No abstract

Using quantitative PET, the authors studied the binding of [11C]PK11195, a marker of activated microglia, in the thalamus of patients with chronic middle cerebral artery infarcts. All patients showed increased [11C]PK11195 binding in the ipsilateral thalamus, indicating the activation of microglia in degenerating projection areas remote from the primary lesion. A persistent increase in [11C]PK11195 binding suggests active, long-term thalamic microstructural changes after corticothalamic connection damage.

Using position emission tomography (PET) and equilibrium imaging with oxygen-15 labelled gases, the cerebral blood flow (CBF), blood volume (CBV), oxygen extraction fraction (OEF) and oxygen consumption rate (CMRO2) were measured in multiple regions of interest over the cerebral cortex of 5 control subjects, 4 patients with strictly unilateral longstanding carotid artery occlusion, 1 patient with middle cerebral artery embolic stroke in the acute stage, and 4 patients with subcortical stroke and no cervical arterial disease. In each control subject, the regional CBV was linearly and positively correlated with both CBF and CMRO2, while the local mean transit time (t = CBV/CBF) was uniformly distributed, reflecting the local adaptation of both the vascular tone and the capillary density to the metabolic demand at constant cerebral perfusion pressure that characterizes the normal brain. In patients with subcortical stroke, cortical blood volume was reduced in proportion to the matched reduction in CBF and CMRO2, suggesting that the metabolic depression resulting from cortical deafferentation increases the resting tone of pial vessels. Unilateral carotid occlusion induced larger CBV and t, and steeper slopes of the CBV-CBF relationship, particularly on the occluded but also on the patent side. The assessment of the local cerebral perfusion pressure (CPP) as judged by the ratio CBF/CBV in 3 patients with focally raised OEF and preserved or reduced CMRO2, allowed the demonstration in multiple cerebral regions of single patients of two well-known physiological phenomena: the autoregulation of CBF, followed by the rise of the OEF as local CPP falls further. In addition, the depression of CMRO2 in the ischaemic cortex was associated with a trend for CBV to return towards normal values, compared with the maximally elevated CBV found in oligaemic but metabolically normal areas. This suggests that a process of metabolic vasoconstriction may participate, among other factors, in the vascular collapse that occurs, and would serve to regenerate some haemodynamic reserve, at very low CPP levels.

Eight patients are reported who shared the combination of bilateral basal ganglia lesions and a frontal lobe-like syndrome. The main features were inertia and loss of drive, with preservation of intellectual function. Some patients showed stereotyped activities with compulsive and obsessive behaviour which were sometimes highly elaborate in pattern. Extrapyramidal clinical signs were absent or mild. Brain damage, related to anoxic or toxic encephalopathy, was demonstrated by CT scans and MRI. The lesions appeared to be confined to the lentiform nuclei, particularly affecting the pallidum, although there was generalized brain atrophy in 2 cases. Positron emission tomography (PET) in 7 patients revealed hypometabolism of the prefrontal cortex relative to other parts of the brain. The PET studies suggest dysfunction of the prefrontal cortex as a result of damage to the lentiform nuclei. These clinical, anatomical and functional observations emphasize the role of the circuits linking the prefrontal associative cortex and some specific areas of the neostriatum, including the pallidum. The existence of distinct nonoverlapping circuits in the motor field or in the associative field can explain the fact that basal ganglia lesions may give rise to a clinical picture that is either purely motor, purely behavioural (as in some of our patients), or both. Similarities existed between some symptoms found in our patients and certain features of major psychiatric illnesses such as severe depression, catatonic schizophrenia, and obsessive-compulsive disorder. This raises the hypothesis that some aspects of these psychiatric disorders could be related to structural and physiological disturbances in the systems linking the frontal associative cortex and the basal ganglia.

Unilateral thalamic stroke is a suitable model to test this hypothesis because the overlying cortex has a different arterial supply and is anatomically distant from the damaged area, thus reducing potentially confounding issues; previous follow up studies of patients with thalamic stroke have shown a significant trend for progressive normalisation of cortical hypometabolism and side to side asymmetry.38 In addition, comparison with healthy controls suggested that not only the ipsilateral but also the contralateral cerebral cortex was hypometabolic3; if confirmed, these bilateral effects could possibly account for the above mentioned discrepancies between side to side metabolic asymmetry and neuropsychological status.The goal of this study was to investigate further the relation between neuropsychological impairment and cortical metabolism after unilateral thalamic lesions. To this end, two complementary approaches were used. In the first, patients with movement disorder in whom a stereotaxic thalamotomy was planned were evaluated cognitively and by PET both before and after surgery; because this approach allows each patient to act as his/her own control it is ideally suited to investigate directly the brain metabolic effects of unilateral thalamic lesion in humans, as well as their relations to cognitive impairment. In the second approach we further investigated the controversial issue of the relations between the occurrence of cognitive impairment and the magnitude and time course of cortical metabolic asymmetry in a large sample of patients with thalamotomy or unilateral thalamic stroke.