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ABSTRACT: Morphological studies after Gamma Knife radiosurgery (GKRS) revealed endothelial destruction followed by spindle-shaped cell proliferation in the subendothelial region and in the connective tissue stroma of arteriovenous malformation (AVM) vessels. Histological, immunohistochemical and ultrastructural characteristics of this spindle-shaped cell population in the irradiated AVMs were reminiscent of those described as myofibroblasts in wound healing processes and pathological fibromatoses. These modified fibroblasts have contractile capacity, therefore this might contribute to the vessel occlusion, shrinking process and final volume reduction of AVMs after GKRS. Similar histopathological changes were observed in a cavernous malformation following high-dose irradiation.
Progress in neurological surgery 01/2013; 27:119-29.
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Abdelwahed Chtarto,
Olivier Bockstael,
Elias Gebara,
Katia Vermoesen,
Catherine Melas,
Catherine Pythoud, Marc Levivier,
Olivier De Witte,
Ruth Luthi-Carter,
Ralph Clinkers,
Liliane Tenenbaum
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ABSTRACT: Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.
PLoS ONE 01/2013; 8(1):e53156. · 4.09 Impact Factor
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Olivier Bockstael,
Mansoor Sharifi,
Jean-Marie Jaspar,
Enni Lehtonen,
Jacques Brotchi,
Marc Levivier,
Abdelwahed Chtarto,
David Blum,
Liliane Tenenbaum,
Xin Yang, Thierry Velu,
Laurence Abeloos
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ABSTRACT: The adult rat brain subventricular zone (SVZ) contains proliferative precursors that migrate to the olfactory bulb (OB) and differentiate into mature neurons. Recruitment of precursors constitutes a potential avenue for brain repair. We have investigated the kinetics and cellular specificity of transgene expression mediated by AAV2/1 vectors (i.e., adeno-associated virus type 2 pseudotyped with AAV1 capsid) in the SVZ. Self-complementary (sc) and single-stranded (ss) AAV2/1 vectors mediated efficient GFP expression, respectively, at 17 and 24 hr postinjection. Transgene expression was efficient in all the rapidly proliferating cells types, that is, Mash1(+) precursors (30% of the GFP(+) cells), Dlx2(+) neuronal progenitors (55%), Olig2(+) oligodendrocyte progenitors (35%), and doublecortin-positive (Dcx(+)) migrating cells (40%), but not in the slowly proliferating glial fibrillary acidic protein-positive (GFAP(+)) neural stem cell pool (5%). Because cell cycle arrest by wild-type and recombinant AAV has been described in primary cultures, we examined SVZ proliferative activity after vector injection. Indeed, cell proliferation was reduced immediately after vector injection but was normal after 1 month. In contrast, migration and differentiation of GFP(+) precursors were unaltered. Indeed, the proportion of Dcx(+) cells was similar in the injected and contralateral hemispheres. Furthermore, 1 month after vector injection into the SVZ, GFP(+) cells, found, as expected, in the OB granular cell layer, were mature GABAergic neurons. In conclusion, the rapid and efficient transgene expression in SVZ neural precursors mediated by scAAV2/1 vectors underlines their potential usefulness for brain repair via recruitment of immature cells. The observed transient precursor proliferation inhibition, not affecting their migration and differentiation, will likely not compromise this strategy.
Human gene therapy 04/2012; 23(7):742-53. · 4.20 Impact Factor
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ABSTRACT: Histopathological investigations revealed acute-, subacute-, and chronic-type tissue responses, accompanied by inflammatory cell reaction in radiosurgery treated cerebral metastases originating from different primary cancers. Immunohistochemistry demonstrated that the preponderance of CD68-positive macrophages and CD3-positive T lymphocytes in the inflammatory infiltration developed in better controlled metastases ( > 5 months). In contrast, it was sparse or absent in poorly controlled neoplasms ( < 5 months) after radiosurgery. This inflammatory reaction may be stimulated by the ionizing energy, probably influenced by the general condition of the patients' immune system as well, and seems to play a role in local tumor control after focused radiation.
Progress in neurological surgery 01/2012; 25:30-8.
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ABSTRACT: To study with a non invasive method any potential radiological change on the superior cerebellar artery (SCA) in patients treated radiosurgically for classic trigeminal neuralgia (CTN).
A retrospective measure of maximal dose received by SCA was performed analyzing the treatment planning in 55 consecutive patients treated by Gamma Knife radiosurgery for an CTN, then, a prospective study was designed using high resolution MR, with T2 SPIR, T1 without and with gadolinium enhancement, Proton density, 3D TONE and MIP reconstructions. Inclusion criteria were: patients followed at our institution, follow-up of one year or more, dose received by the SCA of 15 Gy or more and voluntary patient participation in the study. Patients with repeated Gamma Knife radiosurgery for failure or recurrence were excluded. The end points were: SCA occlusion, stenosis or infarction in the territory supplied by SCA.
Sixteen patients were studied, with a mean follow-up of 25.2 months (12-42 months). The mean maximal dose received by the SCA was 57.5 Gy. (15-87 Gy). Among these 16 patients studied, neither obstruction of the SCA nor infarction was demonstrated. In one patient a suspicion of asymptomatic SCA stenosis was visualized distant to the irradiation field.
SCA can receive a high dose of irradiation during radiosurgical treatment for CTN. This study does not confirm any vascular damage to the SCA after radiosurgery for CTN.
Clinical neurology and neurosurgery 09/2011; 113(9):758-61. · 1.30 Impact Factor
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ABSTRACT: In this paper, the authors' goal was to evaluate the impact of PET data on the clinical management of incidental brain lesions in children.
Between 1995 and 2007, 442 children with a newly diagnosed brain lesion were referred to the authors' department. Of these, 55 presented with an incidental brain lesion and were selected for study because MR imaging sequences revealed limitations in assessing the tumor, its evolving nature, and/or the malignant potential of the lesion diagnosed. Thirteen children were studied using FDG-PET and 42 with L-(methyl-(11)C)-methionine (MET)-PET; 3 children underwent both FDG-PET and MET-PET but only the MET-PET results were used in the analysis. The PET and MR images were combined in image fusion navigation planning. Drawing on their experience with PET in adults, the authors proposed the following treatment plans: 1) surgery in children with imaging evidence of increased PET tracer uptake, which is highly specific of tumor and/or malignant tumor tissue; or 2) conservative treatment in children in whom there was little or no tracer uptake on PET. The authors compared the PET data with the MR imaging-based diagnosis and either 1) the results of histological examination in surgically treated cases, or 2) the long-term outcome in untreated cases. They studied PET and MR imaging sensitivity and specificity in detecting tumor and malignant tissues, and evaluated whether PET data altered their clinical management.
Seventeen children had increased PET tracer uptake and underwent surgery. Tumor diagnosis was confirmed in all cases (that is, there were no false-positive findings). Cases in which there was little or no PET tracer uptake supported conservative treatment in 38 children. However, because PET was under evaluation, 16 of 38 lesions that were judged accessible for resection were surgically treated. Histological examination results demonstrated neither malignant nor evolving tumor tissue but yielded 9 indolent tumors (6 dysembryoplastic neuroectodermal tumors, 2 low-grade astrocytomas, and 1 low-grade astrocytoma and dysplasia) and 7 nontumoral lesions (3 cases of vasculitis, 3 of gliosis, and 1 of sarcoidosis). In 22 of the untreated 38 children, stable disease was noted during follow-up (range 18-136 months). Although an absence of PET tracer uptake might not exclude tumor tissue, PET did not reveal any false-negative findings in malignant or evolving tumor tissue detection in cases in which MR imaging showed false-positive and -negative cases in > 35 and 25% of the cases, respectively.
These data confirmed the high sensitivity and specificity of PET to detect tumor as well as malignant tissue. Regarding the treatment of the incidental brain lesions, the PET findings enabled the authors to make more appropriate decisions regarding treatment than those made on MR imaging findings alone. Therefore, the risk of surgically treating a nontumoral lesion was reduced as well as that for conservatively managing a malignant tumor. Nowadays, it is estimated that these data justify conservative management in incidental lesions with low or absent PET tracer uptake.
Journal of Neurosurgery Pediatrics 05/2010; 5(5):479-85. · 1.53 Impact Factor
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ABSTRACT: In this paper, the authors' goal was to evaluate the impact of PET information on brain tumor surgery in children.
Between 1995 and 2007, 442 children were referred to the authors' institution for a newly diagnosed brain lesion. Of these, 85 were studied with FDG-PET and/or L-(methyl-(11)C)-methionine -PET in cases in which MR images were unable to assist in selecting accurate biopsy targets (35 patients) or to delineate tumors for maximal resection (50 patients). In surgical cases, PET and MR images were combined in image fusion planning for stereotactic biopsies or navigation-based resections. The preoperative planning images were compared postoperatively with MR imaging and PET findings and histological data for evaluating the clinical impact on the diagnostic yield and tumor resection.
The PET data influenced surgical decisions or procedures in all cases. The use of PET helped to better differentiate indolent from active components in complex lesions (in 12 patients); improved target selection and diagnostic yield of stereotactic biopsies without increasing the sampling; provided additional prognostic information; reduced the amount of tissue needed for biopsy sampling in brainstem lesions (in 20 cases); better delineated lesions that were poorly delineated on MR imaging and that infiltrated functional cortex (in 50 cases); significantly increased the amount of tumor tissue removed in cases in which total resection influenced survival (in 20 cases); guided resection in hypermetabolic areas (in 15 cases); improved early postoperative detection of residual tumor (in 20 cases); avoided unnecessary reoperation (in 5 cases); and supported the decision to undertake early second-look resection (in 8 cases).
The authors found that PET has a significant impact on the surgical decisions and procedures for managing pediatric brain tumors. Further studies may demonstrate whether PET improves outcomes in children.
Journal of Neurosurgery Pediatrics 05/2010; 5(5):486-99. · 1.53 Impact Factor
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ABSTRACT: To describe the anatomical characteristics and patterns of neurovascular compression in patients suffering classic trigeminal neuralgia (CTN), using high-resolution magnetic resonance imaging (MRI).
The analysis of the anatomy of the trigeminal nerve, brain stem and the vascular structures related to this nerve was made in 100 consecutive patients treated with a Gamma Knife radiosurgery for CTN between December 1999 and September 2004. MRI studies (T1, T1 enhanced and T2-SPIR) with axial, coronal and sagital simultaneous visualization were dynamically assessed using the software GammaPlan™. Three-dimensional reconstructions were also developed in some representative cases.
In 93 patients (93%), there were one or several vascular structures in contact, either, with the trigeminal nerve, or close to its origin in the pons. The superior cerebellar artery was involved in 71 cases (76%). Other vessels identified were the antero-inferior cerebellar artery, the basilar artery, the vertebral artery, and some venous structures. Vascular compression was found anywhere along the trigeminal nerve. The mean distance between the nerve compression and the origin of the nerve in the brainstem was 3.76±2.9mm (range 0-9.8mm). In 39 patients (42%), the vascular compression was located proximally and in 42 (45%) the compression was located distally. Nerve dislocation or distortion by the vessel was observed in 30 cases (32%).
The findings of this study are similar to those reported in surgical and autopsy series. This non-invasive MRI-based approach could be useful for diagnostic and therapeutic decisions in CTN, and it could help to understand its pathogenesis.
European journal of radiology 10/2009; 81(8):1851-7. · 2.65 Impact Factor
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Xin Yang,
Birgit Mertens,
Enni Lehtonen,
Linda Vercammen,
Olivier Bockstael,
Abdelwahed Chtarto, Marc Levivier,
Jacques Brotchi,
Yvette Michotte,
Veerle Baekelandt,
Sophie Sarre,
Liliane Tenenbaum
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ABSTRACT: Efficient protection of dopaminergic neurons against a subsequent 6-hydroxydopamine lesion by glial cell line-derived neurotrophic factor (GDNF) gene delivery has been demonstrated. By contrast, the neurorestorative effects of GDNF administered several weeks after the toxin have been less characterized. In particular, whether these were permanent or dependent on the continuous presence of GDNF remains elusive.
A tetracycline-inducible adeno-associated virus (AAV)-1 vector expressing human GDNF cDNA was administered unilaterally in the rat striatum 5 weeks after 6-hydroxydopamine. Rats were treated with doxycycline (dox) or untreated from the day of vector injection until sacrifice (4 or 14 weeks). A sub-group was dox-treated for 7 weeks then untreated until 14 weeks. The motor behavior was assessed by amphetamine-induced rotations and spontaneous forelimb asymmetry. The amounts of tyrosine hydroxylase (TH), serine-40-phosphorylated TH (S40-TH) and aromatic amino acid decarboxylase (AADC) proteins were compared by western blotting and the dopamine levels quantified by high-performance liquid chromatography.
Dox-dependent behavioral improvements were demonstrated 4 weeks post-vector injection. At later time points, spontaneous partial recovery was observed in all rats, but no further improvement was found in dox-treated animals. TH levels were significantly increased in dox-treated rats at all time points. By contrast, striatal dopamine and S40-TH were increased at 4 weeks, but not 14 weeks, and AADC remained unchanged. Dox withdrawal after 7 weeks, resulted in TH levels comparable to the controls at 14 weeks.
Delayed GDNF gene delivery only transiently improved dopaminergic function. Over the long term, TH was more abundant, but not functional, and the increase was lost when GDNF gene expression was switched off.
The Journal of Gene Medicine 07/2009; 11(10):899-912. · 2.48 Impact Factor
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ABSTRACT: The role of radiation dose delivered to surrounding tissues outside target is often minimized in radiosurgery. We study histopathological effects of dose fall-offs outside the target using an experimental model of trigeminal nerve irradiation in the rat.
Sixteen rats were irradiated with a Gamma Knife at the right trigeminal nerve using a 90-Gy dose and 4 different gradients of dose fall-off; the brainstem at the trigeminal nerve root entry was histologically analyzed 3 months after irradiation.
Four specific histopathological reactions were found as a consequence of the irradiation. All these reactions were significantly related to the gradient of dose fall-off.
Different dose distributions outside the target could produce various histological effects in the irradiated tissue that could influence the outcome of radiosurgical treatment. A more rapid fall-off of dose (higher selectivity) is associated with less risk of histological changes in tissues surrounding the target.
Stereotactic and Functional Neurosurgery 04/2009; 87(3):137-42. · 1.85 Impact Factor
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ABSTRACT: Integrating positron emission tomographic (PET) images into the image-guided resection of high-grade gliomas (HGG) has shown that metabolic information on tumor heterogeneity and distribution are useful for planning surgery, improve tumor delineation, and provide a final target contour different from that obtained with magnetic resonance imaging (MRI) alone in about 80% of the procedures. Moreover, PET guidance helps to increase the amount of tumor removed and to target image-guided resection to anaplastic tissue areas. The present study aims to evaluate whether PET-guided volumetric resection (VR) in supratentorial HGG might add benefit to the patient's outcome.
PET images using [18F]fluorodeoxyglucose (n=23) and [11C]methionine (n=43) were combined with MRI scans in the planning of VR procedures performed at the initial stage in 66 consecutive patients (43 M/23 F) with supratentorial HGG according to the technique previously described. In all cases (35 anaplastic gliomas [20 astrocytomas, 10 oligoastrocytomas, 5 oligodendrogliomas] and 31 glioblastomas [GBM]), level and distribution of PET tracer uptake were analyzed to define a PET contour projected on MRI scans to define a final target contour for VR. Maximal tumor resection was accomplished in each case, with the intention to remove the entire abnormal metabolic area comprised in the surgical planning. Early postoperative MRI and PET assessed tumor resection. Survival analysis was performed separately in anaplastic gliomas and glioblastoma multiforme according to the presence or absence of residual tracer uptake on postoperative PET and according to the presence or absence of residual contrast enhancement on postoperative MRI.
Preoperatively, metabolic information helped the surgical planning. In all procedures, PET contributed to define a final target contour different from that obtained with MRI alone. Postoperatively, 46 of 66 patients had no residual PET tracer uptake (total PET resection), 23 of 66 had no residual MRI contrast enhancement. No additional neurological morbidity due to the technique was reported. A total PET tracer uptake resection was associated with a significantly longer survival in anaplastic gliomas (P = 0.0071) and in glioblastoma multiforme (P = 0.0001), respectively. A total MRI contrast enhancement resection was not correlated with a significantly better survival, neither in anaplastic gliomas (P = 0.6089) nor in glioblastoma multiforme (P = 0.6806).
Complete resection of the increased PET tracer uptake prolongs the survival of HGG patients. Because PET information represents a more specific marker than MRI enhancement for detecting anaplastic tumor tissue, PET-guidance increases the amount of anaplastic tissue removed in HGG.
Neurosurgery 04/2009; 64(3):471-81; discussion 481. · 2.79 Impact Factor
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ABSTRACT: Radiosurgery is currently performed with different systems of focused radiation providing different dose heterogeneities within the target volume. Here, we aimed to study histological consequences of different dose distributions inside the target area in an experimental model of Gamma Knife irradiation in the rat striatum.
Twelve rats were irradiated by Gamma Knife at the same volume in the right striatum; the same margin dose of 45 Gy was prescribed for all rats. Three different dose distributions inside the target volume were applied. Brain sections at the level of the target area were histologically analyzed 3 months after irradiation.
Of the 7 histopathological reactions found as a consequence of the irradiation, 6 of them were significantly related to the gradient of dose heterogeneity within the target volume.
Dose distribution inside the target volume could influence the histological effects of radiosurgical irradiation on tissue included in the target. A high dose in the target volume is more likely to lead to the desired radiobiological result.
Stereotactic and Functional Neurosurgery 03/2009; 87(2):82-7. · 1.85 Impact Factor
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ABSTRACT: The biodistribution of transgene expression in the CNS after localized stereotaxic vector delivery is an important issue for the safety of gene therapy for neurological diseases. The cellular specificity of transgene expression from rAAV2/1 vectors (recombinant adeno-associated viral vectors pseudotyped with viral capsids from serotype 1) using the tetracycline-inducible (TetON) expression cassette in comparison with the cytomegalovirus (CMV) promoter was investigated in the rat nigrostriatal pathway. After intrastriatal injection, although green fluorescent protein (GFP) was expressed mainly in neurons with both vectors, the relative proportions of DARPP-32-positive projection neurons and parvalbumin-positive interneurons were, respectively, 13:1 and 2:1 for the CMV and TetON vectors. DARP32-positive neurons projecting to the globus pallidus were strongly GFP positive with both vectors, whereas those projecting to the substantia nigra pars reticulata (SNpr) were efficiently labeled by the CMV vector but poorly by the TetON vector. Numerous GFP-positive cells were evidenced in the subventricular zone with both vectors. However, in the olfactory bulb (OB), GFP-positive neurons were observed with the CMV vector but not the TetON vector. We conclude that the absence of significant amounts of transgene product in distant regions (SN and OB) constitutes a safety advantage of the AAV2/1-TetON vector for striatal gene therapy. Midbrain injections resulted in selective GFP expression in tyrosine hydroxylase-positive neurons by the TetON vector whereas with the CMV vector, GFP-positive cells covered a widespread area of the midbrain. The biodistribution of GFP protein corresponded to that of the transcripts and not of the viral genomes. We conclude that the rAAV2/1-TetON vector constitutes an interesting tool for specific transgene expression in midbrain dopaminergic neurons.
Human gene therapy 11/2008; 19(11):1293-305. · 4.20 Impact Factor
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ABSTRACT: Since 11C-methionine (MET) heavily accumulates in brain tumors, PET with MET (MET-PET) is proposed for the image-guided planning of their targeted therapy. Determination of bulk tumor limits is therefore a crucial component of MET-PET image analysis. We aimed at validating a Gaussian model of tumor delineation on MET-PET. We choose MET-PET and MRI data obtained in brain metastases to adjust the model. Indeed, MRI limits of these non-infiltrative hypermetabolic brain lesions are efficiently used for their curative treatment.
We developed a three-dimensional (3D) Gaussian model that relates the tumor-limit-defining threshold to maximum and mean count values in the defined tumor volume and to mean count values in a reference region. To adjust the model to experimental data, we selected 25 brain metastases following these criteria: (i) no surgery or classical radiotherapy within 6 months, (ii) no previous radiosurgery, (iii) MET-PET and MRI acquired within a 48-h interval, (vi) necrosis representing less than 25% of tumor volume on MRI. We applied a progressive thresholding procedure on MET-PET so as to match tumor limits on contrast-enhanced co-registered MRI.
In 22 tumors, a match could be reached between tumor margins on MET-PET and MRI. The relation between mean, maximum and threshold values closely fits the 3D-Gaussian model function. We found a quadratic relation between the mean-to-threshold ratio and the maximum-to-cerebellum activity ratio.
A 3D-Gaussian model may describe the limits of MET uptake distribution within brain metastases, providing a simple method for metabolic tumor delineation.
Radiotherapy and Oncology 10/2008; 89(3):270-7. · 5.58 Impact Factor
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ABSTRACT: The biodistribution of transgene expression in the CNS after localized stereotaxic vector delivery is an important issue for safety of gene therapy for neurological diseases. The cellular specificity of transgene expression from rAAV2/1 vectors using the tetON expression cassette in comparison with the CMV promoter was investigated in the rat nigrostriatal pathway. After intrastriatal injection, although GFP was mainly expressed into neurons with both vectors, the relative proportions of DARPP-32+ projection neurons and parvalbumin+ interneurons were respectively 13:1 and 2:1 for the CMV and tetON vectors. DARP32+ neurons projecting to the globus pallidus were strongly GFP+ with both vectors, whereas those projecting to the substantia nigra pars reticulata (SNpr) were efficiently labeled by the CMV but poorly by the tetON vector. Numerous GFP+ cells were evidenced in the subventricular zone with both vectors. However, in the olfactory bulb (OB), GFP+ neurons were observed with the CMV but not the tetON vector. We conclude that the absence of significant amounts of transgene product in distant regions (SN and OB) constitutes a safety advantage of the AAV2/1-tetON vector for striatal gene therapy. Midbrain injections resulted in selective GFP expression in tyrosine hydroxylase+ neurons by the tetON vector whereas with the CMV vector, GFP+ cells covered a widespread area of the midbrain. The biodistribution of GFP protein corresponded to that of the transcripts and not of the viral genomes. We conclude that the rAAV2/1-tetON vector constitutes an interesting tool for specific transgene expression in midbrain dopaminergic neurons.
Human gene therapy 10/2008; · 4.20 Impact Factor
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Benoit Pirotte,
Philippe Voordecker,
Carine Neugroschl,
Danielle Baleriaux,
David Wikler,
Thierry Metens,
Vincent Denolin,
Alfred Joffroy,
Nicolas Massager,
Jacques Brotchi, Marc Levivier
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ABSTRACT: To evaluate, regardless of the clinical results, the contribution of combining functional magnetic resonance imaging (fMRI) with intraoperative cortical brain mapping (iCM) as functional targeting methods for epidural chronic motor cortex stimulation (MCS) in refractory neuropathic pain.
Eighteen neuropathic pain patients (central stroke in six; trigeminal neuropathy in six; syrinx or amputation in six) who underwent operations for epidural MCS were studied with preoperative fMRI and iCM. fMRI investigated motor tasks of hands (as well as foot and tongue, when painful). fMRI data were analyzed with Statistical Parametric Mapping99 software (University College London, London, England; initial analysis threshold corresponding to P < 0.001), registered in a neuronavigation system, and correlated during surgery with iCM. The primary aim of this study was to improve the topographical precision of MCS. Matching of fMRI and iCM specifically was examined.
Correspondence between the contour of the fMRI activation area and iCM in precentral gyrus (mean distance, 3.8 mm) was found in 17 (94%) of 18 patients. Eleven of them showed correspondence for more restrictive values of the analysis threshold (P < 0.0001); in six patients, the quality of the iCM was reduced by somatosensory wave attenuation and general anesthesia. In this group of six patients, a combination of both techniques was used for the final targeting. Correspondence was not found in one patient as the result of image distortion and residual motion artifact. At follow-up (4-60 mo), MCS induced significant pain relief in a total of 11 patients (61%).
This study confirms the functional accuracy of fMRI guidance in neuropathic pain and illustrates the usefulness of combining fMRI guidance with iCM to improve the functional targeting in MCS. Because appropriate targeting is crucial to obtaining pain relief, this combination may increase the analgesic efficacy of MCS.
Neurosurgery 07/2008; 62(6 Suppl 3):941-56. · 2.79 Impact Factor
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ABSTRACT: Stent-assisted coiling is an accepted endovascular treatment (EVT) for complex intracranial aneurysms. The Enterprise self-expandable stent (Cordis, Miami Lakes, FL) is a new retractable stent that is delivered via a conventional coiling catheter to potentially circumvent the limitations of other stents. The aim of this study was to evaluate the use of this stent for EVT of complex aneurysms.
Between January and May 2007, 14 patients with 15 unruptured wide-necked or fusiform aneurysms were treated. EVT consisted of stent placement and subsequent endosaccular coiling. Clinical outcome was assessed with the modified Glasgow Outcome Scale.
EVT was successfully performed and led to an excellent outcome in all patients. The stent was easily navigated and precisely positioned in all cases. However, the stent's visibility was poor once it was delivered. Moreover, procedural complications occurred in three patients, including stent migration (n = 1) and coil protrusion between the stent and the vessel wall (n = 2). In these latter two cases, a remodeling balloon was required to assist in delivery of the coils. No clinical incidence of complications was observed when the parent artery had a diameter of more than 4 mm. Angiographic results consisted of eight complete occlusions, four neck remnants, and three incomplete occlusions.
The Enterprise stent is very useful for EVT of complex intracranial aneurysms because it is easy to navigate and place precisely. However, the currently available stent has two relatively limiting characteristics: 1) it has poor visibility, and 2) it should only be used for aneurysms located on a parent artery with a maximal diameter of 4 mm.
Neurosurgery 06/2008; 62(5):1063-9; discussion 1069-70. · 2.79 Impact Factor
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ABSTRACT: The objective of this study is to study prognostic factors of survival and 3 stratification systems for life expectancy estimation in patients with brain stem metastases treated with radiosurgery.
Between December 1999 and November 2006, 25 patients with 27 brain stem metastases were treated with Gamma Knife radiosurgery. The lesions' mean volume was 0.6 mL (0.013-3.6 mL). The mean marginal dose was 20 Gy (15-24 Gy). Univariate and multivariate studies were done to identify prognostic factors, and 3 patient stratification systems were applied for survival estimation: RPA, SIR, and BSBM.
The primary tumor location was in the lungs in 12 patients, breast in 8, and other in 5. Fourteen lesions were located in the pons, 9 in the midbrain, and 4 in the medulla. All patients were followed clinically. Radiologic follow-up was available in 21 lesions (78%). Tumor control was achieved in all but one followed lesion (95%). There were no complications related to treatment. Median survival of patients with brain stem metastases was 11.1 months. In multivariate analysis, KPS of 80 or more, control of the primary tumor, absence of radiotherapy, and a marginal dose higher than 18 Gy were associated with better survival. The BSBM in the univariate and multivariate analyses was the strongest predictor of survival (P < .0001).
The BSBM was the most useful tool for estimating survival. Rather than the brain stem location of an intracranial metastasis, the patient integral clinical status seems to be more important in determining survival.
Surgical Neurology 05/2008; 71(2):188-95; discussion 195, 195-6. · 1.67 Impact Factor
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ABSTRACT: Transcranial approaches for transsinusal endovascular therapy of DAVF have been sporadically reported by large craniectomies. Large craniectomies carry nevertheless a risk of postembolization extradural hematoma, reduced by delaying the endovascular procedure. We report a 1-session technique of SIGC for percutaneous transvenous DAVF embolization.
This 58-year-old woman developed a right-sided cerebellar hematoma in relation with a high-grade left transverse and sigmoid sinus DAVF. The DAVF was fed by branches from the left vertebral artery, left internal, and left external carotid arteries, draining into the transverse sinus with retrograde flow in cortical veins. Transvenous retrograde embolization was not feasible either through the left internal jugular vein because of thrombosis, or through the right one because of torcular septa. During the same anaesthetic session, a 5-cm-length selective craniectomy was shaped under magnetic resonance image guidance navigation according to the left transverse sinus with high-speed drill. Thereafter, back in the angiography room, the transverse sinus was taped and coiled resulting in a complete exclusion of the DAVF.
Selective image-guided craniectomy is efficient and safe for direct percutaneous transvenous embolization of DAVF in a single anesthetic session. Leaving bone beside the sinus prevents a parenchymal traumatic puncture. This bone has nevertheless to be drilled to allow an adequate sharp puncture angle. Doing so, postoperative hematoma is prevented by the small bone opening, the natural adherence of the dura matter and the possibility of direct compression.
Surgical Neurology 03/2008; 69(2):192-6; discussion 196. · 1.67 Impact Factor
