Philippe Page

Epileptic seizures in diffuse low-grade gliomas in adults

Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.

Comparison of deep wound infection rates using a synthetic dural substitute (neuro-patch) or pericranium graft for dural closure: a clinical review of 1 year.

OBJECTIVEThe need to repair dural defects has prompted the use of dura mater substitutes. Many synthetic materials have been used for dural closure. Neuro-Patch (B. Braun Médical S.A., Boulogne, France) is a nonabsorbable microporous fleece composed of polyester urethane that has been approved for human use by the European Union since 1995. To the best of our knowledge, no clinical series with Neuro-Patch have been published thus far, particularly with regard to septic complications. The aim of our study was to compare the safety of Neuro-Patch with that of pericranium graft with regard to postoperative wound infections. METHODSThis is a retrospective study of 1 year’s experience including all patients who underwent dural plasty with a Neuro-Patch (n = 61) or pericranium graft (n = 63). The follow-up period was at least 12 months after surgery. Before wound infection rates in the two groups were compared, factors suspected of being risks for neurosurgical site infection were evaluated. RESULTSPatient characteristics (mean age, neurological diagnosis), surgical procedures, prophylactic antibiotics, and risk factors for surgical infections (including duration of surgery, emergency, contaminated operations, and external cerebrospinal fluid drainage) were similar in the Neuro-Patch and pericranium groups. Deep wound infection rates in the Neuro-Patch and pericranium groups were 15 and 5%, respectively (P = 0.06), and cerebrospinal fluid leaks were significantly more frequent in the Neuro-Patch group (13 versus 1.6%, P < 0.05). CONCLUSIONThe results of our investigations show that Neuro-Patch raised the risk of wound infection, as do foreign materials implanted in the body. Synthetic dural grafts should be reserved for when autologous grafts are not sufficient or possible. An extensive prospective multicenter randomized trial is needed to confirm our results.

Pregnancy increases the growth rates of world health organization grade II gliomas

Twelve pregnancies in 11 adult women harboring World Health Organization (WHO) grade II gliomas (GIIGs) prior to pregnancy were reviewed to address whether pregnancy affects tumor growth using a quantitative approach of the radiological velocity of diametric expansion (VDE) on successive magnetic resonance images. VDE was significantly increased during pregnancy as compared to prepregnancy (p < 0.001) and to postdelivery (p = 0.012) periods. Pregnancy increases the radiological growth rates of GIIGs. An increase in seizure frequency was observed concomitantly in 40% of cases and further oncological treatment was started after delivery in 25% of cases. ANN NEUROL 2010;67:398–404

Dynamic imaging response following radiation therapy predicts long-term outcomes for diffuse low-grade gliomas.

Quantitative imaging assessment of radiation therapy (RT) for diffuse low-grade gliomas (DLGG) by measuring the velocity of diametric expansion (VDE) over time has never been studied. We assessed the VDE changes following RT and determined whether this parameter can serve as a prognostic factor. We reviewed a consecutive series of 33 adults with supratentorial DLGG treated with first-line RT with available imaging follow-up (median follow-up, 103 months). Before RT, all patients presented with a spontaneous tumor volume increase (positive VDE, mean 5.9 mm/year). After RT, all patients demonstrated a tumor volume decrease (negative VDE, mean, -16.7 mm/year) during a mean 49-month duration. In univariate analysis, initial tumor volume (>100 cm(3)), lack of IDH1 expression, p53 expression, high proliferation index, and fast post-RT tumor volume decrease (VDE at -10 mm/year or faster, fast responders) were associated with a significantly shorter overall survival (OS). The median OS was significantly longer (120.8 months) for slow responders (post-RT VDE slower than -10.0 mm/year) than for fast responders (47.9 months). In multivariate analysis, fast responders, larger initial tumor volume, lack of IDH1 expression, and p53 expression were independent poor prognostic factors for OS. A high proliferation index was significantly more frequent in the fast responder subgroup than in the slow responder subgroup. We conclude that the pattern of post-RT VDE changes is an independent prognostic factor for DLGG and offers a quantitative parameter to predict long-term outcomes. We propose to monitor individually the post-RT VDE changes using MRI follow-up, with particular attention to fast responders.

Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas

BACKGROUND We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults. METHODS One hundred thirty-one adult patients with newly diagnosed supratentorial diffuse low-grade gliomas were retrospectively studied. RESULTS Isocitrate dehydrogenase 1 mutations were present in 107 patients. The mean spontaneous velocity of diametric expansion was 5.40 ± 5.46 mm/y. During follow-up (mean, 70 ± 54.7 mo), 56 patients presented a malignant transformation and 23 died. The median malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (149 and 198 mo, respectively) than in cases of fast velocity of diametric expansion (46 and 82 mo; P < .001 and P < .001, respectively) and in cases with IDH1 mutation (100 and 198 mo, respectively) than in cases without IDH1 mutation (72 mo and not reached; P = .028 and P = .001, respectively). In multivariate analyses, spontaneous velocity of diametric expansion and IDH1 mutation were independent prognostic factors for malignant progression-free survival (P < .001; hazard ratio, 4.23; 95% CI, 1.81-9.40 and P = .019; hazard ratio, 2.39; 95% CI, 1.19-4.66, respectively) and for overall survival (P < .001; hazard ratio, 26.3; 95% CI, 5.42-185.2 and P = .007; hazard ratio, 17.89; 95% CI, 2.15-200.1, respectively). CONCLUSIONS The spontaneous velocity of diametric expansion and IDH1 mutation status are 2 independent prognostic values that should be obtained at the beginning of the management of diffuse low-grade gliomas in adults.

Abrupt Regression of a Meningioma after Discontinuation of Cyproterone Treatment

SUMMARY: The multiplicity of meningiomas or abrupt lesion growth in patients treated with cyproterone acetate suggests that this progestative treatment may promote lesion growth. We report the rapid regression of an incidental meningioma after discontinuation of a 10-year cyproterone acetate treatment. This unique observation suggests that conservative management of meningiomas may be the best option among users of high doses of cyproterone acetate, given that spontaneous regression may occur after hormonal treatment discontinuation.

Combining intraoperative carmustine wafers and Stupp regimen in multimodal first-line treatment of primary glioblastomas

Abstract Background. The study investigated if intraoperative use of carmustine wafers, particularly in combination with Stupp regimen, is a viable and safe first-line treatment option of glioblastomas. Methods. Eighty-three consecutive adult patients (50 men; mean age 60 years) with newly diagnosed supratentorial primary glioblastomas that underwent surgical resection with intraoperative carmustine wafers implantation (n = 7.1 ± 1.7) were retrospectively studied. Results. The median overall survival (OS) was 15.8 months with 56 patients dying over the course of the study. There was no significant association between the number of implanted carmustine wafers and complication rates (four surgical site infections, one death). The OS was significantly longer in Stupp regimen patients (19.5 months) as compared with patients with other postoperative treatments (13 months; p = 0.002). In addition patients with eight or more implanted carmustine wafers survived longer (24.5 months) than patients with seven or less implanted wafers (13 months; p = 0.021). Finally, regardless of the number of carmustine wafers, median OS was significantly longer in patients with a subtotal or total resection (21.5 months) than in patients with a partial resection (13 months; p = 0.011). Conclusions. The intraoperative use of carmustine wafers in combination with Stupp regimen is a viable first-line treatment option of glioblastomas. The prognostic value of this treatment association should be evaluated in a multicenter trial, ideally in a randomized and placebo-controlled one.

Neuronal immunoexpression and a distinct subtype of adult primary supratentorial glioblastoma with a better prognosis

OBJECT In this study, the authors address whether neurofilament protein (NFP) expression can be used as an independent prognostic factor in primary glioblastoma multiformes (GBMs). METHODS Three hundred and two consecutive adult patients with newly diagnosed supratentorial primary GBMs were analyzed (January 2000-August 2008). Detailed data regarding clinical, imaging, and pathological findings, oncological treatments, and outcomes were recorded. Neurofilament protein immunoexpression served to identify NFP-positive tumor cells (normal entrapped neurons and mature ganglion-like cells excluded). RESULTS Neurofilament-positive cells were identified in 177 GBMs (58.6%). Patients with NFP-positive GBMs were younger (p < 0.0001), and their GBMs presented with more temporal lobe tumor localization (p = 0.029) and more cortical involvement (p = 0.0003). Neurofilament-negative GBMs presented with more ventricular contact (p < 0.0001) and more tumor midline crossing (p = 0.03). Median overall survival and progression-free survival (PFS) were 13.0 and 7.6 months, respectively, for NFP-positive GBMs, and 7.0 and 5.1 months, respectively, for NFP-negative GBMs. Multivariate analysis revealed NFP immunoexpression, tumor midline crossing, complete resection, and radiotherapy combined with chemotherapy as independent factors associated with overall survival. Neurofilament protein-positive immunoexpression was associated with longer overall survival (hazard ratio [HR] 0.54, 95% CI 0.40-0.74; p < 0.0001) and longer PFS (HR 0.71, 95% CI 0.53-0.96; p = 0.02). CONCLUSIONS Neurofilament protein-positive immunoexpression represents a strong, therapeutically independent prognostic factor for primary supratentorial GBM clinical outcome among adult patients. Neurofilament protein-GBMs unique pathological features are not only associated with distinct clinical and anatomical behavior, but are also predictive of overall patient survival and PFS. Neurofilament protein immunoexpression may help identify a distinct subgroup of primary GBMs with a favorable prognosis, which should be considered in the design of future targeted therapies.

Highly vascular solitary plasmacytoma of the calvarium

A 50-year-old woman with an unremarkable medical history presented with a painless soft swelling in the midline of the forehead present for the previous year. A surgical removal was attempted without morphological investigations in an outside institution. Intractable bleeding occurred at the incision site so she was referred urgently to our institution. Cranial computerised tomography (top left, 3D image) demonstrated an osteolytic contrast-enhanced median mass involving the whole layer of the frontal bone, the ethmoidal bone and the left orbital roof. Cerebral angiography revealed a massive vascular tumour blush fed by vessels originating from the right and left (bottom, lateral view) ophthalmic arteries and from the right and left (top right, antero-posterior view) middle meningeal arteries. The feeding arteries originating from the middle meningeal arteries were embolised before partial surgical removal, which significantly reduced the vascular blush. Histological examination confirmed a malignant plasmacytic proliferation with CD138-positive cells. General investigations including complete blood count, serum and urine protein electrophoresis and immunoelectrophoresis, quantitative immunoglobulin analysis, bone marrow aspiration and radiological skeletal survey, excluded multiple myeloma. Solitary plasmacytoma of the frontal bone was proposed as a diagnosis. The postoperative management consisted of local radiotherapy to the skull. Solitary plasmacytomas of the calvaria are uncommon highly vascular tumours that are easily misdiagnosed preoperatively. If a surgical approach is required, the preoperative management of such a plasmacytoma should include cerebral angiography.

Surgical Management of Spinal Synovial Cysts: A Series of 23 Patients and Systematic Analysis of the Literature.

Study Design: Retrospective cohort and review of the literature. Objective: To compare surgical strategies for the management of spinal synovial cysts. Summary of Background Data: The recent multiplication of retrospective series of patients with spinal synovial cysts has led to a reappraisal of their incidence and clinical significance. Although surgery is considered the treatment of choice, there is still no agreement over which surgical technique should be used. Methods: We retrospectively reviewed 23 consecutive patients undergoing surgery for a spinal synovial cyst in our department between 2004 and 2010. Surgical procedures were classified into the following 4 categories: cystectomy by an interlaminar approach, hemilaminectomy, laminectomy, or associated with instrumented spinal fusion. Clinical outcome, cyst recurrence, need for subsequent fusion, and perioperative complications were compared between these groups. Results: Of the patients included in the present cohort, 11 underwent cyst excision by an interlaminar approach, 8 had a hemilaminectomy, 2 had a laminectomy, and 2 underwent instrumented fusion. “Excellent” or “good” clinical outcome on the Macnab modified scale were achieved for 16 patients (69.6%), and there were 2 perioperative complications, 2 cyst recurrences, and 1 secondary fusion. Of the 519 patients reported in the literature, overall clinical outcome was either “excellent” or “good” for 83% of all patients. However, unfavorable outcome was more likely in patients treated with decompression alone (80/396) than decompression with fusion (10/123) (20.2% vs. 8.1%; P=0.003) and cyst recurrence (13/396 vs. 0/123; P=0.028). In contrast, the rate of perioperative complications was significantly higher in the fusion group (23/123) compared with decompression alone (11/396) (18.7% vs. 2.8%; P<0.0001). Conclusions: In patients with spinal synovial cyst, spinal fusion seems to decrease the risk of unfavorable clinical outcome and cyst recurrence and associated with a considerably higher rate of perioperative complications.