Laurence Abeloos

Controlled delivery of glial cell line-derived neurotrophic factor by a single tetracycline-inducible AAV vector.

An autoregulated tetracycline-inducible recombinant adeno-associated viral vector (rAAV-pTet(bidi)ON) utilizing the rtTAM2 reverse tetracycline transactivator (rAAV-rtTAM2) was used to conditionally express the human GDNF cDNA. Doxycycline, a tetracycline analog, induced a time- and dose-dependent release of GDNF in vitro in human glioma cells infected with rAAV-rtTAM2 serotype 2 virus. Introducing the Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) downstream to the rtTAM2 coding sequence, resulted in a more rapid induction and a higher basal expression level. In vivo, 8 weeks after a single injection of the rAAV-rtTAM2-GDNF vector encapsidated into AAV serotype 1 capsids in the rat striatum, the GDNF protein level was 60 pg/mg tissue in doxycycline-treated animals whereas in untreated animals, it was undistinguishable from the endogenous level ( approximately 4 pg/mg tissue). However, a residual GDNF expression in the uninduced animals was evidenced by a sensitive immunohistochemical staining. As compared to rAAV1-rtTAM2-GDNF, the rAAV1-rtTAM2-WPRE-GDNF vector expressed a similar concentration of GDNF in the induced state (with doxycycline) but a basal level (without doxycycline) approximately 2.5-fold higher than the endogenous striatal level. As a proof for biological activity, for both vectors, downregulation of tyrosine hydroxylase was evidenced in dopaminergic terminals of doxycycline-treated but not untreated animals. In conclusion, the rAAV1-rtTAM2 vector which expressed biologically relevant doses of GDNF in the striatum in response to doxycycline with a basal level undistinguishable from the endogenous striatal level, as measured by quantitative ELISA assay, constitutes an interesting tool for local conditional transgenesis.

Minimally invasive spinal arthrodesis in osteoporotic population using a cannulated and fenestrated augmented screw: Technical description and clinical experience

We describe a percutaneous or minimally invasive approach to apply an augmentation of pedicle fenestrated screws by injection of the PMMA bone cement through the implant and determine the safety and efficiency of this technique in a clinical series of 15 elderly osteoporotic patients. Clinical outcome and the function were assessed using respectively the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI). Peri- and post-operative complications were monitored during a minimum of 2 years of follow-up. Radiographic follow-up was based on plain fluoroscopic control at 3, 6 and 12 months and every year. In this approach, four steps were considered with care: optimal positioning of the screws, correct alignment of the screw heads, waiting time before the injection of cement, fluoroscopic control of the cement injection. Using these precautions, only 2 minor complications occurred. VAS scores and ODI questionnaires showed a statistically significant improvement up to 13.3 months postoperatively. No radiological complications were observed. Based on this experience, PMMA augmentation technique through the novel fenestrated screws provided an effective and long lasting fixation in osteoporotic patients. Applying this procedure through percutaneous or minimally invasive approach under fluoroscopic control seems to be safe.

Internal Carotid Occlusion following Gamma Knife Radiosurgery for Cavernous Sinus Meningioma

Gamma knife radiosurgery is a safe and effective treatment for cavernous sinus meningioma, associated with a very low morbidity. However, a high dose of radiation could lead to modifications of the vascular wall such as in radiosurgical treatment of arteriovenous malformations. We present a patient treated by gamma knife radiosurgery for a left cavernous sinus meningioma using a margin dose of 13 Gy at the 50% isodose. A complete occlusion of the intracavernous segment of the ICA occurred during the follow-up, in combination with a regression of the meningioma volume. The patient sustained no neurological deficit. We found that a hot spot of dose was administered to the intracavernous segment of the internal carotid artery, with a maximum dose of 22.3 Gy. Dose heterogeneity inside the target volume can produce hot spots of dose inside the internal carotid artery that can lead to a vascular occlusion. Therefore, we recommend shifting the hot spot during the dosimetry planning in order to reduce the incidence of such vascular injury.

Évaluation à long terme de la stimulation médullaire dans les douleurs lombosciatiques neuropathiques postopératoires : étude rétrospective

BACKGROUND AND PURPOSE Long-term efficiency (>5 years) of spinal cord stimulation for failed back surgery syndrome is poorly described in literature. The aims of our study were to evaluate the long-term efficiency and the quality of life of our series of patients with spinal cord stimulation for failed back surgery syndrome. METHODS The data of 55 patients implanted successively in our institution between 1995 and 2005 for failed back surgery syndrome were collected retrospectively. We contacted them for a telephone survey focused on efficiency, quality of life and treatment satisfaction. RESULTS An internal pulse generator was placed in 42 patients. Thirty-two of them were contacted to answer our survey with a mean follow-up of 8.3 years. Seventy-five percent of our population reported a pain decrease of greater or equal to 50%. The efficiency of percutaneous leads was reported as 50% for the quadripolars and 83% for the octopolars. The surgical leads evaluations were positive in 70% for 4 × 1 as well as for 4 × 2 leads. We observed a default of low back pain relief in 84% of patients with an incomplete pain relief (59%). The ability to sit, get out of the bed, and climb stairs increased in 75%. The walk was better in 82%. Decrease in drug consumption of greater or equal to 50% was observed in 66%. CONCLUSIONS Our retrospective study demonstrates a satisfaction of 75% of the patients after 8.3-years follow-up. Spinal cord stimulation is an effective treatment for refractory failed back surgery syndrome.

Chondroma of the dural convexity: A case report and literature review

Chondromas are unusual tumors that arise from the base of the skull and have a predilection for the spheno‐ethmoidal region. Chondromas represent less than 0.5% of all intracranial tumors. In rare instances, these tumors originate from the dura mater of the convexity. Fewer than 30 cases of dural chondromas arising from the convexity or the falx are reported in the literature. In this study, we describe a new case of convexity chondroma. We discuss the radiological and histological features of this case and also review the literature.

Recombinant AAV viral vectors serotype 1, 2, and 5 mediate differential gene transfer efficiency in rat striatal fetal grafts.

Intrastriatal grafts of fetal ganglionic eminences (GE) can reverse symptoms of striatal lesions in animal models of Huntingtons disease. On the other hand, neurotrophic factors have been shown to protect host striatal neurons from ongoing degeneration. Neurotrophic gene transfer into GE prior to grafting could combine the benefits of striatal neuron replacement and in situ delivery of neurotrophic factors. Here we evaluate the potency of recombinant adeno-associated viruses (rAAV) as vectors for gene delivery into rat embryonic (E15) GE using the eGFP reporter gene under the control of the strong cytomegalovirus (CMV) promoter. We observed a very efficient expression of the eGFP reporter gene in organotypic cultures of GE infected with rAAV serotype 1 from 4 days until at least 4 weeks postinfection. In contrast, transduction was low and absent when using serotype 2 and serotype 5 rAAV, respectively. Two months after transplantation of rAAV2/1-infected embryonic GE in adult rat striatum, more than 20% of grafted cells expressed eGFP. The majority of transduced cells in the graft were neurons as indicated by colabeling of GFP-immunoreactive cells with the NeuN marker. Our study suggests that GE transduced by rAAV-serotype 1 vectors could be an interesting tool to mediate efficient expression of a gene coding a neurotrophic factor in Huntingtons disease.

Ectopic choroid plexus associated with trigeminal neuralgia: case report

IntroductionA 55-year-old man underwent a microvascular decompression procedure for a pharmacoresistant trigeminal neuralgia. Preoperative MRI showed a neurovascular conflict between the Vth nerve root and the superior cerebellar artery.MethodsDissection of the intracisternal trigeminal root was undertaken, and a piece of Teflon was positioned between the artery and the nerve.ResultsChoroid plexus was found squeezing the root entry zone of the Vth nerve and partially removed. The patient did not improve after the vascular decompression procedure. Trigeminal neuralgia could be due to a mechanical irritation of the intracisternal nerve root.ConclusionSince vascular decompression of the trigeminal root did not relieve the pain, we suggest that the presence of choroid plexus at the root entry zone of the nerve may have induced trigeminal neuralgia in this patient.

Effects of an Optimized Automated Disc Preparation on Clinical and Radiological Outcome of Minimally Invasive Transforaminal InterbodyFusion Procedure

Objective: In minimally invasive techniques for transforaminal lumbar interbody fusion (MIS TLIF) access to the disc and by consequence, the extension of the discectomy can be reduced. Insufficient disc removal and endplate violation can lead to non-unions, subsidence and pseudoarthroses. In this study, we compare the quality of disc preparation, volume of bone graft and clinical results in a group of patients who underwent MIS TLIF with discectomy and endplate preparation aided by an automated discectomy device, the enSpireTM Flex MIS Surgical Discectomy System (study group) to a control group with classical, manual instrumentation for disc preparation. Materials and methods: Twenty-seven consecutive patients were enrolled in the study group and 33 patients in the control group. All patients received similar mixture of autologous bone and cadaver allograft. Disc volume and the quantity of graft placed in the disc space was measured on the discharge CT scan and compared in a blinded, independent radiology review. Clinical outcomes assessed using the Visual Analog Scale (VAS) for leg and low back pain and the Oswestry Disability Index (ODI) were compared at 12 months postoperative. Results: The mean volume of bone graft placed and the ratio bone graft/nucleus was higher in the study group (6.21 cm3 vs. 4.39 cm3 ; p<0001 and 76.8% vs. 57.8%; p<0.0001). The mean Patient Satisfaction Index (PSI) of the EnSpire group was statistically higher than the control group (4.6 ± 0.6 vs. 3.9 ± 0.7). Conclusion: In the challenging MIS TLIF approach, we demonstrate that by using the enSpire™ Flex MIS Surgical Discectomy System, we can optimize the extension and quality of the discectomy, increase the volume of bone graft, and achieve better clinical outcomes.

Could serum measurements of S100 proteins be reliable markers to predict recurrence in meningiomas

Abstract Predicting which meningiomas will recur and which will not is clinically important, and still represents a major clinical challenge. A number of different molecular, genetic, and/or biochemical markers involved in cell proliferation, invasion, angiogenesis, and cell transformation have been investigated in attempts to predict the risk of post-surgical meningioma recurrence. In this short review we emphasize what has actually been accomplished in this area. Finally, we highlight the potential of S100 serum protein concentrations as a prognostic factor predicting meningioma recurrence. We conclude that serum concentrations of S100 group proteins may prove to be useful as prognostic markers and suggest further pros-pective trials be done.