Surgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Française (ANOCEF) trial.

OBJECTIVE: The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only-both followed by standard therapy-in such patients. METHODS: Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008-2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017-2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. RESULTS: Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52-1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32-0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. CONCLUSIONS: This study suggests that debulking surgery is safe, and-compared to biopsy-is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov).

Segmental Lordosis Gain Is a Prognostic Radiological Factor of Good Functional Outcome After the Implantation of a Single-Level Prosthesis or a Hybrid Construct for Lumbar Disc Degeneration.

OBJECTIVE: To identify radiological factors and functional outcomes associated with good results after implantation of a single lumbar disc prosthesis or a hybrid construct (anterior lumbar interbody fusion and lumbar disc prosthesis) in the setting of painful degenerative lumbar discopathy. METHODS: This single-center, retrospective 10-year study included 92 patients ˃18 years old with chronic low back pain evolving for at least 1 year. The patients had degenerative disc disease and had failed conservative treatment and underwent lumbar arthroplasty. Radiographic and clinical outcomes were assessed preoperatively and 1 year after surgery. Functional evaluation was based on the Oswestry Disability Index (ODI) and a numerical rating scale. Radiological analysis was based on lumbar x-rays and magnetic resonance imaging parameters. Patients were assigned to 2 groups according to the reduction in ODI score (>15 points or <15 points), and statistical analysis was done in both groups to find predictive radiological factors for a satisfactory functional outcome. RESULTS: Clinically, 60 patients (65.2%) had a satisfactory functional result and 32 patients (34.8%) had a poor outcome according to ODI score. Radiographically, gain in segmental lordosis was statistically associated with good functional outcomes (8.9° for ODI decrease >15 vs. 3.2° for ODI decrease <15). CONCLUSIONS: This study determined that gain in segmental lordosis is associated with a satisfactory functional outcome after a single-level lumbar disc prosthesis or a hybrid construct. Our study demonstrates that segmental lordosis gain may represent a significative useful positive predictor factor of patient outcome.

Transfacet screws using spinal navigation in addition to anterior or oblique lumbar interbody fusion: technical note and preliminary results.

Transfacet screws (TFS) are an alternative to the classic bilateral pedicular screws (BPS) in addition to anterior (ALIF) or oblique (OLIF) lumbar interbody fusion. Spinal navigation could help the surgeon in technically demanding procedures in order to avoid screw malposition. Although spinal navigation is commonly used in BPS, its contribution in TFS remains unclear. Our aim here was to assess the feasibility of TFS using spinal navigation in addition to anterior lumbar fusion. Five patients suffering from lumbar degenerative disc disease were included. During the same general anaesthesia, we performed successively an ALIF or OLIF and then a TFS according to Boucher technique using spinal navigation (O-arm). No peri-operative complication occurred, and all the screws were successfully positioned (n = 10). All clinical scores (ODI, VAS L and VAS R) improved at 6-month follow-up. Segmental lordosis increased from 6° [2.4°-12°] to 13.6° [8°-17°]. Fusion was achieved for the five patients. TFS using O-arm in addition to ALIF/OLIF is feasible. To confirm our early favourable outcomes on clinical and radiological data, this technique must be evaluated on larger samples of patients.

ERK-Mediated Loss of miR-199a-3p and Induction of EGR1 Act as a "Toggle Switch" of GBM Cell Dedifferentiation into NANOG- and OCT4-Positive Cells.

There is great interest in understanding how the cancer stem cell population may be maintained in solid tumors. Here, we show that tumor cells exhibiting stem-like properties and expression of pluripotency markers NANOG and OCT4 can arise from original differentiated tumor cells freshly isolated from human glioblastomas (GBM) and that have never known any serum culture conditions. Induction of EGR1 by EGFR/ERK signaling promoted cell conversion from a less aggressive, more differentiated cellular state to a self-renewing and strongly tumorigenic state, expressing NANOG and OCT4. Expression of these pluripotency markers occurred before the cells re-entered the cell cycle, demonstrating their capacity to change and dedifferentiate without any cell divisions. In differentiated GBM cells, ERK-mediated repression of miR-199a-3p induced EGR1 protein expression and triggered dedifferentiation. Overall, this signaling pathway constitutes an ERK-mediated "toggle switch" that promotes pluripotency marker expression and stem-like features in GBM cells. SIGNIFICANCE: This study defines an ERK-mediated molecular mechanism of dedifferentiation of GBM cells into a stem-like state, expressing markers of pluripotency.See related commentary by Koncar and Agnihotri, p. 3195.

Bevacizumab: Is the lower the better for glioblastoma patients in progression?

INTRODUCTION: Based on the radiological responses obtained with a schedule of ten mg/kg every two weeks bevacizumab was approved by the FDA for recurrent glioblastomas. Due to the negative results concerning overall survival of patients receiving bevacizumab, the European application was rejected. Despite this, many centers apply an off-label prescription. Our aim was to evaluate the safety and efficacy of schedules of low doses of bevacizumab. METHODS: From September 2013 to August 2016, we recruited patients with progressive glioblastoma, whatever the previous treatments. We compared a routine control group (CG) of ten mg/kg, to a low dose group (LDG) composed of 5 subgroups: G5: five mg/kg, G4: four mg/kg, G3: three mg/kg, G2: two mg/kg, G1: one mg/kg; each patient was treated with the same dose every two weeks. RESULTS: Fifty-three patients were treated: 20 women and 33 men, 24 in the CG and 29 in the LDG. The median age at diagnosis was 62 years [35.0-77.0]. No statistical difference was found in overall survival either for the CG or the LDG (P=0.086) or among groups (P=0.251), with even a trend toward improvement for LDG: 62 weeks [20-145] versus 73 weeks [18-178]. The median progression free survival was comparable: 19.5 weeks [6.0-54.0] for the CG and 15.0 weeks [0.0-134.0] for the LDG (P=0.221). Bevacizumab was stopped either due to progression (45.1%) or toxicity (52.9%), without significant differences between doses but maybe less toxicities in the LDG (16.7% for toxicity in G1). DISCUSSION: Use of bevacizumab at progression at lower than usual doses seems to give the same results as the standard dose without giving additional toxicity.

Lumbar interbody fusion with utilization of recombinant human bone morphogenetic protein: a retrospective real-life study about 277 patients.

The purpose of this study was to report an independent real-life experience about the use of recombinant human bone morphogenetic protein 2 in lumbar interbody fusion with a special focus on complications. This is a retrospective single-center cohort study between 2007 and 2013 including 277 patients treated for anterior or posterior lumbar fusion with recombinant human bone morphogenetic protein 2. We report the complications occurring during the 12 first postoperative months and analyze the fusion rate on X-rays. There are 58 cases (22.8%) of clinical complications. In 15 cases (5.9%), these complications were related to the use of recombinant human bone morphogenetic protein 2. Only one patient (0.4%) required a new intervention due to recombinant human bone morphogenetic protein 2. Fusion rate at 1 year was 98%. The low rate of specific complication suggests that recombinant human bone morphogenetic protein 2 can be safe and effective in anterior and posterior interbody fusion when used with simple precautions.

Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth.

Glioblastomas are incurable primary brain tumors that affect patients of all ages. The aggressiveness of this cancer has been attributed in part to the persistence of treatment-resistant glioblastoma stem-like cells. We have previously discovered the tumor-suppressor properties of the microRNA cluster miR-302-367, representing a potential treatment for glioblastoma. Here, we attempted to develop a cell-based therapy by taking advantage of the capability of glioma cells to secrete exosomes that enclose small RNA molecules. We engineered primary glioma cells to stably express the miR-302-367. Remarkably, these cells altered, in a paracrine-dependent manner, the expression of stemness markers, the proliferation and the tumorigenicity of neighboring glioblastoma cells. Further characterization of the secretome derived from miR-302-367 expressing cells showed that a large amount of miR-302-367 was enclosed in exosomes, which were internalized by the neighboring glioblastoma cells. This miR-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain.

Unusual cauda equina syndrome due to multifocal ependymoma infiltrated by lymphoma.

Myxopapillary ependymoma is a rare tumour of the central nervous system (CNS); this subtype of ependymoma occurs most frequently in cauda equina, conus medullaris or filum terminale. The treatment consists of complete removal of the tumour including its capsule when possible since it is usually a solitary lesion. Non-Hodgkin lymphoma of the CNS is found in only 1.3% of cauda equina tumours. We report the case of a 62-year-old man who presented to our institution with progressive weakness of his right lower extremity, with numbness and paresthesia of both feet. He was suffering from one month of right sciatica. Lumbosacral MRI displayed two intradural extramedullary lesions, the first one was located posteriorly to L1-L2 and the second one was spreading from L4 to S2 presenting as a mucoid cyst in its superior part with hyperintense T2 signal, isointense on T1-weighted with high and homogeneous contrast enhancement in the inferior solid component. Imaging also found three additional intradural, extramedullary tumor formations with contrast enhancement, located respectively at C5-C6, C7 and T4. A L1-L2 and S1-S2 laminectomy was performed in emergency and total removal was achieved. Neuropathologist concluded that the tumor was a myxopapillary ependymoma infiltrated by large B-cell lymphoma. Although rare, this phenomenon (coexisting tumors within the same lesion) should be known by neurosurgeons because the occurrence of collision tumors affects the treatment and the patient's prognosis. In our case, two different types of tissue were mingled in the same location-this finding is very uncommon and has, to our knowledge, never been reported before.

In vivo measurement of the frame-based application accuracy of the Neuromate neurosurgical robot.

OBJECT: The application accuracy of the Neuromate neurosurgical robot has been validated in vitro but has not been evaluated in vivo for deep brain stimulation (DBS) electrode implantations. The authors conducted a study to evaluate this application accuracy in routine frame-based DBS procedures, with an independent system of measurement. METHODS: The Euclidian distance was measured between the point theoretically targeted by the robot and the point actually reached, based on their respective stereotactic coordinates. The coordinates of the theoretical target were given by the robot's dedicated targeting software. The coordinates of the point actually reached were recalculated using the Stereoplan localizer system. This experiment was performed in vitro, with the frame fixed in the robot space without a patient, for 21 points spatially distributed. The in vivo accuracy was then measured in 30 basal ganglia targets in 17 consecutive patients undergoing DBS for movement disorders. RESULTS: The mean in vitro application accuracy was 0.44 ± 0.23 mm. The maximal localization error was 1.0 mm. The mean (± SD) in vivo application accuracy was 0.86 ± 0.32 mm (Δx = 0.37 ± 0.34 mm, Δy = 0.32 ± 0.24 mm, Δz = 0.58 ± 0.31 mm). The maximal error was 1.55 mm. CONCLUSIONS: The in vivo application accuracy of the Neuromate neurosurgical robot, measured with a system independent from the robot, in frame-based DBS procedures was better than 1 mm. This accuracy is at least similar to the accuracy of stereotactic frame arms and is compatible with the accuracy required in DBS procedures.

[Gliomas and BRCA genes mutations: fortuitous association or imputability?]. / Gliomes et mutations des gènes BRCA : association fortuite ou imputabilité ?

BRCA is a tumor suppressor gene implicated in the major mechanisms of cellular stability in every type of cell. Its mutations are described in numerous cancers, mainly breast and ovarian in women. It was also found an increase of lifetime risk of pancreas, colon, prostate cancer or lymphoma in men carriers. We report the cases of two female patients aged 40 and 58-years-old female patients and one 35-years-old male patient, with brain or medullar gliomas, carriers of a germline mutation of BRCA gene. Those gliomas were particularly aggressive and were not responding to the standard treatment, with chemo and radiotherapy. The very unusual characteristics in location and evolutive profile of these central nervous system tumors raise the question of a genetical underlying mechanism, maybe linked to the BRCA gene mutation that carry these patients. In addition, a non-fortuitous association between germline mutation of BRCA and occurrence of a glioma can be evoked according to the embryological, epidemiological and biomolecular findings noted in the literature. Other clinical and experimental studies are necessary to precise the physiopathological link existing between BRCA mutations and the occurrence of a glioma; this could have therapeutical and clinical implications in the future.

Salvage treatment of trigeminal neuralgia by occipital nerve stimulation.

BACKGROUND: Although most patients suffering from trigeminal neuralgia (TN) respond to medical or surgical treatment, nonresponders remain in very severe painful condition. CASE RESULT: We describe for the first time a case of severe refractory classical TN treated successfully (follow-up one year) by chronic bilateral occipital nerve stimulation (ONS), because other classic medical and surgical options failed or could not be performed. CONCLUSIONS: This single case suggests that ONS might be offered to TN patients refractory both to standard drugs and interventions, with a favorable risk/benefit ratio, although its long-term efficacy remains unknown.

Intraventricular fibrinolysis for severe aneurysmal intraventricular hemorrhage: a randomized controlled trial and meta-analysis.

UNLABELLED: The aim of this study was to assess the safety and efficacy of intraventricular fibrinolysis (IVF) for aneurysmal subarachnoid hemorrhage (aSAH) with severe intraventricular hemorrhage (IVH). In this randomized controlled trial, between 2005 and 2009, patients with aSAH and severe IVH were randomly assigned into two groups: one treated with external ventricular drainage (EVD) combined with intraventricular recombinant tissue plasminogen activator (rt-PA) and the second with EVD alone. The primary end-point was mortality rate within the first 30 days. We performed meta-analysis including all published articles that compared IVF + EVD to EVD alone in patients with aSAH IVH. Eleven patients were included in the rt-PA group, eight in the control group. At 30 days, mortality rate was lower in the rt-PA group (45.5 vs. 62.5%), but results were not statistically significant (p = 0.65). Clearance of third and fourth ventricles was obtained previously in the rt-PA group (4.25 days) compared to the control group (10.67 days) (p = 0.001). There was no statistically significant difference concerning the occurrence of complications. The meta-analysis showed a better survival rate with IVF without raised statistical significance (odds ratio = 0.32 [95% confidence interval, 0.10-1.03]). This study shows that IVF is as safe as EVD alone for aSAH with severe IVH. It accelerates blood clot resolution in the ventricular system. Mortality rate could be improved by IVF but without significant results. Because of the severity and rarity of this pathology, a multicenter study is required. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov (NCT00823485).

Tumorigenic potential of miR-18A* in glioma initiating cells requires NOTCH-1 signaling.

Stem cell-like properties of glioma initiating cells (GiCs) fuel glioblastoma (GBM) development by providing the different cell types that comprise the tumor. It is therefore likely that the molecular circuitries that regulate their decision to self-renew or commit to a more differentiated state may offer targets for future innovative therapies. In previous micro-RNA profiling studies to search for regulators of stem cell plasticity, we identified miR-18a* as a potential candidate and its expression correlated with the stemness state. Here, using human GiCs we found that miR-18a* expression promotes clonal proliferation in vitro and tumorigenicity in vivo. Mechanistically, ERK-dependent induction of miR-18a* directly represses expression of DLL3, an autocrine inhibitor of NOTCH, thus enhancing the level of activated NOTCH-1. Activated NOTCH-1 in turn is required for sustained ERK activation. This feed-forward loop, driven by miR-18a*, is required to turn on the SHH-GLI-NANOG network, essential for GiC self-renewal. Hence, by tightly regulating expression of DLL3, miR-18a* constitutes an important signaling mediator for fine tuning the level of GiC self-renewal.

Biocomputing: numerical simulation of glioblastoma growth and comparison with conventional irradiation margins.

OBJECT: Estimation of glioblastoma (GBM) growth patterns is of tremendous value in determining tumour margins for radiotherapy. We have previously developed a numerical simulation model for the pattern of spread of glioblastoma tumours. This model involved the creation of a digital atlas of the brain with elasticity and resistance-to-invasion values for specific brain structures and also included probable direction of tumour spread as estimated by Diffusion Tensor Imaging (DTI). The current study is aimed at comparing the outcome of such simulation with conventional irradiation margins currently in use. METHODS: Actual patient data were used to simulate the direction of microscopic extension, using a variety of margin-, proliferation- and diffusion-rate scenarios to generate growth patterns, which were then compared with current standard radiotherapy margins. RESULTS: Our patient growth pattern simulations showed microscopic invasion beyond irradiation margins for both combinations of high-diffusion/low-proliferation and low-diffusion/high-proliferation rate scenarios. The model also indicated that some healthy brain tissue that was projected to be safe from recurrence fell inside treatment margins. CONCLUSION: These results may explain the current inadequacy of our treatment techniques in preventing locoregional recurrences of GBM.

Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache.

Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located <2 mm from the centres of effective contacts were: the mesencephalic grey substance (5/5), the red nucleus (4/5), the fascicle retroflexus (4/5), the fascicle longitudinal dorsal (3/5), the nucleus of ansa lenticularis (3/5), the fascicle longitudinal medial (1/5) and the thalamus superficialis medial (1/5). The contact coordinates (Wilcoxon test) and the structures (Fisher's exact test) were not significantly different between responders and non-responders. These findings suggest that failure of deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems.

Safety and efficacy of deep brain stimulation in refractory cluster headache: a randomized placebo-controlled double-blind trial followed by a 1-year open extension.

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity,sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions.During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation(weekly frequency of attacks decrease [50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).

Short-term restoration of facial sensory loss by motor cortex stimulation in peripheral post-traumatic neuropathic pain.

We report a case in which motor cortex stimulation (MCS) improved neuropathic facial pain due to peripheral nerve injury and restored tactile and thermal sensory loss. A 66-year-old man developed intractable trigeminal neuropathic pain after trauma of the supraorbital branch of the Vth nerve, associated with tactile and thermal sensory loss in the painful area. MCS was performed using neuronavigation and transdural electric stimulation to localize the upper facial area on the motor cortex. One month after surgery, pain was decreased from 80/100 to 20/100 on visual analogic scale, and sensory discrimination improved in the painful area. Two months after surgery, quantitative sensory testing confirmed the normalization of thermal detection thresholds. This case showed that MCS could restore tactile and thermal sensory loss, resulting from peripheral nerve injury. Although the mechanisms leading to this effect remain unclear, this observation enhanced the hypothesis that MCS acts through modulation of the sensory processing.

Rosai-Dorfman disease causing spinal cord compression: case report.

OBJECTIVE: Rosai-Dorfman disease is a rare idiopathic, histiocytic, proliferative disease characterized by massive, painless cervical lymphadenopathy. Extranodal involvement is rare and central nervous system involvement is unusual. We present a patient with Rosai-Dorfman disease with spinal cord compression. Very few cases have been reported in the literature. CLINICAL PRESENTATION: A 17-year-old man presented with a 1-month history of progressive fatigue of the legs. His medical history was significant for Rosai-Dorfman disease diagnosed 7 months earlier. Clinical examination was consistent with a pyramidal syndrome and proprioceptive disturbances on his lower limbs without sensory level. A magnetic resonance imaging scan revealed an intradural extramedullary space-occupying lesion at the T1-T4 level with dural insertion and spinal cord compression. INTERVENTION: A T1-T4 laminotomy was performed. Upon opening the dura, a reddish-gray mass was encountered, which encased the dorsal and lateral arachnoidal membrane. The lesion was relatively well circumscribed and was easily dissected from the underlying arachnoid. Pathological examination of the compressive soft tissue was consistent with Rosai-Dorfman disease. Postoperatively, the patient showed substantial improvement in neurological function. He was followed for 18 months with no complaints and no recurrence. CONCLUSION: Neurosurgeons should consider this rare etiology of spinal cord compression. They must be aware that this lesion can occur in front of an intraspinal lesion, mimic meningiomas, occur in young people, and can potentially be associated with other locations of disease, including intracranial lesions. Surgery is the treatment of choice.

Dynamic model of communicating hydrocephalus for surgery simulation.

We propose a dynamic model of cerebrospinal fluid and intracranial pressure regulation. In this model, we investigate the coupling of biological parameters with a 3-D model, to improve the behavior of the brain in surgical simulators. The model was assessed by comparing the simulated ventricular enlargement with a patient case study of communicating hydrocephalus. In our model, cerebro-spinal fluid production-resorption system is coupled with a 3-D representation of the brain parenchyma. We introduce a new bi-phasic model of the brain (brain tissue and extracellular fluid) allowing for fluid exchange between the brain extracellular space and the venous system. The time evolution of ventricular pressure has been recorded on a symptomatic patient after closing the ventricular shunt. A finite element model has been built based on a computed tomography scan of this patient, and quantitative comparisons between experimental measures and simulated data are proposed.