Octave Migneco

Perfusion Brain SPECT and Statistical Parametric Mapping Analysis Indicate That Apathy Is a Cingulate Syndrome: A Study in Alzheimer's Disease and Nondemented Patients

Apathy is the most frequent behavioral symptom in Alzheimers disease and is also frequently reported in other brain organic disorders occurring in the elderly. Based on the literature, we hypothesized that apathy was related to an anterior cingulate hypofunction. Forty-one subjects were studied. According to ICD 10 diagnostic criteria, 28 patients had Alzheimer dementia (demented: diagnostic group 1), and 13 had organic personality disorders or mild cognitive impairment not attributable to dementia (nondemented: diagnostic group 2). Apathy was evaluated by the Neuro-Psychiatric Inventory. As a result each diagnostic group was divided into two symptomatic subgroups: apathetic or nonapathetic. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) brain SPECT and the images were compared using Statistical Parametric Mapping (SPM96). We began by comparing apathetic vs nonapathetic patients, whatever their diagnostic group (whole population), then analyzed them within each group. Twenty-one subjects were apathetic (14 in group 1 and 7 in group 2) and 20 were not (14 in group 1 and 6 in group 2). For the whole population, the Z map showed a significant decrease in ECD uptake for the apathetic patients in the anterior cingulate (P < 0.002) bilaterally. This area was also identified as hypoactive by SPM analysis in the demented (P < 0.035) and in the nondemented (P < 0.02) apathetic patient groups. Finally, conjunction analysis indicated that the anterior cingulate was the common hypoactive structure of the two apathetic subgroups (Z = 4.35, P < 0.0009). These results point to a close relationship between apathy and the anterior cingulate region.

European Stroke Initiative Recommendations for Stroke Management

This article summarises recommendations for acute management of stroke by the European Stroke Initiative (EUSI), on behalf of the European Stroke Council (ESC), the European Neurological Society (ENS), and the European Federation of Neurological Societies (EFNS).

Behavioral and Psychological Symptoms in Alzheimer’s Disease

Fundamental and therapeutic research in Alzheimer’s disease (AD) focused for a long time exclusively on cognitive aspects. However, AD also frequently involves complex disorders of affect and behavior, which are currently grouped under the heading ‘behavioral and psychological signs and symptoms of dementia’ (BPSSD). Several rating tools have been developed over the years on the basis of a variety of source data. Some are derived from psychiatric practise or have specifically been developed for dementia, such as the Neuropsychiatric Inventory (NPI). In this study we prospectively used the NPI to examine BPSSD. Sixty-three French patients (mean age 74.7 years, SD 7.9) with a Mini-Mental State Examination (MMSE) score higher than 10 were examined. BPPSD were detected by NPI in 95.2% of the patients. Anxiety was the most common abnormality (65.1%), followed by apathy and dysphoria (58.7%). The highest frequency × severity NPI score was observed for apathy. In order to identify the relationship between regional cerebral perfusion and apathy, 20 of these AD patients underwent a technetium-99m-bicisate SPECT protocol within the same week as the NPI evaluation. The mean age of this population was 74.4 years (SD 5.3) and the mean MMSE score was 21 (SD 4.1). The apathy NPI score was correlated with right cingulate deficit whereas the highest correlation for the MMSE was with the left temporoparietal area. This stresses the interest to focus on SPECT imaging of AD patients not only in the posterior areas.

Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis.

Alzheimers disease (AD) is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. These behavioral disorders contribute to the clinical heterogeneity of the disease and probably express different pathophysiological processes. Apathy is one of the most frequent behavioral disorders in AD. The aim of this study was to evaluate brain perfusion of AD patients with and without apathy (as determined by the Neuropsychiatric Inventory) compared with that in healthy elderly subjects. A total of 15 AD patients without apathy (AD/NA; mean age 76.6) and 15 AD patients with apathy (AD/A; mean age 77.6) were studied. Brain perfusion was measured by 99mTc-labeled bicisate (ECD) single-photon emission tomography (ECD SPECT). The images of the two AD subgroups were compared by means of statistical parametric mapping (SPM 99) to corresponding images of 11 healthy elderly control subjects (obtained from the Society of Nuclear Medicine database). Compared with the healthy elderly subjects, the apathy-free AD subgroup had significantly lower perfusion of inferior temporal regions (left fusiform gyrus, left parahippocampal area) and occipital regions (left gyrus lingualis). The apathy subgroup had significantly decreased perfusion of the left anterior cingulate, the right inferior and medial gyrus frontalis, the left orbitofrontal gyrus and the right gyrus lingualis. The differences in the brain areas with reduced perfusion between the apathy-free subjects (mainly the posterior regions) and the apathetic subjects (mainly the anterior regions) indicate that behavioral disorders such as apathy participate in the heterogeneity of brain perfusion in AD.

Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake.

BACKGROUND For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. METHODS Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. RESULTS The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. CONCLUSION An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.

Classification of SPECT Images of Normal Subjects versus Images of Alzheimer's Disease Patients

This work aims at providing a tool to assist the interpretation of SPECT images for the diagnosis of Alzheimers Disease (AD). Our approach is to test classifiers, which uses the intensity values of the images, without any prior information. Such a classifier is built upon a training set, containing images with two different labels (AD patients and normal subjects). It will then provide a classification for any new unknown image. The main problem to be handled is the small number of available images compared to the large number of features (here the images voxels): the so-called small sample size problem. We evaluate here the ability of two linear classifiers to correctly label a set of 79 images. Our experiments show promising results. They also show that image classification based on intensity values only is possible and might be used for other applications as well.

Early 99mTc-Ethylcysteinate Dimer Brain SPECT Patterns in the Acute Phase of Stroke as Predictors of Neurological Recovery

Objectives: Accurate prediction of outcome in acute stroke would help in identifying subgroups of patients for therapeutic trials and intravenous thrombolysis. The purpose of this study was to prospectively test the hypothesis that brain SPECT, with 99mTc-L,L-ethylcysteinate dimer (ECD), a tracer sensitive to cell function, performed in the first hours after stroke onset, adds predictive power to concomitant neurological evaluation. Methods: Twenty-four patients with a first-ever middle cerebral artery stroke were prospectively studied with ECD-SPECT within 12 h after stroke onset. Neurological evaluation was performed using Orgogozo’s scale at admission and 3 months later in order to calculate the percent Martinez-Vila evolution indices (EI%). Semiquantitative visual analysis of SPECT images was performed in 6 cortical regions relevant for carotid artery territory. Both the extent and the intensity of cortical reduced ECD uptake were calculated, leading to an ‘ischemia’ score, corresponding to the sum of regions of interest (ROI) where ECD uptake was between 40 and 80% of the contralateral healthy hemisphere, and an ‘irreversibly damaged tissue’ (IDT) score, corresponding to an uptake below 40%, and a total score (ischemia + IDT). Each patient was assigned to one of three patterns: (1) pattern I with severe ECD cortical uptake reduction defined by at least one ROI with uptake under 40%, (2) pattern II with moderate ECD cortical uptake reduction (40–80%) only and (3) pattern III with normal ECD uptake. Results: There were 11 patients (46%) with pattern I ECD-SPECT. This group had almost invariably (10/11 patients) a poor outcome. The 12 patients (50%) classified in pattern II had a variable clinical outcome, ranging from improvement to deterioration. The single patient with a normal SPECT (pattern III) had a full clinical recovery. Both total score and IDT score were strongly significantly correlated with neurological recovery EI% (respectively p = 0.006 and 0.004). Their predictive value was significantly higher than, and independent of, day 0 neurological evaluation. No patient had an increased ECD uptake. Conclusion: Our results show that the degree of ECD cortical uptake reduction, measured on early brain SPECT, is a strong predictor of neurological recovery. ECD-SPECT data have a higher predictive value than day 0 neurological evaluation. The apparently better predictive value of ECD over hexamethylpropyleneamine oxime may reflect this tracer’s brain retention mechanisms which are weighted more towards cell function than towards perfusion. ECD-SPECT is easily obtainable and may help in selecting out from therapy those patients who are likely to have either very good or very poor spontaneous outcome, and thus improve the assessment of acute stroke and the choice of therapeutic strategy.

Acute cardiac effects of mediastinal irradiation: Assessment by radionuclide angiography☆

Mediastinal irradiation is considered as a long term cardiac risk factor, although no myocardial dysfunction can usually be documented during long term follow-up of the patients having undergone this treatment. We prospectively studied on 124 patients the early effects of irradiation on the myocardium using radionuclide angiography Left ventricular ejection fraction was measured at three different times: before starting the irradiation, 15 days after and more than 2 months after the end of treatment. The patients were divided into four groups according to the type of irradiation received: M group of 53 patients (mediasteinal irradiation), L group of 33 patients (left mammary chain irradiation), R group of 25 patients (right mammary chain irradiation), C group for 13 control patients (irradiation field did not include the heart). Sixty-nine of these patients were treated by chemotherapy, including adriamycin in 48 of them. For all patients for whom the myocardium was included into the field of irradiation (M, L, and R) there is a significant fall of the Left ventricular ejection fraction 15 days after the end of treatment, with recovery after 2 months. This fall is not seen in controls. Patients who received adriamycin follow the same evolution, and there is no significant difference in the basal LVEF value nor in the magnitude of the fall.

Single photon emission computed tomography study of subclinical rhythmic electrographic discharge in adults

Subclinical rhythmic electrographic discharge in adults (SREDA) is considered a benign EEG pattern of uncertain significance, although it may closely resemble an EEG seizure pattern. We investigated a 57-year-old man with a very lateralized epileptiform activity localized to the occipito-temporal areas of the right hemisphere. Neuropsychological tests, clonazepam injection and 99m Tc-HMPAO-SPECT were performed during the SREDA and compared to the interparoxysmal data, providing further evidence that SREDA cannot be considered as an epileptic pattern and that, in some instances, it may be related to chronic hypoxic/ischemic mechanisms.

Voxel‐Based Mapping of Cortical Ischemic Damage Using Tc 99M L, L‐Ethyl Cysteinate Dimer Spect in Acute Stroke

Background and Purpose. When performed soon after stroke onset, single‐photon emission computed tomography (SPECT) with hexamethylpropylenamine oxime or Tc 99m L, L‐ethyl cysteinate dimer (ECD) has significant added predictive value compared to neurological scores. With ECD SPECT, the degree of tracer uptake reduction predicts neurological recovery, and using a 40% threshold to characterize irreversibly damaged tissue (IDT), significant correlations have been observed. How‐ ever, correlations between this uptake threshold and tissue out‐ comes have not been assessed. The purpose of this study was to validate the 40% ECD uptake threshold for the probabilistic mapping of IDT using an automatic, voxel‐based approach. Methods. In 10 acute stroke patients, the authors first com‐ pared early ECD SPECT and late coregistered magnetic reso‐ nance imaging (MRI) data and assessed for IDT and “tissue at risk” (ie, tissue with ECD uptake below and above 40%) the per‐ centage of voxels ultimately infarcted and noninfarcted on late brain MRI. They then assessed the correlations between the vol‐ umes of brain tissue compartments and subsequent neurologi‐ cal recovery. Finally, to assess whether visual SPECT analysis is reliable compared to the more complexvoxel‐based approach, the authors compared the predictive value of the 2 methods for neurological recovery. Results. The majority of IDT voxels (aver‐ age = 84%), defined by ECD uptake < 40%, evolved toward infarction, and 51.8% to 100% of at‐risk voxels (average = 89%) escaped infarction. The extent of IDT correlated significantly with neurological recovery (P= .0009). There was good agree‐ ment between visual and voxel‐based analyses (P= .0004). Conclusion. The results support the validity of the ECD uptake thresholds chosen, suggesting that ECD uptake can reflect neuronal viability and that ECD SPECT can be useful for the early detection of potentially salvageable tissue and irreversible damage. These preliminary results encourage the use of this method in a clinical setting for fast decision making in choosing acute therapy.