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M Levivier

Publications and source records attributed to M Levivier.

At least 37 records · Page 2Linked to original sources
PubMed2000

Tropism of AAV-2 vectors for neurons of the globus pallidus.

A recombinant AAV-2 vector encoding the green fluorescent protein (gfp) under the control of the cytomegalovirus (CMV) promoter was injected into the striatum at varying antero-posterior coordinates. When the virus was delivered to the anterior part of the striatum, transduction efficiency was low and limited to the vicinity of the needle tract. In contrast, after injection into the posterior part of the striatum, in addition to a localized transduced area in the striatum, efficient and widespread transduction was observed at distance from the injection site, in the globus pallidus. In the latter case, labelled cells were also detected in the internal capsule and in the stria terminalis. The number of transduced cells in the striatum increased up to I month and then decreased whereas in the globus pallidus, transduction was maximal as early as 2 weeks post-injection. In the striatum and in the globus pallidus, the labelled cells had a neuron-like morphology. In contrast, in the internal capsule, labelled cells had a glial-like morphology.

Animals↗
PubMed2000

Failure of neuroprotection by embryonic striatal grafts in a double lesion rat model of striatonigral degeneration (multiple system atrophy).

In the present experiment we studied the ability of embryonic striatal grafts to protect against striatal quinolinic acid (QA)-induced excitotoxicity in a previously established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with multiple system atrophy (MSA). Male Wistar rats received under halothane inhalation anesthesia a 6-hydroxydopamine 6-OHDA injection into the left medial forebrain bundle. Four to 5 weeks later apomorphine-induced rotation behavior was tested. Rats were divided into two treatment groups receiving either embryonic striatal cell suspensions or sham injections. Apomorphine-induced rotation behavior was retested 2 and 4 weeks after the grafting procedure. Following the rotation test animals of the striatal and sham graft group received a stereotaxic injection of 150 nmol QA. Again rotation behavior was assessed 2 and 4 weeks after lesioning. Brains were then processed to dopamine reuptake ([(3)H]mazindol), dopamine D1 ([(3)H]SCH23390), and D2 ([(3)H]spiperone) receptor autoradiography. Gliosis was detected using [(3)H]PK11195, a marker for peripheral benzodiazepine binding sites. Behavioral and autoradiographic analysis failed to show striatal protection in 6-OHDA prelesioned animals receiving embryonic striatal grafts. These findings indicate that beneficial protective effects of striatal grafts implanted into host striatum prior to excitotoxic insults are abolished in the presence of severe dopaminergic denervation. Our present results are relevant to future applications of neural grafting in MSA-SND.

Animals↗
PubMed2000

Statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy.

We investigated statistical parametric mapping (SPM) use for positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) data analysis in mesial temporal lobe epilepsy. The study involved 14 patients with temporal lobe epilepsy ultimately treated by anterior temporal lobectomy. Surgical outcome in terms of seizure control was favorable in 12 patients. Two different SPM approaches were designed to analyze each FDG-PET scan: a direct comparison with a control group (n = 27) and a search for significant interhemispheric asymmetry considering the asymmetry existing in the control group. Statistical inference was performed, first, without correction for multiple comparisons (making the hypothesis of temporal hypometabolism) and, second, after correction for multiple comparisons. Search for temporal interhemispheric asymmetry under the hypothesis of temporal hypometabolism was the most reliable SPM approach: hypometabolism was identified on the side chosen for resection in most cases (sensitivity, 71%; specificity, 100%) and was predictive of favorable postsurgical outcome in 90% of the patients. There was no false-positive result within the control group using this approach. After correction for multiple comparisons, SPM also identified in some patients temporal hypermetabolic areas as well as extratemporal cortical and subcortical hypometabolic areas on the side of resection but also on the contralateral side. In a further step, SPM was used for a group analysis of patients with favorable outcome after reversing scans when needed to set an identical lateralization in all patients. This analysis identified multiple ipsilateral temporal and extratemporal hypometabolic regions; when temporal metabolic changes were specifically assessed, the contralateral mesiotemporal region was found hypermetabolic, possibly as a manifestation of compensatory mechanisms in the presence of a unilateral epileptogenic lesion.

Adolescent↗
PubMed2000

FDG-PET as a prognostic factor in high-grade astrocytoma.

BACKGROUND: The prognostic value of the metabolic status of cerebral gliomas determined by positron emission tomography with [18F]-fluoro-deoxy-D-glucose (FDG-PET) has been established in populations with a mixture of grades 2, 3 and 4 gliomas, but remains uncertain when only malignant gliomas are considered (grade 3 and 4). METHODS: FDG-PET performed in 30 patients with anaplastic astrocytoma (grade III) and 61 patients with glioblastoma (grade 4) were classified according to a metabolic grading. The uptake of FDG was lower in the tumor compared to white matter (WM) in grade 1 (4 glioblastoma, 4 anaplastic astrocytoma), it was intermediate between WM and cortex in grade 2 (20 glioblastoma, 22 anaplastic astrocytoma), and it was superior to cortex in grade 3 (38 glioblastoma, 4 anaplastic astrocytoma). RESULTS: Kaplan-Meier survival curves were similar in patient with grades 1 and 2, but were significantly worse (p = 0.007) in grade 3. In multivariate analysis considering age, pathological grade (anaplastic astrocytoma versus glioblastoma), and metabolic grades, the metabolic grade did not appear to be an independent prognostic factor. When anaplastic astrocytomas and glioblastomas were considered separately, metabolic grade is of predictive value only in the group of glioblastomas. CONCLUSION: In malignant gliomas, metabolic grading determined by FDG-PET was not superior to the pathological grading for survival prediction. Still, it remains of predictive value when applied to malignant gliomas histologically classified as glioblastoma.

Adolescent↗
PubMed2000

Metabolic changes after injection of quinolinic acid or 6-hydroxydopamine in the rat striatum: a time-course study using cytochrome oxidase and glycogene phosphorylase a histochemistry.

Injection of excitotoxins, such as quinolinic acid (QA), into the striatum has been extensively used as an experimental model of Huntington's disease, while injection of 6-hydroxydopamine (6-OHDA) into the dopaminergic nigrostriatal pathway provides a well established model of Parkinson's disease. In the present study, we have examined the metabolic changes induced by an intrastriatal injection of QA or 6-OHDA using histochemical staining for the metabolic markers cytochrome oxidase (COx) and active glycogene phosphorylase (GPa). Intrastriatal injection of QA produced major changes in COx (decrease of staining) and GPa (increase of staining, except in the core of the lesion where the staining was virtually absent) histochemistry at the level of the striatum and of most of the other basal ganglia nuclei. Although attenuated over time, these changes persisted up to one year after the lesion. On the contrary, after the intrastriatal injection of 6-OHDA (which induces only a partial lesion of the nigrostriatal pathway), we did not observe any remarkable changes in COx or GPa staining. This study illustrates the discrepancies between the morphological changes and metabolic changes that are induced when using these experimental models of neurodegenerative disorders.

Animals↗
PubMed2000

Combined magnetic resonance imaging- and positron emission tomography-guided stereotactic biopsy in brainstem mass lesions: diagnostic yield in a series of 30 patients.

OBJECT: In the management of brainstem lesions, the place of stereotactic biopsy sampling remains debatable. The authors compared the results of magnetic resonance (MR) imaging, positron emission tomography (PET) scanning, and histological studies obtained in 30 patients who underwent MR imaging- and PET-guided stereotactic biopsy procedures for a brainstem mass lesion. METHODS: Between July 1991 and December 1998, 30 patients harboring brainstem mass lesions underwent a stereotactic procedure in which combined MR imaging and PET scanning guidance were used. Positron emission tomography scanning was performed using [18F]fluorodeoxyglucose in 16 patients, methionine in two patients, and both tracers in 12 patients. Definite diagnosis was established on histological examination of the biopsy samples. Interpretation of MR imaging findings only or PET findings only was in agreement with the histological diagnosis in 63% and 73% of cases, respectively. Magnetic resonance imaging and PET findings were concordant in 19 of the 30 cases; in those cases, imaging data correlated with histological findings in 79%. Treatment based on information derived from MR imaging was concordant with therapy based on histological findings in only 17 patients (57%). Combining MR imaging and PET scanning data, the concordance between the neuroimaging-based treatment and treatments based on histological findings increased to 19 patients (63%). In seven patients who underwent biopsy procedures with one PET-defined and one MR imaging-defined trajectory, at histological examination the PET-guided samples were more representative of the tumor's nature and grade than the MR imaging-guided samples in four cases (57%). In 18 patients PET scanning was used to define a biopsy target and provided a diagnostic yield in 100% of the cases. CONCLUSIONS: Although the use of combined PET and MR imaging improves radiological interpretation of a mass lesion in the brainstem, it does not accurately replace histological diagnosis that is provided by a stereotactically obtained biopsy sample. Combining information provided by MR imaging and PET scanning in stereotactic conditions improves the accuracy of targeting and the diagnostic yield of the biopsy sample; an MR imaging- and PET-guided stereotactic biopsy procedure is a safe and efficient modality for the management of mass lesions of the brainstem.

Adolescent↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed1999

Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD).

In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled "Neurosurgical Interventions in Parkinson's Disease" (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.

Clinical Protocols↗
PubMed1999

Cellular contaminants of adeno-associated virus vector stocks can enhance transduction.

Transduction efficiency of different types of recombinant (r)AAV-2 based vectors preparations markedly differed, with apparently no correlation with the replicative titers. Using HeLa cells as target for transduction, 105 and 30 infectious units were necessary to observe one transductant using respectively cesium-chloride-purified rAAV and crude lysates of producer cells obtained by sonication. The purified vectors were however able to transduce HEK-193 cells efficiently, but transgene expression was detected with some delay compared with crude lysates. The unexpected high transduction efficiency of sonicated crude lysates was due to virally mediated gene transfer, since similar sonicated crude lysates, but with no AAV rep and cap genes, did not lead to detection of transgene products after incubation with HeLa cells. Furthermore, sonicated cellular extracts of 293 or 293/T cells given in trans stimulate transduction of HeLa cells by purified rAAV. In contrast, neither extracts from the adenovirus E1-transformed 911 cell line, nor from other cell lines not harboring any adenovirus gene, had enhancing effect on rAAV-mediated transduction. These data suggest that 293 sonicated extracts contain factors which stimulate rAAV-mediated transduction of cells that are normally poorly transduced and offer a system to identify such factors and to characterize further the steps limiting the transfer of gene by AAV vectors.

Dependovirus↗
PubMed1999

Magnetic resonance imaging and angiography in cerebral fungal vasculitis.

We report on an 11-year old girl treated for leukemia who developed infarcts in the right lentiform nucleus and temporal lobe. Magnetic resonance angiography (MRA) showed mild intraluminal irregularities in the right carotid syphon and stenosis of the right proximal middle cerebral artery, suggesting vasculitis. Magnetic resonance imaging (MRI) follow-up showed evolution of the initial infarct into an abscess. Stereotactic biopsy disclosed filaments of aspergillus. This report emphasizes the fact that cerebral aspergillosis should be considered if MRA and MRI are indicative of vasculitis and cerebral infarction in immunosuppressed children.

Aspergillosis↗
PubMed1999

Prevention of epidural fibrosis in a prospective series of 100 primary lumbo-sacral discectomy patients: follow-up and assessment at re-operation.

An implantable device (ADCON-L), which acts as a resorbable barrier to epidural fibrosis following lumbar discectomy, has been shown to minimize the formation of peridural fibrotic scar and to improve the post-operative outcome, in two large controlled and multi-center clinical trials. In this prospective study, 100 patients were treated with the device during their first-time lumbo-sacral discectomy surgeries and monitored for 12 months. During this time interval, four of these patients required re-operation. In these cases, epidural scar and ease of dissection were systematically evaluated and recorded. At the time of re-operation, in all four patients, absent or minimal soft scar tissue was found where ADCON-L had been placed, no adhesions to the involved root were observed, and the dissection was easier than expected; the healing of the surgical wound was excellent , and no residual implant material was found. These observations indicate that the use of ADCON-L at the time of the first lumbar disc surgery minimizes the hazards and difficulty that can be encountered in a subsequent revision surgery due to the presence of epidural fibrosis, and may therefore improve the chances of satisfactory outcome following re-operation.

Adolescent↗
PubMed1999

[Intracerebral grafts in Parkinson disease. Current experiences and perspectives].

Six patients with advanced Parkinson's disease have been grafted with human fetal neuronal cells. This clinical work is based on the technique originally described by the groups of Lund, Sweden and Créteil, France, with which we closely collaborate. A first group of 3 patients was grafted between 1995 and 1996, with neuronal tissue obtained from same-day abortions. We have observed bilateral improvement of motor functions after unilateral transplantation into the putamen. One patient had a second graft, into the heterolateral putamen, one year after the first one. Another group of 3 patients was operated between 1997 and 1998, and received grafts of hibernated tissue, in order to facilitate the technical organization of the transplantation procedure. Altogether, these clinical results are encouraging, but the technical and ethical limitations related with the use of human fetal tissue prompted us to develop alternative solutions, such as the use of xenografts and the transplantation of genetically modified cells.

Brain Tissue Transplantation↗
PubMed1998

Quinolinic acid-induced lesions of the rat striatum: quantitative autoradiographic binding assessment.

Injection of the excitatory amino-acid analog quinolinic acid into the striatum of rats produces neuropathological and neurochemical alterations that are reminiscent of those observed in Huntington's disease. In the present study, we evaluated quinolinic acid-induced striatal changes using quantitative autoradiographic binding assays for [3H]MK-801-labeled NMDA receptors, [3H]SCH 23390-labeled dopamine D1 and [3H]sulpiride-labeled dopamine D2 receptors, [3H]CGS 21680-labeled adenosine A2a receptors, [3H]mazindol-labeled dopamine uptake sites, [3H]hemicholinium-3-labeled high affinity choline uptake sites and [3H]PK 11195-labeled peripheral-type benzodiazepine binding sites, as markers of different cellular populations of the striatum. We found that decrease in [3H]MK 801 and [3H]SCH 23390 binding, and increase in [3H]PK 11195 binding were the most significant alterations induced by the intrastriatal injection of quinolinic acid. Concentrations of [3H]CGS 21680 and [3H]hemicholinium-3 bindings were also decreased, however, to a lesser extent, and [3H]sulpiride binding was not significantly affected. Quinolinic acid also produced an increase in [3H]mazindol binding. We tested the specificity of the N-methyl-D-aspartate receptor-mediated mechanism of quinolinic acid neurotoxicity using MK 801 pretreatment, an N-methyl-D-aspartate receptor antagonist, and it prevented all quinolinic acid-induced binding changes. Because anticholinergic drugs were proposed to prevent the neurotoxic side-effects of MK 801, we also tested the effect of scopolamine pretreatment and found that it altered neither the neurotoxicity induced by quinolinic acid nor the neuroprotective effect of MK 801.

Animals↗
PubMed1998

Diagnostic and microsurgical presentation of intracranial angiolipomas. Case report and review of the literature.

Angiolipomas (ALs) are hamartomas composed of abnormally differentiated vessels and mature adipose tissue. Although they are most commonly found in peripheral tissues, ALs sometimes grow in the spinal epidural space. Intracranial ALs (ICALs) are rare: only seven cases have been reported in the literature. The authors describe the case of a 70-year-old woman who presented with ocular symptoms from a clinically and radiologically progressing parasellar ICAL. The radiological as well as the microsurgical findings are illustrated and compared with the seven previously published cases. The most frequent location of ALs is the skull base, especially the parasellar region. Other ICALs were diagnosed as components of cerebral arteriovenous malformations and were not symptomatic by themselves. Neuroradiological studies of ICALs usually demonstrate the characteristics of both adipose and vascular tissues. However, a review of the literature shows that the diagnosis had not been suspected preoperatively in any of the cases. Operative descriptions emphasize that most neurosurgeons were caught off guard by the profuse bleeding and the unusual relationship of this unexpected lesion to the cavernous sinus, so that removal was rarely complete. The authors conclude that preoperative diagnosis of ICALs is achievable based on magnetic resonance analysis, which should help optimize the microsurgical management of these lesions.

Aged↗
PubMed1997

Stereotactic brain biopsy guided by positron emission tomography (PET) with [F-18]fluorodeoxyglucose and [C-11]methionine.

The aim of the present study was to compare the contribution of the labelled tracers [C-11]methionine (Met) and [F-18]-fluorodeoxyglucose (FDG) in positron emission tomography (PET)-guided stereotactic biopsy of non resectable brain lesions. Twenty-five patients underwent combined Met-PET-, FDG-PET- and computerized tomography (CT)- or magnetic resonance (MR)-guided stereotactic biopsy according to a previously described technique for stereotactic FDG-PET. Met-PET and FDG-PET images were analyzed to determine which tracer offers the best information to guide at least one stereotactic biopsy trajectory. Histological diagnosis was obtained in all patients (23 tumours and 2 non-tumorous lesions). All tumours had an area of abnormal Met uptake and were biopsied under PET-guidance. FDG uptake in the tumour was higher than in the grey matter and was used for target selection in 12 of 23 tumours. Eleven of them were located in the basal ganglia or the brainstem. Met was used for target selection in 11 of 23 tumours where there was no FDG uptake or where FDG uptake was equivalent to that of the grey matter. Ten of them were located in the cortex. Two nontumoral lesions had no Met uptake and were biopsied under CT- or MR-guidance only. Forty-three out of 53 stereotactic trajectories obtained in these 25 patients were based on PET-defined targets and had an area of abnormal Met uptake. These trajectories always yielded a diagnosis of tumour. Moreover, all tumorous trajectories had an area of abnormal Met uptake. Finally, all non-diagnostic trajectories (n = 4) were CT/MR-defined because there was no area of abnormal Met uptake. These results suggest that patients who can benefit the most from Met-PET guidance could be selected pre-operatively. In conclusion, this work shows that Met is a good alternative to FDG for target selection in PET-guided stereotactic brain biopsy.

Adolescent↗