Marta Rossetto

Detection of IDH1 mutation in the plasma of patients with glioma

Objective: The IDH1R132H mutation is both a strong prognostic predictor and a diagnostic hallmark of gliomas and therefore has major clinical relevance. Here, we developed a new technique to detect the IDH1R132H mutation in the plasma of patients with glioma. Methods: Small-size DNA (150–250 base pairs) was extracted from the plasma of 31 controls and 80 patients with glioma with known IDH1R132H status and correlated with MRI data. The IDH1R132H mutation was detected by a combination of coamplification at lower denaturation temperature and digital PCR. Results: The small size DNA concentration was 1.2 ng/mL (range 0.1–6.6) in controls vs 1.2 ng/mL (range 0.1–50.3) in patients with glioma (p = not significant) and 0.9 ng/mL (0.0–3.0) in low-grade gliomas vs 1.5 ng/mL in high-grade gliomas (p < 0.01). The small size DNA concentration correlated with enhancing tumor volume (1.6 ng/mL [0.4–24.9] when <10 cm3 and 14.0 ng/mL [0.6–50.3] when ≥10 cm3). The IDH1R132H mutation was detected in 15 out of 25 plasma DNA mixtures (60%) from patients with mutated tumors and in none of the 14 patients with a nonmutated tumor. The sensitivity increased with enhancing tumor volume (3/9 in nonenhancing tumors, 6/10 for enhancing volume <10 cm3, and 6/6 for enhancing volume ≥10 cm3). Conclusion: With a specificity of 100% and a sensitivity related to the tumor volume and contrast enhancement, IDH1R132H identification has a valuable diagnostic accuracy in patients not amenable to biopsy.

5-Aminolevulinic Acid Fluorescence in High Grade Glioma Surgery: Surgical Outcome, Intraoperative Findings, and Fluorescence Patterns

Background. 5-Aminolevulinic acid (5-ALA) fluorescence is a validated technique for resection of high grade gliomas (HGG); the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Methods. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR) > 98% and GTR > 90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO). Results. 94 patients were finally enrolled. Overall GTR > 98% and GTR > 90% was achieved in 93% and 100% of patients. Extent of resection (GTR > 98%) was dependent on tumor location, tumor grade (P < 0.05), and tumor size (P < 0.05). In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57%) (P < 0.01) and recurrent (60%) tumors. Conclusions. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

IDH Mutations: Genotype-Phenotype Correlation and Prognostic Impact

IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1R132H, IDH1nonR132H, and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1nonR132H in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated—which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation prognostic impact and genotype-phenotype associations.

Use of a new absorbable sealing film for preventing postoperative cerebrospinal fluid leaks: remarks on a new approach

Cerebrospinal fluid (CSF) leak is an adverse event that can affect the postoperative course of neurosurgical patients. Despite the large intra-operative use effective strategies as well as specific devices, CSF leak post-operative occurrence has been recently reported in up to 11% of cases. TissuePatchDural is a new sealant that is now available in neurosurgery in order to repair dural defects and, consequently, to prevent the postoperative formation of CSF fistulas. The device is a synthetic absorbable film that can actively create a firm temporary connection with the external dural surface and thus favour a satisfactory healing of the wound. The authors report a preliminary experience about the use of such device in 12 selected patients.

Intraventricular astroblastoma. Case report.

Astroblastoma is a rare primary brain neoplasm that accounts for 0.45-2.8% of brain gliomas. Intraventricular localization is extremely rare. The authors report a case of well-differentiated completely intraventricular astroblastoma in a 6-year-old girl and review the relevant literature. Their patient presented with a 5-week history of progressive nausea and vomiting. Magnetic resonance (MR) imaging revealed a large, well-demarcated, solid-cystic mass in the left temporooccipital ventricular horn. Macroscopic radical resection of the tumor was performed via the superior temporal sulcus. The postoperative course was uneventful and no adjuvant therapy was administered after surgery. No recurrence was detected at 9-months follow-up. Gross-total resection has the greatest impact on patient survival. In differentiated tumors, recurrence is usually local, and adjuvant therapy is recommended after repeated resection for the treatment of recurrence. In patients harboring anaplastic astroblastoma, gross-total resection and adjuvant therapy after the initial surgery seems to be the best choice. It is important to distinguish astroblastoma from ependymoma in clinical practice because of the differences in therapeutic approaches.

Carmustine Wafer Implantation When Surgical Cavity Is Communicating with Cerebral Ventricles: Technical Considerations on a Clinical Series

BACKGROUND Implantation of carmustine (1,3-bis (2 chloroetyl)-1-nitrosurea [BCNU]) wafers is an approved local treatment after surgical removal of high-grade gliomas. Safety data have been largely reported by phase III studies. The communication between the final surgical cavity and the ventricular cavities is supposed to be a relative contraindication for positioning of the wafers because of the possible development of hydrocephalus. However, at present there are neither data about this topic published with the exception of a few case reports, nor any proposals for selection criteria for wafer implantation in such circumstances. Furthermore, there are no technical suggestions in literature put forward for the surgical repairing of ventricular defects. Our study was particularly focused on addressing these 3 issues. METHODS Forty-three patients affected by a high-grade glioma underwent surgical removal and BCNU wafer implantation between March 2007 and September 2009 at the Department of Neurosurgery of Padua. Among them, we retrospectively reviewed clinical, surgical, and radiological data of 9 patients who had been treated with carmustine wafers after surgical repair of communication between the surgical cavity and the ventricular cavities. We also focused on the technical details concerning wafers positioning in this particular situation. RESULTS Ventricular defects were present in the atrium in 4, frontal horn in 3, and temporal horn in 2 cases. The maximum diameter of the defect was between 6 and 10 mm. In all cases, the defect was intraoperatively repaired in the same way, and up to 8 wafers were implanted in the surgical cavity. In the series reported, no cases of hydrocephalus were detected. CONCLUSIONS In our experience, integrity of wafers, size of ventricular wall defect, and accuracy in repairing the defect were crucial issues. Nevertheless, more experience and prospective studies would be helpful to clarify both in what measure ventricular opening affects safety data and the best reliable way of repairing ventricular defects when BCNU wafers are implanted.

The endoscopic endonasal approach for cerebrospinal fluid leak repair in the elderly

INTRODUCTION Cerebrospinal fluid (CSF) rhinorrhea can lead to CNS infections, carrying significant morbidity and mortality, especially in the elderly. Endoscopic endonasal surgery is a validated technique in the repair of anterior skull base CSF leaks. The aim of this study is to assess diagnostic management, surgical technique and clinical outcome in a consecutive series of elderly patients. METHODS Patients older than 65 years treated for anterior skull base CSF leaks through endoscopic endonasal surgery between 2003 and 2014 were retrospectively reviewed. All patients underwent preoperative nasal endoscopy, laboratory and radiological assessment. In doubtful cases endoscopic exploration was performed after intrathecal fluorescein (IF) injection. Patients were discharged between 3 and 4 days after surgery, and the endoscopic follow-up ranged from 3 to 24 months. RESULTS 20 patients (age range 65-92) presented with 10 spontaneous and 10 traumatic/iatrogenic CSF leaks. In 40% of patients formal rhinoscopy and radiological assessment did not localize the CSF leak and IF injection was performed. IF enabled the identification of the skull base defect in all cases, with no adverse effects. In 11 cases the dura was repaired with fascia lata graft. All patients had successful endoscopic repair of the CSF fistula with no complications nor recurrences during follow-up. CONCLUSION Endoscopic endonasal surgery is a minimally invasive procedure for CSF leak treatment. In our experience, IF injection proved safe and efficient in detecting skull base defects not identified by preoperative imaging. Endoscopic endonasal surgery proved effective and reliable also in elderly patients, with short hospitalization times and no morbidity.

The "squeezing maneuver" in microsurgical clipping of intracranial aneurysms assisted by indocyanine green videoangiography.

BACKGROUND: Indocyanine green videoangiography (ICGV) is becoming routine in intracranial aneurysm surgery to assess intraoperatively both sac obliteration and vessel patency after clipping. However, ICGV-derived data have been reported to be misleading at times. We recently noted that a simple intraoperative maneuver, the “squeezing maneuver,” allows the detection of deceptive ICGV data on aneurysm exclusion and allows potential clip repositioning. The squeezing maneuver is based on a gentle pinch of the dome of a clipped aneurysm when ICGV documents its apparent exclusion. OBJECTIVE: To present the surgical findings and the clinical outcome of this squeezing maneuver. METHODS: Data from 23 consecutive patients affected by intracranial aneurysms who underwent the squeezing maneuver were analyzed retrospectively. The clip was repositioned in all cases when the dyeing of the sac was visualized after the maneuver. RESULTS: In 22% of patients, after an initial ICGV showing the aneurysm exclusion after clipping, the squeezing maneuver caused the prompt dyeing of the sac; in all cases, the clip was consequently repositioned. A calcification/atheroma of the wall/neck was predictive of a positive maneuver (P = .001). The aneurysm exclusion rate at postoperative radiological findings was 100%. CONCLUSION: With the limits of our small series, the squeezing maneuver appears helpful in the intraoperative detection of misleading ICGV data, mostly when dealing with aneurysms with atheromatic and calcified walls. ABBREVIATIONS: DSA, digital subtraction angiography ICG, indocyanine green ICGV, indocyanine green videoangiography

Multifocal presentation of medulloblastoma in adulthood

Medulloblastoma in adulthood is uncommon but not rare; annual incidence is 2–20/1,000,000. Some peculiarities characterize medulloblastoma in adult patients compared with the child type: lateral cerebellar location, heterogeneous signal intensity on magnetic resonance imaging, desmoplastic histological variant, and more favourable prognosis. Preoperative diagnosis is crucial for correct management of these patients. However, because of the low incidence of medulloblastoma in the adult population, preoperative diagnosis remains challenging and prognostic factors and best treatment options are still controversial. In this setting, some unusual findings, for example multifocal presentation and extra-axial location, can confound diagnosis and make treatment difficult. We present a short case-illustrated review on these remarkable issues.

Open Transcranial Resection of Small (<35 mm) Meningiomas of the Anterior Midline Skull Base in Current Microsurgical Practice

OBJECTIVE Despite technical surgical advance, the ultimate management of midline anterior skull base meningiomas remains to be defined. Open transcranial surgery is usually the first treatment option for large meningiomas, while less invasive techniques such as endoscopic surgery or radiosurgery might represent an alternative to open microsurgery for smaller lesions. The aim of our study is to investigate the outcome of open transcranial microsurgery in the resection of small (<35 mm) meningiomas of the midline anterior cranial base. METHODS Clinical and surgical data from 43 patients affected by small midline anterior skull base meningiomas operated via an open transcranial approach were retrospectively reviewed. RESULTS The tumor diameter on its major axis ranged from 12 to 35 mm, with a mean diameter of 28 mm. Gross total resection (Simpson grades I-II) was achieved in 100% of cases through a pterional approach. Postoperative overall morbidity was 9%. It was 3% among patients <70 years. No mortality was reported. Postoperative visual outcome was significantly associated with preoperative visual performance (P = 0.02), but not with preoperative optic nerve compression as detected by magnetic resonance imaging (P = 0.116). Age >70 years was associated with postoperative visual impairment, although not significantly (P = 0.06). Visual function was preserved or improved in 95% of cases, in 100% of patients <70 years, and in 71% of patients with preoperative visual impairment. CONCLUSIONS In our experience, open transcranial surgery proved safe and effective for midline anterior skull base meningiomas smaller than 35 mm in all patients <70 years and in patients >70 years without preoperative visual deficit. Our data are consistent with the literature. Conversely, the standard of treatment for the subgroup of patients >70 years with preoperative visual deficit has not yet been defined. This specific subgroup of patients offers a topic for further investigation.