Failed visualization of clot signal in cerebral venous thrombosis on initial MR imaging.

Currently, the combination of T1- and T2-weighted spin echo magnetic resonance imaging (MRI) sequences with MR venography is considered the best diagnostic tool for diagnosing cerebral venous thrombosis (CVT), because they allow positive identification of the thrombotic clot along with the disturbed venous flow signal. We report two patients in whom initial MRI with the mentioned techniques did not show a clot signal. In both patients anticoagulation was started despit lacking proof of CVT by imaging and both patients improved. Only on repeated MRI sinus clot signal could be confirmed.

Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke.

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.

OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.

Preoperative activation and intraoperative stimulation of language-related areas in patients with glioma.

OBJECTIVE: Evaluation of the accuracy of preoperative localization of language-related cortex by magnetic resonance imaging-guided positron emission tomography. METHODS: Patients with gliomas in the left dominant hemisphere were examined preoperatively with magnetic resonance imaging-guided positron emission tomography and intraoperatively by electrical stimulation of cortex. RESULTS: A verb generation task yielded more intense and better lateralized local increases of cerebral blood flow in the positron emission tomographic examination than did a naming task. Significant correspondence of preoperative and intraoperative findings was observed for the verb generation task. Cortical sites with aphasic disturbance during electrical stimulation had a significantly higher cerebral blood flow increase during preoperative activation than did sites without intraoperative language impairment. Areas with cerebral blood flow increases above an optimum threshold had 73% sensitivity and 81% specificity to predict aphasic disturbance during intraoperative stimulation. CONCLUSION: The data suggest that with further technical improvements, imaging of language function may become a preoperative diagnostic tool for patients with tumors close to language-related brain structures.

Plasma catecholamines after endotracheal administration of adrenaline during postnatal resuscitation.

To analyse the degradation of adrenaline after cardiopulmonary resuscitation of preterm neonates, free and sulphoconjugated adrenaline, noradrenaline, and dopamine were determined in 31 preterm neonates by a radioenzymatic method. Nine of the neonates received a high dose (250 micrograms/kg) of endotracheally administered adrenaline (1:1000); three of them had more than one dose of adrenaline. With the exception of sulphoconjugated dopamine, the free and sulphoconjugated catecholamine concentrations in preterm infants treated with adrenaline initially exceeded those in the untreated group. The concentrations decreased to the same range about two hours after birth. Free and sulphoconjugated adrenaline concentrations remained significantly increased in the adrenaline treated group, however, indicating a plateau effect. The correlation between free adrenaline and noradrenaline concentrations with their respective sulphoconjugated concentrations was highly significant. It is concluded that free catecholamines are rapidly degraded by sulphoconjugation in preterm neonates.

Clinical applications of registration and fusion of multimodality brain images from PET, SPECT, CT, and MRI.

Several image registration and fusion techniques have been discussed in the context of applying them to patient studies obtained during clinical workup. Mainly retrospective techniques, either automated or interactive, seem to be flexible enough to be adapted to clinical situations. Examples are provided to express the usefulness of multi-modality, multi-tracer brain studies.

Selenium in total parenteral nutrition.

In clinical practice, selenium deficiency may arise under conditions of chronic malnutrition and especially after long-term total parenteral nutrition (TPN). In infants receiving long-term TPN, we observed plasma selenium levels as low as those previously reported in Chinese children with Keshan disease. Low plasma selenium levels were also usually associated with very low activities of glutathione peroxidase. Although clinical symptoms of selenium deficiency did not occur in our patients, several cases have been described in the literature, indicating the need for supplementation in TPN. In order to derive at the appropriate dosage, it is proposed to correlate it with the total protein supply. According to our present knowledge, .5-1.0 micrograms selenium/g of protein appears to be adequate to keep patients in Se balance. For Se repletion of body stores, this dosage has been increased up to 3 micrograms of Se/g of protein. Advantages and disadvantages of selenite and of selenomethionine as possible supplemental forms of Se for TPN solutions are discussed.

[On parenteral infusion therapy adapted to the requirements of the neonatal period (author's transl)]. / Uberlegungen zur Durchführung einer angepassten parenteralen Infusionstherapie bei Früh- und Neugeborenen in der ersten Lebenswoche.

Controversial data in literature and the results of our own investigations of the effects of varying liquid supply in premature and newborn infants have caused the setting up of an infusion pattern adapted to requirements for the neonatal period. The guidelines as proposed largely take into account varying water and energy catabolism of premature and newborn infants. As a matter of principle electrolyte substitution is not related to body weight but to the particular infusion quantity administered. It is of vital importance that no infusion pattern can do without a corresponding monitoring. Observation of the most essential parameters in the sera and urines of 65 solely parenterally infused premature and newborn infants has shown that very rarely, only on special occasions, minor adjustments had to be made.

[Causes of and change in bacterial infections in newborn infants]. / Ursachen und Wandel bakterieller Infektionen bei Neugeborenen.

Despite all the progress made in modern neonatology the morbidity rate caused by bacterial infections has rather gone up than down. The reasons why premature and newborn infants have a greater disposition to bacterial infections have been largely explored; at the same time one must accept these infants to be increasingly vulnerable to infections, the vulnerability being the larger the greater the degree of immaturity is. Every 5th to 10th death of newborn infants is caused by infection. One will have to be constantly on the watch and acquire profound knowledge of channels of infection and the bacterial spectrum to be expected. Since the early beginnings of neonatology, some 60 years ago, a continuous change in bacterial spectra has been going on showing incredible regularity in crossing even borders and continents. With gram-positive cocci (A streptococci) prevailing at the beginning, there was a considerable increase in gram-negative enterobacteriaceae in the 60ies and 70ies, when neonatal intensive medicine was started. There were mainly nosocomial infections resulting from too generously administered antibiotics. Today, plasmacoagulase-negative staphylococci, for a long period thought not to be pathogenous, are the essential bacteria in nosocomial infections. On the whole, one usually has to do with infections vertically transmitted by the mother, especially to preterm infants. The greatest threat still comes from B streptococci since they will lead to pulmonary changes such as pneumonia and RDS. The development reported on is based on data from the literature and my own experience as well as on comprehensive results of the Neonatalerhebung of Lower Saxony and Bavaria.

The effect of feeding human milk and adapted milk formulae on serum lipid and lipoprotein levels in young infants.

The effect of feeding with human milk and commercially available milk substitutes was studied in a group of 154 healthy infants during the first 3 months of life by assessment of body weight, body length, head circumference, skinfold thickness, serum lipid and lipoprotein concentrations. Human milk and the different milk formulae have the same energy content (kcal/100 ml) and total fat, total protein and total carbohydrate contents are comparable but they differ in respect of their fatty acid compositions. The various diets were chosen freely by the parents and the newborns were exclusively fed either human milk (n = 56), Multival 1 (n = 31), Humana 1 (n = 33), or Pre Aptamil (n = 34). No significant differences in body weight, body length or head circumference were observed between any of the different dietary groups. Fat storage, as assessed by measurements of skinfold thickness, was significantly less in breast-fed children compared to those on the formula diets. Breast-fed and Pre Aptamil-fed infants had the highest levels of total serum cholesterol, low density lipoprotein (LDL)-cholesterol and LDL. No differences were observed in the levels of total serum triglycerides, very low density lipoprotein (VLDL)- and high density lipoproteins (HDL)-cholesterol, VLDL and HDL. There were no strong correlations between the physical and the biochemical parameters. No indication of an increased risk of developing atherosclerosis was associated with any of the dietary treatments for the duration of this study. However, these investigations support the hypothesis that subtle early nutritional variation can influence mechanisms that regulate lipoprotein and cholesterol levels in later life.

[Type IIB von Willebrand Jürgens syndrome as the cause of neonatal thrombocytopenia]. / von Willebrand Jürgens Syndrom Typ IIB als Ursache neonataler Thrombocytopenie.

Two newborn male infants with neonatal thrombocytopenia and von Willebrand disease (vWD) in their family history were admitted two our hospital during the last two years. The second patient was later on shown to suffer from vWD type IIB, in the first case there was a typical history but no analysis of the multimeric pattern. The vWD type IIB is a rare cause for neonatal thrombocytopenia. Therapy with platelet concentrates alone is not in all cases able to correct the platelet count for more than some hours. The finding of (recurrent) thrombocytopenia and a familial history of vWD in a newborn infant is of major diagnostic value to identify cases of this rare autosomal dominant disease.

Severe cerebral depression after intoxication with tramadol in a 6-month-old infant.

Accidental intoxication with tramadol of a 6-month old infant was followed by severe cerebral depression. Studies on serum, cerebrospinal fluid, and urine drug levels indicated complete penetration of the blood-cerebrospinal fluid barrier by tramadol.

Investigation of accelerated metabolic function in small for gestational age infants.

Small for gestational age (SGA) infants are known to develop relatively mild transient hyperbilirubinaemia, especially in comparison with premature infants. This may be interpreted as an index of accelerated maturation of particular vital functions. In the present study 12 SGA infants, 12 appropriate for gestational age (AGA) infants, and 12 premature infants had 24 h urine collections under standardized conditions on the third day of life. Urinary excretion of D-glucaric acid and creatinine, which can be increased by drugs (e.g. phenobarbital), were estimated. Haematocrit and bilirubin were determined at the age of 72h. In the 3 groups, the SGA infants had the highest mean haematocrit (SGA = 0.58, AGA = 0.5, Prem = 0.561/1) and the lowest mean bilirubin (SGA = 6.3, AGA = 8.6, Prem = 11.1 mg/dl). Despite a comparatively small urine volume (SGA = 19.6, AGA = 28.3, Prem = 37.3 ml/kg), excretion of D-glucaric acid (SGA = 0.18, AGA = 0.11, Prem = 0.06 mumol/kg) and creatinine (SGA = 101.6, AGA = 79.6, Prem = 80.2 mumol/kg) was significantly higher in the SGA infants. While the results do not provide conclusive evidence, the increased excretion of glucaric acid and creatinine associated with mild transient hyperbilirubinaemia can be considered an indicator of metabolic differences in SGA infants.

[Effects of highly varying parenteral fluid intakes in premature and newborn infants during the first three days of life (author's transl)]. / Die Auswirkungen einer stark unterschiedlichen parenteralen Flüssigkeitszufuhr bei Früh- und Neugeborenen in den ersten drei Lebenstagen.

Under standardized conditions two random groups of 28 premature and newborn infants, each mostly suffering from a respiratory distress syndrome, were given infusions of either 60 or 150 ml/kg per day on the first three days of life. On each of the three days an increase of the infusion quantity resulted in a 2--3 times larger urine flow, the osmolal clearance increasing significantly at the same time. This was mainly due to a higher loss of NaCl, whereas there were no significant or only small differences in the excretion of all other electrolytes, acids, and nitrogenous metabolites. There was no clear evidence that a larger fluid intake had an influence on the endogenous creatinine clearance. Considerably negative effects of an increased infusion quantity were not observed in these investigations, yet one should use extreme caution as ductus arteriosus persistens as well as bronchopulmonal dysplasia are attributed to large fluid intakes during the first days of life.

[Diagnosis of thyroid function in premature infants in intensive care]. / Schilddrüsenfunktionsdiagnostik bei Frühgeborenen in der Intensivpflege.

In 87 premature infants of an neonatal intensive care unit (gestational age 28-37 weeks) serum-T4, -fT4 and TSH were investigated on day 10, 20 and 30 and at term respectively, in addition to the usual TSH-screening (capillary specimen) on day 5. In 47 neonates (54%) T4 and fT4 were found to be low, including all infants under 30 weeks of gestational age and all ventilated infants. Screening TSH was not elevated but in some cases with iodine contamination. 12 of 13 infants in whom TRH-stimulation was performed showed significant response of TSH. We conclude that compromised thyroid function, common in prematures and infants under intensive care, is similar to the euthyroid sick syndrome in adults and does not require therapy. Replacement of thyroid hormone is only indicated in neonates with increased TSH.

Effects of highly overdosed indomethacin in a preterm infant with symptomatic patent ductus arteriosus.

We describe a preterm infant with severe idiopathic respiratory distress syndrome (iRDS, hyaline membrane disease) who needed artificial ventilation with high inspiratory pressure, high frequencies, 100% oxygen and developed a symptomatic patent ductus arteriosus (sPDA) in the course of the disease. The infant was given indomethacin to induce constriction of sPDA. Due to an error in drug dilution the patient received a 100-fold overdose of indomethacin. Compared to the normal study protocol side-effects such as renal failure were not observed probably due to sufficient fluid intake and good clinical condition prior to treatment and to the rapid and persistent ductal closure.

[Diagnosis of monozygosity in multiple births by DNA fingerprinting]. / Diagnose der Monozygotie bei Mehrlingen durch DNA-Fingerprinting.

The incidence of monozygotic twins is one in 250 pregnancies. Triplets are estimated to occur in 1 of 86(2) pregnancies. Determination of zygosity may be done by comparison of physical characteristics, blood group or tissue typing, chromosome studies, or examination of various other polymorphic protein markers. Here we describe the differentiation between monozygotic and dizygotic twins and triplets by DNA-fingerprinting. This is a fast, non-invasive and reliable (error probability 0.003%) method to determine monozygosity of twins or triplets. It is also a reliable paternity test.

Inappropriate secretion of umbilical plasma catecholamines in preterm compared to term neonates.

To investigate the gestation and stimulus related catecholamine secretion and degradation at birth free and sulfoconjugated adrenaline, noradrenaline and dopamine were analysed in the umbilical artery and vein of 35 preterm and 75 term neonates. A highly sensitive radioenzymatic assay was used for the determination of free catecholamine levels, sulfoconjugated catecholamines were analysed after addition of 25 mU arylsulfatase type VI. Levels of free catecholamines were significantly lower in preterm as compared to term newborns. Hereby, adrenaline levels significantly correlated with the gestational age, birth weight, and birth length. Sulfoconjugated catecholamine levels were similarly lower, but only sulfoconjugated noradrenaline reached differences of statistical significance. The placental extraction rate of adrenaline and noradrenaline was significantly lower in preterm as compared to term neonates. Only in term but not in preterm neonates, arterial pH- and pCO2-levels significantly correlated with arterial plasma catecholamine levels. Therefore, lower catecholamine levels in preterm compared to term neonates result from lower secretion of catecholamines rather than increased degradation and may contribute to their frequent surfactant deficiency. In addition, the inadequate and diminished catecholamine secretion of preterm neonates may play a significant part in their postnatal adaptation problems like hypoglycaemia, hypothermia and occurrence of wet lungs.