Search

Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta

Cranial ultrasound (cUS) and magnetic resonance imaging (MRI) are the two most commonly used brain imaging techniques in preterm infants. cUS can be performed at the bedside and detects all major brain abnormalities (haemorrhages, infarctions, cysts, dilatation of the lateral ventricles) that are associated with severe neurodevelopmental disability. However, there are more subtle brain abnormalities that can be visualized with cUS, such as signs of brain atrophy and periventricular echodensities, for which the clinical relevance is less clear. Furthermore, there is no consensus how to quantify the lateral ventricular size on cUS, a procedure that is often necessary to monitor the progression of posthaemorrhagic ventricular dilatation or grade the extent of ventriculomegaly at term age. In comparison to MRI, cUs has been shown to be less sensitive for the detection of non-cystic white matter (WM) injury, the most common form of WM injury in preterm infants. Indeed, MRI at term age has been reported to be superior to cUS in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in that study cUS was performed during the first 6 weeks only and no late scan in parallel to MRI at term age was included. Furthermore MRI data from large population-based cohorts of extremely preterm infants are missing. Therefore, the aim of the present thesis was to study the relevance of subtle brain abnormalities on cUS (brain atrophy and periventricular echodensities) for neurodevelopmental outcome, to acquire and compare MRI and cUS data at term age in a population-based cohort of extremely preterm infants (< 27 weeks) and to determine which 2D linear cUS measurement of the lateral ventricular size is the best to estimate total ventricular volume using 3D MRI as the golden standard. Our main findings were, firstly, that sonographic signs of brain atrophy at term age, but not persistent periventricular echodensities, are related to neurodevelopmenta