Longitudinal thalamic diffusion changes after middle cerebral artery infarcts.

BACKGROUND: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery (MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging (DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans. METHODS: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity (MD), fractional anisotropy (FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls. RESULTS: MD significantly increased in the ipsilateral thalamus between the first and the sixth month (0.766 x 10(-3) mm(2)/s first month; 0.792 x 10(-3) mm(2)/s third month; 0.806 x 10(-3) mm(2)/s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month. CONCLUSION: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings.

Diffusion tensor imaging study of subcortical gray matter in cadasil.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown. METHODS: We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images. RESULTS: A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score. CONCLUSIONS: Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.

Quantitative measurement of cerebral acetylcholinesterase using.

[11C]physostigmine, an acetylcholinesterase inhibitor, has been shown to be a promising positron emission tomography ligand to quantify the cerebral concentration of the enzyme in animals and humans in vivo. Here, a quantitative and noninvasive method to measure the regional acetylcholinesterase concentration in the brain is presented. The method is based on the observation that the ratio between regions rich in acetylcholinesterase and white matter, a region almost entirely deprived of this enzyme, was found to become approximately constant after 20 to 30 minutes, suggesting that at late time points the uptake mainly contains information about the distribution volume. Taking the white matter as the reference region, a simplified reference tissue model, with effectively one reversible tissue compartment and three parameters, was found to give a good description of the data in baboons. One of these parameters, the ratio between the total distribution volumes in the target and reference regions, showed a satisfactory correlation with the acetylcholinesterase concentration measured postmortem in two baboon brains. Eight healthy male subjects were also analyzed and the regional enzyme concentrations obtained again showed a good correlation with the known acetylcholinesterase concentrations measured in postmortem studies of human brain.

Thalamocortical diaschisis: positron emission tomography in humans.

To investigate further the relations between cortical energy metabolism and neuropsychological impairment after unilateral thalamic lesion, 55 patients underwent positron emission tomography studies of either cortical oxygen consumption or glucose utilisation, including eight repeat studies, at times ranging from 4 days to 98 months after the onset of the lesion [stroke (n = 44) or stereotaxic VL-Vim thalamotomy performed for movement disorders (n = 11)]. Patients with thalamotomy were also studied preoperatively and the surgery induced a significant fall in cortical metabolism on both sides (more so ipsilaterally); post-operatively the magnitude of the ipsilateral cortex hypometabolism was positively correlated to the severity of global neuropsychological impairment; similar but less significant findings were obtained for the ipsilateral/contralateral cortical metabolic asymmetry. With respect to the whole patient sample, the cortical metabolic asymmetry was initially pronounced, with subsequent monoexponential recovery, in the cognitively impaired study group, but it was only mild and showed no meaningful trend for recovery in the cognitively unaffected study group; yet even soon (< 3 months) after thalamic lesion there was a noticeable overlap of individual asymmetry values among the two study groups. These results lend further support to the view that the neuropsychological impairment that frequently follows unilateral thalamic lesions is reflected in a depression of synaptic activity in both the overlying and the contralateral cerebral cortices. For individual patients, this study also illustrates the potentially misleading nature of the measured cortical metabolic asymmetry with respect to neuropsychological status, especially at late times after lesion, in part because side to side metabolic ratios do not reflect bilateral changes.

Cortical metabolism in posterolateral thalamic stroke: PET study.

In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.

Brain energy metabolism in bilateral paramedian thalamic infarcts. A positron emission tomography study.

Positron emission tomography (PET) studies of the cerebral metabolic rate of oxygen (CMRO2) were performed in seven consecutive patients with bilateral paramedian thalamic infarcts (BPTI), selected on neuroradiological and clinical criteria. The latter consisted of sudden onset of coma or confusion followed by a persistent amnesia of varying severity, with or without language impairment and frontal lobe signs. There was a highly significant decrease of CMRO2 for the whole cortex as well as for all the regions analysed: medial-frontal, latero-frontal, temporal, sensorimotor and posterior associative cortex. The mean regional metabolic ratios (region/whole cortex CMRO2) were not significantly different from controls, indicating an essentially uniform effect in the cortex, except the sensorimotor ratio which was significantly increased. Diffuse cortical hypometabolism most likely reflects thalamo-cortical deafferentation secondary to damage to the 'non-specific' thalamic nuclei, while sparing of the latero-ventral thalamus presumably explains the relative preservation of the sensorimotor cortex metabolism. Although no clear-cut individual relationship was found between magnitude of cortical hypometabolism and the severity and pattern of neuropsychological impairment, the data suggest that the former underlies and/or reflects the latter. Further studies with higher resolution PET devices might shed more light on the relationships between distinct cognitive patterns and specific topography of cortical hypometabolism in BPTI patients.