R Lane

Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study

AIM Achondroplasia can result in respiratory difficulty in early infancy. The aim of this study was to document lung growth during infancy, together with the cause of any cardiorespiratory and sleep dysfunction. PATIENTS AND METHODS Seventeen prospectively ascertained infants (14 boys and three girls) with respiratory symptoms starting before 1 year of age underwent clinical, sleep, and lung function studies. RESULTS Three distinct groups were identified. Group 1 (n = 6) were the least symptomatic and only had obstructive sleep apnoea. Group 2 (n = 6) had obstructive sleep apnoea of muscular aetiology and, neurologically, hydrocephalus and a small foramen magnum were common. Group 3 (n = 5), the most severely affected group, all developed cor pulmonale, with three deaths occurring as a result of terminal cardiorespiratory failure. All five had obstructive sleep apnoea with a muscular aetiology (a small foramen magnum predominated) with severe or moderately severe gastro-oesophageal reflux. Initially, lung function studies found no evidence of restriction or reduced lung volumes standardised according to weight. However, with growth these infants had worsening function, with raised airway resistance and severe reductions in respiratory compliance. CONCLUSIONS These groups appear to be distinct phenotypes with distinct anatomical aetiologies: “relative” adenotonsillar hypertrophy, resulting from a degree of midfacial hypoplasia (group 1); muscular upper airway obstruction along with progressive hydrocephalus, resulting from jugular foramen stenosis (group 2); and muscular upper airway obstruction, but without hydrocephalus, resulting from hypoglossal canal stenosis with or without foramen magnum compression and no jugular foramen stenosis (group 3). The aetiology of these abnormalities is consistent with localised alteration of chondrocranial development: rostral, intermediary and caudal in groups 1, 2, and 3, respectively.

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 (χ2; p = 0.045), but abnormal structural MRI (χ2; p = 0.7) or magnetic resonance angiography (χ2; 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. Ann Neurol 2005;58:290–302

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.

Timing of recovery of lung function after severe hypoxemic respiratory failure in children

Objective: To describe the timing of recovery of lung function after severe acute hypoxemic respiratory failure (AHRF) in children. Design: A serial observational follow-up study of clinical and lung function measurements up to 53 months after acute illness. Setting: University pediatric intensive care unit in a national childrens hospital. Patients: Five critically ill children aged 5–14 years. Interventions: None Results: Clinical recovery: each patient required a 3–5 month convalescence before being able to attend full-time school because of lethargy and dyspnea. All patients developed wheeze 3–12 months after illness and four received long-term bronchodilator therapy. Lung function recovery: for both the forced vital capacity (FVC) and forced vital capacity in the first second (FEV1) four patients had abnormally low values, regaining only 60–70 % of predicted values for their height and sex, and all of this improvement had occurred by 6–12 months after illness. Beyond this interval, patients remained on their same FVC and FEV1 centile. FEV1/FVC ratios were consistently within the normal range, indicating a predominantly restrictive defect. Changes in peak expiratory flow exhibited a time course of improvement similar to the other lung function tests. Conclusion: In children, pulmonary recovery after severe AHRF may occur for 6–12 months. A 1-year follow-up could offer a rational single point for assessment of outcome and long-term counselling of child and parents.