Evolution in the management of vestibular schwannoma: a single-center 15-year experience.

PURPOSE: To highlight the changes in the management of vestibular schwannoma (VS) since 2004 with a focus on small- to middle-size VS. METHODS: Retrospective analysis of the decisions made in skull base tumor board between 2004 and 2021. RESULTS: 1819 decisions were analyzed (average age 59.25, 54% females). Overall, 850 (47%) cases were allocated to a Wait and Scan (WS) approach, 416 (23%) received radiotherapy and 553 (30%) were treated surgically (MS). All stages considered WS increased from 39% before 2010 to 50% after 2010. Similarly, Stereotactic Radio Therapy (SRT) increased from 5 to 18%. MS decreased from 46 to 25%. It was more commonly proposed to younger patients and larger tumors, p < 0.001. For Koos stages 1, 2, and 3 there was a statistically significant increase in SRT, and a decrease in MS, p < 0.001. WS also increased for stages 1 and 2. However, such a trend was not observed for stage 3. MS remained the primary treatment modality for stage 4 tumors throughout the study period, p = 0.057. The significance of advanced age as a factor favoring SRT decreased over time. The opposite is true for serviceable hearing. There was also a decrease in the percentage of the justification "young age" in the MS category. CONCLUSION: The is a continuing trend towards non-surgical treatment. Small- to medium-sized VS witnessed an increase in both WS and SRT. There is only an increase in SRT for moderately large VS. Physicians are less and less considering young age as a factor favoring MS over SRT. There is a tendency towards favoring SRT when hearing is serviceable.

Intracranial Treatment in Melanoma Patients with Brain Metastasis Is Associated with Improved Survival in the Era of Immunotherapy and Anti-BRAF Therapy.

Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated BM incidence in melanoma patients receiving immune checkpoint inhibitors (ICI) or anti-BRAF therapy and identified prognostic factors for overall survival (OS). Clinical data and treatment patterns were retrospectively collected from all patients treated for newly diagnosed locally advanced or metastatic melanoma between May 2014 and December 2017 with available BRAF mutation status and receiving systemic therapy. Prognostic factors for OS were analyzed with univariable and multivariable survival analyses. BMs occurred in 106 of 250 eligible patients (42.4%), 64 of whom received LT. Median OS in patients with BM was 7.8 months (95% CI [5.4-10.4]). In multivariable analyses, LT was significantly correlated with improved OS (HR 0.21, p < 0.01). Median OS was 17.3 months (95% CI [8.3-22.3]) versus 3.6 months (95% CI [1.4-4.8]) in patients with or without LT. LT correlates with improved OS in melanoma patients with BM in the era of ICI and anti-BRAF therapy. The use of LT should be addressed at diagnosis of BM while introducing systemic treatment.

Glioblastoma survival is better analyzed on preradiotherapy MRI than on postoperative MRI residual volumes: A retrospective observational study.

OBJECTIVES: Establishing an overall survival prognosis for resected glioblastoma during routine postoperative management remains a challenge. The aim of our single-center study was to assess the usefulness of basing survival analyses on preradiotherapy MRI (PRMR) rather than on postoperative MRI (POMR). PATIENTS AND METHODS: A retrospective review was undertaken of 75 patients with glioblastoma treated at our institute. We collected overall survival and MRI volumetric data. We analyzed two types of volumetric data: residual tumor volume and extent of resection. Overall survival rates were compared according to these two types of volumetric data, calculated on either POMR or PRMR and according to the presence or absence of residual enhancement. RESULTS: Analysis of volumetric data revealed progression of some residual tumors between POMR and PRMR. Kaplan-Meier analysis of the correlations between extent of resection, residual tumor volume, and overall survival revealed significant differences between POMR and PRMR data. Both MRI scans indicated a difference between the complete resection subgroup and the incomplete resection subgroup, as median overall survival was longer in patients with complete resection. However, differences were significant for PRMR (25.3 vs. 15.5, p =  0.012), but not for POMR (21.3 vs. 15.8 months, p =  0.145). With a residual tumor volume cut-off value of 3 cm3, Kaplan-Meier survival analysis revealed non-significant differences on POMR (p =  0.323) compared with PRMR (p =  0.007). CONCLUSION: Survival in patients with resected glioblastoma was more accurately predicted by volumetric data acquired with PRMR. Differences in predicted survival between the POMR and PRMR groups can be attributed to changes in tumor behavior before adjuvant therapy.

Incidence and predicting factors of perioperative complications during monitored anesthesia care for awake craniotomy.

STUDY OBJECTIVE: To assess incidence and predicting factors of awake craniotomy complications. DESIGN: Retrospective cohort study. SETTING: Operating room and Post Anesthesia Care unit. PATIENTS: 162 patients who underwent 188 awake craniotomy procedures for brain tumor, ASA I to III, with monitored anesthesia care. MEASUREMENTS: We classified procedures in 3 groups: major event group, minor event group, and no event group. Major events were defined as respiratory failure requiring face mask or invasive ventilation; hemodynamic instability treated by vasoactive drugs, or bradycardia treated by atropine, bleeding >500 ml, transfusion, gaseous embolism, cardiac arrest; seizure, cerebral edema, or any events leading to stopping of the cerebral mapping. Minor event was defined as any complication not classified as major. Multivariate logistic regression was used to determine predicting factors of major complication, adjusted for age and ASA score. MAIN RESULTS: 45 procedures (24%) were classified in major event group, 126 (67%) in minor event group, and 17 (9%) in no event group. Seizure was the main complication (n = 13). Asthma (odds ratio: 10.85 [1.34; 235.6]), Remifentanil infusion (odds ratio: 2.97 [1.08; 9.85]) and length of the operation after the brain mapping (odds ratio per supplementary minute: 1.01 [1.01; 1.03]) were associated with major events. CONCLUSIONS: Previous medical history of asthma, remifentanil infusion and a long duration of neurosurgery after cortical mapping appear to be risk factors for major complications during AC.

Awake Craniotomy and Memory Induction Through Electrical Stimulation: Why Are Penfield's Findings Not Replicated in the Modern Era?

From the 1930s through the early 1960s, Wilder Penfield12 collected a large number of memories induced by electrical brain stimulation (EBS) during awake craniotomy. As a result, he was a major contributor to several neuroscientific and neuropsychological concepts of long-term memory. His 1963 paper, which recorded all the cases of memories he induced in his operating room, remains a substantial point of reference in neuroscience in 2019, although some of his interpretations are now debatable. However, it is highly surprising that, since Penfield's12 reports, there has been no other surgical publication on memories induced during awake surgery. In this review, we explore this phenomenon and analyze some of the reasons that might explain it. We hypothesize that the main reasons for lack of subsequent reports are related to changes in operative procedures (ie, use of anesthetics, time constraints, and insufficient debriefings) and changes in EBS parameters, rather than to the sites that are stimulated, the pathology treated, or the tasks used. If reminiscences are still induced, they should be reported in detail to add valuable contributions to the understanding of long-term memory networks, especially memories that are difficult to reproduce in the laboratory, such as autobiographical memories.

Decreased frontal white-matter diffusion and improved cognitive flexibility after burr-hole surgery in moyamoya angiopathy.

BACKGROUND: In Moyamoya Angioplasty (MMA), increased apparent diffusion coefficient (ADC) in frontal white matter (WM) with a normal appearance has been associated with frontal hypoperfusion and executive dysfunction. Multiple burr-hole surgery enables the revascularization of large frontal areas. GOAL: To assess the effect of multiple burr-hole surgery on the ADC and cognitive functions in adults with MMA. METHODS: ADC was measured in 26 brain hemispheres of 14 consecutive adults with MMA (9 women, mean age ± SD: 38.1 ± 10.7 years) prior to and 6 months after burr-hole surgery. ADC was obtained from regions of interest located in frontal and posterior (temporo-occipital) normal-appearing WM. Ten patients had neuropsychological assessment that focused on executive and attentional functions before and after surgery. RESULTS: Anterior and posterior ADC values did not differ before surgery (815.8 ± 60.1 vs. 812.1 ± 35.3 mm2/s, p = 0.88). After surgery, frontal ADC was lower than prior to surgery (789.9 ± 64.5 vs. 815.8 ± 60.1 mm2/s; p <0.001) whereas no change occurred in posterior ADC (p = 0.31). Trail-making test part B median z-score increased from - 1.47 to - 0.21 (p = 0.018), suggesting improved cognitive flexibility. CONCLUSION: In adults with MMA, indirect revascularization with burr-hole is followed by a decrease of ADC in normal-appearing frontal WM and may have improved some executive functions in the flexibility process. Change in ADC may reflect the improvement in cerebral perfusion after surgery. The measuring of ADC may be a promising tool in exploring potentially reversible microstructural WM damage related to hypoperfusion and cognitive change in MMA.

Neuronal spiking activity highlights a gradient of epileptogenicity in human tuberous sclerosis lesions.

OBJECTIVE: The mechanisms underlying epileptogenicity in tuberous sclerosis complex (TSC) are poorly understood. METHODS: We analysed neuronal spiking activity (84 neurons), fast ripples (FRs), local field potentials and intracranial electroencephalogram during interictal epileptiform discharges (IEDs) in the tuber and perituber of a patient using novel hybrid electrodes equipped with tetrodes. RESULTS: IEDs were recorded in the tuber and perituber. FRs were recorded only in the tuber and only with the microelectrodes. A larger proportion of neurons in the tuber (57%) than in the perituber (17%) had firing-rates modulated around IEDs. CONCLUSIONS: A multi-scale analysis of neuronal activity, FRs and IEDs indicates a gradient of epileptogenicity running from the tuber to the perituber. SIGNIFICANCE: We demonstrate, for the first time in vivo, a gradient of epileptogenicity from the tuber to the perituber, which paves the way for future models of epilepsy in TSC. Our results also question the extent of the neurosurgical resection, including or not the perituber, that needs to be made in these patients.

Impact on survival of early tumor growth between surgery and radiotherapy in patients with de novo glioblastoma.

PURPOSE: Systematic pre-radiotherapy MRI in patients with newly resected glioblastoma (OMS 2016) sometimes reveals tumor growth in the period between surgery and radiotherapy. We evaluated the relation between early tumor growth and overall survival (OS) with the aim of finding predictors of regrowth. METHODS: Seventy-five patients from 25 to 84 years old (Median age 62 years) with preoperative, immediate postoperative, and preradiotherapy MRI were included. Volumetric measurements were made on each of the three MRI scans and clinical and molecular parameters were collected for each case. RESULTS: Fifty-four patients (72%) had an early regrowth with a median contrast enhancement volume of 3.61 cm3-range 0.12-71.93 cm3. The median OS was 24 months in patients with no early tumor growth and 17.1 months in those with early tumor regrowth (p = 0.0024). In the population with initial complete resection (27 patients), the median OS was 25.3 months (19 patients) in those with no early tumor growth between surgery and radiotherapy compared to 16.3 months (8 patients) in those with tumor regrowth. In multivariate analysis, the initial extent of resection (p < 0.001) and the delay between postoperative MRI and preradiotherapy MRI (p < 0.001) were significant independent prognostic factors of regrowth and of poorer outcome. CONCLUSIONS: We demonstrated that, in addition to the well known issue of incomplete resection, longer delays between surgery and adjuvant treatment is an independent factors of tumor regrowth and a risk factor of poorer outcomes for the patients. To overcome the delay factor, we suggest shortening the usual time between surgery and radiotherapy.

EWSR1-PATZ1 gene fusion may define a new glioneuronal tumor entity.

We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1-PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1-PATZ1 fusion transcript. RT-PCR followed by Sanger sequencing confirmed the EWSR1-PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N-terminal transcriptional activation domain of EWSR1 gene and the C-terminal DNA binding domain of a transcription factor gene, PATZ1. PATZ1 protein belongs to the BTB-ZF (broad-complex, tramtrack and bric-à-brac -zinc finger) family. It directly regulates Pou5f1 and Nanog and is essential to maintaining stemness by inhibiting neural differentiation. EWSR1-PATZ1 fusion is a rare event in tumors: it was only reported in six round cell sarcomas and in three gliomas of three exclusively molecular studies. The first reported glioma was a BRAFV600E negative ganglioglioma, the second a BRAFV600E negative glioneuronal tumor, not otherwise specified and the third, very recently reported, a high grade glioma, not otherwise specified. In our study, forty BRAFV600E negative gangliogliomas were screened by FISH using EWSR1 break-apart probes. We performed methylation profiling for the index case and for seven out of the ten FISH positive cases. The index case clustered apart from other pediatric low grade glioneuronal entities, and specifically from the well-defined ganglioglioma methylation group. An additional pediatric intraventricular ganglioglioma clustered slightly more closely with ganglioglioma, but showed differences from the main ganglioglioma group and similarities with the index case. Both cases harbored copy number variations at the PATZ1 locus. EWSR1-PATZ1 gene fusion might define a new type of glioneuronal tumors, distinct from gangliogliomas.

Dedicated Linear Accelerator Radiosurgery for Classic Trigeminal Neuralgia: A Single-Center Experience with Long-Term Follow-Up.

BACKGROUND: During the past decades, stereotactic radiosurgery, and Gamma Knife in particular, has proved its safety and efficacy for drug-resistant classic trigeminal neuralgia. However, few large series exist using linear accelerator (LINAC) reporting long-term follow-up. METHODS: Between 2006 and 2015, 301 patients were treated by LINAC at our institution. The prescribed radiation dose was 90 Gy at the far anterior target. Clinical response was defined using the Barrow Neurological Institute scale. We considered grades I and IIIa as a successful response. Mean duration of follow-up was 54.6 months (range, 12-132 months). RESULTS: Two hundred and seventy-three patients (90.7%) were initially pain free, and 28 patients (9.3%) were unchanged. The actuarial probabilities of maintaining pain relief with or without medication (Barrow Neurological Institute grade I and IIIa) at 0.5, 1, 2, 4, 5, and 10 years were 88.7%, 85.0%, 76.1%, 68.8%, 65.8%, and 48.1%, respectively. Hypesthesia was present in only 26.2% of patients (very bothersome, 0.3%). No anesthesia dolorosa was reported. The actuarial probabilities of maintaining pain relief without further surgery at 0.5, 1, 2, 4, and 5 years were 99.3%, 98.3%, 95.8%, 91.0%, and 89.7%, respectively. Among all treated patients, 86.5% were satisfied by the procedure and would undergo stereotactic radiosurgery again. CONCLUSIONS: Stereotactic radiosurgery with dedicated LINAC is associated with high rates of long-term pain relief, with minimal invasiveness and rare complications. LINAC is a possible therapeutic alternative for drug-resistant trigeminal neuralgia and could be proposed to selected patients as the first intention therapy, among other surgical solutions.

French guidelines on stereoelectroencephalography (SEEG).

Stereoelectroencephalography (SEEG) was designed and developed in the 1960s in France by J. Talairach and J. Bancaud. It is an invasive method of exploration for drug-resistant focal epilepsies, offering the advantage of a tridimensional and temporally precise study of the epileptic discharge. It allows anatomo-electrical correlations and tailored surgeries. Whereas this method has been used for decades by experts in a limited number of European centers, the last ten years have seen increasing worldwide spread of its use. Moreover in current practice, SEEG is not only a diagnostic tool but also offers a therapeutic option, i.e., thermocoagulation. In order to propose formal guidelines for best clinical practice in SEEG, a working party was formed, composed of experts from every French centre with a large SEEG experience (those performing more than 10 SEEG per year over at least a 5 year period). This group formulated recommendations, which were graded by all participants according to established methodology. The first part of this article summarizes these within the following topics: indications and limits of SEEG; planning and management of SEEG; surgical technique; electrophysiological technical procedures; interpretation of SEEG recordings; and SEEG-guided radio frequency thermocoagulation. In the second part, those different aspects are discussed in more detail by subgroups of experts, based on existing literature and their own experience. The aim of this work is to present a consensual French approach to SEEG, which could be used as a basic document for centers using this method, particularly those who are beginning SEEG practice. These guidelines are supported by the French Clinical Neurophysiology Society and the French chapter of the International League Against Epilepsy.

Regenerative potential of primary adult human neural stem cells on micropatterned bio-implants boosts motor recovery.

BACKGROUND: The adult brain is unable to regenerate itself sufficiently after large injuries. Therefore, hopes rely on therapies using neural stem cell or biomaterial transplantation to sustain brain reconstruction. The aim of the present study was to evaluate the improvement in sensorimotor recovery brought about by human primary adult neural stem cells (hNSCs) in combination with bio-implants. METHODS: hNSCs were pre-seeded on implants micropatterned for neurite guidance and inserted intracerebrally 2 weeks after a primary motor cortex lesion in rats. Long-term behaviour was significantly improved after hNSC implants versus cell engraftment in the grip strength test. MRI and immunohistological studies were conducted to elucidate the underlying mechanisms of neuro-implant integration. RESULTS: hNSC implants promoted tissue reconstruction and limited hemispheric atrophy and glial scar expansion. After 3 months, grafted hNSCs were detected on implants and expressed mature neuronal markers (NeuN, MAP2, SMI312). They also migrated over a short distance to the reconstructed tissues and to the peri-lesional tissues, where 26% integrated as mature neurons. Newly formed host neural progenitors (nestin, DCX) colonized the implants, notably in the presence of hNSCs, and participated in tissue reconstruction. The microstructured bio-implants sustained the guided maturation of both grafted hNSCs and endogenous progenitors. CONCLUSIONS: These immunohistological results are coherent with and could explain the late improvement observed in sensorimotor recovery. These findings provide novel insights into the regenerative potential of primary adult hNSCs combined with microstructured implants.

Is there any benefit from short-term perioperative antiepileptic prophylaxis in patients with chronic subdural haematoma? A retrospective controlled study.

BACKGROUND: Chronic subdural haematoma is a common pathology, which can be complicated by seizures. Seizures may worsen the outcome of patients presenting with a chronic subdural haematoma. However, since the overall and postoperative incidence of seizures and their impact on patients' outcome has been diversely appreciated in the literature, the interest of routine antiepileptic prophylaxis remains a controversial question. METHODS: We retrospectively investigated 99 patients who were surgically treated for a chronic subdural haematoma in two French academic hospitals: 48 patients received antiepileptic prophylaxis (group A) and were compared with a group of 51 patients who did not receive any antiepileptic prophylaxis (group B). Incidence of perioperative seizures was determined, and potential risk factors for epilepsy were analysed. RESULTS: Overall postoperative seizure incidence was 5.1%. There was a slight trend towards a lower incidence of seizures in patients who had received antiepileptic prophylaxis, but no significant difference was found between the two groups (4.2% in group A versus 5.9% in group B, P=0.697). Seizures were not correlated with increased death. No risk factor for seizures was identified. CONCLUSIONS: Our retrospective data showed there is no benefit of perioperative antiepileptic prophylaxis in patients surgically treated for chronic subdural haematoma. Since other authors have shown conflicting results, sufficiently powered prospective randomized study should be conducted in order to confirm these results.

Clinical and radiological cervical spine evaluation in retired professional rugby players.

OBJECT Acute cervical spine injuries have been extensively studied in high-level contact sports. However, the relation between the appearance of degenerative cervical spine disease and the exposure to repeated trauma in such sports as rugby is still unclear. Using clinical and MRI evaluation, we aimed to determine if former professional rugby players had more serious degenerative cervical spine symptoms than the general population. METHODS Two groups, one composed of 101 former rugby players (all men, mean age 40.3 years, range 35-47 years, SD 2.3 years) and the other of 85 male volunteers serving as a control group (mean age 41.6 years, range 35-49 years, SD 4.5 years) were studied. The former rugby players were evaluated on average 5.8 years after retirement (range 1-16 years, SD 3.5 years). The groups were matched in terms of sex, age, job, current sports training, and smoking habits. Each participant received a complete neurological evaluation. Clinical symptoms were evaluated using the Japanese Orthopaedic Association (JOA) questionnaire, and chronic neck pain was specifically evaluated using a visual analog scale (VAS) and the Neck Disability Index (NDI). Overall, 25 MRI studies were performed in each group. MRI studies, including dynamic sequences, focused on degenerative lesions (Matsumoto score and canal diameter) and on muscular and medullary morphological analysis. RESULTS Significantly more former rugby players than controls complained of chronic neck pain (51 [50.50%] of 101 vs 27 [31.76%] of 85, p = 0.01). Rugby players also had significant reductions of neck mobility. Nevertheless, in those complaining of pain, there was no statistically significant difference between groups with respect to VAS and NDI scores (p = 0.57). On MRI, former rugby players had a narrower vertebral canal (on average 0.88 ± 0.167 cm vs 0.99 ± 0.130 cm, p = 0.007) and more foraminal stenosis (p = 0.01). No significant difference in the Matsumoto score was found between the 2 groups with respect to other degenerative lesions. Former rugby players had more often undergone surgery for a degenerative condition than had members of the control group (10 cases vs 0 in the control group, p = 0.0021). CONCLUSIONS A few years after retirement, former professional rugby players seem to have more frequent cervical spine pain and MRI degenerative lesions, such as foraminal stenosis and narrowing of the spinal canal, compared with controls who had not been professional rugby players. A longer evaluation is necessary to determine if these findings persist over time.

Can DTI fiber tracking of the optic radiations predict visual deficit after surgery?

OBJECT: Sparing optic radiations can be of paramount importance during epilepsy surgery of the temporal lobe. The anatomical heterogeneity of the Meyer's loop of the optic radiations could be assessed by means of diffusion tensor tractography. We used temporal lobe surgery as a lesion model to validate this method. MATERIAL AND METHODS: We analyzed the distance between the temporal pole (TP) and Meyer's loop (ML) and the correlation between visual impairment and the percentage of virtual fibers injured. MRI studies were performed in 18 patients and 13 controls. Diffusion tensor imaging (DTI) with fiber tracking was performed using four different algorithms and various gradient directions (15 or 32) and fractional anisotropy (FA) thresholds (0.18, 0.20, and 0.22). To find the best DTI model, we tested each gradient direction and FA threshold on 16 operated patients by pre- and post-operative visual field testing that analyzed the percentage of virtual fibers damaged on 3-month-post-operative MRIs. RESULTS: Marked individual differences were noted in the TP-ML distances (mean: 25.4mm; range 18.2-38.3mm; standard deviation: 4.7) but with no significant difference between patients and controls (p=0.9). The percentage of virtual fibers reconstructed by tracking and damaged by surgery was correlated with visual impairment. Significant differences appeared between algorithm types. The tensor-line algorithm with 15-direction resolution and an anisotropy threshold of 0.18 seemed to be the most relevant. A threshold of 5.5% of injured virtual fiber could predict a visual defect with a sensitivity of 71.4% and a specificity of 87.5%. CONCLUSION: Optic radiation tractography by DTI could be a useful method to assess an individual patient's risk of postoperative visual deficit.

αvß3 Integrin and Fibroblast growth factor receptor 1 (FGFR1): Prognostic factors in a phase I-II clinical trial associating continuous administration of Tipifarnib with radiotherapy for patients with newly diagnosed glioblastoma.

BACKGROUND: Based on our previous results showing the involvement of the farnesylated form of RhoB in glioblastoma radioresistance, we designed a phase II trial associating the farnesyltransferase inhibitor Tipifarnib with radiotherapy in patients with glioblastoma and studied the prognostic values of the proteins which we have previously shown control this pathway. PATIENTS AND METHODS: Patients were treated with 200mg Tipifarnib (recommended dose (RD)) given continuously during radiotherapy. Twenty-seven patients were included in the phase II whose primary end-point was time to progression (TTP). Overall survival (OS) and biomarker analysis were secondary end-points. Expressions of αvß3, αvß5 integrins, FAK, ILK, fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) were studied by immuno-histochemistry in the tumour of the nine patients treated at the RD during the previously performed phase I and on those of the phase II patients. We evaluated the correlation of the expressions of these proteins with the clinical outcome. RESULTS: For the phase II patients median TTP was 23.1 weeks (95%CI = [15.4; 28.2]) while the median OS was 80.3 weeks (95%CI = [57.8; 102.7]). In the pooled phase I and II population, median OS was 60.4 w (95%CI = [47.3; 97.6]) while median TTP was 18.1 w (95%CI = [16.9; 25.6]). FGFR1 over-expression (HR = 4.65; 95%CI = [1.02; 21.21], p = 0.047) was correlated with shorter TTP while FGFR1 (HR = 4.1 (95% CI = [1.09-15.4]; p = 0.036)) and αvß3 (HR = 10.38 (95%CI = [2.70; 39.87], p = 0.001)) over-expressions were associated with reduced OS. CONCLUSION: Association of 200mg Tipifarnib with radiotherapy shows promising OS but no increase in TTP compared to historical data. FGFR1 and αvß3 integrin are independent bad prognostic factors of OS and TTP.

Primary sellar neuroblastoma. A new case and review of literature.

The primary intracranial development of olfactory neuroblastomas, outside olfactory epithelium, is rare. We report a case of primary sellar neuroblastoma without any aggressive histopathological features, managed solely surgically without adjuvant therapy, with good outcomes at 3 years. Primary sellar neuroblastomas mostly occur in women in the 4th decade with a context of a non-secreting pituitary tumour. Diagnosis is made on histopathological examination (small cells, fibrillary intercellular background, strong immunoreactivity for neurons markers, negative immunoreactivity for anterior pituitary hormones). Management is based on surgery. Adjuvant treatment is not consensual, largely depends on patient's conditions and aggressive histopathological features.

Evaluation of O-(2-[18F]-Fluoroethyl)-L-Tyrosine in the Diagnosis of Glioblastoma.

OBJECTIVE: To assess the feasibility of synthesis of O-(2-[(18)F]-fluoroethyl)-l-tyrosine (FET), a new positron emission tomographic (PET) tracer described in several studies but not yet considered standard in management of glioma, in routine practice and to determine FET uptake in a homogeneous group of patients with suspected high-grade glioma. DESIGN: Prospective nonrandomized trial. PATIENTS: Twelve patients with suspicion of high-grade glioma. RESULTS: The mean (SD) FET uptake ratio was 3.15 (0.72) for the 12 patients and 3.16 (0.75) for the 11 patients with glioblastoma. CONCLUSION: The initial results are promising and indicate that FET PET is a valuable and applicable tool for the imaging of high-grade glioma.

Human fetal chromaffin cells: a potential tool for cell pain therapy.

Transplantation of adrenal medulla cells has been proposed in the treatment of various conditions. Indeed, these cells possess a bipotentiality: neural and neuroendocrine, which could be exploited for brain repair or pain therapy. In a previous study, we characterized these human cells in vitro over 7-10 gestational weeks (GW) [Zhou, H., Aziza, J., Sol, J.C., Courtade-Saidi, M., Chatelin, S., Evra, C., Parant, O., Lazorthes, Y., and Jozan, S., 2006. Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development. Exp. Neurol. 198, 370-381]. We report here our results on the extension to 23 GW. This developmental period can be split into three stages. During the first stage (7-10 GW), we observed in situ that extra-adrenal surrounding cells display the same morphology and phenotype as the intra-adrenal chromaffin cells. We also found that the intra-adrenal chromaffin cells could be committed in vitro towards an adrenergic phenotype using differentiating agents. During the second stage (11 to 15-16 GW), two types of cells (Type 1 and Type 2 cells) were identified morphologically both inside and outside the gland. Interestingly, we noted that the Type 2 cells stem from the Type 1 cells. However, during this developmental period only the intra-adrenal Type 2 cells will evolve towards an adrenergic phenotype. In the third stage (17-23 GW), we observed the ultimate location of the medulla gland. Both the in situ results and the in vitro experiments indicate that particular procedures need to be implemented prior transplantation of chromaffin cells. First, in order to obtain a large number of immature chromaffin cells, they must be isolated from the intra and extra-adrenal gland and should then be committed towards an adrenergic phenotype in vitro for subsequent use in pain therapy. This strategy is under investigation in our laboratory.

Quantification of true in vivo (application) accuracy in cranial image-guided surgery: influence of mode of patient registration.

OBJECTIVE: Very few studies have attempted to quantify the true (application) accuracy of image-guidance systems during craniotomy. This is, in part, because of the lack of millimetric intraoperative targets to allow such measurements. Few in vivo studies have compared the influence of mode of patient registration on subsequent true accuracy. METHODS: Seven modes of patient registration (anatomic landmarks, 5 or 10 adhesive fiducials, bone-implanted fiducials [Stryker-Leibinger], surface matching using 45 or 100 points over scalp convexity or nose/auditory meatus contours) were compared. Thirty patients were involved in the study. Millimetric targets (bone drill holes or deep 1-mm titanium hemoclips) were placed then localized and saved at surgery. These targets were then identified on postoperative volumetric computed tomography fused with operative data sets. Localization errors of the targets were measured for each registration on an optical image-guidance system (StealthStation). RESULTS: Only implanted cranial fiducials had a statistically significant accuracy advantage (1.7 +/- 0.7 mm). All other registrations had similar accuracies (approximately 4.0 +/- 1.7 mm) except anatomic landmarks, which were worse (4.8 +/- 1.9 mm). Calculated accuracies (root mean squared) had no predictive value for true (application) accuracies. CONCLUSION: Not surprisingly, application accuracy of image-guidance is worse without implanted cranial markers. Unexpectedly, there was no major difference in localization of deep targets between the other registrations tested in this study. Care must be taken when using image-guidance tools to consider error introduced by registration. Cranium-implanted fiducials should be considered when high accuracy and reproducibility are needed.