Loss of striatal [76Br]bromospiperone binding sites demonstrated by positron tomography in progressive supranuclear palsy.

Using positron tomography and 76Br-labeled bromospiperone, a neuroleptic drug with high affinity for the dopamine (DA) receptors, we have estimated the specific binding of the radiotracer to striatal DA receptors in seven patients suffering from progressive supranuclear palsy. Compared with age- and sex-matched control subjects, we found a significant (p less than 0.02) decrease of the striatum-cerebellum uptake ratio in progressive supranuclear palsy patients, suggesting loss of striatal DA receptors. This in vivo study confirms recent postmortem data on progressive supranuclear palsy patients and provides an explanation for the lack of benefit from L-DOPA and DA agonists in this condition, despite reduced nigrostriatal dopaminergic function.

Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons: a PET study.

The cerebral metabolic rate for glucose was measured serially with positron emission tomography and [18F]fluorodeoxyglucose in five baboons with stereotactic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days after lesion, a significant metabolic depression was present in the ipsilateral cerebral cortex, most marked in the frontotemporal region, and which recovered progressively within 6-13 weeks. These data demonstrate that adaptive mechanisms efficiently compensate for the cortical metabolic effects of NbM-lesion-induced cholinergic deafferentation. Moreover, unilateral NbM lesions also induced a transient reduction in contralateral cortical metabolic rate, the mechanisms of which are discussed. Explanation of these effects of cholinergic deafferentation in the primate could further our understanding of the metabolic deficits observed in dementia of the Alzheimer's type.

Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations.

In 41 patients with progressive supranuclear palsy (PSP) that was diagnosed on the basis of eight clinical criteria (25 patients with all eight criteria [probable PSP] and 16 with six or seven criteria [possible PSP]), we studied cerebral energy metabolism by using positron emission tomography and the fludeoxyglucose F 18 or the oxygen 15 method. Compared with age-matched controls, each of the cortical and subcortical metabolic values was significantly reduced, with a predominance in the frontal cortex, in both groups of patients with probable and possible PSP, without a difference between these two groups, suggesting similar underlying disease. The frontal metabolic value decreased with disease duration, but the relative frontal hypometabolism (expressed as the fronto-occipital metabolic ratio) was apparently already present in the early stages of the disease. The parkinsonian motor score was correlated with the caudate and thalamic metabolic values. The intellectual deterioration index was significantly correlated with both the frontal and the nonfrontal metabolic values. Finally, the frontal neuropsychological score was significantly correlated with only the fronto-occipital metabolic ratio. Hence, in PSP, a degenerative brain disease with subcortical lesions, the prominent frontal lobe-like syndrome essentially depends on the relative hypometabolism of the frontal cortex.

Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels.

The percentage occupation of striatal dopamine D2 receptors has been evaluated in 25 patients using 76Br-bromospiperone positron emission tomography (PET) and prolactin plasma levels (PRL) during oral neuroleptic treatment (11 studies), 1-90 days following discontinuation of such treatment (16 studies), and 1-120 days after last intramuscular administration of depot neuroleptics (nine studies). The PET-estimated occupation was highly significantly correlated in a sigmoid-like fashion to the logarithm of the chlorpromazine-equivalent dose of oral neuroleptics (suggesting a strict dose-occupation relationship during oral neuroleptic treatment and supporting the D2-mediated hypothesis of neuroleptic action), while PRL was weakly related to daily dosage. Following withdrawal, return to normal receptor availability, as estimated by PET, occurred within 5-15 days (suggesting that protracted effects of neuroleptics after withdrawal are not due to sustained D2 receptor occupation), but PRL values fell even more rapidly. Efficient treatment with depot neuroleptics resulted in marked PET-estimated D2 receptor occupation, stable over the whole 4-week drug-administration interval, suggesting that longer intervals could be appropriate; PRL values bore no relationship to PET-estimated occupation, indicating variable intersubject tolerance to neuro-endocrine dopamine blockade. Overall, PET was much more sensitive than PRL to estimate striatal D2 receptor occupation in vivo.

In vivo quantitative imaging of dopamine receptors in human brain using positron emission tomography and [76Br]bromospiperone.

The brain regional distribution and kinetics of [76Br]bromospiperone, a derivative of a neuroleptic (spiperone) labeled with the positron emitter bromine-76, were studied by time-of-flight tomography after i.v. injection in man. In a control subject the kinetic distribution study showed an accumulation of radioactivity which reached a maximum 3 h postinjection in the frontal cortex and cerebellum regions and 4-5 h postinjection in the basal ganglia. Thereafter the striatal activity remained essentially constant over a period of 25 h. In a group of 13 control subjects, the mean value for the striatum-to-cerebellum ratio, at 4.5 h postinjection, was 1.84 (S.D. 0.21). In two schizophrenics treated with high doses of haloperidol, this ratio was found to be only 1.22. These data indicate that radiolabeled bromospiperone is very suitable for human pharmacological or pathological investigations of the central dopaminergic system.

Age and cerebral infarction: a postmortem study of 77 cases of cerebral infarcts in the middle cerebral artery territory.

Adverse effect of age on ischemic stroke short-term mortality was reported in some studies and attributed either to more frequent extracerebral causes of death or to an increased severity of ischemia in the aged brain. Relationship between age, size of infarcts, and causes of death were studied in 77 consecutive patients who died from infarction in the middle cerebral artery territory. Area of infarcts was assessed by planimetry, and results were expressed as an index of infarcted area. No significant relationship was found between age and the size of infarcts, the cause of death, or the interval from stroke to death. These results do not support the hypothesis of an increased severity of ischemia in the aged brain.

[Spasmodic laughter caused by unilateral involvement of the brain stem]. / Rire spasmodique par lésion unilatérale du tronc cérébral.

We report a case of spasmodical laughter due to a strictly unilateral lesion located in the pons and the caudal part of the mesencephalon. Pathophysiology of this particular symptom is reviewed.

[Effect of diabetes mellitus and blood glucose on the size of cerebral infarction and causes of death. Neuropathological study of 77 cases of infarction in the sylvian artery area]. / Influence du diabète et de la glycémie sur la taille des infarctus cérébraux et les circonstances du décès. Etude neuropathologique de 77 infarctus sylviens.

The influence of diabetes mellitus and hyperglycemia on cerebral infarction has been studied on 77 patients who died of infarcts in the territory of the middle cerebral artery. The size of the infarcts was assessed by transferring the surface of the infarcted area onto 8 schematic drawings corresponding to 8 brain slices and measuring this surface by means of a planimeter. An infarction volume index (IVI) was calculated by measuring the ratio of the infarcted area to the theoretical area of the middle cerebral artery territory on the 8 slices. The causes of death were assessed by full post-mortem examination. There was no statistically significant difference in size of infarcts and causes of death between diabetics and non-diabetics. However, the stroke-to-death interval was shorter (p = 0.05) in non-diabetic patients. It appears from this study that diabetes mellitus has no deleterious effect on cerebral infarction. Equally, there were non statistically significant differences in size of infarcts, stroke-to-death interval and causes of death between patients with and without hyperglycemia.

[Focal chronic ischemia and concomitant migraine: an atypical form of Sturge-Weber angiomatosis?]. / Ischémie chronique focale et migraine accompagnée: forme atypique d'une angiomatose de Sturge-Weber?

A young man with a left hemifacial hemangioma had during a six months period about forty left hemispheric neurologic attacks suggestive of classic migraine. The neurologic examination was normal during the attack-free period. The CT scan (fig. 1) and the M.R.I. study (fig. 2) only showed a moderate interhemispheric asymmetry. The left internal carotid angiogram showed subtle anomalies of the venous system (fig. 3). All the neurologic manifestations ceased as soon as therapy by aspirin was initiated. A Positron Emission Tomography (PET) study with the oxygen 15 continuous inhalation technique was performed 7 months after the last attack in order to measure the regional Cerebral Blood Flow (rCBF), Oxygen Extraction Fraction (rOEF) and Oxygen Consumption (rCMRO2). Striking, statistically significant, alterations were observed in the left temporo-parieto-occipital area (fig. 4) consisting of a "misery perfusion" syndrome (rCBF = 28-38 ml/100 g/mn; rOEF = 0.64-0.80), without alteration in the rCMRO2 (Table). A repeated PET study 12 months later was unchanged. The association of local chronic oligemia and ipsilateral facial hemangioma, ipsilateral cerebral hypotrophy and venous anomalies suggested the diagnosis of atypical leptomeningeal angiomatosis of the Sturge-Weber type. The importance and persistence of the hemodynamic alterations suggest that chronic oligemia and, hence, tissue hypoxia may participate in the pathogenesis of the migraine-like attacks. Moreover, local circulatory stasis with thrombotic events may be implicated, as suggested by the apparent efficacy of aspirin.

[Subacute brainstem hematoma. A surgically treated case]. / Hématome du tronc cérébral d'installation subaigue. Un cas opéré.

We report a case of pontine haemorrhage in which symptoms and signs developed over a 2-months period. Surgery was successful but the patient subsequently died. The pathophysiology of subacute and chronic symptoms and signs is discussed.

[A peculiar mechanism of hydrocephalus: the "water-hammering" effect]. / Un mécanisme particulier d'hydrocéphalie: l'effet "coup de marteau".

BACKGROUND AND PURPOSE: Aneurysms of the basilar artery can cause hydrocephalus due to compression of the third ventricle or the sylvian aqueduct. The observation of a particular case led to discuss another possible mechanism of hydrocephalus. CLINICAL PRESENTATION AND RADIOLOGICAL STUDIES: An aneurysm of the basilar artery was revealed by an ischemic stroke in a 65-year-old man. Hydrocephalus developed during the following months. The MRI studies showed that it could not be explained merely by a permanent compression. However, the patient improved clearly after a ventriculo-peritoneal derivation. CONCLUSION: The hydrocephalus could be explained by a "water-hammering" effect due to the pulsating blood in the ectatic vessel, which created a cerebrospinal fluid outflow impairment through the third ventricle.

[Cross reactions of HLA A and B antigens in 63 patients with rheumatoid arthritis]. / Etude des réactions croisées des antigènes HLA A et B chez 63 patients atteints de polyarthrite rhumatoïde.

Cross reactions are very frequently observed when HLA A and B antigens are determined by a routine lymphocytotoxicity method. Such cross reactions are probably due to biochemical structural similarities shared by several HLA antigens. In this work, we studied the cross reactions which occurred during HLA A and B typing of 63 patients with classical or definite rheumatoid arthritis (RA) according to the ARA criteria. No association was found between RA and any single HLA A or B antigen. In contrast, when cross reactions were taken into account, the B8 B14 cross reactant group frequency was increased in RA patients (34,9 p. cent) as compared to controls (20 p. cent, p less than 0,004) and was even more clearly elevated in the 42 seropositive RA patients (40,5 p. cent, p less than 0,002). No relation was found between HLA phenotype and Sjögren's syndrome even when cross reactions were considered. The B8 DR3 haplotype has been shown to be associated with drug intolerance . The B8 B14 cross reactant group was present in 22 out of our 63 RA patients, 16 of whom were B8+. Among the latter, 6 patients exhibited poor tolerance to gold salts and 6 other patients did not respond to gold therapy, suggesting that the B8 antigen could predict not only a poor tolerance but also a poor response to disease modifying drugs.

[Study of HLA antigens A and B and their cross reactions in B27-negative ankylosing spondylarthritis]. / Etude des antigènes HLA A et B et de leurs réactions croisées dans la spondylarthrite ankylosante B27 négative.

In an attempt to find common immunogenetic features in B27+ and B27- ankylosing spondylitis patients, the B7 cross reactant antigens (BW22, B27, B40, B12, B13) were systematically tested by a lymphocytotoxicity method in 43 patients suffering from ankylosing spondylitis according to the Rome criteria. These included 25 caucasian patients (20 B27+, 5 B27-), 15 north african patients (11 B27+, 4 B27-) and 3 west indian mulattos (all B27-). The frequency of the B7 cross reactant antigens, when compared to controls, was not increased in the B27- patients as a whole, nor in any of the 3 populations studied. Our negative results are in agreement with those of similar published studies in homogeneous populations. They do not support the hypothesis of a direct involvement of HLA B antigens as cofactors favouring ankylosing spondylitis.

Infarcts in the middle cerebral artery territory. Pathological study of the mechanisms of death.

Correlates of the size of infarcts, the time from stroke to death, and the mechanisms of death were studied in 77 consecutive patients who died from infarction in the middle cerebral artery territory. The area of infarcts was assessed by planimetry on schemas of representative brain levels and the results were expressed as a ratio of infarcted area on the whole MCA territory. No clear relationship was found between the size of infarcts in the MCA territory, and any of the characteristics of the patients, but extensive infarcts were more frequent when the internal carotid artery was occluded. No evidence was found of an adverse effect of age, diabetes or initial hyperglycemia on the size of infarcts. The mechanisms of death were not linked to sex, age, high blood pressure, diabetes, blood glucose level at admission, presence and location of an arterial occlusion, or etiology of the infarct. On the contrary, they varied as a function of interval from stroke to death. Transtentorial herniation, the main cerebral cause of death, occurred mainly in the first week and was related to the large size of infarcts. Rare recurrences of stroke and frequent extracerebral mechanisms of death (mainly pneumonia, pulmonary embolism and cardiopathy) occurred later on.

Remote metabolic effects of cerebrovascular lesions: magnetic resonance and positron tomography imaging.

Combined Positron Emission Tomography (PET) and Proton Magnetic Resonance Imaging (MRI) study were performed in six patients with chronic supratentorial stroke to investigate whether remote hypometabolic regions revealed by PET showed any abnormality on MRI. Either regional oxygen consumption (n = 4) or glucose utilization (n = 2) were measured using PET and the 15O steady state 18FDG technique, respectively. Four patients, with deeply located brain lesions, showed a significant metabolic reduction in the overlying cerebral cortex. In the remaining two patients, affected by a large cortical infarct, there was a significant crossed cerebellar hypometabolism. The MRI weighted by the parameters spin density (rho), spin lattice (T1) and spin-spin (T2) relaxation times were obtained employing various sequences in the same subjects. In no patient did the MRI show any contrast modification in these hypometabolic remote regions, suggesting that subtle loss of tissue and/or biochemical change do not underlie the reduction in metabolic rate.

Effects of capsular or thalamic stroke on metabolism in the cortex and cerebellum: a positron tomography study.

We used positron emission tomography to study the cortical and cerebellar metabolic rates in 21 strictly selected patients with pure internal capsular infarct (n = 8), thalamocapsular hemorrhage (n = 6), or pure thalamic stroke (n = 7). Significant diffuse ipsilateral cortical hypometabolism relative to 62 controls free of cerebrovascular risk factors was frequently, although not consistently, found in the 13 patients with thalamocapsular or thalamic lesions and neuropsychological impairment but was absent from the eight patients with pure internal capsule infarct and free of neuropsychological deficit. These data suggest that damage to the thalamus or the thalamocortical projections is important in the development of ipsilateral cortical hypometabolism and that the latter may underlie the associated neuropsychological impairment. Significant contralateral cerebellar hypometabolism relative to 49 controls was found in three of six patients with pure internal capsule infarct, suggesting a pathogenetic role for the corticopontocerebellar system. However, the occurrence of hypometabolism in two of six patients with thalamic lesions indicates that this phenomenon may also result either from damage to the ascending cerebellothalamocortical system or indirectly from hypofunction of the cerebral cortex. No systematic association was observed between crossed cerebellar hypometabolism and ipsilateral ataxia.