B. Szelies

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

Summary. 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 Alzheimers 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.

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.

Quantitative EEG mapping and PET in Alzheimer's disease.

Quantitative analysis of topographical EEG was studied in comparison with measurement of regional glucose metabolism by PET in 42 patients with clinical diagnosis of probable dementia of Alzheimer type (AD) and in 15 age-matched normal controls. Measures analyzed included global and regional data from areas typically affected and not affected by AD pathology. While disturbance of metabolism followed a typical regional pattern, relative alpha, theta and delta power were more globally altered without selectivity for specific regions. Separation between AD and age matched controls by relative theta power was correct in 86% and was close to that by temporo-parietal glucose metabolism (correct classification 87%). Relative theta power as well as temporo-parietal glucose metabolism were significantly correlated (tau B = 0.54 and -0.53, respectively) to severity of AD assessed by the global deterioration scale. These results indicate that EEG measures may be used with an accuracy close to metabolic values from PET for the assessment of severity of AD.

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.

Effect of Piracetam on Cerebral Glucose Metabolism in Alzheimer's Disease as Measured by Positron Emission Tomography

The effect of piracetam (a putative enhancer of cerebral metabolism) on regional CMRGlu was studied by positron emission tomography of 2[18F]-fluoro-2-deoxy-D-glucose in nine patients with Alzheimers disease, and in seven cases with multiinfarct dementia or unclassified dementia. In Alzheimers disease, i.v. administration of piracetam, 6 g b.i.d. for 2 weeks, significantly improved rCMRGlu in most cortical areas, whereas no effect on CMRGlu of the drug was observed in the multiinfarct dementia/unclassified dementia groups. These results lend further support to the notion that adjuvant piracetam treatment is of benefit in Alzheimers disease. They may also indicate that the typical metabolic depression in Alzheimers disease is caused by complex interaction of disturbed transmitter and cellular function rather than by a specific deficit in the cholinergic system alone.

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.

Long-Term Effects of Phosphatidylserine, Pyritinol, and Cognitive Training in Alzheimer's Disease

70 patients with probable Alzheimers disease were randomly allocated to four groups: 17 patients received only social support, 18 cognitive training twice a week, in 17 cognitive training was combined with pyritinol 2 x 600 mg/day and in 18 cognitive training was combined with phosphatidylserine 2 x 200 mg/day. Treatment duration was 6 months. Before and after treatment, the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose. Before treatment the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. Electrophysiological changes were assessed as EEG power, globally and in 4 frequency bands. This 6-month study in four groups of patients with Alzheimers disease indicated that phosphatidylserine treatment has an effect on different measures of brain function. Since neuropsychological improvements were best documented after 8 and 16 weeks and faded towards the end of the treatment period, it must be concluded that this symptomatic therapy is mainly of short-term benefit and was overcome by the progressive pathological changes at the end of the treatment period.

Quantitative topographical EEG compared to FDG PET for classification of vascular and degenerative dementia

Quantitative topographical EEG was compared with regional glucose metabolism measured by PET with respect to the sensitivity in the classification of mild to moderate dementia. In 24 patients with probable Alzheimers disease (DAT), 19 patients with vascular dementia (VD) and 15 age-matched healthy controls, global and regional EEG and PET data were analyzed. The metabolic ratio between typically affected and non-affected regions differentiated between DAT and VD (P < 0.001) as well as between DAT and normal controls (P < 0.001) even for the subgroup of mild dementia. In contrast to PET, global EEG changes were more sensitive than regional alterations for the classification into the respective groups. Relative theta power was most sensitive for the differentiation of demented patients irrespective of type of normal controls (P < 0.01), whereas OCC/FR alpha ratio (occipital divided by frontal power) separated between dementia types (P < 0.01) as well as between DAT and normals (P < 0.05). Additionally, EEG may help to grade severity especially in DAT. Combined use of EEG and PET was more discriminative and reached higher diagnostic specificity than each test individually. These results suggest that EEG and PET are complementary diagnostic procedures for the differentiation and classification of dementias.

Early electroencephalography in acute ischemic stroke: Prediction of a malignant course?

Objective: In patients with large middle cerebral artery (MCA) infarction space occupying brain edema may lead to a malignant course with up to 80% mortality under conservative treatment. As interventional treatment strategies must be started before the deterioration occurs predictors of a malignant course are necessary. Patients and methods: This study reports on the results of early electroencephalography (EEG) within 24 h after onset of stroke in 25 patients suffering a large MCA infarct (12 patients with a malignant and 13 with a non-malignant course). EEG analysis was performed according well-established indicators for focal as well as global changes. Results: Our findings indicate that the absence of delta activity and the presence of theta and fast beta frequencies within the focus predict a benign course (p < 0.05), whereas diffuse generalized slowing and slow delta activity in the ischemic hemisphere may point to a malignant course.

[18F]fluorodopa uptake in the upper brainstem measured with positron emission tomography correlates with decreased REM sleep duration in early Parkinson's disease

Sleep disturbances are common in patients with Parkinsons disease (PD). Previous studies have shown alterations of polysomnographic sleep parameters in PD, such as overall diminution of slow-wave and REM sleep duration, absence of muscle atonia during REM and increased occurrence of periodic leg movements during sleep. The pathogenesis of sleep dysregulation in PD is unknown. The aim of this study was to determine relations of abnormal polysomnographic sleep parameters and the dopaminergic function of the striatum and the upper brainstem measured with the use of positron emission and magnetic resonance tomography in 10 early-stage PD patients with a history of sleep disturbances. Our data demonstrated a significant inverse correlation of absolute and percentage REM sleep duration with the mesopontine [18F]6-fluorodopa (FDOPA) uptake in PD patients. Therefore, the results point to a REM inhibiting effect of increased monaminergic transmission within the upper brainstem in early-stage PD. This finding emphasises the pathophysiological significance of a disturbed neurotransmitter equilibrium in the rostral brainstem for REM sleep alterations in PD.