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Biomedical subjects

W D Heiss

Publications and source records attributed to W D Heiss.

At least 127 records · Page 7Linked to original sources

Early nitric oxide increase in depolarized tissue of cat focal cerebral ischaemia.

Tissue nitric oxide (NO) concentration was investigated in relation to ion-homeostasis disturbance in the cat model of focal cerebral ischaemia. An NO electrode, a Ca2+ microelectrode and a laser Doppler probe were applied to the cerebral cortex in the core and periphery of the middle cerebral artery. NO concentration increased by 25.1 +/- 6.3 nM at 5 min in severely ischaemic regions exhibiting anoxic depolarization (n = 5, p < 0.0005). This occurred with no reduction in extracellular Ca2+ concentration and before a massive Ca2+ influx into cells started several minutes later. The NO increase was abolished by NG-nitro-L-arginine treatment (n = 6, p < 0.05) and was absent in regions with no depolarization (n = 5, p < 0.0005). We conclude that the early increase in NO associated with depolarization is achieved by activation of constitutive NO synthase, possibly triggered by intracellular Ca2+ release.

Acute Disease↗

Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia.

In a double-blind, placebo-controlled trial in thirty patients with mild to moderate vascular dementia (VD) according to DSM-III-R criteria, the effects of the adenosine uptake blocker propentofylline (HWA 285) on regional cerebral glucose metabolism (rCMRGl) was studied using positron emission tomography of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). 25 subjects completed the 3-months study. Propentofylline significantly improved relative rCMRGl in the motor cortex, while relative rCMRGl in the placebo treated group worsened significantly. Neuropsychologically, visual information processing was improved in the propentofylline group and we observed a trend towards a slowing of the progression of cognitive deterioration in patients with VD. The results of the longitudinal analysis showed further that neuropsychological and metabolic changes are closely related. These findings justify a large-scale clinical trial to prove therapeutic efficacy.

Aged↗

Cerebral representation of one's own past: neural networks involved in autobiographical memory.

We studied the functional anatomy of affect-laden autobiographical memory in normal volunteers. Using H2 15O positron emission tomography (PET), we measured changes in relative regional cerebral blood flow (rCBF). Four rCBF measurements were obtained during three conditions: REST, i.e.,, subjects lay at rest (for control); IMPERSONAL, i.e., subjects listened to sentences containing episodic information taken from an autobiography of a person they did not know, but which had been presented to them before PET scanning (nonautobiographical episodic memory ecphory); and PERSONAL, i.e., subjects listened to sentences containing information taken from their own past (autobiographical episodic memory ecphory). Comparing IMPERSONAL with REST (nonautobiographical episodic memory ecphory) resulted in relative rCBF increases symmetrically in both temporal lobes including the temporal poles and medial and superior temporal gyri. The same loci, however, with a stronger lateralization to the right hemisphere were activated in the comparison PERSONAL to REST (autobiographical episodic memory ecphory). In addition, the right temporomesial, right dorsal prefrontal, right posterior cingulate areas, and the left cerebellum were activated. A comparison of PERSONAL and IMPERSONAL (autobiographical vs nonautobiographical episodic memory ecphory) demonstrated a preponderantly right hemispheric activation including primarily right temporomesial and temporolateral cortex, right posterior cingulate areas, right insula, and right prefrontal areas. The right temporomesial activation included hippocampus, parahippocampus, and amygdala. These results suggest that a right hemispheric network of temporal, together with posterior, cingulate, and prefrontal, areas is engaged in the ecphory of affect-laden autobiographical information.

Adult↗

[Varicella-zoster-virus myelitis without herpes. An important differential diagnosis of the radicular syndrome].

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman was admitted with a 14-day history of general malaise, subfebrile temperature, radicular dysaesthesias in the "riding breeches" area, severe pain in the lumbar region and progressive disorders of bladder and rectal emptying. Physical examination showed a conus-cauda syndrome. Differential diagnosis was between myelitis (inflammatory or infectious), space-occupying intraspinal mass or vascular lesion. INVESTIGATIONS: Cerebrospinal fluid contained 1700/3 cells and there was intrathecal antibody synthesis against varicella zoster virus (VZV) and positive VZV-DNA analysis in the polymerase chain reaction. Magnetic resonance imaging of the lumbar spine revealed an inflamed enlarged conal and epiconal area with small haemorrhagic spots. There was no evidence of an underlying immune-modulated disease. TREATMENT AND COURSE: With the diagnosis of varicella zoster myelitis with cutaneous changes having been established the clinical signs and symptoms regressed almost completely with aciclovir administration (10mg/kg intravenously for 14 days). CONCLUSION: VZV without cutaneous involvement should be considered in the differential diagnosis of the radicular pain syndrome. When clinical signs of beginning myelitis or encephalitis are present, immediate investigations and therapy are necessary.

Acyclovir↗

Visual versus auditory memory stimulation in patients with probable Alzheimer's disease. A PET study with 18 FDG.

Patients with probable Alzheimer's disease were either stimulated with a continuous visual recognition task (n = 18) or with a continuous auditory recognition task during PET measurement with 18 FDG. The PET scanner was a Siemens CTI, ECAT EXACT with 5 mm transaxial and 6 mm axial resolution. The global stimulation effects were nearly identical in both groups and increased of 4.17 +/- 8.14% in the auditory stimulated group and of 4.03 +/- 11.78% in the visual stimulated group. Beyond regional stimulation effects in both groups a common cerebellar stimulation effect was measured. It is concluded that the cerebellar stimulation effect reflects a modality independent cognitive process and that the only small enhancement of global glucose metabolism indicates disturbed stimuli processes and finally explained the patient's failure in memory tasks.

Aged↗

MRI-guided flumazenil- and FDG-PET in temporal lobe epilepsy.

In temporal lobe epilepsy (TLE) patients without lesions, major hippocampal sclerosis, or atrophy on magnetic resonance imaging (MRI), the localizing power of [11C]flumazenil (FMZ) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was compared using high-resolution positron emission tomography (PET) studies and individually coregistered MRI scans. Following complete clinical, neuropsychological, and electrophysiological evaluation, benzodiazepine receptor density was assessed using the FMZ equilibrium method. Thirty minutes later, interictal FDG-PET was performed under resting conditions. PET images were matched to three-dimensionally coregistered, T1-weighted MRI. Each temporal lobe (TL) was divided into 12 volumes of interest. The regional FMZ data were normalized with respect to average cortical values. For each patient the right-left asymmetries of rCMRGlc and normalized FMZ data were calculated. In 7 to 10 patients, mesial TL structures showed reduced FMZ binding, with a decrease by at least 10% in the affected TL. Reductions of 10% or more of rCMRGlc usually were more widespread than FMZ reductions and often involved lateral temporal cortex. The regions of most pronounced disturbances are not necessarily identical in both methods. Three patients had a complex correspondence of lateralization with PET, neuropsychological, and EEG data. In 4 patients, lateralization was less clear from EEG or neuropsychological results but was still consistent with lateralization by PET. In 3 of 10 patients, however, major discrepancies were found. These data suggest that the combination of neuropsychological testing, EEG, and MRI-guided FMZ- and FDG-PET will help to select patients with clearly defined epileptogenic foci especially in mesial TLE. Even in cases without MRI lesions, TL epileptic foci can be lateralized with consistency across the methods; FMZ-PET shows the pathologic focus more circumscribed than FDG-PET.

Adult↗

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.

Acoustic Stimulation↗

Vascular dementia: perfusional and metabolic disturbances and effects of therapy.

Positron emission tomography (PET) has elucidated basic pathophysiological mechanism that produce the cognitive decline in vascular dementia (VD). The typical pattern of glucose metabolism seen in VD with scattered areas of focal cortical and subcortical hypometabolism differs from that in AD with marked hypometabolism affecting the association areas. The total volume of metabolically inactive tissue is significantly related to severity of dementia. Rather than the quantity of tissue destruction, the critical effect may be the quantity of cortical hypometabolism caused by subcortically induced disconnection. Studies with HMPAO SPECT have shown focal deficits in VD and AD patients that are comparable to those seen with FDG PET. In mildly demented patients performance for the classification AD versus VD is much better by PET because it might be more sensitive for imaging small functional pathological changes. A longitudinal analysis of rCMRGl in VD showed that the progression of dementia can be delayed by the adenosine uptake blocker propentofylline and that neuropsychological and metabolic changes are closely related.

Brain↗

Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy.

We investigated whether 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) and carbon-11 methionine are suitable tracers to monitor the effects of therapy for low-grade gliomas. Ten patients with low-grade glioma without previous treatment were studied with FDG positron emission tomography. Additionally, l-[methyl-11C]methionine uptake was measured in five subjects before and 1 year after computerized tomography (CT)-guided stereotactic and computer-assisted implantation of iodine-125 seeds. All scans were 3D-matched to CT, isodose volumes were determined, and changes in glucose metabolism and methionine uptake were evaluated in tumour and brain tissue as a function of radiation dose. After 1 year glucose metabolism was not significantly altered up to a radiation dose of 300 Gy, whereas methionine uptake showed a significant dose-dependent decrease. Higher rates of decline were found in tumours with high basal methionine incorporation activity before therapy. These data suggest that measurement of methionine uptake is more suitable than measurement of FDG uptake for monitoring therapeutic effects in low-grade gliomas.

Adult↗

Diaschisis of specific cerebellar lobules: pontine haematoma studied with high-resolution PET and MRI.

Cerebellar glucose metabolism was studied in one patient with a hemipontine haematoma in order to investigate remote metabolic effects within the cerebellar lobules. In the patient, who suffered a circumscribed hemipontine haemorrhage, and in three normal subjects cerebellar glucose metabolisms was studied using 18F-2-fluoro-2-deoxy-D-glucose and high-resolution positron emission tomography (PET). Regions of interest were placed on sagittal brain slices of co-registered magnetic resonance images for quantitative evaluation of glucose metabolism in each cerebellar lobule. Interruption of corticopontine fibres caused inactivation of pontine nuclei with subsequent contralateral cerebellar diaschisis, mainly in the anterior lobe and the posterior portion of the quadrangular lobule. Damage within the ponto-cerebellar part of the cortico-ponto-cerebellar pathway, e.g. pontine nuclei and crossing ponto-cerebellar fibres from contralateral pontine nuclei, led to ipsi- and contralateral cerebellar diaschisis within the semilunar, gracile and biventral lobules. High-resolution PET is capable of demonstrating bilateral diaschisis involving specific cerebellar lobules to a different degree that is consistent with the pontine anatomy of the cortico-ponto-cerebellar pathway and with the location of the haemorrhagic lesion.

Adult↗

Regional cerebral glucose metabolism and postmortem pathology in Alzheimer's disease.

In four patients with an antemortem diagnosis of probable Alzheimer's disease (AD) regional cerebral glucose metabolism (rCMRGl) was studied prospectively by positron emission tomography (PET) and compared with postmortem semiquantitative neuropathology. The interval between the last PET study and autopsy was 1.3 +/- 0.8 years. In comparison with age-matched controls, the AD patients showed predominant temporoparietal hypometabolism spreading to other cortical and subcortical regions during serial PET scans. All patients had neuropathological findings typical for AD. There was a significant relationship between rCMRGl and density of senile plaques (SP) in one patient (tau b = -0.86, P < 0.05). SP were distributed quite homogeneously in all regions examined. Neurofibrillary tangles (NFT) were concentrated focally in the hippocampus-amygdala-entorhinal complex. In the context of widespread developing cortical hypometabolism, the predilection of NFT for involvement in limbic areas suggests a disruption of projection neurons as the pathogenetic process of cortical dysfunction.

Aged↗

Temporal lobe epilepsy: evidence for interictal uncoupling of blood flow and glucose metabolism in temporomesial structures.

Measurements of regional cerebral glucose metabolism (rCMRGlc) and blood flow (rCBF) are widely considered exchangeable for the detection of dysfunctional zones in temporal lobe epilepsy (TLE). However, the underlying assumption of preserved coupling of rCBF and rcMRGlc is questionable and requires verification. Thirteen patients with unilateral mesiolimbic TLE underwent interictal positron emission tomography (PET) measurements of rCBF using [15(O)]butanol and of rcMRGlc using (18)FDG. rcMRGlc, rCBF and glucose extraction fraction (rGEF) were obtained from temporomesial and temporolateral structures. When compared to the respective homotopic contralateral reference region, in temporomesial structures ipsilateral to the EEG-defined focus ('dysfunctional zone'), average rCMRGlc and rGEF were decreased while rCBF was unaffected. Analysis of (18)FDG kinetics revealed that (18)FDG transport was unaltered but the hexokinase reaction was specifically decreased. In the temporolateral structures, no such mismatch between metabolism and blood flow was observed. In mesiolimbic TLE, interictal rCMRGlc-PET is superior to rCBF-PET with respect to the sensitivity to detect regional functional abnormalities. This seems to be due to focal uncoupling of glucose metabolism and blood-brain barrier transport or blood flow. We hypothesize that the observed uncoupling of transport and metabolism may be characteristic of epileptogenic zones in TLE of typical etiology.

Adult↗

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.

Brain↗

Sleep apnoea in treated acromegaly: relative frequency and predisposing factors.

OBJECTIVES: Sleep apnoea is common in active acromegaly. It is associated with increased morbidity and mortality but can be treated effectively. The objective of this study was to determine the largely unknown relative frequency of, and the predictive factors for, sleep apnoea in treated acromegalic patients. DESIGN: Retrospective cohort study. SETTING: Tertiary referral hospital. PATIENTS: Fifty-four of 100 patients with treated acromegaly. If sleep apnoea had been diagnosed before acromegaly, the patient was excluded. MEASUREMENTS: Sleep studies (using the MESAM-4 device measuring oxyhaemoglobin saturation, heart rate, snoring sounds and body position to determine presence and severity of sleep apnoea); GH and IGF-I levels; body mass index, neck and index-finger circumference; daytime symptoms of sleep apnoea, duration of acromegaly before treatment, shoe and neck-size difference since beginning of acromegaly; age, sex and treatment modes of acromegaly. RESULTS: The relative frequency of sleep apnoea was 39% in the 54 patients with sleep studies and at least 21% in the entire study population of 100 patients. In patients with sleep apnoea, statistically significant higher values were observed for GH (P = 0.002), IGF-I (P = 0.029), age (P = 0.014) and neck circumference (P = 0.016). An index-finger circumference of > or = 8.5 cm was associated with a significantly higher desaturation index (P = 0.012, Mann-Whitney U-test). Adenomectomy had been performed significantly less frequently in patients with sleep apnoea (P < 0.001, X2 test). The body mass index was non-significantly higher in the patients with sleep apnoea. CONCLUSIONS: The relative frequency of sleep apnoea in patients with treated acromegaly is at least 21%. Parameters of predictive value for the presence of sleep apnoea in this population are neck and index-finger circumference as measures of soft tissue hypertrophy, age, GH and IGF-I levels, and whether or not operative therapy was applied.

Acromegaly↗

Acute ischemic stroke.

While case fatality rates in ischemic stroke tend to decline, the total number of strokes is expected to increase further in the future because of more people reaching a greater age. Acute ischemic stroke, usually caused by chronic arterial hypertension, in most cases is induced either by a sudden loss of perfusion pressure or by thromboembolism. Reduction of oxygen supply to brain tissue then leads to a cascade of biochemical reactions. Cell death finally occurs after massive Ca2+ influx into the cell and breakdown of the membranes. A rim of viable tissue called the penumbra often exists around a central necrotic core within the ischemic region. The tissue compartment may be brought back to function if perfusion is restored within a short time. Since some cytotoxic reactions within ischemic tissue are irreversible, current efforts in stroke therapy focus on measures to decrease cellular vulnerability. Restoring perfusion remains the first important therapeutic goal. A variety of compounds have been tested for cytoprotection, but none can yet be recommended for routine clinical use. General management of stroke patients in every case should be implemented for emergency assessment, since the first few hours after onset are crucial for the outcome.

Combined Modality Therapy↗

Prolonged transient ischemia results in impaired CBF recovery and secondary glutamate accumulation in cats.

Effects of prolonged focal ischemia [middle cerebral artery occlusion (MCAO)] of 1, 2, and 4 h followed by 15-h reperfusion on CBF, extracellular amino acids, purine catabolites, evoked potentials, and infarction were studied in core (A:auditory cortex) and border zone (SF: somatosensory cortex) areas of halothane-anesthetized cats. Following MCAO, CBF reduction was severe in A (<15 ml 100 g-1 min-1) and mild to moderate in SF. Prominent elevation of glutamate and abolition of evoked potentials in A contrasted with milder and more variable disturbances in SF. After reperfusion, recovery of CBF, glutamate, and evoked potentials was fast and persistent in the 1- and 2-h groups. In the 4-h group, immediate recovery of CBF, glutamate, and evoked potentials was incomplete, and secondary deterioration of all parameters was obtained at the end of the experiments. Infarction in the 4-h group was significantly larger than in the 1- and 2-h groups. Persistent recovery of extracellular glutamate concentration and electrical function and salvage of neuronal tissue from infarction therefore seem to depend on successful restoration of CBF, which in turn depends on the magnitude and the duration of CBF reduction and of exposure to potentially harmful substances such as glutamate during the ischemic attack.

Amino Acids↗

Heterogeneity of cerebral hemodynamics and metabolism in carotid artery disease.

METHODS: Eight patients with severe unilateral carotid stenosis (> 70%) were evaluated using PET to assess parametric changes in cerebral blood flow, blood volume, metabolic rate for oxygen, metabolic rate for glucose, oxygen extraction fraction and glucose extraction fraction. We performed these examinations because clinical history and physical exam results suggested possible cerebral vascular disease. Four patients were neurologically asymptomatic with other signs of peripheral vascular disease (e.g., episodic vertigo, TIA and claudication). All patients had normal neurologic examinations and normal CT or MRI studies. PET images were analyzed by two methods. First, regions of interest were used for the entire hemisphere, vascular territories and borderzones. Regions ipsilateral to the carotid stenosis were compared to respective regions in the contralateral hemisphere using Student's t-test. Second, visual inspection of each image was performed. RESULTS: Statistical analysis demonstrated no significant differences between hemodynamic and metabolic parameters for regions ipsilateral to the carotid stenosis and contralateral homotopic reference regions. Upon visual examination, however, all patients had focal changes in either cerebral blood flow, blood volume, glucose extraction fraction and/or oxygen extraction fraction. CONCLUSION: Visual inspection is important in the evaluation of pathophysiological changes caused by unilateral carotid stenosis. Clinical decisions in patients with carotid artery disease should be based on careful visual examinations and statistical analyses of appropriately selected regions.

Brain↗