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R Mielke

Publications and source records attributed to R Mielke.

At least 19 recordsLinked to original sources
PubMed2002

[Early diagnosis and treatment of Alzheimer's disease. Implementation in the doctor's office].

The efficacy of antidemential agents proven in comprehensive studies and by clinical experience, now justifies an active and positive approach by the general physician to the diagnosis and treatment of patients with dementia. The proposals on how to implement diagnostic and therapeutic measures in the doctor's office comply both with medical quality criteria and the requirements for appropriateness of treatment and considerations of economy stipulated by German law. They therefore provide the basis for a modern diagnostic work-up and treatment strategy, which will also meet economical demands.

Aged↗
PubMed2002

Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET.

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.

Aged↗
PubMed2002

Prognostic relevance of quantitative topographical EEG in patients with poststroke aphasia.

In this prospective study we analyzed the prognostic value of topographical quantitative EEG (qEEG) in poststroke aphasia. Twenty-three right-handed patients (ages 56 +/- 12 years) with different types of aphasia were studied. Quantitative EEG under resting conditions and an aphasia test battery were applied twice, 2 and 8 weeks after a stroke. EEG power fast Fourier transform was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz), and beta (13.5-20 Hz) frequency bands. EEG abnormalities within and outside speech relevant areas are related to restitution of poststroke aphasia. In the ischemic regions they indicate local disturbances; outside they reflect failures in neuronal networks involved in the generation and propagation of the alpha rhythm.

Adult↗
PubMed2002

Impaired benzodiazepine receptor binding in peri-lesional cortex of patients with symptomatic epilepsies studied by [(11)C]-flumazenil PET.

Individual benzodiazepine receptor (BZR) binding of peri-lesional cortex was investigated in symptomatic epilepsies. Eleven patients aged 19-44 years were studied whose diagnosis was established by medical history, clinical, electroencephalographic, and magnetic resonance imaging (MRI) findings. Three-dimensional [11C]-flumazenil (FMZ) positron emission tomography and MRI scans were obtained and coregistered. Lesions (five low-grade brain tumours, one AV malformation, one cavernoma, one cystic lesion of unknown aetiology, one traumatic brain injury, one post-operative and one post-haemorrhagic defect) were outlined on individual MRI scans. Adjacent to those lesions, and in homologous contralateral structures, FMZ binding was analysed in four pairs of cortical 9 x 9-mm regions of interest (ROIs) placed on transaxial and coronal slices, respectively, as well as in the lesion volume and its mirror region. Percentage asymmetry ratios were calculated and those at or outside the 90-110% range were operationally defined significant. Peri-lesional FMZ binding asymmetries ranged from 70 to 125%, lesional asymmetries from 38 to 82%. Only one patient showed no significant change, whilst nine exhibited significant reductions of FMZ binding in at least one ROI (3 x 1, 4 x 2, 1 x 3, 1 x 4), and significant increases were observed in two ROIs of another patient. Therefore, peri-lesional disturbances of BZR binding are common but variable in location. Because a close correlation between regional decreases in FMZ binding and spiking activity was recently demonstrated in neocortical epilepsies, abnormal peri-lesional FMZ binding may bear some relation to the mechanisms of epileptogenesis in symptomatic epilepsies.

Adult↗
PubMed2001

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Aged↗
PubMed2001

Relation between 1H MR spectroscopic imaging and regional cerebral glucose metabolism in Alzheimer's disease.

1 H Magnetic resonance spectroscopic imaging (MRSI) and positron emission tomography (PET) of (18) F-2-fluoro-2-deoxy-D-glucose (FDG) were performed in 18 patients with probable Alzheimer's disease (AD) and 3 normal controls. We measured the distribution and relative signal intensities of N-acetyl aspartate (NAA; a presumed neuronal marker), choline residues (Cho) representing cellular membrane compounds and of creatine-containing metabolites (Cr), and correlated these to regional cerebral glucose metabolism (rCMRGI) after coregistration of both imaging-techniques. The pattern of choline was significantly different between AD and normals (p < 0.01). RCMRGI was significantly related to Cho/Cr (r=-0.21, p<.05) and NAA/Cho quotients (r=0.35, p<.001). Our results suggest that in AD reduced neuronal energy performance and membrane abnormalities contribute to metabolic deterioration.

Adult↗
PubMed2001

Restitution of alpha-topography by piracetam in post-stroke aphasia.

OBJECTIVE: Electroencephalographic and clinical effects of piracetam in post-stroke aphasia were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. METHODS: In 24 patients with mild to moderate aphasia after ischemic stroke, quantitative topographic EEG at rest was studied before and after a 6-week treatment period. RESULTS: In the active treatment group, a significant shift in the alpha-rhythm from frontal to occipital regions was observed which may be due to a restitution of corticothalamic circuits involved in the generation of alpha-activity. CONCLUSION: Neuropsychological scores improved significantly and markedly in various domains of speech during piracetam treatment, whereas improvements were less marked and restricted to a few categories in the placebo group.

Adult↗
PubMed2000

In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism.

UNLABELLED: Memory and attention are cognitive functions that depend heavily on the cholinergic system. Local activity of acetylcholine esterase (AChE) is an indicator of its integrity. Using a recently developed tracer for positron emission tomography (PET), C-11-labeled N-methyl-4-piperidyl-acetate (C11-MP4A), we measured regional AChE activity in 4 non-demented subjects, 4 patients with dementia of Alzheimer type (DAT) and 1 patient with senile dementia of Lewy body type (SDLT), and compared the findings with measurements of blood flow (CBF) and glucose metabolism (CMRGlc). Initial tracer extraction was closely related to CBF. AChE activity was reduced significantly in all brain regions in demented subjects, whereas reduction of CMRGlc and CBF was more limited to temporo-parietal association areas. AChE activity in SDLT was in the lower range of values in DAT. Our results indicate that, compared to non-demented controls, there is a global reduction of cortical AChE activity in dementia. KEYWORDS: Dementia, cholinergic system, acetylcholine esterase, positron emission tomography, cerebral blood flow, cerebral glucose metabolism.

Acetates↗
PubMed2000

Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry.

The significance of benzodiazepine receptor (BZR) concentration in comparison with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed with temporal lobe epilepsy (TLE) without hippocampal signal change on T2-weighted magnetic resonance imaging (MRI) scans. Focus lateralization was achieved by clinical, electroencephalographic and neuropsychological examinations. Three-dimensional positron emission tomography (PET) and MRI scans were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding, normalized to average cortical values for glucose metabolism (rCMRglc) and volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of interest (VOI) were used for calculation of asymmetries between clinically affected and unaffected sides. Eleven out of 14 TLE patients presented a significant reduction in hippocampal volume. In nine of these 11 patients hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced. In two patients without hippocampal volume asymmetry FMZ binding was markedly reduced in the mesial temporal lobe appropriately to the clinically diagnosed side. In our study volumetry is therefore the most sensitive tool for the detection of hippocampal abnormality in TLE. However, in cases without hippocampal atrophy the reduction of FMZ may indicate functional impairment of BZR before neuronal loss becomes evident. Our results emphasize the complementary nature of these tests in TLE patients.

Adult↗
PubMed1999

EEG power changes are related to regional cerebral glucose metabolism in vascular dementia.

OBJECTIVE: In patients with vascular dementia (VD), the relationship between the EEG power within the 4 frequency bands and the regional metabolic disturbances was investigated. METHODS: Twenty-eight patients (age 69.0+/-6.54 years) with VD according to NINDS-AIREN criteria underwent quantitative EEG recording, according to the 10-20 system, and fluodeoxyglucose F18 positron emission tomography (PET) at resting condition within 24 h. EEG power FFT-analysis was performed for delta (2-3.5 Hz), theta (4-7.5 Hz), alpha (8-13 Hz) and beta (13.5-20 Hz) frequency bands. Regional EEG power bands were related to regional glucose metabolism in anatomically defined regions corresponding to locations of the 10-20 system. RESULTS: Correlation between slow frequency band power and glucose metabolism was found. A widespread inverse relationship of delta power to metabolism was found between various regions; additionally, delta power was negatively correlated to cerebral glucose metabolism in individual regions. Frontal theta power correlated especially with thalamic CMRglc. Alpha power correlated directly with metabolism in the occipital lobe. No significant relationships were found between beta power and metabolism. CONCLUSION: We conclude that EEG power in VD is linked to glucose metabolism, indicating specific regional dependencies.

Aged↗
PubMed1999

Strategies to cope with negative social identity: predictions by social identity theory and relative deprivation theory.

Predictions by social identity theory (SIT) and relative deprivation theory (RDT) concerning preferences for strategies to cope with a negative in-group status position were tested. The focus of the present research was a comparison of the theories regarding their differential patterns of prediction. For this purpose, a natural sample within a specific historical situation was investigated: East Germans after the German unification. First, the predictive power of SIT and RDT variables was tested separately. In a second step, a possible integration of the theories was addressed. Combining the SIT variables and RDT variables led to an integrated model indicating a differential pattern of prediction for intergroup strategies. The RDT components explained the collective responses, whereas SIT constructs were related to individual strategies.

Adaptation, Psychological↗
PubMed1998

Apolipoprotein E polymorphism influences the cerebral metabolic pattern in Alzheimer's disease.

In 49 patients with the clinical diagnosis of probable Alzheimer's disease (AD) apoE genotyping as well as regional cerebral glucose metabolism (rCMRGI) using positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) were studied. The metabolic pattern was condensed to a ratio by dividing the rCMRGI of typically affected regions (temporo-parietal and frontal association cortex) by the rCMRGI of the least affected regions (primary cortical areas, basal ganglia, cerebellum and brainstem). Epsilon4-heterozygotes and epsilon4-homozygotes were grouped together, and also those lacking the epsilon4-allele (non-epsilon4). For the metabolic pattern we found a significant correlation to severity of dementia in both groups (epsilon4: r = 0.49, P = 0.05; non-epsilon4: r = 0.59, P = 0.006). On ANCOVA severity of dementia and epsilon4 status were independent predictors of the cerebral metabolic pattern (P = 0.01). These differences may be attributed to epsilon4 dependent histopathologic changes.

Age Factors↗
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-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

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

[Copying and free drawing by patients with Alzheimer disease of different dementia stages].

In this study we assessed the drawing abilities in 37 patients with probable Alzheimer's disease according to NINCDS-ADRDA criteria. Drawing abilities (drawing: house, flower, clock; Rey-Osterrieth figure; copying: MMST-figure; Rey-Osterrieth figure) were quantified with different rating schemes and related to other neuropsychological assessments. All patients underwent a positron emission tomography with 18-FDG. Drawing performance was highly correlated with severity of dementia--expressed in MMST scores (r = 0.78; p < 0.0001)--with visuo-spatial short-term memory (r = -0.69; p = 0.001), and writing abilities (r = -0.77; p < 0.0001). The summarized drawing score showed a statistically significant correlation with the rate of temporoparietal glucose metabolism measured with positron emission tomography and 18-FDG (r = 0.39; p = 0.017). In the drawings of AD patients omittings and simplifications were typical, whereas perseverations rarely occurred. In severely demented patients closing-in phenomenons could be described, too. A subgroup of AD patients with visuo-constructive impairment as the leading symptom could not be identified.

Aged↗