J. Kessler

Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia.

As previous functional neuroimaging studies could not settle the controversy regarding the contribution of dominant and subdominant hemisphere to recovery from poststroke aphasia, language performance was related to H215O‐positron emission tomographic activation patterns in 23 right‐handed aphasic patients 2 and 8 weeks after stroke. In patients classified according to the site of lesion (frontal, n = 7; subcortical, n = 9; temporal, n = 7) and in 11 control subjects, flow changes caused by a word repetition task were calculated in 14 regions representing eloquent and contralateral homotopic areas. These areas were defined on coregistered magnetic resonance imaging scans and tested for significance (Bonferroni corrected t test, α = 0.0036). At baseline, differences in test performance were only found between the subcortical and temporal group. The extent of recovery, however, differed and was reflected in the activation. The subcortical and frontal groups improved substantially; they activated the right inferior frontal gyrus and the right superior temporal gyrus (STG) at baseline and regained left STG activation at follow‐up. The temporal group improved only in word comprehension; it activated the left Broca area and supplementary motor areas at baseline and the precentral gyrus bilaterally as well as the right STG at follow‐up, but could not reactivate the left STG. These differential activation patterns suggest a hierarchy within the language‐related network regarding effectiveness for improvement of aphasia; ie, right hemispheric areas contribute, if left hemispheric regions are destroyed. Efficient restoration of language is usually only achieved if left temporal areas are preserved and can be reintegrated into the functional network. Ann Neurol 1999;45:430–438

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.

Piracetam Improves Activated Blood Flow and Facilitates Rehabilitation of Poststroke Aphasic Patients

Background and Purpose In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow. Methods Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H215O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images. Results Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P <0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests. Conclusions Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere.

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 (τ = -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.

Clinical Deterioration in Probable Alzheimer's Disease Correlates with Progressive Metabolic Impairment of Association Areas

Regional cerebral glucose metabolism (rCMRG1) measured by positron emission tomography of 18F-2-fluoro-2-deoxy-D-glucose was studied longitudinally (interval ranging from 6 to 27 months) in 25 patients with probable Alzheimers disease (AD). A significant decline of rCMRG1 was noted in the whole brain (p = 0.02) which was most pronounced in the temporoparietal (p = 0.002), frontal (p = 0.01), superior parietal (p = 0.01) and occipital (p = 0.03) association cortex. A similar decline was also present in the thalamus (p = 0.04) but not in the primary visual and sensorimotor cortex, basal ganglia, cerebellum and brainstem. The changes of rCMRG1 in the temporoparietal, frontal and occipital association cortex were related to the change of the Mini Mental State Examination score (temporoparietal: r = 0.49, p = 0.01; frontal: r = 0.40, p = 0.05; occipital: r = 0.44, p = 0.03). The rate of clinical and metabolic decline was not related to age at onset, sex, family history or duration of disease. The results suggest that clinical deterioration and metabolic impairment in probable AD are closely related and dependent on progression of pathological changes in cortical association areas.

Impairment of Neocortical Metabolism Predicts Progression in Alzheimer’s Disease

Progression rates of Alzheimer’s disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment.

Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type

The effect of age on regional cerebral metabolic rate of glucose (rCMRGl) was studied in 14 patients with presenile dementia of Alzheimer type (DAT) and 24 patients suffering from senile DAT in comparison to 20 age-matched normal subjects by positron emission tomography (PET) of 2-(18F)-fluoro-2-deoxy-D-glucose (FDG). The metabolic pattern was condensed to a single metabolic ratio. It was calculated as the quotient of rCMRGl in regions typically affected by AD (frontal and temporoparietal cortex) divided by that in regions typically not affected. In normals this ratio was 1.05 +/- 0.04 and did not depend on age. In patients, the metabolic ratio was generally smaller and there was a significant difference between presenile (0.82 +/- 0.1) and senile DAT (0.90 +/- 0.1). This was due to a different metabolic pattern in the two age groups: metabolic impairment was focused on frontal and temporo-parietal cortex in presenile DAT, whereas more global rCMRGl reductions were present in senile DAT. The results suggest a more generalized disorder in senile dementia impairing metabolism globally in addition to the more localized changes that are typical for DAT.

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.

Impaired metabolic activation in Alzheimer's disease: A pet study during continuous visual recognition

Regional cerebral metabolic rate of glucose (rCMRGl) was studied in 21 patients with probable Alzheimers disease (AD) and nine age-matched normal controls by positron emission tomography (PET) of 2(18F)-fluoro-deoxy-D-glucose (FDG) at rest and during stimulation with a continuous visual recognition task. While global metabolism at rest was comparable in both groups, rCMRGl in the temporo-parietal junction area, the mid-temporal and the frontal cortex was typically decreased in the AD patients. The continuous visual recognition task adapted to the individual performance capacity increased the global metabolic rate in the controls by 21 +/- 18%, while in the AD patients the metabolic change (5.7 +/- 11.1%) during activation was significantly weaker (P = 0.023). Due to the tasks chosen the activation of rCMRGl in both groups was most prominent in the visual cortex and the temporo-parietal association areas, although the recognition task additionally involved widespread brain structures with varying rCMRGl. A significant correlation was found between rCMRGl in areas usually severely affected by AD pathology, e.g. the temporo-parietal cortex, and GDS scores, and became stronger during metabolic activation. Neither at rest nor during stimulation was there a relationship between the rCMRGl of structures usually less involved in AD, e.g. the sensorimotor cortex, and the severity of dementia as assessed by the global deterioration scale (GDS). From these results it can be concluded that metabolic rate at rest reflects the extent of morphologic damage, while PET studies during activation indicate the brains reserve capacity to respond to functional tasks. Since metabolism in AD patients during activation is more severely impaired than at rest, PET studies during functional tests could help in the selection of patients with a potential to benefit from therapeutic intervention.

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.