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Biomedical subjects

W D Heiss

Publications and source records attributed to W D Heiss.

At least 91 records · Page 5Linked to original sources
PubMed1998

Propentofylline enhances cerebral metabolic response to auditory memory stimulation in Alzheimer's disease.

To evaluate efficacy, safety, metabolic and clinical effects of propentofylline in Alzheimer's disease (AD), a prospective, randomized, double-blind, placebo-controlled trial was performed in 30 patients with mild to moderate AD who underwent pretreatment and posttreatment 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography under resting conditions and during stimulation with an auditory memory paradigm. Twenty-eight subjects completed the 3-month study. The drug was well tolerated. In the active treatment group, a significant increase of cerebral metabolic response to the memory task was observed (multiple measurement ANOVA P = 0.02). The placebo group showed a significantly decline in the MMSE score (P = 0.02) while there was no change in the treatment group. This suggests a protective role for propentofylline in slowing the progression of AD.

Acoustic Stimulation↗
PubMed1998

Early intravenous thrombolysis with recombinant tissue-type plasminogen activator in vertebrobasilar ischemic stroke.

BACKGROUND: The optimal therapy of vertebrobasilar ischemic stroke is under debate. In the case of underlying basilar artery occlusion, intra-arterial thrombolysis is recommended. Because this pathologic condition is rarely found and the procedure is time consuming and restricted to specialized centers, the question arises whether early intravenous thrombolysis could also effectively be applied in vertebrobasilar ischemic stroke. OBJECTIVE: To determine if early intravenous thrombolysis could be used effectively in vertebrobasilar ischemic stroke. DESIGN: A case series of 12 consecutive patients with acute vertebrobasilar ischemia were followed up 3 months after thrombolytic treatment at the Department of Neurology of the University Hospital of Cologne, Cologne, Germany, a primary care and referral center. METHODS: Patients with clinically diagnosed moderate to severe vertebrobasilar ischemic stroke with clearly determined symptom onset were treated with intravenous recombinant tissue-type plasminogen activator within 3 hours after symptom onset following a protocol similar to that of the National Institute of Neurological Disorders and Stroke study. RESULTS: On admission, 7 patients exhibited moderate to severe brainstem symptoms without impairment of consciousness and 5 patients had impairment of consciousness, of whom 2 were comatose. Of 12 patients, 10 had a favorable outcome after 3 months defined as full independence (Barthel index score of 100) or return to premorbid condition. One patient had a poor outcome with complete dependency due to reocclusion after primarily successful thrombolysis, and 1 patient died of severe brainstem infarction and additional space occupying parietal hemorrhage. CONCLUSION: Favorable outcome could be achieved in the majority of 12 consecutive patients with moderate to severe vertebrobasilar ischemic stroke treated with intravenous recombinant tissue-type plasminogen activator within 3 hours after symptom onset.

Acute Disease↗
PubMed1998

Early-onset cerebellar ataxia (EOCA) with retained reflexes: reduced cerebellar benzodiazepine-receptor binding, progressive metabolic and cognitive impairment.

A family with two members who had early-onset cerebellar ataxia (EOCA) with retained tendon reflexes had, in addition to their motor deficits, a progressive impairment of cognitive and visuospatial abilities. We used positron emission tomography (PET) with 11C-flumazenil to study gamma-aminobutyric type A/benzodiazepine receptor binding (BZR) and 18F-2-fluoro-2-deoxy-D-glucose to analyze longitudinally regional cerebral glucose metabolism. Flumazenil-PET demonstrated loss of BZR binding that has not been shown in Friedreich's ataxia and olivopontocerebellar atrophy. These findings may be useful for differentiation of EOCA from other types of cerebellar ataxia. In comparison to age-matched control subjects, these patients showed a global metabolic decline and predominant hypometabolism in the thalamus and cerebellum. The progressive metabolic derangement may be explainable by a disturbed integrity of cognition-related networks resulting from secondary degeneration of cerebello-thalamo-cortical projections.

Adult↗
PubMed1998

Brain plasticity in poststroke aphasia: what is the contribution of the right hemisphere?

The brain may use two strategies to recover from poststroke aphasia: the structural repair of primarily speech-relevant regions or the activation of compensatory areas. We studied the cortical metabolic recovery in aphasic stroke patients with positron emission tomography (PET) at rest and during word repetition. The left supplementary motor area (SMA) showed the most prominent compensatory activation in the subacute state of stroke. The restitution of the left superior temporal cortex determined the long-term prognosis of aphasia. The brain recruited right-hemispheric regions for speech processing, when the left-hemispheric centers were permanently impaired. This strategy, however, was significantly less effective than the repair of the original speech-relevant network.

Adult↗
PubMed1998

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.

Adult↗
PubMed1998

Positron emission tomography for diagnosis of Alzheimer's disease and vascular dementia.

In mild or atypical cases of Alzheimer's disease (AD) the differential diagnosis to other dementing diseases, such as vascular dementia (VD), may pose a difficult problem. Beside computed tomography (CT) and magnetic resonance imaging (MRI), functional neuroimaging by positron emission tomography (PET) support the clinical diagnosis by visualizing cerebral function. PET of 18F-2-fluoro-2-deoxy-D-glucose (FDG) for measurement of regional cerebral glucose metabolism (rCMRGl) has shown a typical metabolic pattern in patients with probable AD: hypometabolism in temporoparietal and frontal association areas, but relative recessing of primary cortical areas, basal ganglia and cerebellum. In VD a different pattern is seen. It consists of scattered areas with reduction of rCMRGl typically extending over cortical and subcortical structures. Severity of dementia is correlated with rCMRGl reduction in the temporoparietal association cortex, irrespective of the cause of dementia. Also the total volume of hypometabolic regions is related to severity of dementia but did not differ between AD and VD, even in patients with small lacunar infarction. This indicates that the total volume of functional tissue loss is more important since it also includes the effects of incompletely infarcted tissue and morphologically intact but deafferented cortex. The characteristic metabolic pattern has a high diagnostic accuracy for the discrimination between probable AD, normals and VD, even in patients with mild cognitive impairment. Under clinical and therapeutic aspects the analysis of longitudinal changes of rCMRGl has shown that neuropsychological and metabolic changes are closely related in both, AD and VD.

Aged↗
PubMed1998

[Mixed tumors of the pineal area. Diagnosis and therapy consisting of secreting germ cell tumor].

Primary intracranial germ cell tumors are rare neurological diseases. Secreting germ cell tumors that predominantly appear in the pineal region are characterized by elevated levels of beta-HCG and AFP in CSF. Adequate diagnostic and therapeutic regimens of these tumors are still under debate. We present the case of a patient suffering from spinal metastasis of a secreting germ cell tumor with raised levels of beta-HCG in CSF. Six years before, a pineocytoma of intermediate differentiation had been diagnosed by stereotaxic biopsy. This demonstrates the importance of an early detection of a germ cell neoplasm in case of midline-sized brain-tumors by evaluation of beta-HCG and AFP in CSF and serum. Today, different therapeutic strategies depending on the histological diagnosis are available and justify a high priority of a surgical tumor biopsy. However, the value of stereotaxic procedures remains controversial. Recently published data gave evidence of a definite improved prognosis of secreting CNS germ cell tumors following combined treatment with high-dose polychemotherapy, surgical resection and radiation of the tumor area. beta-HCG and AFP may serve as useful markers to enable follow-up of the disease.

Adult↗
PubMed1998

[Clinical value of positron emission tomography in neuromedicine. Position paper on results of an interdisciplinary consensus conference].

To date, positron emission tomography (PET) is the most powerful method for the in-vivo investigation of human brain metabolism. Besides extensive application of this technology in the neurosciences, PET is also being increasingly used as a clinical tool. However, despite its acceptance in clinical practice a major obstacle is its high costs. The present article reviews the literature on the clinical use of PET in neurology, neurosurgery, and psychiatry in order to substantiate the clinical indications for PET in these specialties as established by an interdisciplinary conference.

Brain Diseases↗
PubMed1998

Normal and pathological aging--findings of positron-emission-tomography.

Normal aging of the brain is predominantly characterized by metabolic changes in the prefrontal cortex. While in middle age there is a trend to hyperfrontality, PET demonstrates in old age a decline of regional cerebral glucose metabolism in frontal areas. In progeric diseases, clinically apparent as premature aging, the metabolic pattern is similar like in normal aging but qualitatively more severe. In patients with the diagnosis of probable Alzheimer's disease (AD) hypometabolism in early dementia is typically present in heteromodal association areas. Hypometabolism then spreads to other cortical and subcortical regions suggesting a characteristic pattern of degeneration that reflects selective vulnerability within limbic-cortical networks. Synaptic plasticity, clinically apparent as cognitive reserve capacity, can be assessed by PET under specific cognitive activation. In AD it is reduced in comparison to age-matched normals and may be influenced by drugs giving trophic support to neurochemical systems.

Aging↗
PubMed1998

Psychic trauma causing grossly reduced brain metabolism and cognitive deterioration.

While amnesia and other cognitive disturbances are usually caused by structural brain damage, there are a few instances in which environmental stress may induce neuronal death in memory-sensitive brain regions such as the hippocampus. Here we report on a patient who, after a single brief exposure to an event reminding him of a similar stressful event from his childhood, deteriorated immediately and persistently without manifesting structural, but manifesting functional, brain damage as measured by position emission tomography. This patient probably represents the first case in which a direct relation between a single psychic event and the occurrence of brain malfunctioning in cognition is documented by dynamic neuroimaging methods. Psychic shock may cause lasting reductions in brain metabolism with the consequence of severe intellectual malfunctioning.

Adult↗
PubMed1998

Collateral inhibition of transcallosal activity facilitates functional brain asymmetry.

The corpus callosum is the largest connection between the functionally asymmetric cerebral hemispheres. The objective of this study was to measure functional activity of callosal fiber tracts during speech processing. We analyzed the regional glucose metabolism of the corpus callosum and of speech-relevant cortical areas in 10 normal individuals at rest and during word repetition. We used three-dimensionally registered magnetic resonance imaging to visualize the individual brain morphology and high-resolution positron emission tomography for metabolic measurements. The task-induced metabolic changes of the callosal midbody and isthmus had a significant negative correlation with key regions of language processing in the left inferior frontal cortex (Brodmann's area 44) and in the right superior temporal cortex (Brodmann's area 22) (e.g., correlation of metabolic changes in the surface aspects of the right Brodmann's area 22 and the callosal midbody/isthmus: r = -0.91, P < 0.001). The study indicates that language processing in asymmetrically organized cortical areas inhibits the reciprocal transcallosal information exchange in favor of the lateralized mental operation. Our data agree with anatomic, electrophysiologic, and pharmacologic experiments that point to the important role of collateral inhibition for the transcallosal information exchange.

Adult↗
PubMed1998

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.

Acute Disease↗
PubMed1998

Quantitative neuroimaging for the evaluation of the effect of stroke treatment.

A prerequisite for the successful treatment of acute ischaemic stroke is the existence of viable tissue that is morphologically intact but functionally impaired due to a flow decrease below a certain threshold. At this stage, tissue at risk of infarction can be identified only by functional imaging. This penumbral tissue can be classified as having a critical flow decrease with preservation of oxygen consumption and therefore increased oxygen extraction. Such 'misery-perfused' tissue has been observed consistently in the first few hours following ischaemic stroke but usually develops into necrosed tissue at follow-up observations. Several studies have indicated that penumbral tissue can be identified up to 17 h or even 48 h after stroke in the border zones of ischaemic tissue and that this condition is occasionally reversible without resulting in permanent infarction. Positron emission tomography studies of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and cerebral metabolic rate of glucose (CMRglc) can be used to demonstrate the effect of treatment on functional variables within tissue showing perfusional disturbances. Such studies have shown the value of these markers of ischaemia, which also correlate with clinical efficacy. However, when therapeutic strategies, such as thrombolysis, do not permit arterial blood sampling, quantitative determinations of CBF and CMRO2 are not feasible. In such cases relative indices, such as those for CBF, must be applied. Such qualitative assessments of perfusion, which were calibrated in an independent cohort of patients with acute stroke, were used to demonstrate the effect of early systemic treatment of acute ischaemia with recombinant tissue plasminogen activator. By applying operationally defined thresholds for tissue viability and the penumbra, and co-registering these tissue compartments to infarcted and non-infarcted tissue on late magnetic resonance imaging, the proportions of at-risk tissue salvaged from infarction could be revealed in individual patients. In the future, functional imaging modalities that could eventually include tracers for neuronal integrity could be used to select patients for thrombolytic therapy. In some instances such techniques may permit the extension of the critical time period for inclusion of patients to aggressive stroke management strategies.

Animals↗
PubMed1998

Permanent cortical damage detected by flumazenil positron emission tomography in acute stroke.

BACKGROUND AND PURPOSE: Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since gamma-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [11C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. METHODS: In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. RESULTS: In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO2 (<60 micromol/100 g per minute) corresponded to regions with decreased FMZ binding (<4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. CONCLUSIONS: These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies.

Aged↗
PubMed1998

Alterations of neuropsychological function and cerebral glucose metabolism after cardiac surgery are not related only to intraoperative microembolic events.

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) during cardiac surgery are capable of causing encephalopathy and cognitive deficits. This study was undertaken to determine whether intraoperative HITS cause alterations of neuropsychological function (NPF) and/or cerebral glucose metabolism (CMRGlc), even in a low-risk patient group, and whether induced changes are interrelated. METHODS: Eighteen patients without signs of cerebrovascular disease underwent elective coronary artery bypass grafting (CABG), and two of these additionally underwent valve replacement in normothermia. Intraoperatively, HITS were recorded by means of transcranial Doppler ultrasonography (TCD). Perioperatively, NPF and CMRGlc were assessed using a standardized complex test battery and positron emission tomography with 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET), respectively. RESULTS: Intraoperatively, the number of HITS ranged from 90 to 1710 per patient and hemisphere, more on the right side than on the left (P<.05). HITS occurred primarily during cardiopulmonary bypass (71.3%) and, to a lesser extent, during aortic manipulation (22.2%). Changes in global and regional CMRGlc between first (one day preoperatively) and second (8 to 12 days postoperatively) FDG-PET scans were mild. No correlations were found between the number of HITS, age of patient, duration of cardiac ischemia or cardiopulmonary bypass and the changes in CMRGlc. In patients with recorded HITS and a postoperative decrease of regional CMRGlc (n=11), the maximal decrease of rCMR Glc in each hemisphere below the individual global change of CMRGlc correlated with the number of HITS (r= -0.46, P<.05). Limitations in NPF occurred 8 to 12 days postoperatively, resolved within 3 months, and were not found to be correlated to the absolute number of HITS or changes in CMRGlc. CONCLUSIONS: HITS during cardiac surgery can cause alterations of both NPF and CMRGlc, even in a low-risk patient group. However, the number of HITS and changes in NPF and CMRGlc are not necessarily interrelated, which indicates that (1) the location of brain damage related to HITS is more important for the development of NPF than is the absolute number of HITS, and (2) factors in addition to HITS might contribute to surgery-related brain damage.

Adult↗
PubMed1998

Early intravenous thrombolysis for acute ischemic stroke in a community-based approach.

BACKGROUND AND PURPOSE: Controlled multicenter studies have demonstrated the efficacy of systemic recombinant tissue-type plasminogen activator (rtPA) treatment in selected cases of acute ischemic stroke. The feasibility of this therapeutic option in clinical practice was assessed in a community-based approach. METHODS: We offered rtPA treatment to stroke patients in a prospective open-label monocenter study applying inclusion criteria similar to those of the National Institute of Neurological Disorders, and Stroke study. In order to treat patients within 3 hours of symptom onset, a referral system was used by which eligible patients from all over the city of Cologne, Federal Republic of Germany, were rushed to the Department of Neurology of the University Hospital. We present data on the effectiveness of the referral system and the outcome results of the first 100 consecutive patients treated within an 18-month period. RESULTS: Of 453 consecutive patients with a presumed diagnosis of acute stroke referred to our department between March 1996 and August 1997, 100 patients (22%) were treated with intravenous thrombolysis, 26% of them within 90 minutes of symptom onset. The average time from stroke onset to arrival at our department was 78 minutes, and from arrival to treatment 48 minutes. After 3 months, 53 patients recovered to fully independent function. The rates of total, symptomatic, and fatal intracerebral hemorrhage were 11%, 5%, and 1%, respectively. Overall mortality was 12%. CONCLUSIONS: Thrombolysis with rtPA was effectively applied in routine management of stroke patients in a community-based approach with acceptable efforts and without additional costs. Under these circumstances, outcome and complication rates were comparable to those of multicenter trials.

Academic Medical Centers↗
PubMed1998

11C-methionine PET for differential diagnosis of low-grade gliomas.

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Adult↗