PubMed HealthSearch

Biomedical subjects

G Pawlik

Publications and source records attributed to G Pawlik.

At least 19 recordsLinked to original sources

Changing patterns of glucose metabolism during the course of subacute sclerosing panencephalitis as measured with 18FDG-positron-emission tomography.

18FDG-positron emission tomography performed at different stages in the course of subacute sclerosing panencephalitis revealed a changing pattern of metabolic disturbance. In clinical stage II patients the inflammation in the basal ganglia appeared to lead to neuronal excitation accompanied by hypermetabolism. Widespread cortical functional inhibition of metabolism followed. The striatal inflammation ended with necrosis and hypometabolism, with resulting functional cortical disinhibition; later, deep midbrain structures and brain stem became hypermetabolic. A patient clinically in remission showed no such changes in cerebral glucose metabolism.

Adolescent

PET correlates of normal and impaired memory functions.

To date, positron emission tomography (PET) has been the only technology for the quantitative imaging of the changes of regional cerebral glucose (rCMRGl) or oxygen metabolism and blood flow (rCBF) associated with psychophysical stimulation and with the performance of mental tasks. So far, the majority of studies performed in healthy subjects demonstrated activation patterns involving not only certain limbic structures, most of all hippocampus, amygdala, parahippocampus, and cingulate, but also temporal, parietal, and occipital association cortex, depending on the applied paradigm. Indeed, the closest correlation between regional metabolism and memory test scores was found in mesiotemporal structures during the performance of memory tasks. Metabolic or CBF studies also seem to indicate that memorizing strategies may differ among individuals. PET was repeatedly used to investigate metabolic and/or blood flow abnormalities in patients with various amnestic syndromes. In cases with uni- or bilateral lesions of mesiotemporal structures, caused by surgery, herpes simplex encephalitis, or permanent ischemic, anoxic, or toxic damage, disturbances of metabolism and blood flow typically extended far beyond the morphological defects detected by computed tomography or magnetic resonance. In acute transient global amnesia, CBF and metabolism were decreased bilaterally in the mesiotemporal lobes, where hypometabolism persisted for some time, while higher values were observed in thalamus and some cortical areas. Diencephalic lesions causing Korsakoff's syndrome were associated with decreased rCMRGl in the hippocampal formation, upper brainstem, cingulate, and thalamus. Discrete thalamic infarcts caused amnesia and metabolic depression in the morphologically intact ipsilateral thalamus and in various projection areas of the infarcted nuclei. In ischemic forebrain lesions, amnestic deficits could be related to involvement of the anterior cingulate and of basal cholinergic nuclei. A large number of pathologies are diffusely spread out in the brain and affect partially or predominantly structures in memory processing. This holds true especially in the various dementias where memory disturbances are a consistent and often leading feature. Notably, Alzheimer's disease can be distinguished from other dementias by its characteristic pattern of metabolic dysfunction, with the most prominent changes occurring in parietotemporal and frontal association cortex whose residual metabolism is related to the severity of the disease. Therefore, activation studies using paradigms involving memory functions enhance that typical pattern. Only in the activated state is metabolism of mesiotemporal structures significantly correlated with the performance in memory tests. Other dementias also affect some of the distributed memory networks, with Huntington's disease suggesting a role of the striatum in memory processing.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Widespread functional effects of discrete thalamic infarction.

In order to investigate functional effects of various thalamic structures on metabolism in remote, morphologically intact cerebral regions, we used positron emission tomography of (18F)-2-fluoro-2-deoxy-D-glucose to study regional cerebral metabolic rates of glucose (rCMRGlu) in 11 patients with chronic unilateral or bilateral infarcts strictly confined to the thalamus. Patients were grouped according to computed tomographic scans showing anterior (three), medial (four), or posterior (four) lesions. Compared with a matched group of 11 healthy subjects (hemispheric CMRGlu 35.2 +/- 3.49 mumol/100 g per minute), glucose metabolism was significantly lower in the hemisphere ipsilateral to the infarction (31.2 +/- 2.97 mumol/100 g per minute). Patients with bilateral infarcts had lower hemispheric CMRGlu (29.9 +/- 2.74 mumol/100 g per minute) than those with unilateral lesions (32.2 +/- 2.97 mumol/100 g per minute). Depending on infarct location within the thalamus, there was differential depression of rCMRGlu, with the largest effects on frontal and occipital areas in medial infarctions. Except for ipsilateral thalamic deactivation, metabolic patterns with anterior thalamic infarcts were close to normal, while posterior infarcts mostly depressed rCMRGlu in the visual and in the inferior limbic cortex. Cerebellar metabolic rates were within normal limits in most cases. These patterns of regional cerebral deactivation may be related to categories of thalamic projections--intrathalamic, to limbic system and basal ganglia, diffuse to most cortical areas, and specific to defined neocortical areas. Even small brain lesions may have widespread functional sequelae, potentially demonstrable by positron emission tomography.

Adult

Quantification of baboon cortical S2 serotonin receptors in vivo with 3-N-(2'-F18)fluoroethylspiperone and positron emission tomography.

We used the ligand 3-N-(2'-F18)fluoroethylspiperone (FESP) and positron emission tomography (PET) to quantify in vivo serotonin S2 neuroreceptor density and affinity in the baboon frontal cortex. In the cortex, FESP binds specifically and exclusively to S2 receptors, and an equilibrium is reached when the rate of ligand-receptor association and dissociation become equal. Using multiple studies in the same baboon, an equilibrium (saturation) analysis approach provided a linear Hill plot with a slope of 1.02 (r2 = 0.988, P less than 0.0001), indicative of ligand binding to a single receptor class. Using serial PET scans, a dynamic approach was also used to quantify S2 receptors in the frontal cortex of the baboon, which provided an estimate of receptor density Bmax = 35.6 +/- 10.9 pmol/g. The rate constants corresponding to transport into and out of tissue were K1* = 0.2720 +/- 0.0299 mol/min.g and k2* = 0.0786 +/- 0.0315 min-1, respectively. The ligand-receptor dissociation constant was k4* = 0.0154 +/- 0.0109 min-1.

Animals

The neocortico to mesio-basal limbic propagation of focal epileptic activity during the spike-wave complex.

In order to localize epileptogenic electrophysiological sources, a multichannel MEG system was used in 3 patients with partial epilepsy during presurgical evaluation. MEG and EEG (including scalp, sphenoidal and intracranial foramen ovale electrodes) were recorded simultaneously during a period of intensive video-EEG monitoring in order to observe single spontaneous spikes. In addition to MRI, SPECT and PET investigations were performed. Electrical activity subsequent to the activity of the epileptic focus could be localized by the MEG after noise reduction using a temporal correlation technique. Simultaneous registration of the magnetic field and the electrical field showed that the source of the primary focal epileptic activity (first period during the total spike wave complex where a dipolar magnetic field pattern is found) is localized in neocortical lateral regions, whereas another focal epileptic activity in a later phase of propagation occurs in temporal mesial regions. In 1 patient (case 1) the primary focal epileptic activity was localized in the surrounding neocortical tissue of an angioma and the middle and inferior temporal gyrus. The second phase of propagation is localized in temporo-basal-mesial regions, including para- and hippocampal structures. The latest center of activity occurred in posterior parts of the gyrus cinguli. In 2 other patients, the primary focal epileptogenic activity was localized at the insula and also spread into temporal basal mesial regions. A multi-modal approach to research of focal epilepsy, combining metabolic, electrical potential, magnetoencephalographic and morphological data, recorded by non-invasive techniques, offers new perspectives for the detection of involved brain regions. The 3-D and time-resolved localization of focal epileptic activity, correlated with the individual anatomy of the human brain, may improve the determination of neuronal populations involved in the individual epileptogenic process, especially in the interaction between temporal or extratemporal neocortex and limbic system.

Adult

Estimation of local cerebral glucose utilization by positron emission tomography: comparison of [18F]2-fluoro-2-deoxy-D-glucose and [18F]2-fluoro-2-deoxy-D-mannose in patients with focal brain lesions.

A comparative PET study of [18F]2-fluoro-2-deoxy-D-glucose (FDG) and [18F]2-fluoro-2-deoxy-D-mannose (FDM) uptake was performed in 13 patients with focal brain lesions. Differences between FDG and FDM with respect to model rate constants, lumped constant, and estimated metabolic rate for glucose were determined on a regional basis. Across whole brain, the transport rate constant K1* was almost unchanged, whereas k2*, describing the transport back from tissue to plasma, was 6% higher, and the phosphorylation rate constant k3* was 9% lower for FDM compared to FDG. This implies a 20% lower lumped constant for FDM. No significant regional variability of this differential tracer behavior was observed in normal or in lesioned brain tissue. Thus, results from previous FDG studies, where the radiotracer was not 100% pure FDG but contained varying amounts of FDM, can easily be corrected by adjustment of the lumped constant employed in metabolic quantitation.

Adult

Complex sensory cross integration deficits in a case of corpus callosum agenesis with bilateral language representation: positron-emission-tomography and neuropsychological findings.

A 45-year-old right-handed patient with total callosal agenesis and absence of the anterior commissure was examined neuropsychologically and with magnetic resonance and positron emission tomography (PET with 18FDG) of the brain. PET results showed, in the resting state, a bilateral metabolic reduction in the hippocampal formation and a left hemispheric reduction in the amygdala, thalamus and in the occipital and temporoparietal junction areas of the cerebral cortex. Under speech activation hypermetabolic glucose activity was observed bilaterally in the region of the Wernicke area and within the left Broca area. Neuropsychologically, on the whole the patient behaved normally, the exceptions being an inability to associate olfactory stimuli with words, a clear left ear advantage in dichotic listening, and a similar high performance in recognizing verbal stimuli presented tachistoscopically to either hemisphere. From comparing the patient's behavior with that of other acallosals it appears that highly individual variants of cerebral organization and/or reorganization result from the lack of the brain's main commissural system and that the processing of sensory information deviates considerably especially in cases in whom the two main telencephalic commissures--corpus callosum and anterior commissure--are absent.

Brain

Positron emission tomography in Creutzfeldt-Jakob disease.

Regional cerebral glucose metabolism was studied in a 73-year-old woman with autopsy-confirmed Creutzfeldt-Jakob disease, using positron emission tomography of 2-(18F)fluorodeoxyglucose. Regional absolute values were analyzed in 14 partially overlapping slices. Clinically, the patient was in an advanced stage of disease when positron emission tomographic scans revealed severe, diffuse hypometabolism, and neuropathological findings showed diffuse spongiform changes throughout the brain, with neuronal cell loss being obvious only in the cerebellum. Computed tomography was unremarkable for age, whereas the positron emission tomographic results were in accordance with histological findings and the patient's clinical condition. This article suggests that positron emission tomography depicts neuronal dysfunction rather than neuronal cell loss.

Aged

Positron emission tomography findings relevant to neurosurgery for epilepsy.

Using the 2-[F-18]fluorodeoxyglucose method, 213 positron emission tomographic (PET) studies of local brain glucose metabolism (CMRglu) were performed in 124 patients with various forms of epilepsy. Interictal PET scans of primary epileptics typically showed some global metabolic depression and decreased functional activity of insular, basal and anterior temporal cortex. Epilepsia partialis continua Kozevnikov was characterized by hypo- or hyper-metabolism of perirolandic cortex. Tuberous sclerosis was distinguished by neocortical foci of significantly decreased glucose consumption. Even in the interictal resting state, with regard to sensitivity (greater than 90%) and accuracy of focus localization. PET was superior to other diagnostic methods in typical temporal lobe epilepsy. Averaging 23% below normal CMRglu, the majority of hypometabolic foci were found in mesial temporal structures. Improved distinction between the epileptogenic area and the surrounding tissue showing comparatively normal functional responsiveness, was achieved by psychophysical activation using emotional speech or continuous visual recognition during PET scanning. In patients who had undergone total cerebral hemispherectomy because of uncontrolled epilepsy, remarkable recruitment of association areas was observed on both motor and speech activation.

Blood Glucose

PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system.

PET studies of dopamine D2-receptor binding were performed in thirty patients with various disorders related to the dopaminergic system and in six healthy controls. Uptake of [18F]fluoroethylspiperone in caudate over three hours was analyzed in terms of several indices of receptor binding:caudate-to-cerebellum activity ratio, concentration of ligand as percentage of injected dose, caudate-to-blood radioactivity ratio, slope of tracer uptake curves, binding potential, kinetic constants of a three compartment model. In 14 patients brain glucose metabolism was also measured. Data on medicated patients demonstrate that the average values of most of the above parameters indicate the decreased number of available D2-receptors whereby, besides an age dependent decline, the caudate-to-cerebellum ratio affords the relatively best distinction among diagnostic groups. In individual cases, large variability among subjects permits only the classification of severe pathologies. Morphological damage and neuronal loss in the striatum may also cause abnormal low values both for the indices of receptor binding and for glucose consumption, thus providing a possible pathogenetic link between receptor dysfunction and impaired energy metabolism.

Adolescent

The quantitative analysis of D2-dopamine receptors in baboon striatum in vivo with 3-N-[2'-18F]fluoroethylspiperone using positron emission tomography.

We used the ligand 3-N-[2'-18F]fluoroethylspiperone (FESP), which binds to D2-dopamine receptors in the striatum, and positron emission tomography (PET) to quantify striatal D2-dopamine densities (Bmax) and binding kinetics in baboon brain in vivo. Sequential PET scans were obtained for 4 h post injection. Various similar models based on a nonlinear kinetic four-compartment model that takes into account the effect of ligand specific activity were used. We investigated the effect of exact model configuration on the reliability of Bmax and other kinetic transfer coefficients. We found that with the ligand FESP and dynamic PET studies, the estimated values of Bmax and other model parameters are sensitive to the choice of model configuration, ligand specific activity, and data analysis technique. The limitations of the reliability of parameter estimates in a complex kinetic model for receptor ligands were studied in simulation calculations. Results showed that the accuracy of estimated values of Bmax is affected by both the ligand binding properties and the injected dose of ligand. The estimated average value of kinetic model parameters was as follows: ligand-receptor dissociation constant k4 = 0.0080 min-1; the product of ligand-receptor association constant and fraction of ligand available to bind to specific receptors f2ka = 0.0052 (min nM)-1; and D2-dopamine receptor density Bmax = 37.5 pmol g-1.

Animals

Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography.

In a randomized double-blind placebo-controlled study of 27 patients with acute ischemic stroke, the effect on regional CMRglc (rCMRglc) of the calcium channel blocking agent nimodipine administered in addition to routine treatment was investigated. Following computed tomography-supported diagnosis of focal ischemia in the middle cerebral artery territory, positron emission tomography (PET) of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was performed, and the patients were entered into the study within 48 h after onset of symptoms, randomly receiving either nimodipine (2 mg/h constant i.v. infusion for 5 days, 120 mg/day orally for another 16 days) or carrier/placebo. FDG PET was repeated after completion of therapy. The clinical course was followed during the treatment period and for 6 months after the stroke, using the Mathew Score for early and the Barthel Index for late assessment. During that observation period, five patients died in the nimodipine group and four in the control group. Subsequently, the code was broken, and the clinical and PET data were analyzed in relation to treatment assignment, with the nimodipine group comprising 11 and the control group 12 eligible cases. The two groups were similar with respect to age and sex distribution, initial clinical deficit, and infarct size and location. While the infarct rCMRglc showed comparable slight increases over time in both groups, the metabolic changes in the other evaluated regions (contralateral infarct mirror region, ipsi- and contralateral cerebral gray matter, contra- and ipsilateral cerebellar hemispheres) differed significantly between treatment groups (side x region x treatment interaction p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Magnetic source localization in focal epilepsy. Multichannel magnetoencephalography correlated with magnetic resonance brain imaging.

Initial results of magnetic source localization by means of multichannel recording using a 10 or a 31 channel system are reported. Simultaneous magnetoencephalographic (MEG) and electroencephalographic (EEG) (scalp, sphenoidal and foramen oval) recording, as well as magnetic resonance imaging (MRI) with a fixed head position, permits the projection of brain structures and the source localized from MEG into a three-dimensional coordinate system. From 8 patients investigated it can be clearly seen that the method is of diagnostic relevance for patients with temporal lobe epilepsy. Results are demonstrated for 3 patients with interesting findings concerning the anatomical correlation with source localization. The findings indicate that MRI-correlated magnetic source localization by means of multichannel recordings provides important advantages in epilepsy research. (1) Increased precision permits noninvasive localization. Deeper sources in the temporal lobe are localized from MEG combined with scalp or minor invasive EEG. (2) Investigation time is considerably shortened. (3) Single events can be localized for supplementary presurgical information concerning the three-dimensional anatomical localization of focal epileptic activity in the brain.

Adult

Effect of nimodipine on glucose metabolism in the course of ischemic stroke.

We investigated the effect of the calcium channel-blocking agent nimodipine on regional cerebral metabolic rate of glucose in acute ischemic middle cerebral artery infarction diagnosed clinically and by computed tomography. Twenty-seven patients entered the study within 48 hours after onset of symptoms and randomly received either nimodipine (2 mg/hr constant intravenous infusion for 5 days, 120 mg/day orally for another 16 days) or placebo. Four of the 27 patients died within the first 3 weeks and could not be evaluated. Of the remaining 23 patients, 11 were assigned to the nimodipine group and 12 to a control group. We analyzed data from positron emission tomography, performed twice before and after completion of therapy, and clinical data from the treatment period and the next 6 months based on the Mathew Score for early assessment and the Barthel Index for late assessment. During the post-treatment period, two patients from the nimodipine group and three from the control group died. The evaluated patients were comparable for age and sex distribution, initial clinical deficit, and infarct size and localization. We found significant metabolic changes between both treatment groups for contralateral infarct mirror region, ipsilateral and contralateral cerebral gray matter, and contralateral and ipsilateral cerebellar hemispheres (side x region x treatment interaction p less than 0.025). The nimodipine group had bilaterally increased regional cerebral metabolic rate of glucose of morphologically intact cerebral (14.6% and 17.1%, respectively) and cerebellar structures (6.9% and 10%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain

Cerebral glucose metabolism in the course of subacute sclerosing panencephalitis.

Regional cerebral glucose metabolism was studied in a 15-year-old boy with subacute sclerosing panencephalitis before and after therapy with human interferon beta, using positron emission tomography of fluorine 18-2-fluoro-2-deoxyglucose. At first examination, metabolism was symmetrically decreased in the thalamus, cerebellum, and all cortical areas except prerolandic motor cortex, but increased in lentiform nucleus. A computed tomographic scan was normal. Six months later, bilateral focal necrosis centered in the previously hypermetabolic putamen was demonstrated by computed tomography and magnetic resonance imaging. The caudate nucleus and the superoposterior part of the putamen were spared, still showing increased metabolism. Corresponding with some clinical improvement, cortical glucose consumption rates had returned to a normal level.

Adolescent

Measurement of blood-brain hexose transport with dynamic PET: comparison of [18F]2-fluoro-2-deoxyglucose and [11C]O-methylglucose.

Blood-to-tissue transport of [18F]2-fluoro-2-deoxyglucose (FDG) and [11C]O-methylglucose (CMG) was compared by dynamic positron emission tomography in four patients with recent ischemic infarcts and in three patients with intracerebral tumors. Local blood volume, tracer transport from tissue to blood, and FDG phosphorylation rates were also determined. A regional analysis of parametric images showed a close correlation of FDG and CMG transport rate constants in pathological tissue. Transport rates of FDG and CMG showed correspondingly less asymmetric remote effects than FDG phosphorylation rates. Transport rate constants were consistently higher for FDG than for CMG in pathological and normal tissue, in accordance with the higher affinity of carrier enzymes to FDG. There was a significant correlation between fitted regional blood volume values and correspondence of average absolute values with both tracers. It is concluded that dynamic FDG PET for measurement of cerebral glucose metabolism is also useful to measure alterations of hexose transport and local blood volume in pathological tissue.

Aged