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Biomedical subjects

Y Samson

Publications and source records attributed to Y Samson.

At least 73 records · Page 4Linked to original sources

Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach.

Five patients with Parkinson's disease, unilaterally transplanted with foetal mesencephalic cells into putamen (n=1) or putamen and caudate (n=4), were followed throughout a period of 15-36 months after surgery, according to the recommendations of the core assessment programme for intracerebral transplantations (CAPIT). All these patients exhibited an increase in the fluorodopa uptake in the grafted putamen, which was most significant in the first and last patient of the series. Long-term bilateral improvement of skilled hand movements was observed, starting between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A mild to moderate effect on the amount of 'off' time and 'on-off' fluctuations was observed, whereas, apart from one case, no other clear effect on gait, walking and speech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dementia process after surgery. Daily living activities were clearly improved in only one of the other four patients. At the end of the study period, all patients needed L-dopa therapy at a similar or higher dose than before grafting, but, in most of them, other dopaminergic drugs were reduced or stopped. All patients exhibited bilateral dyskinesias before grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side displaying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural transplants may influence two central mechanisms involved in motor function and the onset of dyskinesias. These effects are likely to occur through complex interactions with the post-synaptic dopaminergic receptors. The occurrence of dyskinesias might simply reflect increased presynaptic storage and release of dopamine. Alternatively, it might, in part, represent some other long-term deleterious effect of the graft. Since PET-scan data indicate that the reinnervation obtained is sub-optimal, it will be of interest to obtain a larger and denser reinnervation of the host striatum and to try, thereafter, to reduce the dose of L-dopa.

Aged↗

A clinical and neurophysiological study of a patient with an extensive transection of the spinal cord sparing only a part of one anterolateral quadrant.

In 1976, Noordenbos and Wall studied sensory functions in a woman with a surgically verified T3 spinal cord transection which spared only a part of the left anterolateral quadrant, We re-investigated this unique case 18 years after the lesion and included a comparable sensory examination, MRI of the spinal cord, somatosensory evoked potentials, PET-activation study during hand and foot vibration and analysis of flexion reflex modulation during the Jendrassik manoeuvre. Our results show that the residual anterolateral quadrant contains ascending pathways carrying a wide range of sensory information as well as descending pathways modulating flexion reflex activity at the spinal level. Moreover, the changes in sensory functions and the unique pattern of cortical activation suggest a functional reorganization of the connectivity between the periphery and the cerebral cortex. Changes of facilitation and/or of inhibition at different levels of the somatosensory system may account for these longterm plastic changes.

Evoked Potentials, Somatosensory↗

Variability of presentation in medial temporal lobe epilepsy: a study of 30 operated cases.

INTRODUCTION: To evaluate the homogeneity of patients operated on for MTLE. MATERIAL AND METHODS: 30 consecutive patients prospectively investigated with clinical, EEG, neuropsychology, MRI, FDG-PET criteria and eventually intracranial EEG, who underwent antero-medial temporal resection (follow-up: 24 months). RESULTS: Clear and well-lateralised MTLE was non-invasively ascertained in 22 patients (73%). Eight patients (27%) had a less pure presentation due to divergent scalp EEG features (bitemporal, widespread or extratemporal), unusual auras or absence of MRI-based hippocampal sclerosis or FDG-PET hypometabolism. They were explored by invasive monitoring which confirmed medial temporal origin of seizures. Outcome was excellent in 95% of the pure cases (Engel's class I) and less favorable in the more difficult ones (65% of class I). CONCLUSIONS: MTLE criteria, including the strong contribution of brain imaging, permit to select accurately a large percentage of patients. However a consistant number of patients present a less pure presentation suggesting more complex epileptogenic networks.

Adolescent↗

Recovery from nonfluent aphasia after melodic intonation therapy: a PET study.

We examined mechanisms of recovery from aphasia in seven nonfluent aphasic patients, who were successfully treated with melodic intonation therapy (MIT) after a lengthy absence of spontaneous recovery. We measured changes in relative cerebral blood flow (CBF) with positron emission tomography (PET) during hearing and repetition of simple words, and during repetition of MIT-loaded words. Without MIT, language tasks abnormally activated right hemisphere regions, homotopic to those activated in the normal subject, and deactivated left hemisphere language zones. In contrast, repeating words with MIT reactivated Broca's area and the left prefrontal cortex, while deactivating the counterpart of Wernicke's area in the right hemisphere. The recovery process induced by MIT in these patients probably coincides with this reactivation of left prefrontal structures. In contrast, the right hemisphere regions abnormally activated during simple language tasks seem to be associated with the initial persistence of the aphasia. This study supports the idea that abnormal activation patterns in the lesioned brain are not necessarily related to the recovery process.

Adult↗

Quantitation of benzodiazepine receptors in human brain using the partial saturation method.

UNLABELLED: The in vivo quantification of the benzodiazepine receptor concentration in humans using PET and flumazenil (FMZ) is usually based on Scatchard analysis when the goal is to avoid blood sampling. The experimental protocols, however, include several (at least two) experiments with various specific activities in the same subject to obtain a range of bound ligand concentrations. METHODS: We propose the partial saturation method, which is based on a natural decrease in bound ligand concentration after an FMZ injection with an average dose between a tracer dose and a saturation dose. An adequate range of bound ligand concentrations can thus be obtained from a single experiment. The free ligand concentration is estimated from the PET measurement in the pons after correction for the effect of the small receptor site concentration in this reference region. RESULTS: The receptor concentration and affinity estimates obtained with this approach in six regions of interest agree with previously published values obtained by using more complex approaches. Receptor concentration appears to be insensitive to the uncertainties with regard to the receptor site concentration in the pons. CONCLUSION: The partial saturation protocol can be used to estimate both the benzodiazepine receptor concentration and the FMZ affinity in routine examinations in adults (or even in children) using a single 40-min experiment without blood sampling.

Adult↗

[Contribution of position emission tomography in a case of Marchiafava Bignami disease: Morel's laminar sclerosis?].

We report the case of a 26-year old alcoholic woman who abruptly presented with confusion associated with a major hypertonia. She evolved into a chronically vegetative state. Magnetic resonance imaging (MRI) was consistent with the diagnosis of Marchiafava Bignami disease. The corpus callosum first presented an oedematous aspect, then a central atrophy with an axial band. The clinical presentation and the functional imaging strongly suggest an association between the Marchiafava Bignami disease and diffuse cortical lesions, such as the laminar sclerosis of Morel.

Acute Disease↗

Post-stroke changes in cortical 5-HT2 serotonergic receptors.

UNLABELLED: Fluorine-18-setoperone PET imaging was used to investigate serotonergic 5-HT2-specific binding in unlesioned cerebral cortex in stroke patients. METHODS: Seventeen stroke patients (mean age 50 +/- 31 yr) with right (n = 9) or left (n = 8) chronic stroke (middle or anterior cerebral artery territory) underwent [18F]setoperone PET and MR imaging. The distribution volume of the 5-HT2-specific binding at equilibrium (DVSe) was determined in the unlesioned cortical regions. The results were compared with those obtained in 14 age-matched controls. In addition, we investigated the effect of the side of the stroke, lesion volume and its localization. RESULTS: After removing the age effect by covariance analysis, we found a significant DVSe decrease in the temporal (p < 0.05) and frontal (p < 0.05) unlesioned cortices ipsilateral to the stroke. The changes were similar in patients with left and right stroke and did not correlate with the volume of the stroke. However, the localization of the stroke affected the topography of DVSe abnormalities. When the lesion did not extend more medially than the internal capsule, DVSe was significantly reduced in the temporal lobe (-30%, p < 0.05) but not in the frontal lobe (-21%, p = ns). Conversely, when the lesion extended subcortically in the anteromedial region, close to the midline, DVSe was reduced in both temporal (-40%, p < 0.05) and frontal (- 49%, p < 0.05) lobes. CONCLUSION: This study confirms that stroke may alter 5-HT2 receptors in large unlesioned cortical areas and that the changes depend on the subcortical extent of the lesion.

Adult↗

Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian patients.

To assess the efficacy of fetal mesencephalic grafts in Parkinson's disease, it is important to know if the grafted cells survive and are functional. Positron emission tomography (PET) and [18F]fluorodopa ([18F]dopa) have been used to demonstrate the survival of the grafted cells, but the relationship of [18F]dopa uptake changes in the grafted striatum to motor function remains unclear. We investigated this question with 16 serial PET scans in 5 severe parkinsonian patients unilaterally grafted in whom we found a significant and progressive increase of the [18F]dopa uptake in the grafted putamen. The number of patients was too small to assess the sensitivity of [18F]dopa PET scans in individual patients. Yet, by analyzing the 16 serial PET scans we found a correlation between the [18F]dopa uptake (Ki) in the grafted putamen and the percentage of daily time spent "on," suggesting that Ki changes have a functional meaning. In addition, the Ki values were correlated with the contralateral finger dexterity to the same extent in both the grafted and nongrafted putamen. These results indicate that [18F]dopa uptake reflects the motor function of the opposite side of the body, similarly in the grafted and ungrafted putamen, at least in terms of these tasks. Finally, extrapolating from these correlations offers the suggestion that clinical optimal results of the graft could be achieved if the graft brings the Ki values in the putamen to about two standard deviations of mean control values.

Brain↗

Striatal dopaminergic denervation in pallidopyramidal disease demonstrated by positron emission tomography.

Pallidopyramidal disease is a rare disease of young patients in which they manifest a parkinsonian syndrome and pyramidal signs. Pallidopyramidal disease has been attributed to a degeneration of the pallidum and the pyramidal tract, although only 1 patient has been studied postmortem. In the present report, [18F]fluorodopa positron emission tomography in 2 patients showed a marked dopaminergic denervation of the striatum, suggesting that this disease corresponds more to a nigropallidopyramidal dysfunction.

Adolescent↗

Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol.

A kinetic method using a multiinjection protocol, positron emission tomography (PET), and [11C]flumazenil as a specific ligand was used to study in vivo the flumazenil-benzodiazepine receptor interactions in the human brain. The model structure is composed of three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of the five model parameters in various brain regions from a single experiment. In particular, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (KDVR, VR being the volume of reaction) were estimated in five brain regions, including the pons, in which these parameters are identified for the first time (B'max = 4.7 +/- 1.7 pmol/ml and KDVR = 4.4 +/- 1.3 pmol/ml). Due to the large range of measured receptor concentrations, a linear correlation between B'max and KDVR was pointed out (r = 0.88, p < 0.0005) and was interpreted as a linear relationship between B'max and VR, the parameter KD being assumed constant. This result and its concordance with the published data are discussed. Simulation of the usual two-experiment Scatchard analysis, using the pons as a reference region, showed that the bias on the receptor concentration estimates introduced by this method is significant (from 20 to 40%) but can be corrected using an estimate of the receptor concentration in the pons. Furthermore, we propose a new experimental protocol, based on a Scatchard analysis of the PET data obtained with a partial-saturation experiment. This single-injection protocol is entirely noninvasive, and thus the estimation of the benzodiazepine receptor concentration and of the flumazenil affinity is now possible in human patients using a single 1-h experiment without blood sampling.

Adult↗

5HT2 receptors in cerebral cortex of migraineurs studied using PET and 18F-fluorosetoperone.

Since the brain 5HT2 receptors might be implicated in migraine pathogenesis, we have used positron emission tomography and 18F-fluorosetoperone, a 5HT2 specific radioligand, to investigate in vivo the cortical 5HT2 receptors in migraine subjects. Nine migraineurs who had either migraine with and without aura (n = 5) or only migraine without aura (n = 4) were studied between attacks. Twelve unmedicated healthy subjects of similar mean age were used as controls. Brain radioactivity was measured after 18F-setoperone IV injection for 90 min. A decrease of the regional specific distribution volumes (SDV) of the ligand was observed both in migraineurs and in controls. The age adjusted group means of SDV did not differ between patients and controls for the whole and for the right or left frontal, temporal, parietal and occipital cortex. These results suggest that cortical 5HT2 receptors may be unaltered between attacks in migraine sufferers.

Adult↗

Is interictal temporal hypometabolism related to mesial temporal sclerosis? A positron emission tomography/magnetic resonance imaging confrontation.

The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.

Adult↗

First selective amygdalohippocampal radiosurgery for 'mesial temporal lobe epilepsy'.

All the well-documented radiosurgery of epilepsy cases are secondary epilepsies with space-occupying lesions. These results have prompted the idea of testing radiosurgery as a new way of treating epilepsy without space-occupying lesions. We have treated 4 patients with 'mesial temporal lobe epilepsy'. The preoperative evaluation programme was one we usually perform for patients selected for microsurgery of epilepsy. We report the baselines of this treatment, the radiosurgical protocol details, and preliminary results for the first patient treated (follow-up 16 months). Since treatment, the patient has been seizure free, but it is too soon to draw long-term conclusions about the efficiency of the radiosurgery of epilepsy. Morphological (MRI) and functional (PET scan) changes are discussed in relation to our technical choices. Our amygdaloentorhinohippocampal target has been selectively injured.

Adult↗

Generic model for the localization of the cerebral cortex and preoperative multimodal integration in epilepsy surgery.

In cerebral cortex neurosurgery and particularly in epilepsy surgery, the recognition of individual cortical anatomic landmarks is necessary for presurgical evaluation and planning. To overcome the classical great variability in the superficial aspect of the human cerebral cortex, we have developed an original generic description of the cerebral cortex in a three-dimensional structure. The result is a generic model matching the cortical topography of each brain regardless of inter- and intra-individual variability. In this model, sulcal roots (fundi) are separated by more or less superficial annectent gyrus, and buried by operculization during the gyrification. This original generic model of the cerebral cortex enabled us to develop a mathematical methodology for the construction of a structural representation of the cortical topography from a T1-weighted three-dimensional MR image. This program can provide automatic detection and recognition of the main cortical sulci.

Algorithms↗

Delayed maturation of the frontal cortex in childhood autism.

OBJECTIVE: The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. METHOD: Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. RESULTS: A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. CONCLUSIONS: Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.

Adolescent↗

Parameter and index images of benzodiazepine receptor concentration in the brain.

UNLABELLED: In vivo studies of ligand-receptor interactions with PET data are based on different approaches that provide either quantitative results (receptor density and affinity) or indices that are assumed to be correlated with the receptor concentration. The aims of this study are to obtain parametric images of benzodiazepine receptor concentration and of flumazenil affinity and to study the validity of two receptor concentration indexes. METHODS: A three-compartment ligand-receptor model, [11C]flumazenil, and experimental data obtained using a three-injection protocol in human volunteers were used to acquire parametric images. The delayed activity method and the apparent distribution volume (estimated using a two-compartment model) were also tested and their results compared with those of the multi-injection approach. RESULTS: Parametric images of receptor density, affinity and all kinetic parameters were obtained with acceptable variation coefficients. A correlation between receptor density and apparent affinity was found (r = 0.83; p < 0.0005). The correlation between receptor concentration and apparent distribution volume (estimated with three- and two-compartment models, respectively) was accessed using both a linear (the usual hypothesis) and a nonlinear correlation derived from the relationship between the receptor density and the affinity. CONCLUSION: In spite of the complexity of this protocol (three injections, a 2-hr experiment, blood sampling and a metabolite study), we showed that the multi-injection approach is suitable for parametric brain imaging. By using this approach as a reference, we deduced that the distribution volume and delayed activity images are valid methods in the usual range of the benzodiazepine receptor concentrations found in the human brain.

Brain↗

[Late neurologic complications of galactosemia: study of 3 cases].

Galactosemia is an autosomal recessive, inborn error of galactose metabolism due to the deficiency of galactose-I-phosphate uridyl transferase. Late-onset neurologic complications may develop despite Galactose restriction. Three adult patients are reported. They suffered from mental retardation. Two of them developed progressive cerebellar ataxia, spastic gait and postural tremor. The magnetic resonance imaging revealed moderate cortical atrophy, multifocal areas of increased signal in the periventricular white matter on T2-weighted images, and in one case, abnormal myelination. The Fluoro-2-deoxy-D-glucose position emission tomography showed different patterns of regional hypometabolism.

Adult↗