O. Daniëls

Congenital cataract and mitochondrial myopathy of skeletal and heart muscle associated with lactic acidosis after exercise

Congenital cataract involving the nucleus, cortex, and capsule of the lens, and cardiomyopathy were found in seven of 22 children from three unrelated families. Histologic examination showed a mitochondrial myopathy of skeletal and heart muscle with storage of lipid and glycogen. When the patients performed submaximal exercise for 60 minutes they developed metabolic acidosis with lactic acidemia.

Detrimental sequelae on the hemodynamics of the upper left limb after subclavian flap angioplasty in infancy.

The long-term effect of two surgical techniques for repair of coarctation of the aorta in infancy, namely, resection and end-to-end anastomosis (RETE) and subclavian flap angioplasty (SFA) on the blood supply of the upper left limb, was quantified by Doppler spectrum analysis of blood flow velocities in the left brachial artery at rest and during postocclusive reactive hyperemia. Twenty-three patients participated in this study: nine patients after SFA (median age, 8 years), 14 patients after RETE (median age, 8 years), and 10 control subjects (median age, 9.5 years). At rest, a highly significant decrease of blood flow velocities in the left brachial artery was measured in all patients of the SFA group compared with those of the RETE and control groups, as documented by various Doppler spectrum parameters: maximal frequency of advancing curve (p = 0.0001), pulsatility index (p = 0.0005), and resistance index (p = 0.039). During reactive hyperemia, a moderate capacity of physiologic augmentation of blood flow velocities was observed in five patients of the SFA group. This capacity was marginal in two patients with complaints of claudication in the left upper limb during strenuous exercise, which can be related to the number of branches of the left subclavian artery ligated during operation. This study indicates that SFA in infancy may lead to compromised hemodynamics of the upper left limb with potential for symptoms of ischemia during exercise.

The vibratory innocent heart murmur in schoolchildren: difference in auscultatory findings between school medical officers and a pediatric cardiologist.

SummaryIn 810 schoolchildren heart auscultation was performed by both a school medical officer (SMO) and a pediatric cardiologist (PC). The prevalence for a grade 1, 2, or 3 vibratory innocent heart murmur (VIHM), a grade 2 or 3 VIHM, and a grade 3 VIHM heard by the PC was 41%, 13%, and 1%, respectively. The SMO noted such murmurs in 26%, 9%, and 1%, respectively. In 30% of the cases in which the PC had noted a grade 2 or 3 VIHM, the SMO agreed; in 30% of such cases the SMO did not hear any heart murmur. If the PC heard a grade 2 or 3 VIHM phonocardiography was performed in a case-control study in which the controls did not have a heart murmur (94 pairs). In four children with a grade 2 or 3 VIHM no heart murmur could be registered and in three other children the murmur did not have the typical diamond shape. In contrast, in three children without a heart murmur at school a VIHM was seen on the phonocardiogram. In 26 children with a phonocardiographically proven grade 2 or 3 VIHM the SMO did not hear any heart murmur. One child with a grade 3 VIHM (both by the PC and SMO) had a minor subvalvular aortic stenosis. There is quite a difference in auscultatory detection of a venous hum: 9% (PC) and 2% (SMO). The prevalence of the pulmonary ejection murmur is identical at 4%. The carotid bruit is heard in 4% (PC) and 2% (SMO). Pathologic murmurs were heard in 12 children by the PC, agreed by the SMO in two cases. Eight of the 12 pathologic murmurs were confirmed by further cardiologic examination and one was decided to be an innocent pulmonary ejection murmur. The auscultatory findings of 4 SMOs, who examined >100 children each, differ remarkably when compared separately to the results of the PC. Variation in intensity of the heart murmurs and difference in auscultatory skills explain the great difference in ausculatory findings between the PC and the SMO. Specialized training of SMO to recognize (pathological) heart murmurs is advocated.

Fatal neonatal cardiomyopathy associated with cataract and mitochondrial myopathy.

Three patients suffering from the neonatal form of a syndrome characterized by congenital cataract, hypertrophic cardiomyopathy, and mitochondrial myopathy are described. The patients died at 7, 10 and 18 days, respectively from cardiorespiratory failure. Mitochondrial abnormalities were observed in the heart and skeletal muscle. Despite the presence of a severe lactic acidaemia pointing to a disturbed pyruvate oxidation rate in vivo, a normal pyruvate oxidation rate was demonstrated in skeletal muscle homogenates. The activities of several enzymes of the mitochondrial respiratory chain appeared to be normal, indicating an intact respiratory chain. A myoglobinopenia could be excluded. The activities of some mitochondrial enzymes and the concentration of myoglobin increase with age.

The vibratory innocent heart murmur in schoolchildren: A case-control Doppler echocardiographic study

SummaryIn 810 schoolchildren (aged 5–14 years) the prevalence of a grade 1–3/6 vibratory innocent heart murmur (VIHM) is 41%. Restricted to a grade 2 or 3 VIHM, the prevalence is 14%, decreasing from 21% in the age-class 5–6 years to 8% for children 13–14 years of age. The prevalence of a grade 3 VIHM is 1%. Together with a matched control, 84 children with a grade 2 or 3 VIHM underwent further cardiologic examination including electrocardiography, phonocardiography, and Doppler echocardiography. A positive correlation was found between the presence of a VIHM and higher left ventricular voltages on the ECG, but within the normal range; lower heart rate; smaller diameter of the ascending aorta (AAO); and higher blood flow velocity and higher maximal acceleration of the blood flow in the LVOT and the AAO. In 40% of the children with a VIHM, a systolic aortic valve vibration was seen with a frequency ≥100 Hz and an amplitude ≥1 mm, whereas this type of vibration was present in only one case control. No significant difference was found concerning the prevalence of false tendons in the left ventricle, systolic and diastolic diameter of the left ventricle, systolic time intervals, and shortening fraction of the left ventricle. The VIHM is strongly associated with a smaller AAO, with higher velocity and acceleration of the blood flow in the LVOT and AAO, and with a vibratory phenomenon of the aortic valve, pointing towards the LVOT-aortic valve region as the site of origin of the VIHM.

Hereditary mitochondrial hypertrophic cardiomyopathy with mitochondrial myopathy of skeletal muscle, congenital cataract and lactic acidosis.

A six day old boy died from an hereditary hypertrophic cardiomyopathy which was associated with mitochondrial myopathy of skeletal muscle, congenital cataract and lactic acidosis. In heart and skeletal muscle identical mitochondrial abnormalities were found: paucity and abnormal arrangement of cristae, formation and extrusion of vesicle-like structures and crystalline inclusions in the matrix compartment. Electron-cytochemistry revealed that only part of the mitochondria reacted positively for cytochrome oxidase activity. Morphometric analysis indicated that the cardiomegaly was due to cellular hypertrophy, which might be caused by an increase in the mitochondrial mass. The cardiac hypertrophy in this syndrome can be classified histopathologically as mitochondrial hypertrophic cardiomyopathy.

Cerebral blood flow velocity and pulsation in neonatal respiratory distress syndrome and periventricular hemorrhage

The present study addressed the hypotheses that cerebral ischemia and/or excessive cerebral blood pulsation contribute to periventricular hemorrhage in preterm newborns with respiratory distress and that the pulse width is a valuable tool to estimate the contribution of cerebral blood pulsation. These hypotheses were tested by following preterm newborns at risk for respiratory distress and periventricular hemorrhage. We monitored for cerebral blood flow velocity (CBFV), cerebral pulse width, and cerebral pulsatility index; for patent ductus arteriosus, capillary Pco2, heart rate (HR) and behavior; and for the occurrence of respiratory distress and periventricular hemorrhage (PVH). The data obtained were analyzed with linear regression with the mode of respiration (spontaneous or supported) and postnatal age as additional covariates. We observed that (a) respiratory distress, either uncomplicated or complicated by PVH, correlates with a low CBFV and a high cerebral pulsatility index; (b) PVH also correlates with a high cerebral pulse width; (c) the increased pulse width precedes the onset of the hemorrhage; and (d) these CBF alterations can be partly attributed to ductal shunting and are ameliorated by mechanical ventilation.

Limits of reproducibility of mitral pulsed Doppler spectra

The total intrinsic variability of pulsed Doppler spectra of mitral blood flow was evaluated in this study. Doppler examinations were performed in 10 normal volunteers (7 men, 3 women), ages 29 to 57 years (mean 41) with an interval period of 3 months. The recordings were made in the apical 4-chamber view, using a 2.25-MHz transducer. The sample was placed approximately 1 cm proximal (left atrium) and 1 cm distal (left ventricle) from the middle of the anulus of the mitral valve at the onset of diastole. Processing of the raw Doppler spectra was done in a way that avoided subjective manipulation by the investigators. Mitral peak velocities, accelerations and spectral widths were measured in early diastole and late diastole. From the parameters under investigation, maximal velocities showed the best reproducibility with a range of coefficients of variation of 9 to 13%. Peak acceleration in early diastole and spectral widths showed rather large coefficients of variation, ranging from 19 to 30 and 14 to 24%, respectively. Mitral pulsed Doppler spectra in the left atrium were more reproducible than in the left ventricle.

Neonatal pulmonary hypertension during extracorporeal membrane oxygenation.

OBJECTIVESnThis prospective study was designed to monitor severe pulmonary hypertension during extra corporeal membrane oxygenation using echo Doppler variables.nnnBACKGROUNDnAll neonates treated with extracorporeal membrane oxygenation also have severe pulmonary hypertension. A study which monitors the reaction of the pre-existing pulmonary hypertension during extracorporeal oxygenation by frequent sampling of those variables related to pulmonary pressure is still lacking. Such a study is necessary to analyze the complex haemodynamic changes in patients undergoing extracorporeal membrane oxygenation.nnnMETHODnIn 29 neonates, we estimated pulmonary arterial pressure using peakflow velocity of regurgitation across the tricuspid- and pulmonary valve, peakflow velocity of shunting across persistent arterial ductus, and systolic time intervals of the right ventricle. Correlation between the several estimations of pulmonary arterial pressure were analysed with the Spearman correlation coefficient.nnnRESULTSnSystolic pulmonary arterial pressure measured by the velocity of tricuspid regurgitation illustrated severe pulmonary hypertension prior to extra corporeal membrane oxygenation (mean 63 mmHg, sd 20). Similar levels for the systolic pulmonary arterial pressure could be derived (mean 73 mmHg, sd 17) from ductal shunting. A fair correlation of 0.76 (p< 0.002) could be demonstrated. Pulmonary hypertension responded well and quickly to treatment by extra corporeal membrane oxygenation, with reductions within 24 hours to mean systolic levels of 35 mmHg, sd 23. This very early reaction has not previously been demonstrated and could be of importance in defining parameters for weaning from cardiopulmonary bypass. Diastolic pulmonary arterial pressure was investigated because of its relation to vascular resistance. It proved more difficult to measure because of the low incidence of pulmonary regurgitation. Derived diastolic pressures did not show any good correlations.nnnCONCLUSIONnPulmonary hypertension is well documented prior to extra corporeal membrane oxygenation and response very quickly to the institution of treatment. Ultra sound techniques are indicated at the bedside, and prove useful in monitoring pulmonary blood pressure during the procedure.

Ultrasound detection of congenital Arteriovenous aneurysm of the great cerebral vein of Galen

Using combined echoencephalography and Doppler flow determination the diagnosis Arteriovenous aneurysm of the great cerebral vein of Galen could be made in two infants. Without vascular surgery one patient died, the other recovered completely. CT scanning confirmed the diagnosis. Invasive methods such as cerebral angiography were avoided.Case histories, neuropathological findings, ultrasound method and results are presented. Pathogenesis, clinical signs, treatment and prognosis are discussed. With the ultrasound method presented, the nature and location of the vascular anomaly were demonstrable, thus additional higher risk diagnostic methods could be avoided or planned more purposefully.