetic resonance imaging (MRI) obtained < or =1 week, identified from prospectively maintained registries of children with trauma. Clinical and radiological data during the hospital stay were extracted from medical records. MRIs were analyzed by study examiners blinded to clinical status and scored by type, severity and location of lesions attributable to traumatic, hypoxic-ischemic, or mixed injury patterns. 30 IT patients and 22 AT patients met inclusion criteria. IT cases were younger than AT, 3.0 versus 8.5 months. Mean time to MRI in IT (2.1 days) was similar to AT (1.9 days). HII was more common in IT (11 of 30) than AT (2/22, p = 0.03). Children with HII more commonly had seizures, needed intubation at presentation, and needed neurosurgical intervention compared to those without HII. Most patients with HII (10/14) required in-patient rehabilitation compared to those without HII (4/38). Our study is the first to characterize HII using diffusion-weighted MRI in young children, comparing IT and AT. The higher rate of HII on DWI-MRI in IT than in AT is likely multifactorial, involving respiratory insufficiency, seizures, and intracranial mass-occupying lesions requiring neurosurgical intervention. HII predicted need for in-patient rehabilitation in a large majority of children.

Malignant hyperthermia (MH) is a pharmacogenetic disorder that predisposes to a sometimes fatal hypermetabolic reaction to halogenated anaesthetics. MH is considered to originate from abnormal regulation of skeletal muscle Ca(2+) release. Current diagnosis of MH susceptibility (MHS) relies on in vitro contracture testing (IVCT) of skeletal muscle. The ryanodine receptor (RYR1) encoding the major Ca(2+) release channel in the skeletal muscle sarcoplasmic reticulum has been shown to be mutated in a number of MH pedigrees. The large Maori pedigree reported here is the largest MHS pedigree investigated to date and comprises five probands who experienced clinical episodes of MH and 130 members diagnosed by the IVCT. Sequencing of the 15 117 bp RYR1 cDNA in a MHS individual from this pedigree identified a novel C14477T transition that results in a Thr4826 to Ile substitution in the C-terminal region/transmembrane loop of the skeletal muscle ryanodine receptor. This is the first mutation in the RyR1 C-terminal region associated solely with MHS. Although linkage analysis showed strong linkage (max LOD, 11.103 at theta = 0.133) between the mutation and MHS in the pedigree using the standardized European IVCT phenotyping protocol, 22 MHS recombinants were observed. The relationship between the IVCT response and genotype was explored and showed that as IVCT diagnostic cut-off points were made increasingly stringent, the number of MHS discordants decreased with complete concordance between the presence or absence of the C14477T mutation and MHS and MH normal phenotypes, respectively, using a cut-off of 1.2 g tension at 2.0 mM caffeine and 1.8 g tension at 2.0% halothane. Many MHS pedigrees investigated have been excluded from linkage to the RYR1 gene on the basis of a small number of recombinants; however, the linkage analysis reported here suggests that other recombinant families excluded from linkage to the RYR1 gene may actually demonstrate linkage as the number of members tested within the pedigrees increases. The high number of discordants observed using the standardized diagnostic cut-off points is likely to reflect the presence of a second MHS susceptibility locus in the pedigree.