Presurgical predictors of early cognitive outcome after brain tumor resection in glioma patients.

Gliomas are commonly characterized by neurocognitive deficits that strongly impact patients' and caregivers' quality of life. Surgical resection is the mainstay of therapy, and it can also cause cognitive impairment. An important clinical problem is whether patients who undergo surgery will show post-surgical cognitive impairment above and beyond that present before surgery. The relevant rognostic factors are largely unknown. This study aims to quantify the cognitive impairment in glioma patients 1-week after surgery and to compare different pre-surgical information (i.e., cognitive performance, tumor volume, grading, and lesion topography) towards predicting early post-surgical cognitive outcome. We retrospectively recruited a sample of N = 47 patients affected by high-grade and low-grade glioma undergoing brain surgery for tumor resection. Cognitive performance was assessed before and immediately after (∼1 week) surgery with an extensive neurocognitive battery. Multivariate linear regression models highlighted the combination of predictors that best explained post-surgical cognitive impairment. The impact of surgery on cognitive functioning was relatively small (i.e., 85% of test scores across the whole sample indicated no decline), and pre-operative cognitive performance was the main predictor of early post-surgical cognitive outcome above and beyond information from tumor topography and volume. In fact, structural lesion information did not significantly improve the accuracy of prediction made from cognitive data before surgery. Our findings suggest that post-surgery neurocognitive deficits are only partially explained by preoperative brain damage. The present results suggest the possibility to make reliable, individualized, and clinically relevant predictions from relatively easy-to-obtain information.

Intraoperative Measurement of Arterial Blood Flow in Aneurysm Surgery.

Intraoperative flowmetry (IF) has been recently introduced during cerebral aneurysm surgery in order to obtain a safer surgical exclusion of the aneurysm. This study evaluates the usefulness of IF during surgery for cerebral aneurysms and compares the results obtained in the joined surgical series of Verona and Padua to the more recent results obtained at the neurosurgical department of Verona.In the first surgical series, between 2001 and 2010, a total of 312 patients were submitted to IF during surgery for cerebral aneurysm at the neurosurgical departments of Verona and Padua: 162 patients presented with subarachnoid hemorrhage (SAH) whereas 150 patients harbored unruptured aneurysms. In the second series, between 2011 and 2016, 112 patients were submitted to IF during surgery for cerebral aneurysm at the neurosurgical department of Verona; 24 patients were admitted for SAH, whereas 88 patients were operated on for unruptured aneurysms.Comparison of the baseline values in the two surgical series and the baseline values between unruptured and ruptured aneurysms showed no statistical differences between the two clinical series. Analysis of flowmetry measurements showed three types of loco-regional flow derangements: hyperemia after temporary arterial occlusion, redistribution of flow in efferent vessels after clipping, and low flow in patients with SAH-related vasospasm.IF provides real-time data about flow derangements caused by surgical clipping of cerebral aneurysm, thus enabling the surgeon to obtain a safer exclusion; furthermore, it permits the evaluation of other effects of clipping on the loco-regional blood flow. It is suggested that-in contribution with intraoperative neurophysiological monitoring-IF may now constitute the most reliable tool for increasing safety in aneurysm surgery.

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.

Tuberculum Sellae Meningioma Resection: Technical Nuances on the Frontopterional Approach.

Tuberculum sellae meningioma remains a surgical challenge. Deep location of tumor, vascular and nerve encasement, and pituitary stalk involvement are the main technical issues. The frontopterional approach represents a natural, simple, and elegant approach to this area enabling surgeon to have a direct control on all anatomical structures. A 42-year-old woman was referred with a delayed diagnosis of tuberculum sellae meningioma due to the presence of HLA-B27-associated uveitis. She presented with 1/10 visual acuity in the left eye and no right visual function. A left frontopterional craniotomy was performed. Visual function improved postoperatively. The video illustrates the cisternal anatomy via pterional approach. The link to the video can be found at: https://youtu.be/Hmbf5bt7A64 .

Utility of indocyanine green videoangiography in subcortical arteriovenous malformation resection.

Subcortical arteriovenous malformations (AVMs) are surgically challenging. Localization is crucial for eloquent areas, and complete resection evaluation is uncertain. Indocyanine green videoangiography (ICG-VA) can assist this surgery. An illustrative video of a subcortical frontoparietal bleeding AVM resection assisted by ICG-VA is presented. A bleeding arterial feeder aneurysm was embolized in the acute phase to protect against rebleeding. ICG-VA helped to detect the AVM's superficial arterialized draining vein, distinguishing it from normal cortical veins. This enabled a customized sulcus approach. ICG-VA showed normalized flow through the previously arterialized vein, confirming the AVM's complete resection. This applies when there is a single drainage remaining. The video can be found here: https://youtu.be/L7yJEE66kV0 .

Beyond breast specific-Graded Prognostic Assessment in patients with brain metastases from breast cancer: treatment impact on outcome.

Brain metastases are a serious relatively common complication of breast cancer. We evaluated prognostic factors for survival after diagnosis of brain metastases from breast cancer in a contemporary cohort of patients. Patients diagnosed with breast cancer brain metastases at our institution between 1999 and March 2016 were evaluated. Overall survival was defined as time from brain metastasis diagnosis to death or last follow-up. Patients were classified according to the Breast cancer-specific Graded Prognostic Assessment (BS-GPA), based on age, Karnofsky performance score and breast cancer phenotype. 181 patients were identified. Tumor phenotype distribution was as follows: triple negative (TN, 18.8%), hormone receptor (HR)-HER2+ (16.6%), HR+HER2+ (23.2%) and HR+HER2- (30.9%), not available (10.5%). Median overall survival from brain metastasis diagnosis was 7.7 mos (95% CI 5.4-10.0 mos). Although TN patients experienced the worse outcome, no significant difference was observed across tumor phenotypes (median 5.1, 7.7, 11.0 and 8.6 months in TN, HR-HER2+, HR+HER2+, HR+HER2-, p = 0.081). The BS-GPA index was significantly associated with overall survival (median 18.8, 8.8, 6.2 and 3.6 months, respectively, for BS-GPA categories 3.5-4, 2.5-3, 1.5-2 and 0-1, p = 0.014). Increased number of local treatments for brain metastasis (radiotherapy or neurosurgery) or the administration of systemic therapy after brain metastasis diagnosis were also significant predictors of better overall survival (p < 0.001) and, when evaluated in multivariate analysis with BS-GPA, both added independent prognostication beyond BS-GPA. Patient-related features, tumor phenotype and multimodal treatments all independently contribute to modulate prognosis of patients diagnosed with breast cancer brain metastases.

The "ICG Entrapment Sign" in Cerebral Aneurysm Surgery Assisted by Indocyanine Green Videoangiography.

BACKGROUND: Indocyanine green videoangiography (ICG-VA) after clipping can be misleading in evaluating aneurysm exclusion when the dye is injected before clipping. This is due to indocyanine green (ICG) entrapment by the clip blades in the aneurysm dome. METHODS: We examined the intraoperative findings of 7 patients presenting ICG entrapment. In all cases, the clipped aneurysms were opened intraoperatively at the end of the procedure to confirm aneurysm exclusion. RESULTS: In 4 cases ICG entrapment was caused by dye injection before clipping for the surgical strategy and in 3 cases because the clip was repositioned based on ICG-VA findings. In all cases, the final sac opening confirmed that the dye entrapment indicated complete aneurysm exclusion. In our experience ICG entrapment avoided a second ICG injection in 2 cases and yielded a better understanding of the videoangiographic findings in 5 patients. CONCLUSIONS: The "ICG entrapment sign" can be used intraoperatively as an indirect sign of excluded aneurysm and can be helpful in the decision-making process for aneurysm treatment when ICG-VA is performed before clipping.

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.

Multimodal Flow-Assisted Resection of Brain AVMs.

OBJECT: The authors report their personal experience with brain arterio-venous malformations (bAVMs) surgery with a multimodal flow-assisted approach. METHODS: Data from patients who consecutively underwent bAVM resection with the assistance of indocyanine green video-angiography (ICG-VA), micro-flow probe flowmetry, and temporary arterial clipping test under intra-operative monitoring, were retrospectively analyzed. RESULTS: Twenty seven patients were enrolled in the study. Re-operation for residual nidus was needed in one case (3 %). Average mRS change 1 month after surgery was +0.02. In our experience, the multimodal flow-assisted approach enabled surgeons to shift from one technique to another, according to the stage of resection, AVM location, or specific issues to be addressed. Before resection, the value of ICG-VA and flowmetry in showing AVM angio-architecture and guiding surgical strategy was related to AVM features. The temporary arterial clipping-test presented a 100 % sensitivity to differentiate between an AVM feeder and a transit artery to the sensi-motor area. At the final stage of resection, flowmetry was more effective than ICG-VA in detecting residual nidus missed at dissection. CONCLUSIONS: Multimodal flow-assisted approach in AVM surgery proved a feasible, safe, and reliable methodology to achieve AVM resection with high radicality and low morbidity rate.

Indocyanine Green Videoangiography Transoptic Visualization and Clipping Confirmation of an Optic Splitting Ophthalmic Artery Aneurysm.

OBJECTIVE: Ophthalmic artery aneurysms with medial and superior projection in exceptionally rare cases can split the optic nerve. Treatment of these aneurysms is challenging, because the aneurysm dome is hidden from the optic nerve, rendering its visualization and clipping confirmation difficult. In addition, optic nerve function should be preserved during surgical maneuvers. Preoperative detection of this growing feature is usually missing. CASE DESCRIPTION: We illustrate the first case of indocyanine green videoangiography (ICG-VA) application in an optic penetrating ophthalmic artery aneurysm treatment. A 57-year-old woman presented with temporal hemianopsia, slight right visual acuity deficit, and new onset of headache. The cerebral angiography detected a right ophthalmic artery aneurysm medially and superiorly projecting. The A1 tract of the ipsilateral anterior cerebral artery was elevated and curved, being suspicious for an under optic aneurysm growth. Surgery was performed. Initially the aneurysm was not visible. ICG-VA permitted the transoptic aneurysm visualization. After optic canal opening, the aneurysm was clipped and transoptic ICG-VA confirmed the aneurysm occlusion. ICG-VA showed also the slight improvement of the optic nerve pial vascularization. Postoperatively, the visual acuity was 10/10 and the hemianopsia did not worsen. CONCLUSIONS: The elevation and curve of the A1 tract in medially and superiorly projecting ophthalmic aneurysms may be an indirect sign of under optic growth, or optic splitting aneurysms. ICG-VA transoptic aneurysm detection and occlusion confirmation reduces the surgical maneuvers on the optic nerve, contributing to function preservation.

Intraoperative Flow Measurement by Microflow Probe During Spinal Dural Arteriovenous Fistula Surgery.

OBJECTIVE: Flow measurement by microvascular ultrasonic flow probe is an established procedure in intracranial vascular surgery. This study tested the application of this procedure in spinal dural arteriovenous fistula (SDAVF) treatment. METHODS: Data from 12 SDAVF patients who consecutively underwent microsurgical resection with the assistance of both microflow probe and indocyanine green videoangiography (ICG-VA) were retrospectively analyzed. Flowmetry was performed on a dilated perimedullary venous plexus at different distances from the fistula point (FP). In addition, measurements were made at different phases of surgery to address specific issues: at the beginning, to identify the fistula; after temporary clipping, to evaluate proper disconnection; and after section, to exclude residual filling. RESULTS: Flowmetry was reliable in assessing both the value and direction of flow in all cases, thereby aiding fistula localization and confirming its disconnection. Indeed, fistula localization was helped by detection of increasing flow values approaching the FP (mean flow: 11 mL/min <10 mm vs. 3 mL/min >20 mm), while fistula disconnection was confirmed by a flow value lower than 1 mL/min (0-1 mL/min). Data from microflow probe measurements were concordant with ICG-VA data in all cases. In 3 cases, ICG-VA findings on fistula disconnection uncertain due to residual ICG dye were clarified by flowmetry. CONCLUSIONS: With the limits of our small series, multistage intraoperative quantitative flow measurement is a feasible, safe, and reliable adjunct in the surgical treatment of SDAVFs. The procedure provides data helpful in guiding the surgical strategy or clarifying ICG-VA data when necessary.

ICG-VA application in subtemporal transtentorial treatment of a Cognard V dural arteriovenous fistula.

Intracranial dural arteriovenous fistulas (dAVF) with cervical perimedullary drainage, Cognard V, are a surgically challenging rare entity. In this video we show the disconnection of a right tentorial Cognard V dAVF, done through a subtemporal transtentorial approach with the application of indocyanine green video angiography. A 47-year-old man presented with severe tetraparesis. Only partial embolization was possible. An osteoplastic frontotemporal craniotomy was performed to obtain a wide view along with CSF release to safely mobilize the temporal lobe. Neuronavigation was used to detect the fistula and indocyanine to detect the tentorial afferent arteries and to confirm final disconnection. The video can be found here: https://youtu.be/Yr8tAiiHNXU .

Facial asymmetry quantitative evaluation in oculoauriculovertebral spectrum.

OBJECTIVES: Facial asymmetries in oculoauriculovertebral spectrum (OAVS) patients might require surgical corrections that are mostly based on qualitative approach and surgeon's experience. The present study aimed to develop a quantitative 3D CT imaging-based procedure suitable for maxillo-facial surgery planning in OAVS patients. MATERIALS AND METHODS: Thirteen OAVS patients (mean age 3.5 ± 4.0 years; range 0.2-14.2, 6 females) and 13 controls (mean age 7.1 ± 5.3 years; range 0.6-15.7, 5 females) who underwent head CT examination were retrospectively enrolled. Eight bilateral anatomical facial landmarks were defined on 3D CT images (porion, orbitale, most anterior point of frontozygomatic suture, most superior point of temporozygomatic suture, most posterior-lateral point of the maxilla, gonion, condylion, mental foramen) and distance from orthogonal planes (in millimeters) was used to evaluate the asymmetry on each axis and to calculate a global asymmetry index of each anatomical landmark. Mean asymmetry values and relative confidence intervals were obtained from the control group. RESULTS: OAVS patients showed 2.5 ± 1.8 landmarks above the confidence interval while considering the global asymmetry values; 12 patients (92%) showed at least one pathologically asymmetric landmark. Considering each axis, the mean number of pathologically asymmetric landmarks increased to 5.5 ± 2.6 (p = 0.002) and all patients presented at least one significant landmark asymmetry. CONCLUSIONS: Modern CT-based 3D reconstructions allow accurate assessment of facial bone asymmetries in patients affected by OAVS. The evaluation as a global score and in different orthogonal axes provides precise quantitative data suitable for maxillo-facial surgical planning. CLINICAL RELEVANCE: CT-based 3D reconstruction might allow a quantitative approach for planning and following-up maxillo-facial surgery in OAVS patients.

Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis.

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.