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International audience; BACKGROUND: Delayed cerebral ischaemia from vasospasm is an important cause of complications and death after aneurysmal subarachnoid haemorrhage. There is currently no established biomarker for identifying patients at high risk of delayed cerebral ischaemia.ăOBJECTIVE: Considering the important role of inflammation in the pathogenesis of delayed cerebral ischaemia, we investigated whether matrix metalloproteinase-9 (MMP-9) may be an efficient biomarker for predicting elayed cerebral ischaemia after subarachnoid haemorrhage.ăDESIGN: Single-centre prospective observational study.ăSETTING: Neuroscience Critical Care Unit of a teaching hospital.ăPARTICIPANTS: Thirty consecutive patients with severe subarachnoid haemorrhage requiring external ventricular drainage were enrolled during 2013 and 2014.ăINTERVENTIONS: Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h and between 48 and 72 h after admission. We evaluated the activity and concentrations of MMP-9 and endothelin-1 with zymography and ELISA. Patients were allocated to groups with delayed cerebral ischaemia (n = 16) or without delayed cerebral ischaemia (n = 14).ăRESULTS: Within 24 h, median [interquartile range] MMP-9 concentrations in CSF were significantly higher in patients with delayed cerebral ischaemia (47 [21 to 102] ng ml) than in those without delayed cerebral ischaemia (4 [2 to 13] ng ml, P = 0.001). CSF MMP-9 activity and endothelin-1 concentrations were correlated (r = 0.6, P = 0.02). The areas under the receiver operating characteristic curves were 0.73 (95% confidence interval [0.53 to 0.87]) and 0.91 (95% confidence interval [0.75 to 0.98]) for MMP-9 concentrations in plasma and CSF, respectively, at 24 h to predict delayed cerebral ischaemia CSF MMP-9 concentrations more than 14.3 ng ml at 24 h predicted the occurrence of delayed cerebral ischaemia with a sensitivity and specificity of 88 and 86%, respectively. After multivariate logistic analysis, only CSF MMP-9 concentrations at 24 h predicted the occurrence of delayed cerebral ischaemia (P = 0.01).ăCONCLUSION: MMP-9 concentrations in both plasma and CSF, measured within 48 h after subarachnoid haemorrhage, were highly predictive of the occurrence of delayed cerebral ischaemia within the first 2 weeks.ăTRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02397759.

International audience; OBJECTIVE: To analyze complications of endoscopic transsphenoidal surgery (ETS) for nonfunctioning pituitary macroadenomas (NFPAs).ăMETHODS: A retrospective study of 300 NFPAs was performed. Complications and factors that could influence these complications were analyzed.ăRESULTS: Visual and pituitary functions worsened in 2.4% and 13.7% of cases, respectively. Postoperative diabetes insipidus was permanent in 6.2% of cases. Postoperative meningitis occurred in 3.3% of patients. Meningitis was strongly associated with intraoperative cerebrospinal fluid (CSF) leaks (P = 0.01), postoperative CSF leaks (P = 0.0001), and operation times longer than 1 hour (P = 0.023). Detection of Staphylococcus aureus and preoperative treatment with mupirocin in the nostrils did not impact the occurrence of meningitis. Two patients with meningitis died (unique causes of death). Postoperative CSF leaks occurred in 2.7% of cases and were associated with intraoperative CSF leaks (P = 0.007) and permanent diabetes insipidus (P = 0.028). The rate of CSF leak decreased from 4% to 0.8% (P = 0.048) after we moved from a soft to hard reconstruction of the sella. The rate of postoperative epistaxis decreased from 6.7% to 1.25% after we stopped using monopolar coagulation (P = 0.013).ăCONCLUSIONS: ETS permits a wide view, allowing good conditions for a satisfactory resection in the majority of NFPAs. Some pitfalls of endoscopy can lead to complications that improve with modification of the operative technique (i.e., CSF leak and postoperative epistaxis). This study confirms an acceptable rate of complications associated with ETS.

International audience; Haemorrhage stroke is a major issue for public health care. The prevalence of intracranial aneurysms in the general population ranges between 3 and 6.6% (Wardlaw and White 2000). Fortunately, very few aneurysms rupture. The incidence of ruptured aneurysms is approximately 0.5% per year. However, patients are stressful and wants to be treated. But, endovascular treatment of unruptured aneurysms, which is the safest treatment, is not without risk and has about 1% mortality rate (Sluzewski et al. 2001). So, unruptured intracranial aneurysms represent a dilemma for the physicians.In 2011 (Costalat et al.), we have proposed an indicator base on the relationship between the mechanical properties of wall aneurysm tissues and the rupture risk. First conclusions suggested that the softer tissue is, the higher rupture risk is.The present study aims to confirm these results, initiates with only 16 samples, studying 26 more aneurysms.

Meningeal solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are distinct entities in the World Health Organization (WHO) classification of central nervous system (CNS) tumors while they belong to the same spectrum of tumors in other locations. Well-defined histological prognostic factors are also lacking for these tumors. In order to clarify the relationship between SFT and HPC and to find histological and immunohistochemical prognostic factors, we carried out a retrospective study in 89 patients. The following histological parameters were recorded: hypercellularity, collagenic areas, cytonuclear atypias, necrosis, mitotic count per 10 high-power fields, vasculo-nervous adherences defined by engulfment of vessel or nerve by the tumor, brain infiltration. We found overlapping histological and immunohistochemical features between SFT and HPC. The most relevant histological prognostic factors in the whole cohort for both progression-free survival (PFS) and overall survival (OS) in univariate analysis were hypercellularity, high mitotic count (>5 per 10 high-power fields) and necrosis. On the basis of these results, we propose a new grading scheme for these tumors which was of pronostic value for both PFS and OS in uni- and multivariate analysis. As extent of surgery was also a prognostic factor for both PFS and OS in univariate analysis, we propose that management of SFT/HPC might be based both on quality of removal and histological grade.

International audience; Nonfunctioning pituitary adenomas (NFPA; gonadotroph derived), even not inducing hormonal hypersecretion, cause significant morbidity by compression neighboring structures. No effective and specific medical methods are available so far for treating these tumors. The pituitary homeobox 2 (PITX2) gene is a member of the bicoid-like homeobox transcription factor family, which is involved in the Wnt/Dvl/β-catenin pathway. PITX2 is overexpressed in NFPA. PITX2 mutations are known to be responsible for Axenfield Rieger syndrome, a genetic disorder in which pituitary abnormalities have been detected. The R91P mutant identified in Axenfeld Rieger syndrome is a dominant-negative factor, which is able to block the expression of several pituitary genes activated by PITX2. To better understand the role of Pitx2 on gonadotroph tumorigenesis and to explore new approach for inhibiting tumoral growth, the R91P mutant was transferred via a lentiviral vector in tumoral gonadotroph cells of two kinds: the αT3-1 cell line and human adenoma cells. R91P mutant and small interfering RNA directed against Pitx2 both decreased the viability of αT3-1 cells via an apoptotic mechanism involving the activation of executioner caspase. Similar effects of the R91P mutant were observed on human gonadotroph cells in primary culture. Therefore, Pitx2 overexpression may play an antiapoptotic role during NFPA tumorigenesis.

e14050Background: we previously reported the occurrence of IDH wild-type (IDHwt) low grade glioma (LGG) involving the insula that carried a poor prognosis. Our objective was to characterize the mol...

The study design includes prospective evaluation of percutaneous osteosynthesis associated with cement kyphoplasty on 18 patients. The objective of the study is to assess the efficacy of a percutaneous method of treating burst vertebral fractures in patients without neurological deficits. Even if burst fractures are frequent, no therapeutic agreement is available at the moment. We report in this study the results at 2 years with a percutaneous approach for the treatment of burst fractures. 18 patients were included in this study. All the patients had burst vertebral fractures classified type A3 on the Magerl scale, between levels T9 and L2. The patients' mean age was 53 years (range 22-78 years) and the neurological examination was normal. A percutaneous approach was systematically used and a kyphoplasty was performed via the transpedicular pathway associated with percutaneous short-segment pedicle screw osteosynthesis. The patients' follow-up included CT scan analysis, measurement of vertebral height recovery and local kyphosis, and clinical pain assessments. With this surgical approach, the mean vertebral height was improved by 25% and a mean improvement of 11.28 degrees in the local kyphotic angle was obtained. 3 months after the operation, none of the patients were taking class II analgesics. The mean duration of their hospital stay was 4.5 days (range 3-7 days) and the mean follow-up period was 26 months (range 17-30 months). No significant changes in the results obtained were observed at the end of the follow-up period. Minimally invasive methods of treating burst vertebral fractures can be performed via the percutaneous pathway. This approach gives similar vertebral height recovery and kyphosis correction rates to those obtained with open surgery. It provides a short hospital stay, however, and might therefore constitute a useful alternative to open surgical methods.

Somatostatin (SST) receptors, specially sst2 and sst5, provide a valuable target to inhibit excessive hormone release and cell growth in pituitary tumors by using SST analogs (SSAs). Unfortunately, an appreciable proportion of tumors fail to respond to SSA despite expressing high levels of one or more ssts. Recently we identified two novel truncated sst5 variants, sst5TMD5, and sst5TMD4, absent in normal pituitary but expressed in pituitary tumors.We aimed at exploring the potential role of sst5TMD5 and sst5TMD4 in the poor response of some tumors to SSA in vivo and in vitro. Specifically, 25 somatotropinomas showing different responses to octreotide in vivo and sst2 (BIM-23197)- and sst5(BIM-23268)-selective compounds in vitro were screened for sst5TMD5/sst5TMD4 expression by real-time PCR. Relationships between ssts expression and in vivo and in vitro secretory response of the corresponding pituitary samples were assessed.sst5TMD5 was absent in all samples analyzed. sst5TMD4 was found in 85% of tumors, and its expression was positively correlated to that of sst5 (R(2) = 0.79, P0.001). Expression of sst5TMD4 was negatively correlated with the ability of octreotide to reduce GH levels in vivo and partially negatively correlated with inhibition of GH secretion by an sst5 selective agonist (BIM-23268) in vitro.These results indicate that sst5TMD4 is related to the reduced ability of octreotide at normalizing hormone secretion in poorly responsive tumors in vivo. Further studies will help to evaluate the potential use of sst5TMD4 expression in surgically removed pituitary adenomas as a predictor of the subsequent response of different pituitary tumors to SSA therapy.

Stereotactic radiosurgery can be performed to control tumor growth and hypersecretion of pituitary tumors, which are the most frequent type of intercranial tumors and lead to high rates of morbidity and mortality. Results of long-term studies of this treatment are discussed in this Review, with recommendations for therapeutic management. Trans-sphenoidal neurosurgery is the gold standard treatment for pituitary adenomas, but it can be contraindicated or ineffective. Stereotactic radiosurgery is a procedure aimed at controlling hormone hypersecretion and tumor size of pituitary adenomas. This Review discusses the long-term efficacy and adverse effects of stereotactic radiosurgery with the Gamma Knife® in secreting and nonsecreting pituitary adenomas. Long-term data confirm the antisecretory efficacy of the procedure (about 50% remission in hypersecreting tumors) but also a previously unknown low risk of recurrence (2–10% of cases). The time to remission is estimated to range from 12 to 60 months. The antitumoral efficacy of this treatment against nonsecreting tumors is observed in about 90% of cases. Hypopituitarism is the main adverse effect, observed in 20–40% of cases. Comparisons with conventional fractionated radiotherapy reveal a lower rate of remission with Gamma Knife® radiosurgery, counterbalanced by a more rapid efficacy and a lower rate of hypopituitarism. Short-term follow-up results on stereotactic fractionated radiotherapy suggest a risk of hypopituitarism similar to the one observed with radiosurgery. Therefore, stereotactic radiosurgery is probably still useful to treat some cases of pituitary adenoma, despite the fact that antisecretory drugs, particularly for acromegaly and prolactinomas, are becoming more effective and are well tolerated, thus increasing the probability of success with nonsurgical therapy.

Object The cervicothoracic junction is always a difficult area to approach. When operating on this specific area (for tumor or trauma), the aim is generally to decompress and stabilize the spine. The authors describe an improved median sternotomy method for reaching the anterior aspect of the spine down to T-5. Methods Seven patients with a mean age of 40 years (range 17–68 years) were included in this study. The vertebral lesion was due to trauma in 4 cases and tumor in the other 3. A single vertebral body was involved in 2 cases, 2 in 3 cases, and 3 in 2 cases. The vertebra most often involved was T-3 (6 cases), although T-4 was involved in 2 cases, T-5 in 2 cases, and T-1 and T-2 in 1 case each. All patients underwent the same preoperative workup: CT scanning, MR imaging, and CT angiography of the aortic arch. Results The median sternotomy made it possible to effectively decompress and stabilize the spinal cord. An anterior screw plate was used in 5 cases. The plate extended from T-2 to T-5 in 3 cases, from T-2 to T-4 in 2 cases, and from C-7 to T-4 in 1 case. The mean duration of surgery was 195 minutes (range 180–240 minutes). No neurological deterioration occurred. The mean hospital stay was 8 days (range 6–15 days). In 2 cases (28.6%), recurrent left nerve palsy was observed postoperatively; the palsy was transient in both of these cases, and full recovery occurred within 3 months. The mean follow-up among this series of patients was 29 months (range 22–38 months). Conclusions The median sternotomy provided a good means of reaching the upper thoracic spine (T2–5) and cervicothoracic junction. It enables surgeons to decompress the spinal cord and stabilize the spine.

Recurrence of Cushing's disease (CD) after transsphenoidal surgery (TSS) occurs in about 25% of cases. Twenty percent of patients with immediate postsurgical corticotroph deficiency will present late recurrence.The aim of the study was to evaluate a coupled dexamethasone desmopressin test (CDDT) as a predictor of recurrence of CD.We conducted a prospective bicenter study (Marseille and Grenoble, France).We studied 38 patients treated by TSS for CD with a mean follow-up of 60 months.We evaluated 24-h urinary free cortisol, ACTH, and cortisol plasmatic levels and performed low-dose dexamethasone suppression test and CDDT 3 to 6 months after surgery and then yearly.After CDDT, ACTH ratio (ACTHr) was defined as (PeakACTH - BaseACTH)/BaseACTH. Cortisol ratio (Cortisolr) was defined as (PeakCortisol - BaseCortisol)/BaseCortisol. Basal values were observed after low-dose dexamethasone suppression test. Receiver operator characteristics curve defined ACTHr and Cortisolr giving the best sensitivity and specificity associated with recurrence.Ten patients presented recurrence. ACTHr and Cortisolr were superior or equal to 0.5 in all patients with recurrence and in three of 28 patients in remission (100% sensitivity, 89% specificity). The test became positive in eight of 10 patients with recurrence 6-60 months before classical markers of hypercortisolism. Six patients with immediate postsurgical corticotroph deficiency presented recurrence. All of them presented CDDT positivity during the 3 yr after surgery, and recurrence 6 to 60 months after CDDT positivity.CDDT is an early predictor of recurrence of CD and could be of particular interest in the first 3 yr after surgery, by selecting patients at high risk of recurrence despite falsely reassuring classical hormonal markers.

OBJECTIVE: Osteoporotic compression fractures, which can lead to neurological com- plications in some cases, are an increasingly frequent occurrence. These lesions require decompression surgery with or without spinal stabilization procedures. In this article, we present the preliminary results obtained using open kyphoplasty, a new method of treating vertebral compression disorders. METHODS: Sixteen patients were included in this prospective study, and a total of 17 vertebrae were treated. All of the patients had vertebral compression fractures associated with neurological disorders. The surgical treatment consisted of open kyphoplasty after laminectomy and decompression. Short-segment vertebral osteosynthesis was also performed in patients with pronounced local kyphosis. Pain was rated at clinical assessments, and radiological assessments were performed to determine the restored vertebral height and the correction of any local vertebral kyphosis. RESULTS: Analysis of the results obtained using this method showed that vertebral height was significantly improved (P < 0.001) and local kyphosis was significantly reduced (P < 0.001). The mean operating time was 90 minutes. The neurological status of all patients improved; 14 patients recovered completely from their neurological symptoms. The last 2 patients had associated neurological disease but were able to walk. There were 2 superficial postoperative infections. CONCLUSION: This method for treating severe osteoporotic compression fractures associated with neurological disorders gives successful results and can be used to treat neurological compression fractures while consolidating the vertebral body. Therefore, this less invasive approach seems to be particularly useful for treating compression fractures in the thoracolumbar spine junction in elderly patients who often have comorbidities.

In human somatotroph adenomas, growth hormone (GH) hypersecretion can be inhibited by somatostatin analogues such as octreotide. Unfortunately, serum GH levels reach normal values in only 60% of treated patients. The decreased sensitivity to octreotide is strongly related to a lower expression of somatostatin receptor sst2. In this present study, the sst2 gene was transferred by an adenoviral vector (Ad-sst2) in human somatotroph (n = 7) and lactotroph (n = 2) adenomas in vitro. Sst2 mRNA levels and sst2 immunostaining dramatically increased after infection. Ten days after infection at 20 multiplicity of infection (MOI), sst2 gene transfer decreased cell viability from 19% to 90% by caspase-dependent apoptosis. At low viral doses (5 MOI), Ad-sst2 decreased GH or prolactin (PRL) basal secretion and mRNA expression. Somatotroph tumors were classified in three groups according to their octreotide sensitivity. Four days after infection by 5 MOI Ad-sst2, the maximal GH suppression by octreotide increased from 31% to 57% in the octreotide partially resistant group and from 0% to 27% in the resistant ones. In the octreotide-sensitive group, EC50 values significantly decreased from 1.3 × 10−11 to 6.6 × 10−13 mol/L without improving maximal GH suppression. Finally, lactotroph tumors, nonresponding to octreotide in basal conditions, became octreotide sensitive with a maximal PRL suppression of 43% at 10−8 mol/L. Therefore, sst2 reexpression is able to improve octreotide sensitivity. Sst2 gene transfer may open new theapeutic strategies in treatment combined with somatostatin analogues. [Cancer Res 2008;68(24):10163–70]

Growth-hormone hypersecretion, acromegaly, is associated with reduced life expectancy. First line treatment remains surgery, but remission rates vary between 50% and 90%. In case of lack of surgical remission or recurrence, somatostatin agonists can be proposed. However, about 30% of patients are partially or totally resistant to this treatment. The growth hormone receptor antagonist pegvisomant currently needs more prolonged follow-up studies. Conventional radiotherapy and radiosurgery are two radiation treatment modalities that can be proposed to these resistant patients. Reported rates of remission for conventional radiotherapy range between 50% and 60% in patients with acromegaly, with a time to remission delayed by several years, and adverse effects including high rates of hypopituitarism. This treatment could be proposed to patients with aggressive adenomas, in whom surgery cannot allow biochemical control. In contrast, studies on stereotactic radiosurgery reported lower rates of remission, with faster growth hormone hypersecretion decline, and a lower risk of adverse effects. However, this latter technique requires a well defined target volume, which limits its indications. The high precision of this technique makes it possible to be used as an alternative primary treatment to surgery. We reviewed major advantages and drawbacks of each of these techniques, based on recent studies to try to define their respective indications in the therapeutic algorithm of acromegaly.

International audience; Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760. The protocol was utilized by four independent laboratories, studying 38 fibroblast-deprived NFPA cell cultures. Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) mRNA expression and for alpha-subunit, LH, and FSH release. D2R, sstr3, and sstr2 mRNAs were consistently observed, with the dominant expression of D2R (2.9+/-2.6 copy/copy beta-glucuronidase; mean+/-s.e.m.), when compared with sstr3 and sstr2 (0.6+/-1.0 and 0.3+/-0.6 respectively). BIM-23A760, a molecule with high affinity for D2R and sstr2, significantly inhibited [3H]thymidine incorporation in 23 out of 38 (60%) NFPA cultures (EC50=1.2 pM and Emax=-33.6+/-3.7%). BIM-23A760 effects were similar to those induced by the selective D2R agonist cabergoline that showed a statistically significant inhibition in 18 out of 27 tumors (compared with a significant inhibition obtained in 17 out of 27 tumors using BIM-23A760, in the same subgroup of adenomas analyzed), while octreotide was effective in 13 out of 27 cases. In conclusion, superimposable data generated in four independent laboratories using a standardized protocol demonstrate that, in vitro, chimeric dopamine/sstr agonists are effective in inhibiting cell proliferation in two-thirds of NFPAs.

Purpose This phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy (RT) in patients with inoperable newly diagnosed glioblastoma. Patients and Methods Patients received temozolomide (150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a total of 60 Gy) and for four cycles thereafter or until disease progression. The primary end point was tumor response. Tumor tissue from 25 patients was analyzed for O6-methylguanine-DNA methyltransferase (MGMT) expression. Results Twenty-nine patients with a median age of 60 years were treated, and 28 were assessable for response. Seven (24%) of 29 patients had a partial response, nine patients (31%) had stable disease, and 12 patients (41%) had progressive disease. Median progression-free survival (PFS) time was 3.8 months, and median overall survival (OS) time was 6.1 months. Patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months, respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003). The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and neutropenia (17%). Conclusion This dose-dense temozolomide regimen resulted in modest antitumor activity with an acceptable safety profile in the neoadjuvant setting, and expression of MGMT correlated with response to temozolomide. However, this treatment approach seems to be inferior to standard concomitant RT plus temozolomide.

Objective This is a retrospective study of 18 patients harboring a solitary fibrous tumor of the central nervous system. Therapeutic management and outcome were analyzed. Methods Between 1999 and 2004, 18 patients harboring central nervous system solitary fibrous tumors were surgically treated at our two institutions. There were nine men and nine women. The patient ages ranged from 33 to 75 years, with a median age of 56.1 years. The locations were spinal in six cases (33.3%), the posterior fossa in six cases (33.3%), supratentorial in four cases (22.2%), and orbital in two cases (11.2%). Results The median follow-up period was 45.3 months. Gross total resection was achieved in 10 cases (55.6%); tumor recurrence or progression occurred in nine cases (50%). Incomplete surgical resection was significantly associated with recurrence (P = 0.018). On univariate analysis, extent of surgery was also associated with a longer progression-free survival (P = 0.05). No statistically significant correlation can be found between histological features and recurrence. Conclusion Prognosis of solitary fibrous tumors of the central nervous system remains unclear; consequently, careful and close monitoring of patients and long-term follow-up are mandatory. Radical surgical excision seems to be a significant and reliable prognosis factor, although pathological prognostic features must be defined. In other respects, the role of postoperative radiotherapy in atypical or incompletely resected solitary fibrous tumors of the central nervous system remains to be determined and, therefore, warrants larger series with longer follow-up periods.

Objective: Though transsphenoidal surgery remains the first-line treatment of Cushing’s disease, recurrence occurs frequently. Conventional radiotherapy and anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs to be evaluated more precisely. The aim of this study was to determine long-term hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing’s disease. Design: Forty patients with Cushing’s disease treated by GK were prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven of them were treated with GK as a primary treatment. Methods: Radiosurgery was performed at the Department of Functional Neurosurgery of Marseille, France, using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy. Patients were considered in remission if they had normalized 24-h free urinary cortisol and suppression of plasma cortisol after low-dose dexamethasone suppression test. Results: Seventeen patients (42.5%) were in remission after a mean of 22 months (range 12–48 months). The two groups did not differ in terms of initial hormonal levels. Target volume was significantly higher in uncured than in remission group (909.8 vs 443 mm3, P = 0.038). We found a significant difference between patients who were on or off anticortisolic drugs at the time of GK (20 vs 48% patients in remission respectively, P = 0.02). Conclusion: With 42% of patients in remission after a median follow-up of 54 months, GK stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may represent an alternative to other therapeutic options in view of their adverse effects.

Background Metastatic disease of the spine requires a multidisciplinary and comprehensive approach to patient care, especially, for patients in a lot of pain with neurological deficit or spinal instability requiring surgical stabilization. Objectives The purpose of the study is to report our experience on 34 patients who underwent spinal metastasis resection. We used a single-stage posterior approach with vertebral body reconstruction by an expandable titanium cage and a posterior instrumentation. The parameters assessed were neurologic status, OMS score, angle of sagittal deformity, and morbidity. Methods Between January 2011 and June 2014 we performed a monocentric consecutive case review of 34 patients with vertebral body tumor. All of them underwent a single-stage vertebrectomy with circumferential reconstruction and an arthrodesis by posterior approach. Results 34 patients underwent a single stage surgery by posterior approach, including 30 thoracic lesions and 4 lumbar lesions. Pre operatively, sixteen patients presented a neurologic impairment. The mean follow-up was 13.7 months [1-32m]. No neurologic impairment was observed in the 34 cases. At the last term of follow-up, neurologic status was improved in 23 cases. OMS score was improved in 23 cases (67.6 %), and worsened in one case. Before surgery, the average of visual analogic scale was 8.94/10 [7-10] and decreased to 2.62/10 [1-5] after surgery. Single posterior approach surgery significantly reduced the average sagittal deformity to 10.0° (0.01–19.96; P = 0.013, Mann-Whitney test). Conclusion Our outcomes suggest that it will be more efficient to perform an aggressive approach in spinal metastatic treatment in order to improve quality of life.

Object The goal of this study was to evaluate the clinical and angiography results in 10 patients with transverse–sigmoid dural arteriovenous fistulas (DAVFs) treated using sinus angioplasty and dural sinus stent insertion. Methods Between 2001 and 2003, 10 consecutive patients (six men and four women, age range 54–79 years) who had presented with transverse and/or sigmoid sinus DAVFs with or without sinus thrombosis underwent self-expanding stent placement and balloon angioplasty. Eight fistulas involved the transverse sinus, three the sigmoid sinus, and one the torcular and occipital sinuses. According to the Djindjian-Merland grading system, there were two Type I, five Type IIa, one Type IIb, and two Type IV DAVFs. The mean clinical follow-up period was 21.1 months. At the last follow-up examination, seven patients were asymptomatic and three were dramatically improved. The mean angiography follow-up period was 7.5 months for the available population: four patients had complete DAVF occlusion, four had significant flow reduction, and two who experienced clinical improvement refused conventional angiography control studies. Delayed computerized tomography angiography scans were obtained to evaluate stent permeability in nine of the 10 patients. Stent permeability was demonstrated in eight of the nine patients with available control studies at a mean follow up of 20.8 months. There were two transient neurological deficits but no severe and permanent complications. Conclusions In this series, sinus stent insertion resulted in a cure or significant clinical improvement in all patients harboring a DAVF, with no severe or permanent complication. Stent placement for transverse and/or sigmoid sinus DAVFs is a promising technique whose viability should be confirmed in larger series with longer follow-up periods.

OBJECTIVE: To investigate the respective role of fractionated radiotherapy (FR) and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma (CSM) treatment. METHODS: The authors report the long-term follow-up of two populations of patients harboring CSMs treated either by FR (Group I, 38 patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I) and in 23 patients (Group II), FR and GKS radiosurgery were performed as first line treatment. In our early experience with GKS radiosurgery (1992, date of gamma knife availability in the department), patients with tumors greater than 3 cm, showing close relationship with the optic apparatus ( RESULTS: The median follow-up period was 88.6 months (range, 42–168 mo) for Group I and 63.6 months (range, 48–92 mo) for Group II. According to Sekhar's classification, 26 (68.4%) patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P < 0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%) patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm3 in Group I and 5.2 cm3 in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and 94.4% in Group I and II, respectively. Clinically, improvement was seen for 24 (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05). Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and 2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II. CONCLUSION: FR and GKS radiosurgery are safe and efficient techniques in treatment of CSMs, affording comparable satisfactory long-term tumor control. However, GKS radiosurgery provides better radiological response, is far more convenient, and fits into most patients lives much better than FR. Therefore, in the authors' opinion, GKS radiosurgery should be advocated in first intention for patients with CSMs, whereas conventional radiotherapy should be reserved for cases that are not amenable to this technique, thus making these two therapeutic modalities not alternative but complementary tools in CS meningioma treatment strategy.

Because surgical and medical therapies of acromegaly all have specific limitations, radiotherapy has been used as an adjunctive strategy. Stereotactic radiosurgery has not yet been widely evaluated.The objective was to perform an analysis of long-term hormonal effects and tolerance of gamma knife radiosurgery.Eighty-two patients were prospectively studied over a decade, with a mean follow-up of 49.5 months.All patients were treated at the Department of Functional Neurosurgery of Marseille, France.The patients included 82 with active acromegaly, of whom 63 had previous transsphenoidal surgery.Intervention included radiosurgery using the Leksell Gamma Unit B model.Remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (at least 3 months).Seventeen percent of the patients were in remission without any treatment. Twenty-three percent previously uncontrolled on somatostatin agonists fulfilled the same criteria after gamma knife while maintained on medical treatment. Initial GH and IGF-I levels off somatostatin agonists were significantly higher in uncured than in remission group (P = 0.01 and 0.047, respectively). Withdrawal of somatostatin agonists at the time of radiosurgery had no incidence on the outcome. No significant difference was found in success rate whether patients had previously been treated or not. Long-term side effects included complete (n = 2) or partial (n = 12) hypopituitarism diagnosed 1-7 yr after gamma knife.Gamma knife radiosurgery may represent a therapeutic approach in patients with moderate initial or residual GH hypersecretion.

Methods. We report a preoperative neuropsychological evaluation for ten adult patients with aqueductal stenosis, and compare the results of this group with a normal pressure hydrocephalus group. Findings. For executive functions, aqueductal stenosis patients failed on isolated tests and results were heterogeneous; the normal pressure hydrocephalus group was more impaired, except for tasks which required memory processing. Memory deficits in aqueductal stenosis group are qualitatively dissimilar and more homogeneous and severe, despite the younger age, than in the normal pressure hydrocephalus group. Interpretation. These findings indicate that neuropsychological deficits of patients with aqueductal stenosis are linked with fornix damage and frontal dysfunction. In the normal pressure hydrocephalus group, deficits could be linked with a prefrontal lobe disconnection.

Object. Microsurgical excision is an established treatment for vestibular schwannoma (VS). In 1992 the authors used a patient questionnaire to evaluate the functional outcome and quality of life in a series of 224 consecutive patients. In addition, starting with gamma knife surgery (GKS) in 1992, the authors decided to use the same methodology to evaluate prospectively the results of this modality to compare the two alternatives. Methods. Among the 500 patients who were included prospectively, the authors only evaluated patients in whom GKS was the primary treatment for unilateral VS. Four years of follow up was available for the first 104 consecutive patients. Statistical analysis of the GKS and microsurgery populations has shown that only a comparison of Stage II and III (according to the Koos classification) was meaningful in terms of group size and preoperative risk factor distribution. Objective results and questionnaire answers from the first 97 consecutive patients were compared with the 110 patients in the microsurgery group who fulfilled the inclusion criteria. Questionnaire answers indicated that 100% of patients who underwent GKS compared with 63% of patients who underwent microsurgery had no new facial motor disturbance. Forty-nine percent of patients who underwent GKS (17% in the microsurgery study) had no ocular symptoms, and 91% of patients treated with GKS (61% in the microsurgery study) had no functional deterioration after treatment. The mean hospitalization stay was 3 days after GKS and 23 days after microsurgery. All the patients who underwent GKS who had been employed, except one, had kept the same professional activity (56% in the microsurgery study). The mean time away from work was 7 days for GKS (130 days in the microsurgery study). Among patients whose preoperative hearing level was Class 1 according to the Gardner and Robertson scale, 70% preserved functional hearing after GKS (Class 1 or 2) compared with only 37.5% in the microsurgery group. Conclusions. Functional side effects happen during the first 2 years after radiosurgery. Findings after 4 years of follow up indicated that GKS provided better functional outcomes than microsurgery in this patient series.

Pituicytoma is a rare benign primary tumor of the neurohypophysis, occurring in the sellar and suprasellar spaces. We report here three new cases with immunohistochemical and electron microscopic study. Particular attention was paid to the expression of some cell adhesion molecules. These tumors were characterized by bundles of elongated cells strongly immunoreactive to anti-vimentin, S-100 protein, neural cell adhesion molecule and neuron-specific enolase antibodies. Glial fibrillary acidic protein (GFAP) was not recorded. It expressed the very late antigen alpha2 (VLAalpha2), but not VLAalpha5, and lacked epithelial markers expression (epithelial membrane antigen, E-cadherin), and specific neuronal markers (synaptophysin, chromogranin, neurofilament). Staining for pituitary hormones was negative. At the ultrastructural level, tumor/blood vessel basal lamina and cytoplasmic intermediate filaments were observed but desmosome or pericellular basal lamina were lacking. In one case few secretory granules were recorded. Differential diagnoses include granular cell tumors, pilocytic astrocytomas and spindle cell tumors such as solitary fibrous tumors, fibroblastic meningiomas and schwannomas. However, the unique pattern of antigenic expression and ultrastructural features of pituicytomas distinguish this rare tumor. As a subpopulation of pituicytes (which are distinctive glial cells of the neurophypophysis), some pituicytomas do not expressed GFAP. This suggests that pituicytomas presumably arise from pituicytes at various stages of their differentiation.

OBJECTIVE AND IMPORTANCE A Chiari I malformation associated with syringomyelia and hydrocephalus is a rare condition. We report the successful use of endoscopic third ventriculostomy for the treatment of this pathological entity. The successful use of this technique in such a case has not been previously described, and the results allow us to speculate on the pathophysiological mechanism involved. CLINICAL PRESENTATION A 34-year-old woman presented with headaches, a motor deficit of the right upper limb, and gait dyspraxia. Magnetic resonance imaging scans demonstrated dilation of all ventricles, compression of the retrocerebellar cerebrospinal fluid space, downward displacement of the tonsils, and syringomyelia. Syringomyelia involved the cervicodorsal cord below C3, with a syrinx-free segment between C1 and C3 and no enlargement of the rostral part of the central canal. INTERVENTION Endoscopic third ventriculostomy resulted in prompt improvement of the clinical symptoms. Postoperative magnetic resonance imaging scans demonstrated shrinkage of the syrinx and return of the cerebellar tonsils to their physiological positions. CONCLUSION This experience demonstrates that endoscopic third ventriculostomy, which is a simple, safe technique, may be the treatment of choice for associated Chiari I malformations, hydrocephalus, and syringomyelia (even the noncommunicating type).

The diagnosis of Gliomatosis cerebri (GC) is known to be difficult and is still a matter of debate. In order to better define this entity, we studied clinical, neuroradiological, pathological and follow-up data of 9 patients affected with GC. MRI were done with T1 before and after gadolinium injection, and with T2-weighted images and Flair in 3 cases. Histological confirmation of glial proliferation was obtained in all patients by craniotomy or stereotactic biopsies. Patients were treated and followed-up in our center. The histological analyses highlighted a heterogeneous glial proliferation with various degrees of anaplasia in all the cases including 2 cases of oligodendroglioma, 1 case of anaplastic oligodendroglioma, 2 cases of anaplastic mixed oligoastrocytoma, 1 case of anaplastic astrocytoma, 2 cases of glioblastoma and 1 case of astrocytic proliferation typical of GC. The topography of the tumoral infiltration was characteristic involving mainly the white matter, basal ganglia and thalamus, brainstem and less often hypothalamus. More than two cerebral lobes were involved. Contrast enhancement, mass effect and necrosis were minimal compared to the extent of tumoral infiltration. Patients were treated with various schemes of treatment all including nitrosourea. Survival from diagnosis was under one year except for 2 patients (17 and 14 months). This study shows that the diagnosis of GC needs to be based not on pathological data alone, but on pathological, clinical and, above all, on radiological criteria. Response to therapy could not clearly be observed in GC, despite oligodendroglial component in 6/9 cases. Prognosis of GC was constantly poor.

2011 Background: After iterative surgeries and radiotherapy (RT)/radiosurgery (RS) failure, aggressive meningiomas remain an unmet medical need. We have shown in vitro that everolimus (EVE) combined to octreotide (OCT) is active in meningiomas. Methods: Prospective multicentric single arm phase II study (NCT02333565) including pts with recurrent meningioma with documented progression ( > 10% increase of tumor surface over 6 months) after surgery and RT/RS. EVE was orally administrated at 10mg/day and OCT by IM injection 30 mg/28 days. MRI was performed every 3 months with planned central review of imaging including volumetric progression at inclusion and during treatment. The primary endpoint was PFS6. The criteria for success was defined as a PFS6 > 40%. Results: 20 pts were included, aged 30-75 years (median 55) with 37 progressive intra cranial meningiomas (WHO: 2 grade I, 27 grade II, 8 grade III) including 4 NF2 pts. Median KPS was 70%. All pts previously underwent at least one surgery and more than 1 in 18/20 patients. 19/20 pts were treated with radiotherapy or radiosurgery and 5 pts with prior chemotherapy. 1 pt was not evaluable at 3 months. With a median f/u of 12.3 months (2-24 months), PFS6 was 58.2% (95% CI 33.5-76.5%) and PFS12 was 38% (95% CI 16-60%). Volumetric analysis at 3 months demonstrated a decrease in tumor volume superior to 10% in 8 tumors (4 pts). Pre therapeutic growth rate was decreased of more than 50% in 29/35 tumors (18/20 pts) during the first 3 months. Inclusion (I)-to-3 months tumor growth rate (mean at 1.9%/month) was significantly lower than pre inclusion (Pre-I)-to-I growth rate (mean at 18.5%/month) (p = 0.0003). 3 highly aggressive tumors (3 pts) were separately assessed: Pre-I-to-I growth rate superior to 1000%/month was decreased to 3%, 15% and 44%/month in the first 3 months. Toxicity included 7 grade III AE (stomatitis, 3; pneumopathy, 1). AE of special interest included stomatitis (10, 50%), rash (8, 40%), abdominal pain and diarrhea (11, 55%) and nausea and vomiting (4, 20%). Conclusions: Everolimus and octreotide combination appears active in refractory aggressive and progressive meningiomas with acceptable and manageable toxicity and should request further evaluation. Clinical trial information: NCT02333565.

Resume Une patiente de 62 ans est hospitalisee pour une tumeur hypophysaire decouverte devant une asthenie et des troubles visuels evoluant depuis un an. L’IRM cerebrale mettait en evidence une tumeur de la selle turcique comprimant le chiasma optique, se rehaussant fortement apres injection de gadolinium. Le bilan biologique notait une insuffisance antehypophysaire globale ainsi qu’une hyperprolactinemie. Le diagnostic de macro-adenome hypophysaire etait retenu et la patiente a recu un traitement hormonal substitutif ainsi qu’un agoniste dopaminergique. Six mois apres on retrouvait une aggravation des troubles visuels motivant une exerese chirurgicale. Le diagnostic de melanocytome hypophysaire a ete porte apres confrontation anatomoclinique et la patiente a recu une radiotherapie complementaire.

Introduction. Management of elderly patients with thoracolumbar fractures is still challenging due to frequent osteoporosis and risk of screws pull-out. The aim of this study was to evaluate results of a percutaneous-only procedure to treat these fragile patients using cement-augmented screws.Methods. 12 patients diagnosed with a thoracolumbar fracture associated with an important loss of bone stock were included in this prospective study. Surgical procedure included systematically a percutaneous osteosynthesis using cemented fenestrated screws. When necessary, additional anterior support was performed using a kyphoplasty procedure. Clinical and radiographic evaluations were performed using CT scan.Results. On the whole series, 15 fractures were diagnosed and 96 cemented screws were inserted. The difference between the pre- and postoperative vertebral kyphosis was statistically significant (12.9° versus 4.4°,P=0.0006). No extrapedicular screw was reported and one patient was diagnosed with a cement-related pulmonary embolism. During follow-up period, no infectious complications, implant failures, or pull-out screws were noticed.Discussion. Aging spine is becoming an increasing public health issue. Management of these patients requires specific attention due to the augmented risk of complications. Using percutaneous-only screws fixation with cemented screw provides satisfactory results. A rigorous technique is mandatory in order to achieve best outcomes.

BACKGROUND AND PURPOSE: The present study follows an experimental work based on the characterization of the biomechanical behavior of the aneurysmal wall and a numerical study where a significant difference in term of volume variation between ruptured and unruptured aneurysm was observed in a specific case. Our study was designed to highlight by means of numeric simulations the correlation between aneurysm sac pulsatility and the risk of rupture through the mechanical properties of the wall. MATERIALS AND METHODS: In accordance with previous work suggesting a correlation between the risk of rupture and the material properties of cerebral aneurysms, 12 fluid-structure interaction computations were performed on 12 “patient-specific” cases, corresponding to typical shapes and locations of cerebral aneurysms. The variations of the aneurysmal volume during the cardiac cycle (ΔV) are compared by using wall material characteristics of either degraded or nondegraded tissues. RESULTS: Aneurysms were located on 6 different arteries: middle cerebral artery (4), anterior cerebral artery (3), internal carotid artery (1), vertebral artery (1), ophthalmic artery (1), and basilar artery (1). Aneurysms presented different shapes (uniform or multilobulated) and diastolic volumes (from 18 to 392 mm3). The pulsatility (ΔV/V) was significantly larger for a soft aneurysmal material (average of 26%) than for a stiff material (average of 4%). The difference between ΔV, for each condition, was statistically significant: P = .005. CONCLUSIONS: The difference in aneurysmal pulsatility as highlighted in this work might be a relevant patient-specific predictor of aneurysm risk of rupture.

OBJECTIVE AND IMPORTANCE To describe the surgical resection of a giant intracerebral arteriovenous fistula with involvement of dura mater and surrounding bone. Intraoperative bleeding was controlled by hypothermic circulatory arrest. CLINICAL PRESENTATION This 46-year-old woman complained of persistent headache for 1 year; her diagnostic workup revealed the presence of an arteriovenous fistula in the dura mater of the left temporal region fed by the meningeal artery of the external and internal carotid arteries, with normal run-off into Labbé's and Trolard's veins. Magnetic resonance imaging depicted a Chiari I malformation that was most likely a result of insufficient cerebral venous drainage. INTERVENTION In preparation for surgery, staged embolization of feeders from the left meningeal artery and the left occipital artery was performed under controlled hypotension. This procedure failed to achieve a significant reduction in flow because of the immediate recruitment of internal branches of the internal carotid artery and dural branches of the right external carotid artery. Surgical treatment was undertaken without further embolization. Because of involvement of surrounding bone and the high risk of uncontrollable bleeding, the procedure was carried out with the patient under deep hypothermic cardiopulmonary bypass. Forty-five minutes of low flow (1.5 L/min) at 18°C allowed total resection of the involved dura mater and surrounding bone. Postoperative recovery was marked by left brain edema that disappeared within 10 days. Findings on follow-up angiography were normal, and the patient was discharged with no neurological deficit. CONCLUSION Low-flow deep hypothermic cardiopulmonary bypass can be used to control intraoperative bleeding for surgical excision of a giant intracerebral dural arteriovenous fistula.

PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m2/d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.

OBJECTIVE To specify that postoperative radiotherapy is useful for preventing local recurrence and neuraxis recurrence of surgically treated meningeal hemangiopericytomas. METHODS We retrospectively studied 21 patients with meningeal hemangiopericytoma who were followed in our department during a 34-year period. In 17 patients, the meningeal hemangiopericytoma was intracranial, and in 4 there was an intradural extramedullary localization. These groups were studied separately. RESULTS Of the 17 patients with intracranial hemangiopericytoma, all underwent surgery; 8 also underwent radiotherapy (5000–6400 rads) (Group I), and 9 did not (Group II). The mortality rate was zero for Group I patients and 55% for Group II. The mean local recurrence rate was 52% (12.5% in Group I and 88% in Group II; P < 0.05). Neuraxis recurrences occurred in two patients in Group II, and none occurred in Group I (P = 0.4). Peripheral metastasis took place in two patients (22%) in Group II and in one patient (12.5%) in Group I (P = 0.5). Of the four patients with intradural extramedullary hemangiopericytoma, all underwent surgery. Two patients received 4000 rads of radiotherapy after intervention. No patient in this group had a recurrence. CONCLUSION For patients with intracranial meningeal hemangiopericytoma, surgical removal followed by external radiotherapy reduced the risk of local recurrence. It was not demonstrated that postoperative radiotherapy protected against neuraxis metastasis. Radiotherapy did not protect against peripheral metastasis, which can occur up to several years after the first operation. It appears that radiotherapy after surgery for local or neuraxis recurrence did not avoid further recurrence. Radiosurgery is indicated for recurrent tumors measuring less than 25 mm in greatest diameter. For intradural extramedullary localizations, the value of postoperative radiotherapy is more questionable.

✓ A 36-year-old woman with an uneventful medical history was admitted to the emergency department following an initial generalized seizure. Neuroimaging workup disclosed a homogeneous mass at the vertex, which first was diagnosed as vertex meningioma. Anticonvulsant drug therapy was administered and the patient was discharged. Two months later the patient was examined in our neurosurgery department for additional therapeutic recommendations. A repeated neuroimaging examination showed considerable regression of the lesion. The findings on magnetic resonance imaging were consistent with those of a regressing extradural hematoma (EDH). A complete blood-coagulation study displayed no evidence of abnormality. Thorough questioning of the patient revealed no history of pericranial infection or head trauma occurring within the last 2 years. The final diagnosis was spontaneously occurring vertex EDH. In this report the authors describe the clinical and neuroimaging features of the case as well as the management strategy, and discuss etiological aspects within the context of a careful review of the literature.

Although both somatostatin receptor subtype 2 (SSTR2) and SSTR5 messenger ribonucleic acid (mRNA) are consistently expressed in GH-secreting adenomas, SSTR2 has been believed to be the key modulator of somatostatin-mediated inhibition of GH release. The somatostatin agonists currently in clinical use, octreotide and lanreotide, are directed mainly to SSTR2 (IC50 12- to 18-fold higher than for SSTR5). Recently, however, it was demonstrated that an SSTR5 preferential agonist, BIM-23268, not only suppressed PRL release from prolactinomas and mixed GH-PRL adenomas, but also inhibited GH release in about half of GH adenomas. In addition, the SSTR5-preferring analog showed a slight additive effect when used in combination with SSTR2 preferential drugs at submaximal concentrations in octreotide partially sensitive adenomas. In the present study we quantified SSTR2 and SSTR5 mRNA expression and the GH-suppressive effects of somatostatin-14; octreotide; a SSTR2-preferential compound, BIM-23197; a SSTR5-preferential compound, BIM-23268; and a new SSTR2- and SSTR5-bispecific compound, BIM-23244, in GH-secreting tumors classified as either full responders to octreotide (n = 5) or partially sensitive to octreotide (n = 5). The octreotide-sensitive GH secretory adenomas presented with a high level of both SSTR2 and SSTR5 mRNA expression [222 ± 61 and 327 ± 136 pg/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively]. In these tumors the suppression of GH release was similarly achieved at picomolar ranges by octreotide, BIM-23197, and BIM-23244 (EC50 = 25 ± 15, 3 ± 2, and 3 ± 3 pmol/L, respectively). The compounds preferential for only SSTR5 were unable to inhibit GH release in such tumors. Among the octreotide partially responsive tumors, SSTR2 mRNA expression was 9-fold lower than in the octreotide-sensitive tumors (25 ± 12 vs. 222 ± 61 pg/pg GAPDH; P < 0.015), whereas SSTR5 mRNA expression was approximately 7-fold higher than in the octreotide-sensitive tumors (2271 ± 1197 pg/pg GAPDH). In these octreotide partially responsive tumors, the SSTR5-preferential compound, BIM-23268, and the SSTR2- and SSTR5-bispecific compound, BIM-23244, were quite effective in suppressing GH secretion (EC50 = 25 ± 13 and 50 ± 31 pmol/L, respectively). Similarly, BIM-23244, was able to suppress by 51 ± 5% PRL release from five mixed GH- and PRL-secreting adenomas. These data indicate that due to heterogeneous expression of SSTR2 and SSTR5 receptor subtypes, in GH-secreting tumors, a bispecific analog, such as BIM-23244, that can activate both receptors could achieve better control of GH hypersecretion in a larger number of acromegalic patients.

Supplemental education is desirable for neurosurgical training, and the use of human cadaver specimen and virtual reality models is routine. An in vivo porcine training model for cranial neurosurgery was introduced in 2005, and our recent experience with this unique model is outlined here. For the first time, porcine anatomy is illustrated with particular respect to neurosurgical procedures. The pros and cons of this model are described. The aim of the course was to set up a laboratory scenery imitating an almost realistic operating room in which anatomy of the brain and neurosurgical techniques in a mentored environment free from time constraints could be trained. Learning objectives of the course were to learn about the microsurgical techniques in cranial neurosurgery and the management of complications. Participants were asked to evaluate the quality and utility of the programme via standardized questionnaires by a grading scale from A (best) to E (worst). In total, 154 residents have been trained on the porcine model to date. None of the participants regarded his own residency programme as structured. The bleeding and complication management (97 %), the realistic laboratory set-up (89 %) and the working environment (94 %) were favoured by the vast majority of trainees and confirmed our previous findings. After finishing the course, the participants graded that their skills in bone drilling, dissecting the brain and preserving cerebral vessels under microscopic magnification had improved to level A and B. In vivo hands-on courses, fully equipped with microsurgical instruments, offer an outstanding training opportunity in which bleeding management on a pulsating, vital brain represents a unique training approach. Our results have shown that education programmes still lack practical training facilities in which in vivo models may act as a complementary approach in surgical training.

Among the mixed glioneuronal tumours, a new variant called papillary glioneuronal tumour has recently been delineated. A case occurring in a 23-year-old man is reported. The tumour was cystic with a mural nodule enhanced by gadolinium injection. It was located within the left parieto-occipital lobe. Surgical excision showed a greyish friable tumour with cystic areas. Histopathological examination revealed a pseudopapillary component comprising a single layer of regular cells, arranged around hyalinised vessels. These cells were immunoreactive with anti-glial fibrillary acidic protein and HNK1 antibodies. A neurocytoma-like component coexisted with round blind cells and focal fibrillary rosettes. These cells were immunostained by anti-neuron-specific enolase and anti-synaptophysin antibodies. Neither mitoses nor ganglioid cells were seen. HNK1, the three isoforms of NCAM, and the L1 adhesion molecule were detected by Western blot analysis. Ultrastructural study showed three different types of cells. The first contained gliofilaments, the second showed long processes with true synapses, and the third was poorly differentiated. However, all had identical nuclei and contained dense bodies. These findings suggest a common origin for the tumour cells derived from a bipotential neuroglial progenitor. As for other mature mixed neuroglial tumours, the prognosis is good. Our patient is free of disease 7 years after complete surgical treatment.

Background Recurring subdural empyema despite adequate surgical drainage and antibiotic treatment is still a life-threatening disease. This is mainly due to poor diffusion of the antibiotic into the subdural space. Case Description We report 2 cases of recurring subdural empyema due to Streptococcus , after repeat surgery and high-dose antibiotic treatment including β -lactamines and vancomycin. Both patients showed marked clinical and radiologic improvement after introduction of linezolid. There was no drug-related adverse effect despite 36 and 90 days of treatment. Conclusion Off-label use of linezolid for treatment of subdural empyema due to gram-positive bacteria should be considered after failure of conventional antibiotic treatment.

We report an unusual case of spinal Langerhans' cell histiocytosis of the cervicothoracic junction in a young adult man. A 17-year-old male was referred to our institution with a 3-week history of cervicothoracic pain associated to a weakness of his right upper limb. Computed tomography and magnetic resonance imaging showed a collapsed T1 vertebral body with epidural soft tissue showing mass effect on spinal cord. The patient underwent a classic anterior cervicotomy. Complete removal of the lesion could be achieved, but the soft consistency of C7 and T2 body precluded a solid anterior fixation and an extended resection of C7 and T2 body had to be performed. Then a C6 - T3 stabilisation using an anterior plate fixation and cyanomethylacrylate graft was performed. Postoperative course was uneventful. At 2 years follow-up, the patient was asymptomatic and radiological workup showed a perfect stability of anterior fixation system. Aggressive surgical management of eosinophilic granuloma should be considered in some selected cases particularly when spinal instability or neurological deficit occurs. In this young patient a modified anterior cervicotomy allowed a comfortable approach to the anterior aspect of T3 vertebra for spinal fixation.

BACKGROUND Anterior lumbosacral dislocation is a rare traumatic anterior spondylolisthesis. METHODS We report a new case surgically treated and review the eight cases previously reported. RESULTS The mechanism of injury is hyperflexion-distraction. Neurological signs are inconsistent. Indirect radiological signs such as bilateral multiple transverse process fractures are strongly suggestive of the diagnosis. This complete soft tissue injury induces a definitive instability and requires an open reduction with posterior fixation. CONCLUSIONS Suspicion of lumbosacral dislocation requires a computed tomography scan exploration with multiplanar reconstructions. Early reduction is associated with neurologic recovery. However, prognosis is correlated with the initial neurologic status and the severity of other associated injuries.

We report our preliminary results concerning 25 patients with secreting pituitary adenomas treated with stereotactic radiosurgery after partial transsphenoidal surgery and followed over a 6-36 month-period. Among the 15 acromegalic patients, a decrease of 65% in mean GH levels was achieved after 6 months and of 77% at 12 months after radiosurgery. Presently, only 3 patients (20%) are considered as in remission (mean GH and IGF1 level into the normal range). A decrease of 46% and 64% was observed at 6 and 12 months after radiosurgery in 4 patients with prolactinomas although no normalization of PRL levels occurred. Presently, 3/4 patients have individual PRL level slightly above the normal range. A normalization of Urinary Free Cortisol (UFC) was noticed in 4/6 (66%) patients with Cushing's disease within 6-12 months. No pituitary deficiency was noticed in this series with the exception of 4/25 patients (16%) who received subtotal or total pituitary irradiation for post-operative remnants of secreting adenomas poorly defined on MRI. One woman, who had undergone previously a conventional irradiation and presenting with a cavernous sinus adenoma reaching the optic nerve, developed an optic neuropathy. A second woman, with a cavernous sinus remnant, presented a cranial nerve palsy (VI) after the irradiation. We can conclude that radiosurgery using the Cobalt-60 Gamma-unit is, at least, as effective as conventional radiotherapy in the control of pituitary hormone hypersecretion from postoperative adenomas remnants with less adverse effects.

OBJECTIVE: The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients. METHOD: In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales. RESULTS: Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant be...

International audience; Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology. However, no one knows what triggers muscle defect and when alteration arises. To gain further insights into the molecular mechanisms of the disease, we evaluated at the molecular level, the perturbation linked to the FSHD genotype with no a priori on disease onset, severity or penetrance and prior to any infiltration by fibrotic or adipose tissue in biopsies from fetuses carrying a short pathogenic D4Z4 array (n 5 6) compared with fetuses with a non-pathogenic D4Z4 array (n 5 21). By measuring expression of several muscle-specific markers and 4q35 genes including the DUX4 retrogene by an RT-PCR and western blotting, we observed a global dysregulation of genes involved in myogenesis including MYOD1 in samples with

Introduction Carotid cavernous sinus fistulas are a potentially severe pathology. Their basic standard treatment is an occlusion of the CCF performed by retrograde venous catheterization via the inferior petrous sinus. When the inferior petrous sinuses are occluded, other alternative venous routes are possible with various subsequent difficulties and risks. We report an original and safe method for endovascular treatment using submandibular puncture of the facial vein. Clinical cases We report 4 cases of patients with severe unilateral carotid cavernous sinus fistula associated with the occlusion of both inferior petrous sinuses. A submandibular surgical puncture of the ipsilateral inferior facial vein permitted the catheterization of the fistula. Complete occlusion of carotid cavernous sinus fistula was obtained by using a combination of microcoils and Onyx™. Discussion When inferior petrous sinuses are occluded, endovascular treatment of carotid cavernous sinus fistulas is more difficult. After reviewing the other treatment options reported in the literature and their respective advantages and adverse effects, we describe an original technique based on the surgical puncture of the ipsilateral facial vein. The occlusion of the fistula is then obtained by using a combination of microcoils and Onyx™. Conclusion When the inferior petrous sinuses are occluded, an endovascular treatment for a carotid cavernous sinus fistula can be performed using an original and secure method. This method relies on a simple surgical puncture of the facial vein in the submandibular region, which then permits a retrograde catheterization of the carotid cavernous sinus fistula with no significant risk.

Septic cervical facet joints arthritis is a rare pathology, usually revealed by fever and neck pain. As symptoms may be indolent, a high index of suspicion needs to be maintained. Magnetic resonance imaging (MRI) is effective for early diagnostic, looking for local spread and guiding potential preoperative planning. We present a case exhibiting an uncommon pathology with possible significant morbidity if misdiagnosed.A 75-year-old woman presented with fever, neck stiffness and torticollis accompanied with altered level of consciousness.The diagnosis was established by computed tomography and MRI, identifying atlantoaxial facet joint destruction with para spinal muscles and epidural abscesses. A surgical treatment consisting in posterior decompression of the spinal canal and atlantoaxial pars articularis fixation known as Harms technique, associated with a targeted antibiotic therapy, succeeded in obtaining favorable clinical course.Atlantoaxial septic arthritis is an under reported and severe infection. Early use of MRI should avoid delayed diagnosis and would guide the practitioner in choosing an appropriate therapy. Early surgical treatment for uncontrolled sepsis is also a critical element of the prognosis.

OBJECTIVE : It is classically considered that the morbidity and mortality rates are greater for stereotactic biopsies of pineal region tumors, compared with tumors in other regions. However, to date, the number of cases studied in the literature has been insufficient to evaluate these parameters and compare them with the morbidity and mortality rates for stereotactic biopsies of tumors located elsewhere. METHODS : With the aim of evaluating these parameters, we reviewed 370 stereotactic biopsies of pineal region tumors, from 15 French neurosurgical centers. We statistically verified the absence of heterogeneity of the different French centers with regard to diagnostic, mortality, and morbidity rates. In contrast, statistical heterogeneity was clearly seen for the large stereotactic biopsy series (for all tumor locations) in the literature. RESULTS : The mortality rate was 1.3% (5 patients of 370), and 3 patients suffered severe neurological complications. This study is the first to clearly demonstrate that the mortality, morbidity, and diagnostic rates for stereotactic biopsies are not different in the pineal region. CONCLUSION : Our conclusion is that stereotactic biopsy must remain a main diagnostic modality for tumors of the pineal region.

International audience; Pituitary carcinomas are rare, accounting for about 0*2% of all pituitary tumours. They represent a challenge to clinical practice in both diagnosis and treatment. They may present initially as typical pituitary adenomas, with a delayed appearance of aggressive signs, or as aggressive tumours from the outset. Predicting the pituitary tumour behaviour remains difficult: increased mitotic, Ki-67 and P53 indices might be associated with tumour aggression. The treatment of pituitary carcinomas and aggressive pituitary tumours includes surgery, adjuvant medical treatment, external beam radiotherapy and chemotherapy. Until recently, the treatment of pituitary carcinomas was mainly palliative and did not seem to increase overall survival. Recent case reports have detailed the successful use of temozolomide, an orally administered alkylating agent used to treat malignant gliomas, in the management of pituitary carcinomas and aggressive pituitary tumours. The outcome of treatment might depend on the expression of O (6) -methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that potentially interferes with drug efficacy. This review describes the clinical presentation and response to temozolomide in 44 patients with pituitary carcinomas or aggressive pituitary tumours reported in the literature. The results suggest that temozolomide should be considered a drug of major importance in the therapeutic algorithm of aggressive pituitary tumours and pituitary carcinomas. Because of the inconsistency of published data, MGMT expression should probably not be taken as a reason to deny these patients the potential benefit of temozolomide treatment, taking into account the paucity of other available treatments.