Petrous apex's dural arteriovenous fistula (DAVF) mimicking a pineal region tumour: a rare cause of Hakim triad.

A dural arteriovenous fistula (DAVF) is a dural-based shunt between meningeal arteries and meningeal veins, sinuses and/or cortical veins; they have been classified and named according to the location and the flow pattern. Petrous apex DAVFs are located where the petrosal vein penetrates the dura mater into the superior petrosal sinus; there are only few cases reported in the literature, they can show an aggressive behaviour (subarachnoid haemorrhage, severe brainstem oedema) with a high mortality rate. The described case is, to the best of our knowledge, the first case of a DAVF presenting with symptoms mimicking idiopathic normal pressure hydrocephalus. After worsening of gait impairment, memory loss and urinary incontinence an urgent CT of the brain showed hydrocephalus and a hyperdense mass in the pineal region mimicking a pineal tumour; an emergent digital subtraction angiogram showed a left petrous apex Borden type III DAVF. A transvenous embolisation was performed obtaining a complete obliteration.

Microsurgical Clipping of Intracranial Aneurysms Assisted by Neurophysiological Monitoring, Microvascular Flow Probe, and ICG-VA: Outcomes and Intraoperative Data on a Multimodal Strategy.

OBJECTIVE: The aim of this study is to report data on a multimodal monitoring strategy based on the intraoperative use of neurophysiological monitoring, flowmetry by microflow probe, and intraoperative indocyanine green video angiography (ICG-VA) during microsurgical clipping of intracranial aneurysms. METHODS: This retrospective analysis was performed on 85 consecutive patients undergoing clipping of 96 intracranial aneurysms with the present monitoring strategy. Patient outcomes were evaluated by assessing rate of aneurysm exclusion and postoperative occurrence of ischemic injury. Intraoperative data for the strategy in addition to changes in each monitoring technique depending on aneurysm features were reported. RESULTS: Complete aneurysm exclusion was achieved in 98.9% of cases. Postoperative symptomatic ischemic injury was recorded in 2.08% aneurysms. Clip repositioning occurred in 40.6% of cases: because of motor evoked potential (MEP) decrease in 9.3%, flowmetry in 22.91%, and ICG-VA in 8.3% of treated aneurysms (1.05% after ICG injection, 7.4% after the squeezing maneuver). The role of each technique differed according to aneurysm features; flowmetry alterations occurred more frequently in distal than in proximal aneurysms (P = 0.0001) and in atherosclerotic aneurysms (P = 0.0001). MEP impairment occurred more often in proximal aneurysms (P < 0.05). ICG-VA disclosed remnant aneurysms mainly in atherosclerotic aneurysms (P < 0.05); only one false negative remnant neck was recorded with a negative predictive value of 98.8%. CONCLUSIONS: Microsurgical clipping assisted by a multimodal monitoring strategy achieved a high rate of aneurysm exclusion with low morbidity in our series. Our data show that the 3 techniques used in our strategy were complementary and that a monitoring strategy can be tailored to aneurysm features.

Addressing the selective role of distinct prefrontal areas in response suppression: A study with brain tumor patients.

The diverging evidence for functional localization of response inhibition within the prefrontal cortex might be justified by the still unclear involvement of other intrinsically related cognitive processes like response selection and sustained attention. In this study, the main aim was to understand whether inhibitory impairments, previously found in patients with both left and right frontal lesions, could be better accounted for by assessing these potentially related cognitive processes. We tested 37 brain tumor patients with left prefrontal, right prefrontal and non-prefrontal lesions and a healthy control group on Go/No-Go and Foreperiod tasks. In both types of tasks inhibitory impairments are likely to cause false alarms, although additionally the former task requires response selection and the latter target detection abilities. Irrespective of the task context, patients with right prefrontal damage showed frequent Go and target omissions, probably due to sustained attention lapses. Left prefrontal patients, on the other hand, showed both Go and target omissions and high false alarm rates to No-Go and warning stimuli, suggesting a decisional rather than an inhibitory impairment. An exploratory whole-brain voxel-based lesion-symptom mapping analysis confirmed the association of left ventrolateral and dorsolateral prefrontal lesions with target discrimination failure, and right ventrolateral and medial prefrontal lesions with target detection failure. Results from this study show how left and right prefrontal areas, which previous research has linked to response inhibition, underlie broader cognitive control processes, particularly involved in response selection and target detection. Based on these findings, we suggest that successful inhibitory control relies on more than one functionally distinct process which, if assessed appropriately, might help us to better understand inhibitory impairments across different pathologies.

Outcome of patients affected by newly diagnosed glioblastoma undergoing surgery assisted by 5-aminolevulinic acid guided resection followed by BCNU wafers implantation: a 3-year follow-up.

The purpose of the study was to evaluate the clinical outcome of the association of BCNU wafers implantation and 5-aminolevulinic acid (5-ALA) fluorescence in the treatment of patients with newly diagnosed glioblastoma (ndGBM). Clinical and surgical data from patients who underwent 5-ALA surgery followed by BCNU wafers implantation were retrospectively evaluated (20 patients, Group I) and compared with data of patients undergoing surgery with BCNU wafers alone (42 patients, Group II) and 5-ALA alone (59 patients, Group III). Patients undergoing 5-ALA assisted resection followed by BCNU wafers implantation (Group I) resulted long survivors (>3 years) in 15 % of cases and showed a median PFS and MS of 11 and 22 months, respectively. Patients treated with BCNU wafers presented a significantly higher survival when tumor was removed with the assistance of 5-ALA (22 months with vs 18 months without 5-ALA, p < 0.0001); these data could be partially explained by the significantly higher CRET achieved in patients operated with 5-ALA assistance (80 % with vs 47 %% without 5-ALA). Moreover, patients of Group I showed a significant increased survival compared with Group III (5-ALA without BCNU) (22 months with vs 21 months without BCNU wafers, p = 0.0025) even with a comparable CRET (80 % vs 76 %, respectively). The occurrence of adverse events related to wafers did not significantly increase with 5-ALA (20 % with and 19 % without 5-ALA) and did not impact in survival outcome. In conclusion, our experience shows that on selected ndGBM patients 5-ALA technology and BCNU wafers implantation show a synergic action on patients' outcome without increasing adverse events occurrence.

Remote cerebellar hemorrhage after supratentorial procedures (part 1): a systematic review.

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which may rarely occurs as a complication of supratentorial procedures, and it shows a typical bleeding pattern defined "the zebra sign." However, its pathophysiology still remains unknown. We performed a comprehensive review collecting all cases of RCH after supratentorial craniotomies reported in literature in order to identify the most frequently associated procedures and the possible risk factors. We assessed percentages of incidence and 95 % confidence intervals of all demographic, neuroradiological, and clinical features of the patients. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 49 articles reporting 209 patients with a mean age of 49.09 ± 17.07 years and a male/female ratio 130/77. A RCH was more frequently reported as a complication of supratentorial craniotomies for intracranial aneurysms, tumors debulking, and lobectomies. In the majority of cases, RCH occurrence was associated with impairment of consciousness, although some patients remained asymptomatic or showed only slight cerebellar signs. Coagulation disorders, perioperative cerebrospinal fluid drainage, hypertension, and seizures were the most frequently reported risk factors. Zebra sign was the most common bleeding pattern, being observed in about 65 % out of the cases, followed by parenchymal hematoma and mixed hemorrhage in similar percentages. A multivariate analysis showed that symptomatic onset and intake of antiplatelets/anticoagulants within a week from surgery were independent predictors of poor outcome. However, about 75 % out of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless in the event of the occurrence of complications.

Remote cerebellar hemorrhage after spinal procedures (part 2): a systematic review.

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which can be rarely observed as a complication of spine surgery. As well as for RCH reported after supratentorial procedures, it shows a characteristic bleeding pattern defined "zebra sign". Nowadays, RCH pathophysiology still remains unknown. We performed a comprehensive review, collecting all cases of RCH after spine surgery reported in literature in order to identify the procedures most frequently associated with RCH and the possible risk factors. We assessed percentages of incidence and 95 % confidence interval of all demographic, neuroradiological, and clinical features. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 44 articles reporting 57 patients with mean age of 57.6 ± 13.9 years and a male/female ratio of 23/34. A RCH was more frequently reported as a complication of decompressive procedures for spinal canal stenosis, particularly when associated with instrumented fusion, followed by spinal tumor debulking and disc herniation removal. In the majority of cases, RCH occurrence was characterized by progressive impairment of consciousness, whereas some patients complained non-specific symptoms. Coagulation disorders, hypertension, and placement of postoperative subfascial drainages were the most frequently reported risk factors. The occurrence of intraoperative dural lesions was described in about 93 % of patients. Zebra sign was the most common bleeding pattern (about 43 % of cases) followed by parenchymal hematoma (37.5 %) and mixed hemorrhage (about 20 %). Impairment of consciousness at clinical onset and intake of anticoagulants/antiplatelets appeared associated with poor outcome at univariate analysis. However, more than 75 % of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless of the occurrence of complications.

Surgery on motor area metastasis.

The role of surgery on central area metastasis remains unclear, and outcome data are still controversial. The aim of our study is to analyze the predictive value of clinical and surgical data on motor and functional outcome of patients, taking into account new emerging data on boundary irregularity of brain metastasis. We retrospectively analyzed 47 consecutive patients who underwent surgery assisted by neurophysiologic monitoring for a solitary metastasis in central area between 2010 and 2013. Inclusion criteria were as follows: good functional status (Karnofsky Performance Status (KPS) ≥70), controlled systemic disease, and absence of extra-cranial dissemination. At 1-month follow up, motor and functional outcomes were compared with preoperative clinical status, response to corticosteroids, extent of tumor resection, boundary irregularity, and size of tumor. Gross total resection was achieved in 93.6% of cases. In preoperative symptomatic patients, motor outcome (according to Medical Research Council grading scale) improved in 55.5% and worsened in 16.7%, while functional outcome (according to KPS score) improved in 50% and worsened in 14.2% of cases. No worsening occurred in preoperative asymptomatic patients. Motor outcome resulted to be not correlated with preoperative deficits, tumor volume, or preoperative response to corticosteroid treatment. Remarkably, motor outcome and extent of surgical resection appeared strongly correlated with tumor boundary irregularity (p < 0.05). Surgery with neurophysiologic monitoring on motor area metastasis can improve functional and motor condition in selected patients. Tumor volume does not represent a limit in surgery. The high correlation between clinical outcome, resection rate, and tumor boundary irregularity strengthens a new belief on the infiltrative growing pattern of brain metastasis. Motor function was evaluated according to Medical Research Council grading scale (Ott et al. 2014) while functional status was assessed according to KPS score.

Intraparenchymal ventricular diverticula in chronic obstructive hydrocephalus: prevalence, imaging features and evolution.

BACKGROUND: Intraparenchymal cavities communicating with the ventricles may appear in patients with chronic obstructive hydrocephalus despite no identifiable surgerical, vascular or traumatic causes. The rate, features, pathogenesis, evolution and clinical impact of intraparenchymal diverticula have not been outlined, yet. METHODS: Brain MRIs of 130 patients (mean age: 11.3 years; age range: 0-67; 60 females) with chronic obstructive hydrocephalus were analyzed. The pathogenesis, neurosurgical treatment, ventricle size, signs of transependymal reabsorption and septum pellucidum integrity of the hydrocephalus were recorded. Subarachnoid outpouching of the ventricles, post-hemorrhagic parenchymal cavities, paths of ventricular shunting and cavities not communicating with the ventricles were excluded. Of patients with intraparenchymal diverticula, all previous available CT and MRI scans were evaluated. RESULTS: Eight patients (6.2 %, mean age: 18.7 years; age range: 2-42) harbored 11 intraparenchymal diverticula sprouting from the temporal (6), occipital (3) or frontal (2) horns of the lateral ventricles. Intraparenchymal diverticula were more frequent in males (p = 0.04) and older patients (18.7 ± 12.7 vs 11.3 ± 9.8 years, p = 0.04). Their presence or evolution (mean neuroradiological follow-up 3.6 years; range: 0-8) showed a trend of association with hydrocephalus severity (bifrontal index) and did not correlate with the surgical treatment. In three patients the diverticula progressed during follow-up. One patient presented with hemiparesis consistent with the intraparenchymal lesion and improved after ventricular shunting. A DTI study revealed that the cortico-spinal tract was partly included in the septum between the ventricle and the intraparenchymal diverticulum. CONCLUSIONS: Clinicians dealing with chronic severe obstructive hydrocephalus should be aware of ventricular intraparenchymal diverticulation. Studies aiming at clarifying their pathogenesis and proper management are warranted.

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.

Intraoperative functional mapping of calculation in parietal surgery. New insights and clinical implications.

BACKGROUND: Parietal areas play a crucial role in calculation processing. The purpose of this study is to report our experience in the assessment of calculation processing during awake surgery in parietal areas, focusing on clinical implications and new insights provided by this approach. METHODS: We retrospectively reviewed clinical and surgical data of 13 patients who underwent parietal surgery with calculation mapping. Cortical and sub-cortical areas (in 13 and five patients, respectively) involved in single-digit multiplications and additions were identified using bipolar electro-stimulation. RESULTS: Cortical stimulation data showed that the inferior parietal lobule and the intraparietal sulcus were specifically related to calculation in all cases, regardless of the side (100% of cases, in both sides). Conversely, the superior parietal lobule was inconstantly involved in calculation processing (40% of cases in the left and 75% in the right side), whereas the somatosensory area was never involved. Sub-cortical stimulation was able to detect functional areas for calculation in all patients: in 90% of cases the sub-cortical sites positive for calculation were in close anatomical connection with the cortical sites mapping for the same function. The intraoperative preservation (-or damaging-) of functional sites correlated with the absence (- or occurrence-) of post-operative calculation processing impairment. CONCLUSIONS: Our findings support the specificity of the reported technique in the intraoperative identification of sites functional for calculation. Our data show the bilateral involvement of parietal cortex, especially of the inferior lobule, in calculation processing. Furthermore, our study suggests the existence of a sub-cortical pathway specific for calculation, whose better understanding might be crucial for the clinical outcome of patients.

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.

Combined analysis of TERT, EGFR, and IDH status defines distinct prognostic glioblastoma classes.

OBJECTIVE: To identify the prognostic significance of TERT promoter mutations (TERTp-mut) and their associations with common molecular alterations in glioblastomas (GBMs). METHODS: We sequenced the TERTp-mut in DNA from 395 GBMs and analyzed the results with their respective histology, genetic profile (IDH1 mutation, EGFR amplification, CDKN2A homozygous deletion, loss of chromosome 10, TP53 mutation), and overall survival (OS). RESULTS: TERTp-mut were found in 299 of 395 GBMs (75.7%) and were associated with an older age (median 59.6 years for TERTp-mut vs 53.6 years for TERT promoter wild type [TERTp-wt], p < 0.0001). TERTp-mut was an independent factor of poor prognosis (OS = 13.8 vs 18.4 months), in both IDH-mutated (OS = 13.8 vs 37.6 months, p = 0.022) and IDH-wt GBMs (OS = 13.7 vs 17.5 months, p = 0.006). TERTp-mut was associated with IDH-wt, EGFR amplification, CDKN2A deletion, and chromosome 10q loss, but not with MGMT promoter methylation. In the TERTp-wt group, OS was twice longer in EGFR-wt than in EGFR amplification GBMs (OS = 26.6 vs 13.3 months; p = 0.005). In the EGFR-wt group, patients with TERTp-wt had a significantly better outcome (OS = 26.3 vs 12.5 months, p < 0.0001), whereas in the EGFR amplification group, patients with TERTp-mut survived longer (OS = 15.8 vs 13.3 months, p = 0.05). Taken together, the absence of both EGFR amplification and TERTp-mut is associated with longer survival in patients with GBM (26.5 months for patients with IDH-wt, 36.7 months for patients with IDH mutation). CONCLUSIONS: The analysis of TERTp-mut, in combination with EGFR amplification and IDH mutation status, refines the prognostic classification of GBMs.

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 IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) 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.

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.

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.

Lateral ventricle's choroid plexus tumors surgery in children: how I do it.

BACKGROUND: Choroid plexus tumors (CPTs) are intraventricular lesions originating from ventricular neuroepithelium and represent up to 4% of brain neoplasms affecting pediatric population. They are more frequently benign papillomas, but malignant carcinomas can sometimes occur. METHOD: The authors present a description of surgical approach for CPTs, particularly focusing on the complications related to the cerebrospinal fluid (CSF) circulation, which may affect outcome. CONCLUSION: Microsurgical resection represents the first line treatment for CPTs. The goal is the complete removal of the tumor and the restoration of a physiological CSF circulation.

5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature.

BACKGROUND: Only few data are available on the specific topic of 5-aminolevulinic acid (5-ALA) guided surgery of high-grade gliomas (HGG) located in eloquent areas. Studies focusing specifically on the post-operative clinical outcome of such patients are yet not available, and it has not been so far explored whether such approach could be more suitable for some particular subgroups of patients. METHODS: Patients affected by HGG in eloquent areas who underwent surgery assisted by 5-ALA fluorescence and intra-operative monitoring were prospectively recruited in our Department between June 2011 and August 2012. Resection rate was reported as complete resection of enhancing tumor (CRET), gross total resection (GTR) >98 % and GTR > 90 %. Clinical outcome was evaluated at 7, 30, and 90 days after surgery. RESULTS: Thirty-one patients were enrolled. Resection was complete (CRET) in 74 % of patients. Tumor removal was stopped to avoid neurological impairment in 26 % of cases. GTR > 98 % and GTR > 90 % was achieved in 93 % and 100 % of cases, respectively. First surgery and awake surgery had a CRET rate of 80 % and 83 %, respectively. Even though at the first-week assessment 64 % of patients presented neurological impairment, there was a 3 % rate of severe morbidity at the 90th day assessment. Newly diagnosed patients had a significantly lower morbidity (0 %) and post-operative higher median KPS. Both pre-operative neurological condition and improvement after corticosteroids resulted significantly predictive of post-operative functional outcome. CONCLUSIONS: 5-ALA surgery assisted by functional mapping makes high HGG resection in eloquent areas feasible , through a reasonable rate of late morbidity. This emerges even more remarkably for selected patients.

Deciphering the 8q24.21 association for glioma.

We have previously identified tagSNPs at 8q24.21 influencing glioma risk. We have sought to fine-map the location of the functional basis of this association using data from four genome-wide association studies, comprising a total of 4147 glioma cases and 7435 controls. To improve marker density across the 700 kb region, we imputed genotypes using 1000 Genomes Project data and high-coverage sequencing data generated on 253 individuals. Analysis revealed an imputed low-frequency SNP rs55705857 (P = 2.24 × 10(-38)) which was sufficient to fully capture the 8q24.21 association. Analysis by glioma subtype showed the association with rs55705857 confined to non-glioblastoma multiforme (non-GBM) tumours (P = 1.07 × 10(-67)). Validation of the non-GBM association was shown in three additional datasets (625 non-GBM cases, 2412 controls; P = 1.41 × 10(-28)). In the pooled analysis, the odds ratio for low-grade glioma associated with rs55705857 was 4.3 (P = 2.31 × 10(-94)). rs55705857 maps to a highly evolutionarily conserved sequence within the long non-coding RNA CCDC26 raising the possibility of direct functionality. These data provide additional insights into the aetiological basis of glioma development.