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J G Villemure

Publications and source records attributed to J G Villemure.

At least 19 recordsLinked to original sources
PubMed2001

Isolation of multipotent neural precursors residing in the cortex of the adult human brain.

Multipotent precursors able to generate neurons, astrocytes, and oligodendrocytes have previously been isolated from human brain embryos and recently from neurogenic regions of the adult human brains. The isolation of multipotent neural precursors from adult human should open new perspectives to study adult neurogenesis and for brain repair. The present study describes the in vitro isolation from adult human brains of a progenitor responsive to both epidermal and basic fibroblast growth factors that forms spheres as it proliferates. Single spheres derived from various regions of the brain generate in vitro neurons, astrocytes, and oligodendrocytes. The clonal origin of the spheres was revealed by genomic viral insertion using lentiviral vector. Interestingly, this vector appears to be a potent tool for gene transfer into human neural progeny. Ninety-six percent of the spheres investigated were multipotent. Multipotent precursors were isolated from all brain regions studied, including the temporal and the frontal cortex, the amygdala, the hippocampus, and the ventricular zone. This study is the first evidence that primitive precursors such as multipotent precursors exist in the adult human cortex and can reside far from the ventricles. Neurogenesis derived from adult human progenitors differ to murine neurogenesis by the requirement of laminin for oligodendrocyte generation and by the action of basic-fibroblast growth factor and platelet derived growth factor that prevented the formation of oligodendrocytes and neurons. Moreover, the differentiation of human adult precursors seems to differ from fetal ones: adult precursors do not necessitate the removal of mitogen for differentiation. These results indicate that the study of adult multipotent precursors is a new platform to study adult human neurogenesis, potentially generate neural cells for transplantation, and design protocols for in vivo stimulation.

Adolescent↗
PubMed2001

[Anesthesia for epilepsy surgery].

Epilepsy is rather common, affecting 0.5 to 2% of the population. Numerous patients, particularly those resistant to the antiepileptic therapy, can be surgically treated after a thorough evaluation. Surgery for epilepsy can be carried out either under general or local anaesthesia with sedation. This second approach is reserved for the extirpation of foci localised in motor, sensory or language areas. During the preoperative anaesthetic evaluation, two specific points have to be taken into account: the psychological aspect and the antiepileptic medication. During the procedure, an electrocorticography with or without stimulation may be indicated, particularly when a perioperative stimulation is scheduled. Low doses of volatile agents are chosen, and no curare and large doses of benzodiazepines and barbiturates. Awakening takes place on the operation table for a rapid and reliable neurological evaluation. During procedures performed under local anaesthesia, the anaesthetist must be ready at any time to intubate the patient in order to secure the airway.

Anesthesia↗
PubMed2001

Intractable epilepsy after a functional hemispherectomy: important lessons from an unusual case. Case report.

Residual seizures after functional hemispherectomy occur in approximately 20% of patients with catastrophic epilepsy. These episodes are traditionally attributed to incomplete disconnection, persistent epileptogenic activity in the ipsilateral insular cortex, or bilateral independent epileptogenic activity. The authors report on the case of an 8-year-old boy with an intractable seizure disorder who had classic frontal adversive seizures related to extensive unilateral left hemispheric cortical dysplasia. The initial intervention consisted of extensive removal of the epileptic frontal and precentral dysplastic tissue and multiple subpial transections of the dysplastic motor strip, guided by intraoperative electrocorticography, Subsequently, functional hemispherectomy including insular cortex resection was performed for persistent attacks. After a seizure-free period of 6 months, a new pattern ensued, consisting of an aura of fear, dystonic posturing of the right arm, and unusual postictal hyperphagia coupled with an interictal diencephalic-like syndrome. Electroencephalography and ictal/interictal single-photon emission computerized tomography were used to localize the residual epileptic discharges to deep ipsilateral structures. Results of magnetic resonance imaging indicated a complete disconnection except for a strip of residual frontobasal tissue. Therefore, a volumetric resection of the epileptogenic frontal basal tissue up to the anterior commissure was completed. The child has remained free of seizures during 21 months of follow-up review. Standard hemispherectomy methods provide extensive disconnection, despite the presence of residual frontal basal cortex. However, rarely, and especially if it is dysplastic, this tissue can represent a focus for refractory seizures. This is an important consideration in determining the source of ongoing seizures posthemispherectomy in patients with extensive cortical dysplasia. It remains important to assess them fully before considering their disease refractory to surgical treatment.

Cerebral Cortex↗
PubMed2000

Sturge-Weber syndrome: indications and results of surgery in 20 patients.

OBJECTIVE: To discuss the indications and timing for resective surgery in patients with Sturge-Weber syndrome (SWS) and medication-resistant epilepsy. BACKGROUND: SWS that causes epilepsy severe enough to merit surgery is rare. Because of the variable natural history of the disease, it is difficult to establish clear-cut indications for surgery and prospective studies are not feasible. Attitudes of clinicians and surgeons remain variable. METHODS: The authors assessed the presurgical epilepsy profile, criteria for surgery, monitoring techniques, and the postoperative outcome of epilepsy in all patients with SWS consecutively admitted between 1972 and 1990 to two referral centers (Paris and Montreal) and underwent surgery for intractable seizures. RESULTS: All 20 patients had a minimal postoperative follow-up of 4 years and all but one are still followed by one of the authors. One patient had a callosotomy, five underwent hemispherectomy, and 14 had cortical resection. Despite variability in the age at onset of seizures (range: 2 months to 12 years), age at operation (range: 8 months to 34 years) and surgical methods, almost all patients benefited from surgery. Visually guided complete resection of the pial angioma and underlying cortex, whenever possible, seemed sufficient; results were no better with intraoperative corticography. In children with previous hemiparesis, hemispherectomy proved particularly effective: all five became seizure free. None of the patients showed any aggravation of cognitive impairment following surgery; none of those who were operated on early presented with severe mental retardation, and 13 of 20 became seizure free. CONCLUSION: Although the natural history of SWS is imperfectly known, increasing duration of seizures and of postictal deficits, increase in atrophy or of calcified lesions or both, are indicative of its progressive nature. Despite the expected heterogeneity that renders formal comparison of the various approaches difficult, the current study provides new evidence to support early surgery in patients with SWS and drug-resistant epilepsy. The authors' results suggest that lesionectomy is a good approach, provided that the pial angioma is unilateral and the resection can be complete.

Child↗
PubMed2000

Sensorimotor organization in patients who have undergone hemispherectomy: a study with (15)O-water PET and somatosensory evoked potentials.

To identify cortical structures that subserve residual motor and sensory function in patients with congenital hemiparesis due to a porencephalic cyst, we examined, using [(15)O]H2O, PET and somatosensory evoked potentials (SEPs) in three patients with left-sided hemiparesis who had undergone hemispherectomy. Motor stimulation of the affected hand produced ipsilateral activation in the premotor area in all patients, the SMA in two patients, and SII in two patients. Vibrotactile stimulation resulted in activation of the ipsilateral SII in all subjects. Median nerve stimulation of the affected hand produced ipsilateral long-latency SEPs in fronto-centro-parietal areas, whereas stimulation of the non-affected hand produced normal early cortical potentials in the contralateral hemisphere. Our results suggest that residual function in the paretic hand is warranted through non-primary motor and sensory areas, and higher order associative areas in the intact hemisphere.

Adult↗
PubMed2000

EEG-triggered functional MRI in patients with pharmacoresistant epilepsy.

Functional magnetic resonance imaging (fMRI) triggered by scalp electroencephalography (EEG) recordings has become a promising new tool for noninvasive epileptic focus localization. Studies to date have shown that it can be used safely and that highly localized information can be obtained. So far, no reports using comprehensive clinical information and/or long-term follow-up after epilepsy surgery in a larger patient group have been given that would allow a valuable judgment of the utility of this technique. Here, the results of 11 patients with EEG-triggered fMRI exams who also underwent presurgical evaluation of their epilepsy are given. In most patients we were able to record good quality EEG inside the magnet, allowing us to trigger fMRI acquisition by interictal discharges. The fMRI consisted of echoplanar multislice acquisition permitting a large anatomical coverage of the patient's brain. In 8 of the 11 patients the exam confirmed clinical diagnosis, either by the presence (n = 7) or absence (n = 1) of focal signal enhancement. In six patients, intracranial recordings were carried out, and in five of them, the epileptogenic zone as determined by fMRI was confirmed. Limitations were encountered a) when the focus was too close to air cavities; b) if an active epileptogenic focus was absent; and c) if only reduced cooperation with respect to body movements was provided by the patient. We conclude that EEG-triggered fMRI is a safe and powerful noninvasive tool that improves the diagnostic value of MRI by localizing the epileptic focus precisely.

Adolescent↗
PubMed2000

Dysgenetic mesial temporal sclerosis: an unrecognized entity.

Mesial temporal sclerosis (MTS) is the most frequently encountered lesion in adult patients with intractable temporal epilepsy; it is found in isolation in approximately two-thirds of surgically treated cases. Whereas the exact etiology of MTS is still controversial, several reports suggest that this pathologic lesion is both the cause and the consequence of chronic seizures and develops progressively during childhood secondary to recurrent seizures. In order to evaluate the clinical importance of MTS in children, we retrospectively reviewed the clinical charts of children who underwent surgery for medically intractable temporal epilepsy and report cases presenting an amygdalo-hippocampic dual pathology. Six children aged 1.5-16 years (mean +/- SD: 7.5 +/- 3 years) presenting with partial complex seizures (5 cases) or extension spasms (1 case), with onset from 6 months to the age of 8.5 years (mean seizure onset +/- SD: 3 +/- 5 years) underwent anterior temporal lobectomy including resection of the amygdala and hippocampus. All patients exhibited variable degrees of severity of neuronal loss and gliosis in the amygdala and/or hippocampus. The pathological picture of MTS was not isolated, however. Careful pathological examination has thus shown foci of amygdalo-hippocampic neuronal dysplasia in six patients, with concomitant bilaminated fascia dentata in two cases. Postoperatively, no mortality or morbidity was encountered. After a mean follow-up of 2.5 years, four patients are seizure free. One patient had a 80% rate of improvement in seizure frequency, though still having occasional febrile convulsions. In another patient, complex partial seizures resolved, but rare episodes of absence were still observed. These data are in keeping with the hypothesis that MTS could be secondary to repeated seizures. The analysis of this series of patients could suggest that mesiotemporal dysplastic lesions within the amygdalo-hippocampic structures induce seizures, which, in turn, will favor the development of MTS during childhood. MTS could then lead to synaptic reorganization, which can express abnormal hyperexcitability and result in more recurrent seizures. In this way a vicious circle is set up, which may explain the progression of seizures in some patients.

Adolescent↗
PubMed2000

Sleep in right hemispherectomized patients: evidence of electrophysiological compensation.

OBJECTIVES: The goal of this study is to provide a better understanding of the role of the cortex in sleep's macro- and microstructure modulation. METHODS: Sleep architecture and phasic events were investigated in 4 patients having undergone right functional or anatomical hemispherectomy and 8 control subjects. Between-groups differences were assessed using the Wilcoxon-Mann-Whitney test. RESULTS: Findings provide evidence for overall similarity between patients' and control subjects' left hemispheric sleep architecture. In addition, results clearly indicate that it is possible to detect electrical activity over the operated side of a hemispherectomized patient's brain, even when resection of the hemi-cortex has been complete. Finally, findings provide evidence for similar left and right hemispheric relative spectral activities and for an increase in fast activity bands over the intact hemisphere in anatomical hemispherectomized patients. CONCLUSIONS: This study provides evidence that right hemispherectomy does not produce significant sleep architecture alterations as recorded over the intact hemisphere. In addition, residual activity detected over the operated side in anatomical hemispherectomized patients is interpreted as resulting from volume conduction originating from generators located in the intact hemisphere. Finally, there is strong evidence for electrophysiological compensation in the intact hemisphere following complete resection of the contralateral hemi-cortex.

Adolescent↗
PubMed2000

Using proton magnetic resonance spectroscopic imaging to predict in vivo the response of recurrent malignant gliomas to tamoxifen chemotherapy.

OBJECTIVE: Most patients with a malignant glioma spend considerable time on a treatment protocol before their response (or nonresponse) to the therapy can be determined. Because survival time in the absence of effective therapy is short, the ability to predict the potential chemosensitivity of individual brain tumors noninvasively would represent a significant advance in chemotherapy planning. METHODS: Using proton magnetic resonance spectroscopic imaging (1H MRSI), we studied 16 patients with a recurrent malignant glioma before and during treatment with high-dose orally administered tamoxifen. We evaluated whether 1H MRSI data could predict eventual therapeutic response to tamoxifen at the pretreatment and early treatment stages. RESULTS: Seven patients responded to tamoxifen therapy (three with glioblastomas multiforme; four with anaplastic astrocytomas), and nine did not (six with glioblastomas multiforme; three with anaplastic astrocytomas). Responders and nonresponders exhibited no differences in their age, sex, tumor type, mean tumor volume, mean Karnofsky scale score, mean number of weeks postradiotherapy, or mean amount of prior radiation exposure. Resonance profiles across the five metabolites measured on 1H MRSI spectra (choline-containing compounds, creatine and phosphocreatine, N-acetyl groups, lactate, and lipids) differed significantly between these two groups before and during treatment. Furthermore, linear discriminant analyses based on patients' in vivo biochemical information accurately predicted individual response to tamoxifen both before and at very early treatment stages (2 and 4 wk). Similar analyses based on patient sex, age, Karnofsky scale score, tumor type, and tumor volume could not reliably predict the response to tamoxifen treatment at the same time periods. CONCLUSION: It is possible to accurately predict the response of a tumor to tamoxifen on the basis of noninvasively acquired in vivo biochemical information. 1H MRSI has potential as a prognostic tool in the pharmacological treatment of recurrent malignant gliomas.

Administration, Oral↗
PubMed2000

Acquired hippocampal damage after temporal lobe seizures in 2 infants.

Two infants developed unilateral hippocampal swelling on magnetic resonance imaging after prolonged seizures of temporal origin. Subsequent images suggested hippocampal sclerosis. The first child had febrile status epilepticus with exanthem subitum and developed refractory complex partial seizures. Histological findings after temporal lobectomy confirmed hippocampal sclerosis but also revealed sequelae of a focal encephalitis and microdysgenesis of the hippocampus. The second child had signs of brain dysgenesis, but acquired hippocampal damage affecting each side successively was documented by serial magnetic resonance imaging. These cases illustrate that different clinical conditions combining preexisting and acquired pathological characteristics can lead to hippocampal sclerosis.

Epilepsy, Temporal Lobe↗
PubMed1999

Brain biopsy in patients with acquired immunodeficiency syndrome: diagnostic value, clinical performance, and survival time.

BACKGROUND: Despite extensive discussion in recent years, brain biopsy in patients positive for human immunodeficiency virus who manifest cerebral mass lesions remains an ill-defined step in management. METHODS: Prebiopsy data of 26 human immunodeficiency virus-positive patients with cerebral mass lesions who underwent computed tomography-guided stereotactic brain biopsy (SBB) were reviewed by a specialist in infectious diseases and by a neuroradiologist to establish a clinical diagnosis and a treatment plan for each patient. The postbiopsy diagnosis was compared with the prebiopsy diagnosis. Long-term patient outcome after SBB was recorded by means of a clinical performance scale to estimate its impact on life expectancy and clinical performance. RESULTS: The SBB was diagnostic in 25 patients (96%). Potentially treatable disease was diagnosed in 21 patients (81%), and specific therapy was initiated in 17 patients (65%); 10 patients (39%) were able to complete therapy. The SBB corroborated the clinical diagnosis in 13 (52%) of 25 patients. The group with identical clinical and biopsy-proved diagnoses showed significantly better response to therapy (P = .02), clinical performance (P = .04), and survival after biopsy (P = .01), as compared with the group with different clinical and biopsy-proved diagnosis, although no significant difference was found for the degree of immunosuppression. Only completion of the treatment plan increased life expectancy significantly (P = .008). CONCLUSIONS: These data show that in human immunodeficiency virus-positive patients with brain mass lesions, SBB has a high diagnostic yield. A subgroup of patients will benefit from specific therapy guided by the SBB result. The procedure should, however, be strictly limited to patients able to tolerate specific therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Multiple microvascular and astroglial 5-hydroxytryptamine receptor subtypes in human brain: molecular and pharmacologic characterization.

Physiologic and anatomic evidence suggest that 5-hydroxytryptamine (5-HT) neurons regulate local cerebral blood flow and blood-brain barrier permeability. To evaluate the possibility that some of these effects occur directly on the blood vessels, molecular and/or pharmacologic approaches were used to assess the presence of 5-HT receptors in human brain microvascular fractions, endothelial and smooth muscle cell cultures, as well as in astroglial cells which intimately associate with intraparenchymal blood vessels. Isolated microvessels and capillaries consistently expressed messages for the h5-HT1B, h5-HT1D, 5-HT1F, 5-HT2A but not 5-HT7 receptors. When their distribution within the vessel wall was studied in more detail, it was found that capillary endothelial cells exhibited mRNA for the h5-HT1D and for the 5-HT7 receptors whereas microvascular smooth muscle cells, in addition to h5-HT1D and 5-HT7, also showed polymerase chain reaction products for h5-HT1B receptors. Expression of 5-HT1F and 5-HT2A receptor mRNAs was never detected in any of the microvascular cell cultures. In contrast, messages for all 5-HT receptors tested were detected in human brain astrocytes with a predominance of the 5-HT2A and 5-HT7 subtypes. In all cultures, sumatriptan inhibited (35-58%, P < .05) the forskolin-stimulated production of cyclic AMP, an effect blocked by the 5-HT1B/1D receptor antagonists GR127935 and GR55562. In contrast, 5-carboxamidotryptamine induced strong increases (> or = 400%, P < .005) in basal cyclic AMP levels that were abolished by mesulergine, a nonselective 5-HT7 receptor antagonist. Only astroglial cells showed a ketanserin-sensitive increase (177%, P < .05) in IP3 formation when exposed to 5-HT. These results show that specific populations of functional 5-HT receptors are differentially distributed within the various cellular compartments of the human cortical microvascular bed, and that human brain astroglial cells are endowed with multiple 5-HT receptors. These findings emphasize the complex interactions between brain serotonergic pathways and non-neuronal cells within the CNS and, further, they raise the possibility that some of these receptors may be activated by antimigraine compounds such as brain penetrant triptan derivatives.

Astrocytes↗
PubMed1999

Psychosocial functioning in chronic epilepsy: relation to hippocampal volume and histopathological findings.

MRI volumetric measurements of the ipsi- and contralateral hippocampal volume (HV) were performed in a group of 37 patients with lesional and non-lesional temporal (TLE), and extratemporal lobe (ETLE) lobe epilepsy. Twenty-six patients underwent surgery and the resected tissues subjected to histopathological examination. Psychosocial scores were calculated on the basis of employment, partnership/family status and presence of a positive psychiatric history. Poorest values were obtained for the group with right lesional and non-lesional TLE (RTLE, p < 0.001). In this group, significant positive correlations between psychosocial functioning and the left hippocampal volume or age of onset were observed. We found that the left hippocampal volume in RTLE was smaller with increasing epilepsy duration. We conclude that patients with RTLE represent a particular group with regard to the structural and psychosocial consequences of chronic epilepsy. With regard to histopathological analysis, no particular type of lesion was identified as the major determinant of the results described above.

Adult↗
PubMed1998

Apoptosis is induced in glioma cells by antisense oligonucleotides to protein kinase C alpha and is enhanced by cycloheximide.

The protein kinase C (PKC) activity of human glioma cells correlates with their rate of proliferation. We report here that the down-regulation of the predominant PKC isoform of glioma cells, alpha, by antisense phosphorothioate oligonucleotides (AS PTO) significantly reduced the rate of proliferation of three human glioma cell lines. This reduction in growth rate was attributed to apoptosis, as assessed by terminal deoxynucleotidyl transferase (TdT) assay. Unexpectedly, when low concentrations of the protein synthesis inhibitor cycloheximide (CHX) were administered to A172 cells immediately prior to AS PTO treatment, a marked enhancement in the number of apoptotic cells was observed. These findings suggest that PKC alpha plays a pivotal role in the ability of gliomas to avoid apoptotic cell death.

Apoptosis↗
PubMed1998

The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy.

OBJECTIVE: The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. MATERIALS & METHODS: We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. RESULTS: Of the 77 patients in the study, 36 had target volumes positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. CONCLUSION: We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volumes and fractionation regimens minimizing possible toxicity to normal tissue.

Adolescent↗
PubMed1998

Continuous unilateral epileptiform discharge and language delay: effect of functional hemispherectomy on language acquisition.

PURPOSE: To assess the efficacy of functional hemispherectomy in promoting language acquisition in a child with severe language delay and continuous left hemispheric epileptiform discharge in the absence of clinical seizures. We report a 6-month-old girl who initially presented with a right hemiparesis secondary to a lesion of probable prenatal origin in the distribution of the left middle cerebral artery. Weeks later, she developed infantile spasms. At 1.5 years of age, because of intractable seizures, the patient had fenestration of the left porencephalic cyst and anterior temporal lobectomy. The seizures ceased; however, language development remained limited to 35 words at 3.5 years of age. The EEG showed almost continuous epileptiform activity over the left hemisphere with no independent epileptiform potentials contralaterally. She underwent a functional left hemispherectomy. METHODS: Imaging, electroencephalographic investigation, pre- and postoperative psychological and speech assessment were carried out. RESULTS: Considerable language, speech, and behavior improvement was noted within 2 months of surgery. CONCLUSIONS: Interictal epileptiform discharges can interfere with the development of contralateral hemispheric function in the absence of clinical seizures. Early functional hemispherectomy may have a role in promoting optimal language development in appropriately selected patients. Although the primary indication for functional hemispherectomy is to control intractable seizures, a secondary proposed indication is to reduce functional impairment of the other hemisphere by electrical interference.

Brain↗
PubMed1998

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography.

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.

Adult↗