Cyanosis associated to low oxygen saturation may reveal hemoglobin pathology. A 3 year-old child ... more Cyanosis associated to low oxygen saturation may reveal hemoglobin pathology. A 3 year-old child had a nephroblastoma with pleural effusion. He suddenly developed persistent cyanosis despite pleural effusion drainage; transcutaneous and measured oxygen saturations were low and PaO2 on arterial blood gases was high. Methemoglobinemia was diagnosed, due to prilocaine-lignocaine cream used for local anesthesia, associated to partial G6PD deficiency.
Neurology and Pregnancy - Pathophysiology and Patient Care, 2020
Transient anatomical entities play a role in the maturation of brain regions and early functional... more Transient anatomical entities play a role in the maturation of brain regions and early functional fetal networks. At the postmenstrual age of 7 weeks, major subdivisions of the brain are visible. At the end of the embryonic period, the cortical plate covers the neopallium. The choroid plexus develops in concert with it, and the dorsal thalamus covers about half the diencephalic third ventricle surface. In addition to the fourth ventricle neuroepithelium the rhombic lips are an active neuroepithelial production site. Early reciprocal connections between the thalamus and cortex are present. The corticospinal tract has reached the pyramidal decussation, and the arteries forming the mature circle of Willis are seen. Moreover, the superior sagittal sinus has formed, and at the rostral neuropore the massa commissuralis is growing. At the viable preterm age of around 24 weeks PMA, white matter tracts are in full development. Asymmetric progenitor division permits production of neurons, subventricular zone precursors, and glial cells. Myelin is present in the ventral spinal quadrant, cuneate fascicle, and spinal motor fibers. The neopallial mantle has been separated into transient layers (stratified transitional fields) between the neuroepithelium and the cortical plate. The subplate plays an important role in organizing the structuring of the cortical plate. Commissural tracts have shaped the corpus callosum, early primary gyri are present, and opercularization has started caudally, forming the lateral fissure. Thalamic and striatal nuclei have formed, although GABAergic neurons continue to migrate into the thalamus from the corpus gangliothalamicum. Near-term PMA cerebral sublobulation is active. Between 24 and 32 weeks, primary sulci develop. Myelin is present in the superior cerebellar peduncle, rubrospinal tract, and inferior olive. Germinal matrix disappears from the telencephalon, except for the GABAergic frontal cortical subventricular neuroepithelium.
IntroductionVery and extremely preterm infants frequently have brain injury-related long-term neu... more IntroductionVery and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically.MethodsA systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants.ResultsIn total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and...
White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (... more White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will ...
Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal g... more Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal ganglia. The neurological outcome is often poor. In the past decades there seems to have been an increase in the number of reported cases of kernicterus. In order to raise awareness of this condition, we present two patients with kernicterus caused by different pathophysiological mechanisms. In both cases we make suggestions for the improvement of the medical care process. The first patient is a 7-day-old girl with kernicterus due to haemolysis caused by G6PD deficiency. Patient B is a 3-day-old boy with hyperbilirubinaemia based on 0/B blood group incompatibility. Kernicterus resulted in significant disabilities in these children. A proper diagnostic approach and precise treatment of hyperbilirubinaemia are essential to prevent major neurological damage. Awareness of this condition, education of health care professionals and changes in in- and outpatient care are needed to achieve this g...
Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by ... more Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by a newly developed immunoenzymatic assay. Newborns with a documented neurologic disorder (intraventricular hemorrhage, postasphyxial encephalopathy, central nervous system infection, or persistent periventricular intraparenchymal echodensities) showed markedly higher concentrations of immunoreactive CK-BB than did the normal newborns or those with subarachnoid hemorrhage. In neonates with seizures the data suggest that the underlying neurologic disorder accounts for the higher CK-BB values and not the seizures per se. High concentrations of CK-BB in the neonatal period were followed by poor short-term outcome.
Congenital nonprogressive (bilateral) facial palsy and external ophthalmoplegia are essential cli... more Congenital nonprogressive (bilateral) facial palsy and external ophthalmoplegia are essential clinical features for the diagnosis of Moebius syndrome. One century after its initial thorough description, the precise delineation and pathogenesis of the syndrome still remain obscure. Heuristic hypotheses concerning the latter have been put forward. Three major theories of etiology remain valid: primary brainstem nuclear hypoplasia, secondary brainstem nuclear degeneration, and brainstem atrophy secondary to muscular defect. None of these theories easily explains why, apart from cranial nerve dysfunction, the Moebius syndrome is frequently a part of oral-limb deficiency anomaly syndromes.
A term female firstborn infant had unexplained nonimmune fetal hydrops and recurrent left chyloth... more A term female firstborn infant had unexplained nonimmune fetal hydrops and recurrent left chylothorax at 4 weeks of age. A few months before conception, her mother had had acute dystrophic nail changes and is being treated for recurrent sinusitis, bronchiectasis, and a deficiency of serum IgG2. We suggest that they both suffer from a dominantly inherited congenital lymphedema syndrome known as `yellow nail dystrophy.' Prenatal manifestation of this disorder has not been reported previously. The child's anthropometric and neurological development was normal at 1 year of age, whereas mild ankle edema and marbling of the skin of the limbs were salient clinical findings. Inherited lymphedema leading to nonimmune fetal hydrops also has been recognized in chromosomal disorders, Noonan's syndrome, multiple pterygium syndrome, pulmonary lymphangiectasis, and mixed-vessel lymphatic dysfunction. Indicators of parental lymphedema are not on record in those instances.
Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neur... more Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to
We present the improvements made to and subsequent validation of an automated approach to detect ... more We present the improvements made to and subsequent validation of an automated approach to detect neonatal seizures. The evaluation of the algorithm has been performed on a new and extensive data set of neonatal EEGs. Previously, we have classified neonatal seizures visually into two types: the spike train and oscillatory type of seizures and developed two separate algorithms that run in parallel for their automated detection. The first algorithm analyzes the correlation between high-energetic segments of the EEG, whereas the second one detects increases in low-frequency activity (<8 Hz) and then uses an autocorrelation. An improved version of our automated system (called 'NeoGuard') uses more informative features for classification and optimized parameters for thresholding. The validation was performed on 756 hours of 'unseen' continuous EEG monitoring data from 24 neonates with encephalopathy and recorded seizures. The seizure detection system showed a median sen...
The incidence of stroke is reported to be 28 in 100.000 live births. All age groups show an unexp... more The incidence of stroke is reported to be 28 in 100.000 live births. All age groups show an unexplained male predominance. Of the two types of cerebral stroke, arterial ischaemic stroke and (sino-)venous thrombosis, the arterial one is most frequent. Non-invasive methods such as ultrasound, computerized-tomography (CT) or magnetic resonance imaging (MRI) can detect these thrombotic events in the brain. Etiologic (genetic or acquired) factors predisposing to thrombosis may shift the haemostatic balance towards elevated procoagulant activity resulting in a hypercoagulable state that predisposes to venous or arterial thrombosis. Lower concentrations of antithrombin, protein S and C, along with reduced fibrinolytic capacity, put neonates at greater risk of thromboembolic complications than older children.
CMV is the most common congenital viral infection, with a birth prevalence of 0.48-1.3% in recent... more CMV is the most common congenital viral infection, with a birth prevalence of 0.48-1.3% in recent decades. The congenital infection may be asymptomatic or symptomatic; the symptomatic disease can be severe and life-threatening. Both asymptomatic and symptomatic newborns are at risk of developing long-term neurodevelopmental morbidity, particularly deafness. Recently, the neurological complications caused by congenital CMV infection in affected infants have been successfully treated with antiviral agents, but the early diagnosis of congenital infection is vital for this treatment to be effective. To identify primary CMV infection, maternal blood tests for CMV-specific immunoglobulin (Ig) M antibodies (CMV IgM) are widely used. However, CMV IgM tests can remain positive for years after the primary infection, so a positive result for CMV IgM does not always indicate primary infection during pregnancy. A CMV IgG avidity test is also used for identifying a recent infection....
Cyanosis associated to low oxygen saturation may reveal hemoglobin pathology. A 3 year-old child ... more Cyanosis associated to low oxygen saturation may reveal hemoglobin pathology. A 3 year-old child had a nephroblastoma with pleural effusion. He suddenly developed persistent cyanosis despite pleural effusion drainage; transcutaneous and measured oxygen saturations were low and PaO2 on arterial blood gases was high. Methemoglobinemia was diagnosed, due to prilocaine-lignocaine cream used for local anesthesia, associated to partial G6PD deficiency.
Neurology and Pregnancy - Pathophysiology and Patient Care, 2020
Transient anatomical entities play a role in the maturation of brain regions and early functional... more Transient anatomical entities play a role in the maturation of brain regions and early functional fetal networks. At the postmenstrual age of 7 weeks, major subdivisions of the brain are visible. At the end of the embryonic period, the cortical plate covers the neopallium. The choroid plexus develops in concert with it, and the dorsal thalamus covers about half the diencephalic third ventricle surface. In addition to the fourth ventricle neuroepithelium the rhombic lips are an active neuroepithelial production site. Early reciprocal connections between the thalamus and cortex are present. The corticospinal tract has reached the pyramidal decussation, and the arteries forming the mature circle of Willis are seen. Moreover, the superior sagittal sinus has formed, and at the rostral neuropore the massa commissuralis is growing. At the viable preterm age of around 24 weeks PMA, white matter tracts are in full development. Asymmetric progenitor division permits production of neurons, subventricular zone precursors, and glial cells. Myelin is present in the ventral spinal quadrant, cuneate fascicle, and spinal motor fibers. The neopallial mantle has been separated into transient layers (stratified transitional fields) between the neuroepithelium and the cortical plate. The subplate plays an important role in organizing the structuring of the cortical plate. Commissural tracts have shaped the corpus callosum, early primary gyri are present, and opercularization has started caudally, forming the lateral fissure. Thalamic and striatal nuclei have formed, although GABAergic neurons continue to migrate into the thalamus from the corpus gangliothalamicum. Near-term PMA cerebral sublobulation is active. Between 24 and 32 weeks, primary sulci develop. Myelin is present in the superior cerebellar peduncle, rubrospinal tract, and inferior olive. Germinal matrix disappears from the telencephalon, except for the GABAergic frontal cortical subventricular neuroepithelium.
IntroductionVery and extremely preterm infants frequently have brain injury-related long-term neu... more IntroductionVery and extremely preterm infants frequently have brain injury-related long-term neurodevelopmental problems. Altered perfusion, for example, seen in the context of a hemodynamically significant patent ductus arteriosus (PDA), has been linked to injury of the immature brain. However, a direct relation with outcome has not been reviewed systematically.MethodsA systematic review was conducted to provide an overview of the value of different cerebral arterial blood flow parameters assessed by Doppler ultrasound, in relation to brain injury, to predict long-term neurodevelopmental outcome in preterm infants.ResultsIn total, 23 studies were included. Because of heterogeneity of studies, a meta-analysis of results was not possible. All included studies on resistance index (RI) showed significantly higher values in subjects with a hemodynamically significant PDA. However, absolute differences in RI values were small. Studies using Doppler parameters to predict brain injury and...
White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (... more White matter injury (WMI) is the most frequent form of preterm brain injury. Cranial ultrasound (CUS) remains the preferred modality for initial and sequential neuroimaging in preterm infants, and is reliable for the diagnosis of cystic periventricular leukomalacia. Although magnetic resonance imaging is superior to CUS in detecting the diffuse and more subtle forms of WMI that prevail in very premature infants surviving nowadays, recent improvement in the quality of neonatal CUS imaging has broadened the spectrum of preterm white matter abnormalities that can be detected with this technique. We propose a structured CUS assessment of WMI of prematurity that seeks to account for both cystic and non-cystic changes, as well as signs of white matter loss and impaired brain growth and maturation, at or near term equivalent age. This novel assessment system aims to improve disease description in both routine clinical practice and clinical research. Whether this systematic assessment will ...
Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal g... more Kernicterus is a severe neurological condition, caused by bilirubin-induced damage in the basal ganglia. The neurological outcome is often poor. In the past decades there seems to have been an increase in the number of reported cases of kernicterus. In order to raise awareness of this condition, we present two patients with kernicterus caused by different pathophysiological mechanisms. In both cases we make suggestions for the improvement of the medical care process. The first patient is a 7-day-old girl with kernicterus due to haemolysis caused by G6PD deficiency. Patient B is a 3-day-old boy with hyperbilirubinaemia based on 0/B blood group incompatibility. Kernicterus resulted in significant disabilities in these children. A proper diagnostic approach and precise treatment of hyperbilirubinaemia are essential to prevent major neurological damage. Awareness of this condition, education of health care professionals and changes in in- and outpatient care are needed to achieve this g...
Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by ... more Creatine kinase brain isoenzyme (CK-BB) was determined in cerebrospinal fluid of 150 neonates by a newly developed immunoenzymatic assay. Newborns with a documented neurologic disorder (intraventricular hemorrhage, postasphyxial encephalopathy, central nervous system infection, or persistent periventricular intraparenchymal echodensities) showed markedly higher concentrations of immunoreactive CK-BB than did the normal newborns or those with subarachnoid hemorrhage. In neonates with seizures the data suggest that the underlying neurologic disorder accounts for the higher CK-BB values and not the seizures per se. High concentrations of CK-BB in the neonatal period were followed by poor short-term outcome.
Congenital nonprogressive (bilateral) facial palsy and external ophthalmoplegia are essential cli... more Congenital nonprogressive (bilateral) facial palsy and external ophthalmoplegia are essential clinical features for the diagnosis of Moebius syndrome. One century after its initial thorough description, the precise delineation and pathogenesis of the syndrome still remain obscure. Heuristic hypotheses concerning the latter have been put forward. Three major theories of etiology remain valid: primary brainstem nuclear hypoplasia, secondary brainstem nuclear degeneration, and brainstem atrophy secondary to muscular defect. None of these theories easily explains why, apart from cranial nerve dysfunction, the Moebius syndrome is frequently a part of oral-limb deficiency anomaly syndromes.
A term female firstborn infant had unexplained nonimmune fetal hydrops and recurrent left chyloth... more A term female firstborn infant had unexplained nonimmune fetal hydrops and recurrent left chylothorax at 4 weeks of age. A few months before conception, her mother had had acute dystrophic nail changes and is being treated for recurrent sinusitis, bronchiectasis, and a deficiency of serum IgG2. We suggest that they both suffer from a dominantly inherited congenital lymphedema syndrome known as `yellow nail dystrophy.' Prenatal manifestation of this disorder has not been reported previously. The child's anthropometric and neurological development was normal at 1 year of age, whereas mild ankle edema and marbling of the skin of the limbs were salient clinical findings. Inherited lymphedema leading to nonimmune fetal hydrops also has been recognized in chromosomal disorders, Noonan's syndrome, multiple pterygium syndrome, pulmonary lymphangiectasis, and mixed-vessel lymphatic dysfunction. Indicators of parental lymphedema are not on record in those instances.
Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neur... more Background and Objective: High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to
We present the improvements made to and subsequent validation of an automated approach to detect ... more We present the improvements made to and subsequent validation of an automated approach to detect neonatal seizures. The evaluation of the algorithm has been performed on a new and extensive data set of neonatal EEGs. Previously, we have classified neonatal seizures visually into two types: the spike train and oscillatory type of seizures and developed two separate algorithms that run in parallel for their automated detection. The first algorithm analyzes the correlation between high-energetic segments of the EEG, whereas the second one detects increases in low-frequency activity (<8 Hz) and then uses an autocorrelation. An improved version of our automated system (called 'NeoGuard') uses more informative features for classification and optimized parameters for thresholding. The validation was performed on 756 hours of 'unseen' continuous EEG monitoring data from 24 neonates with encephalopathy and recorded seizures. The seizure detection system showed a median sen...
The incidence of stroke is reported to be 28 in 100.000 live births. All age groups show an unexp... more The incidence of stroke is reported to be 28 in 100.000 live births. All age groups show an unexplained male predominance. Of the two types of cerebral stroke, arterial ischaemic stroke and (sino-)venous thrombosis, the arterial one is most frequent. Non-invasive methods such as ultrasound, computerized-tomography (CT) or magnetic resonance imaging (MRI) can detect these thrombotic events in the brain. Etiologic (genetic or acquired) factors predisposing to thrombosis may shift the haemostatic balance towards elevated procoagulant activity resulting in a hypercoagulable state that predisposes to venous or arterial thrombosis. Lower concentrations of antithrombin, protein S and C, along with reduced fibrinolytic capacity, put neonates at greater risk of thromboembolic complications than older children.
CMV is the most common congenital viral infection, with a birth prevalence of 0.48-1.3% in recent... more CMV is the most common congenital viral infection, with a birth prevalence of 0.48-1.3% in recent decades. The congenital infection may be asymptomatic or symptomatic; the symptomatic disease can be severe and life-threatening. Both asymptomatic and symptomatic newborns are at risk of developing long-term neurodevelopmental morbidity, particularly deafness. Recently, the neurological complications caused by congenital CMV infection in affected infants have been successfully treated with antiviral agents, but the early diagnosis of congenital infection is vital for this treatment to be effective. To identify primary CMV infection, maternal blood tests for CMV-specific immunoglobulin (Ig) M antibodies (CMV IgM) are widely used. However, CMV IgM tests can remain positive for years after the primary infection, so a positive result for CMV IgM does not always indicate primary infection during pregnancy. A CMV IgG avidity test is also used for identifying a recent infection....
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