Biomedical subjects

Philippe Coubes

Publications and source records attributed to Philippe Coubes.

16 recordsLinked to original sources

PubMed2006

Correlation of preoperative thallium SPECT with histological grading and overall survival in adult gliomas.

BACKGROUND: The management and prognosis of a glioma depend on the tumour's histological grade. Thus, preoperative prediction of the grade is routinely needed to indicate whether surgery or biopsies are required. It has been proposed that thallium single photon emission computed tomography (SPECT), in a relative short series, will aid this prediction. AIM: To confirm the correlation between the results of preoperative thallium SPECT and grade of tumour as well as patient survival, and to define the cut-off value of the optimal thallium index for the detection of high grade gliomas in a large series of patients. METHODS: One hundred and eighteen patients treated for glioma were retrospectively included in this study. All patients underwent preoperative 201Tl SPECT upon initial presentation and were referred for neurosurgery. Initial scintigraphic findings were correlated with the histological grade of the tumour and overall patient survival. RESULTS: Thallium uptake was highly correlated with histological grade; the mean thallium indices for low grade and high grade gliomas were 1.8 and 4.9, respectively. On the basis of receiver operating characteristic analysis, the optimal cut-off value of the thallium index for the detection of high grade glioma was determined. By using 2.2 as the value for the threshold thallium index, the sensitivity and specificity were 93% and 72%, respectively. Kaplan-Meier estimates of the overall survival curves, as a function of the thallium index, indicated that it was correlated with the overall survival (P<0.001). CONCLUSION: Thallium SPECT provides useful information about the histological grade of the tumour and overall patient survival. Additionally, in spite of its relatively weak resolution, it appears to be a powerful routine clinical tool for the management of gliomas.

Brain Neoplasms↗

PubMed2005

Co-registration of stereotactic MRI and isofieldlines during deep brain stimulation.

OBJECT: The parameter adjustment process during deep brain stimulation (DBS) for dystonia remains time consuming and based on clinical observation alone. The aim was to correlate the electric field with the GPi anatomy to be able to study the stimulated volume. METHODS: We developed a computer-assisted method (model) for visualizing electric field in reference to the stereotactic space. Electric field values were correlated with the GPi anatomy (stereotactic Magnetic Resonance Imaging) in one reference patient. RESULTS: Using this methodology it becomes possible to correlate the electric field distributions for patient specific parameters with the anatomical information. The application to one patient showed that the 0.1V/mm isofieldline fits best with the lateral GPi borders at the level of the stimulated contacts. CONCLUSIONS: The electric field is a crucial parameter as it is assumed to be responsible for triggering action potentials. Electric field visualisation allows the calculation of the stimulated volume for a given isoline. Its application to our whole patient population might help in determining a threshold for obtaining a therapeutic effect, to date unknown, and consequently in optimizing the parameter setting in each patient.

Brain↗

PubMed2005

Pallidal stimulation improves pantothenate kinase-associated neurodegeneration.

Pantothenate kinase-associated neurodegeneration (PKAN) causes a progressive generalized dystonia which remains pharmacologically intractable. We performed bilateral internal globus pallidus stimulation in six patients with genetically confirmed PKAN who obtained a major and long-lasting improvement of their painful spasms, dystonia, and functional autonomy. This study shows the benefits of pallidal DBS for the dystonia of PKAN patients.

Adolescent↗

PubMed2005

Increased number of neural progenitors in human temporal lobe epilepsy.

An increased neurogenesis is reported in animal models of mesial temporal lobe epilepsy (MTLE) but the fate of newborn cells is unknown. Here, we attempted to demonstrate neurogenesis in adult epileptic tissue obtained after hippocampectomy. MTLE hippocampi showed increased expression of division markers and of Musashi-1, a marker of neural progenitors, compared to control hippocampi. Large quantities of Musashi-1+ cells were obvious in the subgranular layer and the subventricular zone, both known neurogenic areas, and in the fissura hippocampi. Musashi-1 was expressed by small cells that were mainly vimentin+ or nestin+, rarely Dcx+ or PSA-NCAM+ and negative for markers of mature neurons or astrocytes. Some of them are present in the granular layer, the hilus, and CA1 area resembling the ectopic positions described in rodents. These findings demonstrate that neural progenitors proliferate in chronic epilepsy and suggest that the fissura hippocampi behaves like another neurogenic area.

Adolescent↗

PubMed2005

Deep brain stimulation in movement disorders: stereotactic coregistration of two-dimensional electrical field modeling and magnetic resonance imaging.

OBJECT: Adjusting electrical parameters used in deep brain stimulation (DBS) for dystonia remains time consuming and is currently based on clinical observation alone. The goal of this study was to visualize electrical parameters around the electrode, to correlate these parameters with the anatomy of the globus pallidus internus (GPI), and to study the relationship between the volume of stimulated tissue and the electrical parameter settings. METHODS: The authors developed a computer-assisted methodological model for visualizing electrical parameters (the isopotential and the isoelectric field magnitude), with reference to the stereotactic target, for different stimulation settings (monopolar and bipolar) applied during DBS. Electrical field values were correlated with the anatomy of the GPI, which was determined by performing stereotactic magnetic resonance imaging in one reference patient. By using this method it is possible to compare potential and electrical field distributions for different stimulation modes. In monopolar and bipolar stimulation, the shape and distribution of the potential and electrical field are different and depend on the stimulation voltage. Distributions visualized for patient-specific parameters can be subsequently correlated with anatomical information. The application of this method to one patient demonstrated that the 0.2-V/ mm isofield line fits best with the lateral GPI borders at the level of the stimulated contacts. CONCLUSIONS: The electrical field is a crucial parameter because it is assumed to be responsible for triggering action potentials. Electrical field visualization allows the calculation of the stimulated volume for a given isoline. Its application to an entire series of patients may help determine a threshold for obtaining a therapeutic effect, which is currently unknown, and consequently may aid in optimizing parameter settings in individual patients.

Adolescent↗

PubMed2005

Stereotactic coregistration of 201Tl SPECT and MRI applied to brain tumor biopsies.

UNLABELLED: The aim of the present study was to determine the clinical feasibility of integration of stereotactic SPECT (sSPECT) with 201Tl in the stereotactic MRI (sMRI)-based planning of brain tumor biopsy. Furthermore, the predictive value of the integrated techniques was analyzed by comparison with the corresponding histologically determined metabolic activity. METHODS: Ten patients underwent combined 201Tl SPECT- and MRI-guided stereotactic biopsy of intracranial lesions according to a previously described technique. An area of abnormal 201Tl uptake was used to guide the stereotactic biopsy trajectory. Several samples were taken along the trajectory above and beneath the target. An extensive histologic diagnosis (tumor grade, mitotic index [MI], and Ki67 index) and the 201Tl index were obtained for all samples and compared statistically. RESULTS: Combined 201Tl sSPECT- and sMRI-guided biopsy could be performed on all patients. Ki67 index, MI, and tumor grade correlated significantly. The correlations between MI or Ki67 index and 201Tl index were not significant (0.18 and 0.09, respectively). A trend to significance existed between tumor grade and 201Tl index (R = 0.31; P = 0.06). Mean 201Tl index for grade III tumors (3.27 +/- 1.89 [SD]) was significantly different from that for grade IV tumors (4.34 +/- 1.29). The sample position on the trajectory correlated with the MI (R = 0.39; P = 0.01). In 4 of the 10 patients, a variation in tumor grade could be observed along the trajectory. In all patients, the highest proliferative activity was within 5-10 mm of the target. CONCLUSION: These results support the view that 201Tl SPECT may contribute to the successful management of brain tumor patients requiring stereotactic biopsy, without causing a significant increase in discomfort or morbidity. The development of similar techniques integrating sSPECT data in the planning of stereotactic biopsy should be considered by centers performing stereotactic surgery and having access to SPECT technology. In the long term, this technique could become a support for focused gene therapy and cell transfer.

Adult↗

PubMed2004

Thallium SPECT-based stereotactic targeting for brain tumor biopsies. A technical note.

MR or CT images acquired under stereotactic conditions are often used to plan and guide brain tumor biopsies. The objective of this study was to design and test a methodology to increase target selection reliability by acquiring stereotactic 201Tl-SPECT data and by integrating them into the surgical planning. The three-headed Philips gamma camera system (Prism 3000) was adapted to stereotactic acquisitions (patient pallet, headholder). A software was developed for the stereotactic target determination based on SPECT images (pixel with the highest metabolic activity inside the tumor). The whole system accuracy was tested with the Elekta phantom adapted to SPECT imaging. The methodology was applied to one brain tumor biopsy. Comparison of the specific phantom coordinates evaluated in SPECT with the theoretical ones did not reveal any significant difference. In this way, our methodology including our homemade software (identification of the stereotactic frame, determination of the pixel with highest metabolic activity within the tumor in the stereotactic coordinate system) was validated. No significant geometric deformations were detected. Clinical feasibility was confirmed in 1 patient with a brain glioma. This study illustrates the feasibility and the accuracy of SPECT acquisitions with the stereotactic Leksell G-frame. The clinical relevance of this methodology is under evaluation. This definition of the target, based on the point with the highest metabolic activity within the tumor, might lead to improved diagnosis in biopsies and patient management. Furthermore, it might prepare the future for therapy aimed at delivering a therapeutic agent within a tumor.

Biopsy↗

PubMed2004

Deep brain stimulation in myoclonus-dystonia syndrome.

Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder characterized by bilateral myoclonic jerks. An 8-year-old boy presenting with early onset, medically intractable, MDS due to a mutation in the epsilon-sarcoglycan gene (SGCE) underwent chronic bilateral stimulation of the globus pallidus internus, which eliminates both myoclonus and dystonia. We conclude that deep brain stimulation can be an effective and safe treatment for MDS.

Anticonvulsants↗

PubMed2004

Deep brain stimulation for dystonia confirming a somatotopic organization in the globus pallidus internus.

OBJECT: In patients with dystonia, symptoms vary greatly in their extent and severity. The efficacy of pallidal stimulation is now established, but an interindividual variability in the responses to this treatment exists. A retrospective analysis of postoperative magnetic resonance (MR) images demonstrated millimetric variations in the positions of electrode contacts inside the posterolateroventral portion of the globus pallidus internus (GPi). It therefore seemed very likely that there is a somatotopic organization within the GPi. The goal of this study was to examine the positions of specific electrode contacts according to patients' clinical evolution, so that a somatotopic organization within the GPi could be defined. METHODS: This study included 19 patients (17 of whom were right handed) with generalized dystonia who were treated by bilateral stimulation of the GPi. Patients were examined pre- and postoperatively by using the Burke-Fahn-Marsden Dystonia Rating Scale. Dividing the patient's body into three parts--cervicoaxial area, superior limb, and inferior limb--we determined the following: 1) where the dystonic symptoms started; 2) where symptoms predominated at the time of surgery; and 3) where the highest postoperative improvement was observed. Variations in clinical response were correlated to the positions of the electrode contacts. All activated electrode contacts were in the posterolateroventral portion of the GPi (Laitinen target). A correlation between the contact location measured longitudinally and the part of the body in which the highest improvement was observed (three different areas; p = 0.004) showed that a location more anterior for the inferior limb and one more posterior for the superior limb were delineated for the right side, but not for the left side. CONCLUSIONS: Inside the posterolateroventral subvolume of the GPi on the right side, three statistically different locations of electrode contacts were determined to be primary deep brain stimulation treatment sites for particular body parts in cases of dystonia.

Adult↗

PubMed2004

Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results.

OBJECT: Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation. METHODS: Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation. The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (+/- standard deviation) clinical and functional BFMDRS scores had improved by 79 +/- 19% and 65 +/- 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95). CONCLUSIONS: Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.

Adult↗

PubMed2002

Inflammatory reactions in human medial temporal lobe epilepsy with hippocampal sclerosis.

Many experimental studies suggest that NFkappaB, a transcription factor involved in acute inflammation, and cytokines participate in neuronal excitability and/or glial scar formation in epilepsy. In this report, we looked for the expression of NFkappaB in hippocampi surgically removed in patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS) who had an history of febrile convulsions. We analyzed 18 hippocampi from epileptic patients with MTLE and HS, and we used as control specimens three hippocampi from non-epileptic patients and four hippocampi from patients with cryptogenic MTLE without HS. We used antibodies raised against the NFkappaB-p65 subunit and we identified glial cells with specific antibodies. Hippocampi from patients with MTLE and HS displayed severe neuronal loss surrounded by gliosis in CA1 area and more or less in CA3/CA4 areas. Double immunolabeling showed that reactive astrocytes of lesioned areas over-expressed NFkappaB-p65 (significantly when compared to control specimens). Moreover, some surviving pyramidal neurons in these areas and numerous dentate granule cells were strongly positive for NFkappaB-p65 in cytoplasm and nucleus, whereas control hippocampi showed a faint basal cytoplasmic staining in neurons. These results suggest that in epileptic hippocampi with typical sclerosis, inflammatory processes are chronically active or transiently re-induced by recurrent seizures. Whether NFkappaB over-expression reflects protective or deleterious mechanisms in the epileptic focus remains to be elucidated.

Adolescent↗

PubMed2002

Immature-like astrocytes are associated with dentate granule cell migration in human temporal lobe epilepsy.

In human temporal lobe epilepsy, a dispersion of dentate granule cells is frequently described in adults who had an early risk factor. To elucidate the role of glia in this phenomenon, we investigated neuronal dispersion, astrocyte organization and expression of intermediate filaments of mature and immature astrocytes (i.e. glial fibrillary acidic protein (GFAP) and vimentin, respectively) in seven subjects with early febrile seizures (F(+)) and five subjects with other etiologies than febrile seizures (F(-)). Compared to F(-) patients, a majority of F(+) subjects showed neuronal dispersion and vimentin expression in radial glia. However, in two patients with the maximal dispersion, radial processes expressed only GFAP. We suggest that granule cell migration that occurs in adult epileptic focus results from the transient occurrence of immature-like glia throughout the granular layer.

Adult↗

PubMed2002

Deep brain stimulation for dystonia. Surgical technique.

Stimulation electrodes are implanted under general anesthesia, without intra-operative electrophysiology or clinical testing, based only on stereotactic MRI and direct anatomical localization of the postero-ventro-basal GPi. We retrospectively analyzed the surgical procedure that has been designed and implemented in our center, using the Leksell G frame, for initiating deep brain stimulation in 65 dystonic patients. We report the surgical technique and the hardware and software complications. We recommend immediate postoperative stereotactic MRI under general anesthesia as a prerequisite to check the reliability of MR acquisition (magnet stability) and the exact localization of each electrode. This technique allowed us to reduce the duration of the operation to 4 h, including general anesthesia, frame fixation, MRI acquisition, implantation of two electrodes under radioscopic control, immediate postoperative stereotactic MRI and frame removal. Surgery-related morbidity was very low with a 0% hemorrhage rate and three delayed unilateral infections re-operated 6 months later. Hardware and software complications were rare. The advances in 3D-MR imaging permit the electrode implantation for deep brain stimulation without resorting to intraoperative localization techniques, which is especially helpful in children and for treating dystonia. The maximum follow-up period is 58 months (first case: November 1996). GPi stimulation has proven to be an effective treatment for most dystonic syndromes with particular efficacy in the disease due to the DYT1 mutation.

Adolescent↗

PubMed2002

Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting of the globus pallidus internus in the performance of deep brain stimulation for treatment of dystonia.

OBJECT: To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia. METHODS: Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure-posterior commissure (AC-PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging-based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates by applying the Student t-test. A significant difference (p < 0.001) was demonstrated in x, y, and z directions between MR imaging-based and Schaltenbrand atlas-derived target coordinates. The comparison with normalized Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in the y and z directions, although not in the x direction (p = 0.12). No significant correlation existed between MR imaging-based target coordinates and patient age (p > 0.1). No significant correlation was observed between MR imaging-based target coordinates and patient sex in the y and z directions (p > 0.9), although it was significant in the x direction (p < 0.05). A significant variation in coordinates and the length of the AC-PC line was revealed only in the y direction (p < 0.005). CONCLUSIONS: A significant difference was found between target coordinates obtained by direct visual targeting on MR images (validated by postoperative clinical results) and those obtained by indirect targeting based on atlases.

Adolescent↗

PubMedDate not supplied

Wicket spikes during rapid eye movement sleep.

Wicket spikes correspond to a normal variant activity. They usually occur in adults over 50 years of age during drowsiness and light nonrapid eye movement (NREM) sleep. No data exist in the precise distribution of this activity during all the different sleep stages, particularly during rapid eye movement (REM) sleep. The authors report five observations of persistence of this activity during REM sleep. Only one patient was over 50 years of age. The authors found a predominant expression on one temporal side, but inconsistently on the left side (three on the left side versus two on the right side). Wicket spikes always persist in REM sleep. They have an identical morphology as drowsiness or stage 2 sleep. There were no changes in their location. The authors found no correlation with the tonic or phasic phases of REM sleep.

Adult↗

PubMedDate not supplied

Quantifying motion in dystonic syndromes: the bare essentials.

Quantifying movement disorders is becoming crucially important in neurosurgery units to evaluate the efficacy of new therapeutic interventions such as deep brain stimulation. Kinematic analysis, available for more than a century, may represent an adequate solution to this problem. However, quantifying movement disorders poses a number of technical problems. To help clinicians quantify movement disorders, the authors present data recorded in patients with dystonic syndromes and explore the question of movement "normality" in these patients when they receive deep brain stimulation of the internal globus pallidus. In particular, they show that when one control group (n = 11) and a group of dystonic patients (n = 11) are compared, it is possible to detect subtle changes in the performance of a double-handed finger to nose test. These differences persist in the absence of differences in the clinical evaluation of these patients. Suggestions regarding the compromises to make and pitfalls to avoid when quantifying movement disorders are discussed.

Dystonic Disorders↗