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Biomedical subjects

M Levivier

Publications and source records attributed to M Levivier.

At least 19 recordsLinked to original sources

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.

Animals↗

Endovascular treatment of intracranial aneurysms with a branch arising from the sac.

BACKGROUND AND PURPOSE: The endovascular treatment (EVT) of intracranial aneurysms is no more limited by the presence of a branch at the neck or by the neck width. Saccular aneurysms with a branch arising from the sac, however, are mostly candidates for surgery rather than embolization. We prospectively evaluated the feasibility and safety of the EVT in such cases. METHODS: Between May and November 2004, 9 consecutive patients with a saccular aneurysm that presents a branch arising from the sac were treated by embolization. There were 7 women and 2 men (mean age, 58 years). Six patients presented with a subarachnoid hemorrhage (SAH), and 3 were asymptomatic. All patients were treated by selective coiling with (n = 6) or without (n = 3) the remodeling technique. Clinical outcome was assessed with a modified Glasgow Outcome Scale at 3 months. RESULTS: EVT was successfully performed in all patients and resulted in 7 excellent outcomes and 2 deaths related to SAH complications. The arterial branch could be preserved in 7 cases and intentionally occluded in 2. Neither embolic nor ischemic complication occurred in the vascular territory of the involved branch. Angiographic results showed 5 neck remnants, 2 incomplete occlusions, and 2 complete occlusions. No rebleeding occurred. CONCLUSION: Our study, though limited by its small patient population, suggests that saccular intracranial aneurysms with a branch arising from the sac may be treated by endovascular approach with excellent clinical results; however, larger series with long-term follow-up are mandatory to confirm these preliminary results mostly in terms of anatomic stability.

Adult↗

11C-methionine PET for the diagnosis and management of recurrent pituitary adenomas.

PURPOSE: The detection of recurrent pituitary adenoma by magnetic resonance imaging (MRI) is rendered uncertain by the tissue remodelling that follows surgery or radiotherapy. We aimed to evaluate the contribution of PET with 11C-methionine (MET-PET) in the detection and management of recurrent pituitary adenoma. METHODS: Thirty-three patients with pituitary adenoma were evaluated postoperatively by MET-PET, either because of biological evidence of active residual tumour or because of MRI demonstration of non-functional adenoma growth. We studied 24 secreting adenomas and nine non-functional adenomas. RESULTS: In 30 patients, MET-PET detected abnormally hypermetabolic tissue. In 14 out of these, MRI did not differentiate between residual tumour and scar formation. In nine of these 14 cases, major therapeutic decisions were undertaken (radiosurgery and surgery). In another group of 16 patients, both MET-PET and MRI detected abnormal tissue. In one case, neither MRI nor MET-PET detected adenomatous tissue. Finally, abnormal tissue was detected in two patients on MRI solely. In these two cases, failure of MET-PET to reveal the adenoma was attributable to concomitant inhibitory therapy. The sensitivity of MET-PET and MRI varied as a function of the tumour type: all non-functional adenomas were localised by both modalities, while MET-PET detected all adrenocorticotropic hormone-secreting adenomas whereas MRI depicted only one of these eight lesions. Fifteen out of 17 patients treated by radiosurgery showed clinical improvement after treatment. CONCLUSION: We suggest that MET-PET is a sensitive technique complementary to MRI for the detection of residual or recurrent pituitary adenomas. It should gain a place in the efficient management of these tumours.

Adult↗

[Transsphenoidal approach with low field MRI for pituitary adenoma].

INTRODUCTION: Appropriate evaluation of resection remains one of the major difficulties of surgical treatment of pituitary adenoma. The transsphenoidal approach does not allow direct visual control. Endoscopy provides useful information but may no distinguish well residual adenoma from the pituitary gland. Intraoperative MRI offers new perspectives for assessing the quality of resection. We report our experience with low field intraoperative MRI in surgical treatment of pituitary adenoma. POPULATION: Intraoperative MRI (Polestar N10, 30 patients and Polestar N20, 17 patients) was performed in 45 consecutive patients undergoing surgery for pituitary adenoma. Thirty-seven patients had a macroadenoma. Patients were in the prone position with the head fixed with a three-pin MRI-compatible headholder. METHOD: Coronal T1 MRI scans with enhancement were acquired pre and per operatively. We compared scans and surgical filling (complete removal). If there was a difference, a surgical control was undertaken. RESULTS: Intraoperative images were unavailable for two patients due to small size of the neck and the pituitary glands which were not in the middle in the field of view. For the others, the pituitary glands were in the field of view and the intraoperative scans could be used for comparison. For four patients, there was a discrepancy between surgeon filling and the intraoperative MRI. A control showed no residual adenoma but hemostatic tissue. CONCLUSION: Low field intraoperative MRI is an excellent technique for controlling the size of pituitary adenoma resection.

Adenoma↗

Recombinant AAV-mediated gene delivery to the central nervous system.

Various regions of the brain have been successfully transduced by recombinant adeno-associated virus (rAAV) vectors with no detected toxicity. When using the cytomegalovirus immediate early (CMV) promoter, a gradual decline in the number of transduced cells has been described. In contrast, the use of cellular promoters such as the neuron-specific enolase promoter or hybrid promoters such as the chicken beta-actin/CMV promoter resulted in sustained transgene expression. The cellular tropism of rAAV-mediated gene transfer in the central nervous system (CNS) varies depending on the serotype used. Serotype 2 vectors preferentially transduce neurons whereas rAAV5 and rAAV1 transduce both neurons and glial cells. Recombinant AAV4-mediated gene transfer was inefficient in neurons and glial cells of the striatum (the only structure tested so far) but efficient in ependymal cells. No inflammatory response has been described following rAAV2 administration to the brain. In contrast, antibodies to AAV2 capsid and transgene product were elicited but no reduction of transgene expression was observed and readministration of vector without loss of efficiency was possible from 3 months after the first injection. Based on the success of pioneer work performed with marker genes, various strategies for therapeutic gene delivery were designed. These include enzyme replacement in lysosomal storage diseases, Canavan disease and Parkinson's disease; delivery of neuroprotective factors in Parkinson's disease, Huntington disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemia and spinal cord injury; as well as modulation of neurotransmission in epilepsy and Parkinson's disease. Several of these strategies have demonstrated promising results in relevant animal models. However, their implementation in the clinics will probably require a tight regulation and a specific targeting of therapeutic gene expression which still demands further developments of the vectors.

Animals↗

Modern multimodal neuroimaging for radiosurgery: the example of PET scan integration.

Radiosurgery relies critically on medical imaging modalities. Leksell Gamma Knife (LGK) radiosurgery presents the highest requirements in terms of imaging accuracy as the treatment is applied in a single high-dose session with no other spatial control than medical imaging. The advent of new imaging modalities opens challenges for LGK planning strategies. The integration of stereotactic PET in LGK represents an example of such application of modern multimodality imaging in radiosurgery. Our experience consists of 80 patients treated with the combination of MR/CT and PET guidance. In order to analyze the specific contribution of PET findings, we developed a classification reflecting the strategy used to define the target volume. When combining PET and MR information, 102 target volumes were defined, because some patients presented with multiple lesions or multifocal tumor areas. Abnormal PET uptake was found in 86% of the lesions, and this information altered significantly the MR-defined tumor in 73%. In conclusion, integration of PET in radiosurgery provides additional information opening new perspectives for the treatment of brain tumors. The use of a standardized classification allows to assess the relative role of PET. A similar approach could be useful and may serve as a template for the evaluation of the integration of other new imaging modalities in radiosurgery.

Adenoma↗

Efficient early and sustained transduction of human fetal mesencephalon using adeno-associated virus type 2 vectors.

The success of transplantation of human fetal mesencephalic tissue into the putamen of patients with Parkinson's disease (PD) is still limited by the poor survival of the graft. In animal models of fetal transplantation for PD, antiapoptotic agents, such as growth factors or caspase inhibitors, or agents counteracting oxidative stress enhance the survival and reinnervation potential of the graft. Genetic modification of the transplant could allow a local and continuous delivery of these factors at physiologically relevant doses. The major challenge remains the development of strategies to achieve both early and sustained gene delivery in the absence of vector-mediated toxicity. We recently reported that E14 rat fetal mesencephalon could be efficiently tranduced by adeno-associated virus type 2 (AAV2) vectors and that gene expression was maintained until at least 3 months after transplantation in the adult rat striatum. Here we report that an AAV2 vector can mediate the expression of the EGFP reporter gene under the control of a CMV promoter in organotypic cultures of freshly explanted solid fragments of human fetal mesencephalic tissue as early as 3 days to at least 6 weeks postinfection. These results suggest that AAV2 vectors could be used to genetically modify the human fetal tissue prior to transplantation to Parkinson's patients to promote graft survival and integration.

Animals↗

[Imaging for stereotaxic treatment of vestibular schwannomas. Error factors and corrections].

BACKGROUND AND PURPOSE: Gamma Knife radiosurgery treatment of vestibular schwannomas requires high accuracy for the prescribed dose definition and delivery. The main factors contributing to the error are the anatomical distortions of imaging modalities used for treatment planning. Imaging limitations and error factors are reviewed and detailed. Multimodality rationale for the delineation of vestibular schwannomas and surrounding structures are assessed. Quality control strategies are discussed and a distortion correction technique using a radiological phantom is presented. METHODS: Computed tomography is considered as the reference for spatial accuracy after appropriate scanner quality control using the stereotaxic fiducials system. Magnetic resonance imaging pulse sequence distortions are measured with a phantom designed for 3D non-linear local distortion evidence. A distortion correction transformation is computed from the phantom images and applied to the patient images. Results are verified using the stereotaxic fiducials system. RESULTS: Fiducials registration errors show spatial accuracy improvement, approaching computed tomography quality, after distortion correction of magnetic resonance images. CONCLUSIONS: The multimodal imaging approach for the dose planning of vestibular schwannomas radiosurgery treatment is relevant. Quality control of spatial accuracy for imaging modalities is mandatory and realistic in clinical routine.

Ear Neoplasms↗

[Dosimetric planning for radiosurgical treatment of vestibular schwannomas].

Dosimetry planning is certainly the most typical neurosurgical instant in the radiosurgical procedure for the treatment of vestibular schwannomas (VS). Indeed, it is a key-moment in which the therapeutical choices will have a major influence on the clinical results, in terms of efficacy and safety. The therapist has to inform the patient about the rationale of the treatment, its limitations, the expected results, and the specific risks. Deep knowledge of the radiosurgical technique, of the principles of dosimetry, and of the therapist's personal experience, allows an a posteriori analytical study of the influence of the dosimetry therapeutic choices on the patient's outcome. Correlation between the preoperative therapeutic choices and the postoperative clinico-radiological information is mandatory to optimize therapeutic strategies. These therapeutic choices should be the result of a reflection integrating the clinical status of the patient, an understanding of the specific pathology of VS, awareness of the other therapeutic choices, and knowledge of radiological and surgical anatomy. The way a certain number of parameters will be defined during the dosimetry planning will have a major influence on the clinical results. This explains wide variability of clinical results from one operator to another, for the same radiological and radiosurgical tools. This emphasizes the need for specific and long-term training, associated with continuous education and a good knowledge of the very active literature.

Ear Neoplasms↗

[In vivo evaluation of tumor response to radiosurgery: application to vestibular schwannomas].

Imaging follow-up of vestibular schwannomas (VS), such as CT or MR, does not allow assessing the response of the tumor tIssue to radiosurgery. Changes in contrast enhancement are frequently observed, with a loss of contrast enhancement within the treated VS. However, this typical aspect does not anticipate the long-term success of radiosurgery for VS. New functional and metabolic image modalities could be useful to assess in vivo radiosurgery-induced tIssue changes. Such data already exist, using techniques such as MR spectroscopy, positron emission tomography (PET) and SPECT, but they concern almost exclusively the evaluation of primary SNC tumors and metastases of systemic cancers. There are, however, very sparse metabolic and functional data concerning the in vivo evaluation of the response of the tumor tIssue to radiosurgery. Moreover, such information is only anecdotal in VS. In other disorders, PET and MR spectroscopy data suggest interesting new directions for the assessment of radiosurgery follow-up. Based on the predictive information provided by PET and MR spectroscopy in primary CNS tumors, it would be worthwhile to design a prospective study evaluating the role of these imaging modalities for in vivo assessment of radiosurgery-treated SV.

Brain↗

Tetracycline-inducible transgene expression mediated by a single AAV vector.

Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator. In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required. However, efficient regulation is hampered by interferences between the inducible promoter and (i) the promoter used to express the transactivator and/or (ii) promoter/enhancer elements present in the viral vector backbone. We describe a single AAV vector in which transcription of both the reverse tetracycline transactivator (rtTA) and the transgene is initiated from a bidirectional tetracycline-responsive promoter and terminated at bidirectional SV40 polyadenylation sites flanking both ITRs. Up to 50-fold induction of gene expression in human tumor cell lines and 100-fold in primary cultures of rat Schwann cells was demonstrated. In addition an 80-fold induction in vivo in the rat brain has been obtained. In vitro, the autoregulatory vector exhibits an induced expression level superior to that obtained using the constitutive CMV promoter. Although extinction of the transgene after removal of tetracycline was rapid (less than 3 days), inducibility after addition of tetracycline was slow (about 14 days). This kinetics is suitable for therapeutic gene expression in slowly progressive diseases while allowing rapid switch-off in case of undesirable effects. As compared to previously described autoregulatory tet-repressible (tetOFF) AAV vectors, the tet-inducible (tetON) vector prevents chronic antibiotic administration in the uninduced state.

Animals↗

Preservation of hearing in vestibular schwannomas treated by radiosurgery using Leksell Gamma Knife: preliminary report of a prospective Belgian clinical study.

INTRODUCTION: Radiosurgery is an alternative to the microsurgical resection of vestibular schwannoma (VS). Since its introduction, radiosurgery has been used in more than 8000 patients with VS worldwide and the long term tumor control rates are reported to be 86 to 100%. The aim of this study is to report our experience with Leksell Gamma Knife (LGK) radiosurgery in the management of VS and to evaluate the serviceable hearing preservation rate after one-year follow-up. MATERIAL AND METHODS: Between January 2000 and October 2002, 95 patients with unilateral VS underwent LGK radiosurgery at the University Erasmus Hospital of Brussels with the first worldwide installed LGK C. All patients in our series underwent evaluation with high resolution neurodiagnostic imaging including computed tomography and MRI, and clinical evaluation as well as audiological tests that included tonal and vocal audiometries. The Gardner Robertson (GR) classification is used to report the results of this study. We identified 48 patients treated for VS with LGK, tested and retested with vocal and tonal audiometries by the same team, and followed for a minimum of one year. There were 38 patients with previously untreated VS (9 grade I, 9 grade II, 20 grade III according to Koos) and 10 patients with postoperative evolutive residual tumor. RESULTS: Before LGK, 24 patients had serviceable (17 GR class I and 7 GR class II) hearing; 16 (67%) of these patients had preservation of serviceable hearing (Pure tone average < 50 db and Speech discrimination > 50%) at the one-year audiological follow-up. It was observed that 9 of the 17 GR class I patients (52.9%) maintained their level of audition and 14 of these (82.3%) preserved serviceable hearing. No deterioration of hearing occurred in the 7 patients with preradiosurgery radiosurgery nonserviceable hearing (GR class III) at the one-year follow-up. One patient improved from GR class V to III after LGK. No patient developed trigeminal neuropathy and only one patient who had preradiosurgery facial nerve dysfunction experienced deterioration at one-year follow-up. CONCLUSIONS: In view of the high tumor control rate and excellent long-term cranial nerve preservation rates, LGK radiosurgery should now be considered as an excellent alternative strategy to microsurgery for the management of VS grade I to III as well as in cases of residual tumor after microsurgery. Compared to results obtained in centers with long-term experience, our data suggest that LGK radiosurgery is an efficient reproducible therapeutic approach that offers high rate of hearing preservation. This justifies the choice of radiosurgery as the first treatment option in VS.

Auditory Threshold↗

AAV2 vectors mediate efficient and sustained transduction of rat embryonic ventral mesencephalon.

The success of transplantation of human embryonic mesencephalic tissue to treat parkinsonian patients is limited by the poor survival of the transplant. We show that an AAV2 vector mediates efficient expression of the egfp reporter gene in organotypic cultures of freshly explanted solid fragments of rat embryonic ventral mesencephalon (VM). We observed early and sustained transgene expression (4 days to > or = 6 weeks). Furthermore, rAAV-infected rat embryonic VM transplanted in the adult striatum continued to express EGFP for > or = 3 months. More than 95% of the transduced cells were neurons. Dopaminergic neurons were transduced at low frequency at earlier time points. This method of gene delivery could prove useful to achieve local, continuous secretion of neurotrophic factors at physiologically relevant doses to treat Parkinson's disease.

Animals↗

Neuroprotective gene therapy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterised by a progressive loss of the dopaminergic neurones in the substantia nigra pars compacta. Accumulating evidence indicates that apoptosis contributes to neuronal cell death in PD patients' brain. Excitotoxicity, oxidative stress, and mitochondrial respiratory failure are thought to be the key inducers of the apoptotic cascade. Even though the initial cause and the mechanism of degeneration are poorly understood, neuroprotection can be achieved by interfering with neuronal cell death either directly or by preventing neuronal dysfunction. Potential agents for neuroprotection are neurotrophic factors, inhibitors of apoptosis or anti-oxidative agents. However, the existence of the blood-brain barrier precludes systemic delivery of these factors. In situ gene delivery provides strategies for local and sustained administration of protective factors at physiologically relevant doses. Viral vectors mediating stable gene expression in the central nervous system exist and are still under development. Efficacy of these vectors has repeatedly been demonstrated in the animal models both ex vivo and in vivo. Ex vivo gene delivery could furthermore be combined with cell replacement therapies by transplanting genetically modified cells compensating for the lost neuronal cell population in order to provide neuroprotection to both the grafted cells and degenerating host neurones. However, several aspects of gene transfer, such as uncontrolled diffusion, axonal transport, unpredictable site of integration and immunological responses, still raise safety concerns and justify further development of viral and non-viral vectors as well as genetic elements with tightly controlled gene expression. Various relevant animal models for Parkinson's disease are available for the evaluation of gene therapy strategies. These include induction of cell death in specific neurone population through administration of toxins either directly in the brain or systemically, as well as transgenic mice expressing human disease-associated mutations.

Animals↗

[The neurosurgery department].

Opened on November 1st, 2001, the Department of Neurosurgery has progressively grown to become worldwide renown in a few years. All the pathologies are covered, from lumbar disc hernia to intracranial tumors and vascular malformations. But the originality stays into the exceptional environment by the concentration of logistic resources and the ability of clinician and researchers who daily collaborate with the neurosurgical team. The Department of Neurosurgery has a strong reputation in several fields like intraspinal cord tumors or Pet-guided Neurosurgery in stereotactic biopsies, neuronavigation and Gamma Knife and, generally speaking, in the original approach of the treatment and follow-up of brain tumors. Neurodegenerative diseases also benefit of modern approaches trough the Gamma Knife, deep brain stimulation or fetal cell grafting into the brain in Parkinson and soon in Huntington diseases. Last but not least, the arrival for the 25th anniversary of Erasme Hospital of an interventional MRI will allow to follow in real-time the resection of brain tumors with an obvious benefit for the surgical performances and the quality of life of the patients. It will also open a new window for neurosurgical research through combination with functional MRI and Pet-Scan, reinforcing the reputation of Erasme Neurosurgical Department who has been distinguished in 1997 by the World Health Organisation as "WHO Collaborating Center for Research and Training in Neurosurgery" and nominated again in 2002 for a new 4-year period, which is unique in the Neurosurgical World.

Belgium↗

[Radiosurgery of the brain at the beginning of the 21st century: gamma knife with C-table].

The goal of stereotactic radiosurgery by definition is "the delivery of a single, high dose of radiation allowing the precise and complete destruction of chosen target structures containing healthy and/or pathological cells, without significant concomitant or late radiation damage to adjacent tissues". This effect is obtained by the precise focusing of multiple low energy radiation beams crossing at the target. Three different techniques can be used for radiosurgery: linear accelerator (LINAC) based radiosurgery, Bragg-peak (proton) therapy and Gamma Knife radiosurgery. Leksell Gamma Knife (LGK) is a dedicated neurosurgical device for brain surgery to destroy predetermined intracranial targets through the intact skull. It operates via the radiobiological effect of stereotactically directed, highly focused ionizing gamma-beams of 201 cobalt-60 sources. The LGK offers the best precision of target during irradiation. The mechanical accuracy is about 0.3 mm, which makes it particularly suitable for highly sophisticated neurosurgical interventions. Radiosurgery was originally developed to treat functional neurological disorders, but soon after its introduction cerebral arteriovenous malformations, and brain tumors became the main targets for the technique. Since the first LGK installation at the Sophiahemmet Hospital, Stockholm, Sweden in 1967, over 150,000 patients have already been treated in more than 150 units worldwide. The accumulated clinical experience with the LGK has established this method as the "golden standard" of radiosurgery. In December 1999, a new development, the LGK Model-C was installed at the Centre Gamma Knife, Université Libre de Bruxelles, Hôpital Académique Erasme, Brussels, Belgium. This was followed by completion of two similar units in Krefeld, Germany, and at the Presbyterian University Hospital, Pittsburgh, Pennsylvania, U.S.A. The major innovation in the design of the LGK Model-C is the robotic Automatic Positioning System, which allows computer-controlled automatic and sequential positioning of multiple shots during treatment. Thus all steps of the procedure are performed through an unbroken digital chain, from stereotactic image acquisition to the control of the irradiation sequence. This represents a significant achievement which increases the accuracy and practicality of the treatment. The technical details of the method are described, and the main treatment indications are reviewed.

Brain Neoplasms↗

The Zeiss-MKM system for frameless image-guided approach in epidural motor cortex stimulation for central neuropathic pain.

OBJECT: Twelve patients (seven female, and five male, mean age 55.6 years) suffering from refractory central (ischemic/traumatic [eight cases]) and neuropathic pain (trigeminal neuropathy [four cases]) underwent surgery for the implantation of an epidural motor cortex stimulation (MCS) device in which the authors used a frameless neuronavigation system, the Zeiss-MKM microscope. METHODS: The authors assessed the spatial accuracy of the neuronavigation system and its potential contribution to improve the quality of targeting pain. In these patients, the positions of the central sulcus, defined by stereotactic magnetic resonance MR imaging, intraoperative somatosensory evoked potentials (SSEPs) and subdural visual verification, were correlated into the stereotactic neuronavigation planning procedure. The mean spatial accuracy of distance between (MR) imaging-defined and actual central sulcus was 2.4 mm (range 5-10 mm). The intraoperative SSEPdefined central sulcus was close to that defined by MR imaging (mean distance 6.4 mm). Although very precise, intraoperative SSEP recordings were impaired by artifacts and wave attenuation in six of the 12 patients. Stereotactic correlations between anatomical and functional data in the navigation system corrected final targeting in 10 of 12 cases. Pain relief was obtained in eight patients. Indeed, inappropriate targeting probably explains the reported variable success rate of MCS and certainly underestimates the actual efficacy. CONCLUSIONS: Since intraoperative SSEP monitoring has, for many years, been considered the standard procedure to approach motor target, the development of an accurate stereotactic image guidance system could help to increase the efficacy of MCS on the alleviation of pain. The excellent spatial accuracy provided by the Zeiss-MKM navigation system allows precise data correlations that represent a remarkable means to validate functional MR imaging as an alternative to SSEP. The authors believe that developing stereotactic image guidance with such a navigation system could improve the success rate of MCS.

Deep Brain Stimulation↗

Trigeminal neuralgia. Pathophysiology and treatment.

Trigeminal neuralgia is a very peculiar disease. The pain, also known as "tic douloureux", is paroxystic and very severe. It can be triggered by a light cutaneous stimulus on a very localized spot on the face (the so-called "trigger zone"). The patient can sometimes benefit from long remissions without any treatment. With the exception of multiple sclerosis and of uncommon cases of posterior fossa tumours or other lesions impinging on the trigeminal nerve, ganglion or root, trigeminal neuralgia is considered as "idiopathic". Some benign abnormality had for long been suspected. The current opinion is now in favour of a "neurovascular conflict": an artery, most often a loop of the superior or anteroinferior cerebellar artery, has an offending contact with the trigeminal nerve root, which results in localized demyelination and ectopic triggering of neuronal discharges. This hypothesis is in agreement with the relief provided by antiepileptic drugs and is supported by recent neuroimaging data. Therapeutic options are reviewed: very efficient drugs are available but fail to provide a significant relief and/or have important side effects in many cases. Surgical alternatives are available, for which guidelines are proposed.

Anticonvulsants↗