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.

Randomized, multicenter trial of two different formulas for very early enteral feeding advancement in extremely-low-birth-weight infants.

BACKGROUND: In extremely-low-birth-weight (ELBW) infants, formula feeding is required if human milk is not available. The tolerance of a new 'high' lactose (55 g/L), low protein, low phosphate, hydrolyzed protein formula (HLF) for early enteral feeding advancement of ELBW infants was compared with that of a low lactose (1 g/L) hydrolyzed protein formula (LLF). METHODS: In a randomized multicenter trial, 99 ELBW infants were fed according to a standardized protocol beginning at 48 hours of age with 12 ml/kg daily increments. Primary outcome was the cumulative milk feeding volume (CFV) from days 3 to 14. The authors hypothesized that feeding HLF as a supplement to human milk would increase the CFV at least by 20% in at least 60% of matched pairs compared with LLF. A secondary issue was to investigate whether human milk would increase the CFV compared with formula. RESULTS: The CFV was 720 mL/kg (range, 0-962 mL/kg) with HLF and 613 mL/kg (range, 3-1,283 mL/kg) with LLF feeding. There was no 20% difference. On day 14, the median feeding volume was 103 mL/kg. The CFV was 533 mL/kg (range, 0-962 mL/kg) in infants who received less than 10% of human milk and 832 mL/kg (range, 74-1,283 mL/kg) in infants who received more than 10%. Necrotizing enterocolitis (Bell stage > or =2) occurred only with LLF feeding (n = 5; P < 0.05). CONCLUSIONS: The study failed to find the hypothesized 20% advantage of the new HLF. The observed advantage of human milk supports the hypothesis that it should be the first diet in ELBW infants; however, this hypothesis still must be confirmed in a controlled, randomized trial.

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.

Unusual pattern of leukoencephalopathy after morphine sulphate intoxication.

We report a 14-year-old girl with an unusual pattern of leukoencephalopathy after intentional intoxication with morphine sulphate tablets. Toxicological analysis showed exceedingly high levels of morphine and its metabolites. MRI disclosed a leukoencephalopathy with high signal from the centrum semiovale, corpus callosum and cerebellar white matter on T2-weighted images. These findings could be only partially explained by a hypoxic-ischaemic event; neurotoxic effects must be considered in this atypical leukoencephalopathy.

Short-term memory deficit after focal parietal damage.

The neuropsychological symptomatology is reported for a 44-year-old patient of normal intelligence, EE, after removal of a circumscribed left hemispheric tumor the major part of which was located in the angular gyrus and in the subcortical white matter. EE had a distinct and persistent short-term memory impairment together with an equally severe impairment in transcoding numbers. On the other hand, his performance was flawless in calculation tasks and in all other tests involving number processing. Impairments in language tests could be attributed to his short-term memory deficit, which furthermore was characterized by a strong primacy effect in the absence of a recency effect. His graphomotoric output was temporarily inhibited. The patient, with a strong left-sided dominance, manifested a bi-hemispherical activation of the Broca and Wernicke regions in a positron-emission-tomographic investigation when required to produce verbs which he was to derive from nouns. The findings in EE suggest that unilateral and restricted lateral parietal damage can result in a profound short-term memory deficit together with a transcoding deficit for stimuli extending over only a few digits or syllables in the absence of any symptoms of the Gerstmann syndrome.

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.

Perioperative fluid and electrolyte management in children undergoing surgery for craniopharyngioma. A 10-year experience in a single institution.

In a retrospective study, the intra- and early postoperative data of 39 children with 46 operations for craniopharyngioma were analyzed. Diabetes insipidus (DI) occurred in 30 out of 32 cases without preoperative evidence of DI. We observed that all children who did not have a pituitary stalk preserved and 5 out of 7 patients with preserved pituitary stalk developed DI within 18 h of surgery. Short-term inappropriate secretion of antidiuretic hormone (SIADH) occurred in 2 children, but was quickly followed by DI. The time of onset of DI and SIADH did not correlate with sex, age, body weight, location of tumor, or duration or extent of surgery. Parenteral desmopressin was an effective treatment for intra- and postoperative DI. The duration of the clinical effect of desmopressin administration varied in different patients between 4 and 23 h. An approach to the immediate intra- and postoperative management of children with craniopharyngioma is presented.

Localization of language-related cortex with 15O-labeled water PET in patients with gliomas.

Measurement of relative cerebral blood flow (CBF) with 15O-labeled water PET has been widely used for brain mapping experiments on language functions in normal volunteers and patients with epilepsy. We focused on the question of whether PET during speech activation is an appropriate method for noninvasive determination of language-related cortex in patients with brain tumors. Furthermore, the suitability of the method for determination of hemispheric language dominance was examined and compared to the results of the Edinburgh Handedness Inventory. Ten right-handed and six left-handed patients with gliomas were examined prior to surgery while repeatedly performing word repetition and verb generation tasks. A set of volumes of interest (VOIs) was drawn on coregistered MRI in order to account for anatomic variability as well as anatomical alterations due to tumor mass effect. Repetition of nouns did not produce significant hemispheric differences. During stimulation by verb generation, reliable lateralized activations of Broca's area and supplementary motor area were detected in all right-handed patients. Of the left-handed patients, two showed clear right lateralization, two activated Broca's area bilaterally, and two had a pattern similar to that of right-handers. Patients with bilateral activations showed the strongest tendency toward bihandedness according to the handedness inventory. Lateralization of supplementary motor area in left-handers corresponded to lateralized activity in Broca's area. Tumors in the vicinity of language-related regions did not alter activation responses. In conclusion, measurement of CBF changes during verb generation permits identification of language-related areas in patients with gliomas with strong lateralization related to hemispheric dominance. These findings may be of particular clinical interest for left-handed patients.

[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.

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.

Chemiluminescence activity of phagocytes from tracheal aspirates of premature infants after surfactant therapy.

The effect of surfactant on the respiratory burst of phagocytic cells was studied in the tracheobronchial tract of 40 mechanically ventilated neonates (gestational age 24-37 weeks) over the first week of life. We measured the luminol-dependent chemiluminescence (CL) activity of granulocytes and macrophages isolated from tracheal aspirates in 23 preterm infants 1-6 days after administration of bovine surfactant and in 17 untreated controls. Following stimulation by the chemotactic peptide N-formylmethionylleucylphenylalanine, CL activity was not or only slightly impaired in the surfactant group. In contrast, treatment with exogenous surfactant significantly reduced CL response to opsonized zymosan (OPZ), which involves phagocytosis, for up to 6 days (p < 0.05). The impairment of CL activity seemed to be dose dependent, as repeated surfactant applications (cumulative phospholipid dose of 200 mg/kg) reduced OPZ-elicited CL activity to a greater extent than application of a single dose of 100 mg/kg. In agreement with in vitro studies, our data suggest that high-dose application of exogenous surfactant may affect the antibacterial function of phagocytic cells in the lung.

Individual functional anatomy of verb generation.

Examination of the individual functional anatomy of language is of particular interest in clinical neurology to explain the variability of aphasic symptoms after focal lesions and to avoid damage of language-related brain areas by surgery. For a silent verb generation task, we examined whether activation PET with 3D data acquisition, multiple replication of conditions, and coregistration with MRI provides results that are consistent and reproducible enough to be useful clinically. Visual analysis was performed on PET-MRI fusion images, including renderings of the brain surface. Quantitative analysis was based on volumes of interest. In seven right-handed normals, activation of the triangular part of the left inferior frontal cortex [Brodman area (BA) 45] was the most significant finding that was present in each subject. Two subjects showed minor anatomical variants of the ascending or horizontal ramus of the sylvian fissure that were associated with the least activation of BA 45. In the left hemisphere the other frontal gyri, the superior temporal and posterior part of the middle temporal gyrus, and the paracingulate gyrus were also significantly activated. There was significant bilateral cerebellar activation, but it was significantly more intense on the right than on the left side. The consistency and high interindividual reproducibility of these findings suggest that this technique may be useful for clinical assessment of language-related areas.

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.

Immunologic parameters in cord blood indicating early-onset sepsis.

Different immunologic parameters were measured in cord blood to test their usefulness in the early diagnosis of early onset sepsis. Cord blood levels of circulating intercellular adhesion molecule-1 (cICAM-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly elevated in septic compared to nonseptic neonates. No significant difference between either population was seen for cord blood C3a and elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI). Measured concentrations of cICAM-1, IL-6 and IL-8 in fetal and maternal blood did not correlate, indicating that the neonate's response to sepsis is clearly different from the mother. Our data suggest that cord blood measurements of cICAM-1, IL-6 and IL-8 might be useful in identifying neonates with early-onset sepsis.

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.

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.