Glioneuronal and Neuronal Tumors of the Central Nervous System.

Glioneuronal and neuronal tumors (GNTs) are rare neoplasms composed of neural and glial elements frequently located in the temporal lobe. Epilepsy is the main symptom and diagnosis mostly occurs before adulthood. The great majority of GNTs are WHO grade I tumors, but anaplastic transformations and forms exist. Their common association with focal cortical dysplasia is well recognized and should be taken into consideration during neurophysiological presurgical and surgical planning since the aim of surgery should be the removal of the tumor and of the entire epileptogenic zone according to anatomo-electrophysiological findings. Surgery still remains the cornerstone of symptomatic GNT, while radiotherapy, chemotherapy, and new target therapies are generally reserved for anaplastic, unresectable, or evolving tumors. Furthermore, since many GNTs show overlapping clinical and neuroradiological features, the definition of specific histopathological, genetic, and molecular characteristics is crucial. Epileptological, oncological, neurosurgical, and pathological issues of these tumors make a multidisciplinary management mandatory.

Endoscopic transventricular biopsy in brainstem diffuse midline glioma: how I do it.

BACKGROUND: Brainstem diffuse midline gliomas represent infiltrative and rare pediatric tumors with a dismal prognosis. Surgical biopsy is emerging as a valid technique to define diagnosis and molecular markers for future targeted therapies. METHOD: We describe the key steps of an endoscopic trans-ventricular biopsy of a brainstem diffuse midline glioma and associated ventriculomegaly. The relevant surgical anatomy along with an illustrative video is described. CONCLUSION: The endoscopic third ventriculostomy combined with a punch biopsy of a brainstem diffuse midline glioma associated with ventriculomegaly represent a feasible and low-risk procedure to simultaneously treat incipient hydrocephalus and molecular diagnosis for future treatment and research.

Open-aqueduct LOVA, LIAS, iNPH: a comparative clinical-radiological study exploring the "grey zone" between different forms of chronic adulthood hydrocephalus.

PURPOSE: The definition of chronic adult hydrocephalus encompasses different pathological entities with overlapping characteristics, including long-standing overt ventriculomegaly in adults (LOVA), late-onset idiopathic aqueductal stenosis (LIAS) and idiopathic normal pressure hydrocephalus (iNPH). The aim of our study was to identify preoperative clinical and radiological features peculiar of these diseases providing some pathophysiology inferences on these forms of hydrocephalus. METHODS: Clinical and radiological preoperative records, type of surgical treatment and clinical outcome of patients with chronic adult hydrocephalus who were surgically treated between 2013 and 2019 were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the contribution of each variable to the differential diagnosis. RESULTS: In total, 105 patients were included: 18 with LOVA, 23 with LIAS and 64 with iNPH. On multivariate analysis, an enlarged cisterna magna and a more severe ventriculomegaly were associated with the diagnosis of LOVA, while an older age and DESH with iNPH. LIAS patients tend to have an higher prevalence of raised ICP symptoms. Based on that, a clinical and radiological scoring system was developed to distinguish between iNPH and no iNPH cases. A precise cut-off value with a sensitivity of 95.1% and a specificity of 90.6% was identified. CONCLUSIONS: LOVA, LIAS and iNPH are different forms of chronic adulthood hydrocephalus and present different and peculiar clinical and radiological features, with an impact on the treatment and outcome prediction. The implementation of a clinical-radiological score for differential diagnosis may help the differentiation. Further studies are warranted.

Management of sellar and parasellar tumors becoming symptomatic during pregnancy: a practical algorithm based on multi-center experience and systematic literature review.

INTRODUCTION: Sellar/parasellar tumors (SPTs) very rarely become symptomatic during pregnancy. No specific guidelines exist for their management, that is extremely challenging as mother and fetus health can be jeopardized. MATERIALS AND METHODS: Data of patients with SPTs becoming symptomatic during pregnancy treated at two Italian referral Centers were retrospectively collected. Systematic literature review was also performed. RESULTS: Our series consisted of 6 cases, 3 meningiomas, 1 ACTH-secreting adenoma, 1 pituicytoma and 1 craniopharyngioma. Mean age at presentation was 33.6 ± 6.0 years. Five patients complained of visual disturbances, associated with headache in one case, that occurred between gestation week (GW) 22 and 34. In 5 cases, pregnancy was uneventful with the delivery of a healthy baby between GW 33 and 35, followed by endoscopic surgical tumor exeresis (n = 4) or proton bean therapy (n = 1). Another patient presented with stigmata typical of Cushing's syndrome and rapidly worsening pre-eclampsia, that required pregnancy interruption and adenomectomy. Based on personal and literature cases, a practical algorithm was proposed to help clinicians dealing with these patients. CONCLUSIONS: SPTs becoming symptomatic in pregnancy deserve careful monitoring and multidisciplinary management. Overall, wait-and-see approach is suggested, reserving surgery to patients with rapidly progressive/life-threatening situations, significant risk of permanent neurological impairment or malignant lesions.

Longstanding overt ventriculomegaly in adults (LOVA) with patent aqueduct: surgical outcome and etiopathogenesis of a possibly distinct form of chronic hydrocephalus.

PURPOSE: Longstanding overt ventriculomegaly in adults (LOVA) represents a form of chronic adulthood hydrocephalus with symptomatic manifestation in late adulthood. Based on the patency of the aqueduct, two different subcohorts of LOVA can be distinguished. Surgical treatments of this condition are also debated. Therefore, we analyzed preoperative characteristics and clinical outcome after different surgical treatments in a subgroup of LOVA patients with a patent aqueduct. METHODS: Eighteen LOVA patients with a patent aqueduct consecutively treated at our institution between July 2013 and December 2019 were analyzed for this study. Median age was 70 years. Preoperative radiological and clinical features, surgical procedures (ventriculo-peritoneal shunt or endoscopic third ventriculostomy), and outcomes were collected. Successful outcome was qualitatively defined as an improvement or a halt of progression of the presenting symptoms at follow-up, and quantitatively by changes in mRS and iNPHGS scales. RESULTS: Twelve patients underwent an ETV as a primary treatment, while 6 underwent VPS. A total of 22.2% of them were lost to follow-up. Median follow-up time was 38 months. Six patients (66.7%) in the ETV cohort achieved a successful outcome after treatment, with a complication rate of 11.1%. Two patients underwent rescue VPS after ETV failure with a good outcome. Four patients (100%) underwent primary VPS and achieved a satisfactory outcome after treatment, with a reported complications rate of 25%. CONCLUSION: LOVA with patent aqueduct represents, in our opinion, a distinct clinical form of chronic hydrocephalus. For this subgroup, as well as for other forms of LOVA, ETV remains an acceptable first-line treatment option considering the good results, and the low complication rate, obtained in those patients and the hypothesis that hydrocephalus is due to an "intracisternal" obstruction.

Peri-operative prognostic factors for primary skull base chordomas: results from a single-center cohort.

BACKGROUND: Skull base chordomas (SBC) are rare malignant tumors and few factors have been found to be reliable markers for clinical decision making and survival prognostication. The aim of the present work was to identify specific prognostic factors potentially useful for the management of SBC patients. METHODS: A retrospective review of all the patients diagnosed and treated for SBC at the Fondazione IRCCS Istituto Neurologico "Carlo Besta" between January 1992 and December 2017 has been performed. Survival analysis was performed and a logistic regression model was used. Statistically significant predictors were rated based on their log odds in order to preliminarily build a personalized grading scale-the Peri-Operative Chordoma Scale (POCS). RESULTS: Fifty-nine primary chordoma patients were included. The average follow-up from the first treatment was 82.6 months (95% CI, 65.5-99.7). POCS was built over PFS and MR contrast enhancement (intense vs mild/no, value 4), preoperative motor deficit (yes vs no, value 3), and the development of any postoperative complications (yes vs no, value 2). POCS ranges between 0 and 9, with higher scores being associated with reduced likelihood of survival and progression-free state. CONCLUSIONS: Our results show that preoperative clinical symptoms (motor deficits), surgical features (extent of tumor resection and surgeon's experience), development of postoperative complications, and KPS decline represent significant prognostic factors. The degree of MR contrast enhancement significantly correlated to both OS and PFS. We also preliminarily developed the POCS as a prognostic grading scale which may help neurosurgeons in the personalized management of patients undergoing potential adjuvant therapies.

Atlanto-axial rotatory fixation complicating ventriculo-peritoneal shunt surgery: a case report and literature review.

INTRODUCTION: Atlanto-axial rotatory fixation (AARF) is a rare complication of ventriculo-peritoneal shunt (VPS) surgery. CASE PRESENTATION: The authors present a unique case of AARF developing early after VP shunting, with persistent torticollis, a "cock-robin" head position, and a thick fibrous band along the catheter path. Due to refractoriness to conservative treatments, AARF, which can be an early-onset complication of VPS surgery, was resolved by removing the distal catheter along with the fibrous band encasing it. CONCLUSION: Surgical removal of the fibrous band might be enough to solve such complication with no need of further surgical fusion procedures.

Anterior communicating artery division in the endoscopic endonasal translamina terminalis approach to the third ventricle: an anatomical feasibility study.

BACKGROUND: Endonasal endoscopic approaches (EEA) to the third ventricle are well described but generally use an infrachiasmatic route since the suprachiasmatic translamina terminalis corridor is blocked by the anterior communicating artery (AComA). The bifrontal basal interhemispheric translamina terminalis approach has been facilitated with transection of the AComA. The aim of the study is to describe the anatomical feasibility and limitations of the EEA translamina terminalis approach to the third ventricle augmented with AComA surgical ligation. METHODS: Endoscopic dissections were performed on five cadaveric heads injected with colored latex using rod lens endoscopes attached to a high-definition camera and a digital video recorder system. A stepwise anatomical dissection of the endoscopic endonasal transtuberculum, transplanum, translamina terminalis approach to the third ventricle was performed. Measurements were performed before and after AComA elevation and transection using a millimeter flexible caliper. RESULTS: Multiple comparison statistical analysis revealed a statistically significant difference in vertical exposure between the control condition and after AComA elevation, between the control condition and after AComA division and between the AComA elevation and division (p < 0.05). The mean difference in exposed surgical area was statistically significant between the control and after AComA division and between elevation and AComA division (p < 0.01), whereas it was not statistically significant between the control condition and AComA elevation (NS). CONCLUSION: The anatomical feasibility of clipping and dividing the AComA through an EEA has been demonstrated in all the cadaveric specimens. The approach facilitates exposure of the suprachiasmatic optic recess within the third ventricle that may be a blind spot during an infrachiasmatic approach.

Long and Very-Long-Chain Ceramides Correlate with A More Aggressive Behavior in Skull Base Chordoma Patients.

BACKGROUND: Skull base chordomas are rare tumors arising from notochord. Sphingolipids analysis is a promising approach in molecular oncology, and it has never been applied in chordomas. Our aim is to investigate chordoma behavior and the role of ceramides. METHODS: Ceramides were extracted and evaluated by liquid chromatography and mass spectrometry in a cohort of patients with a skull base chordoma. Clinical data were also collected and correlated with ceramide levels. Linear regression and correlation analyses were conducted. RESULTS: Analyzing the association between ceramides level and MIB-1, total ceramides and dihydroceramides showed a strong association (r = 0.7257 and r = 0.6733, respectively) with MIB-1 staining (p = 0.0033 and p = 0.0083, respectively). Among the single ceramide species, Cer C24:1 (r = 0.8814, p ≤ 0.0001), DHCer C24:1 (r = 0.8429, p = 0.0002) and DHCer C18:0 (r = 0.9426, p ≤ 0.0001) showed a significant correlation with MIB-1. CONCLUSION: Our lipid analysis showed ceramides to be promising tumoral biomarkers in skull base chordomas. Long- and very-long-chain ceramides, such as Cer C24:1 and DHCer C24:1, may be related to a prolonged tumor survival and aggressiveness, and the understanding of their effective biological role will hopefully shed light on the mechanisms of chordoma radio-resistance, tendency to recur, and use of agents targeting ceramide metabolism.

BRAF V600E mutant papillary craniopharyngiomas: a single-institutional case series.

PURPOSE: To describe the clinical, radiographic and surgical outcomes in a cohort of patients with BRAF V600E mutant papillary craniopharyngiomas. METHODS: A retrospective review was performed to identify all patients with a histological diagnosis of CP operated upon at a single institution between 2005 and 2017. All cases with adequate material were sequenced to confirm the presence of BRAF V600E mutation. RESULTS: Sixteen patients were included in the present study. Approach was endoscopic endonasal (EEA) in 14 and transcranial (TCA) in 2. All patients were adult with an average age of 50 years (24-88). Radiographic review demonstrated that the majority (93.7%) were suprasellar and twelve (75%) had third ventricular involvement. No tumor showed evidence of calcifications and 68.7% were mixed solid-cystic. All patients had some evidence of hypopituitarism and 62.5% had hypothalamic disturbances. GTR was achieved in 11/14 (78.6%) EEA and 0/2 (0%) TCA (p < 0.05). The mean length of stay was 17.5 days in the TCA group and 7.6 days in the EEA group (p < 0.05). There were no CSF leaks. Post-operatively, eleven (68.7%) developed new DI or new hypopituitarism. Nine increased their BMI with a mean increase of 12.3%, whereas six patients lost weight with a mean decrease of 5.3%. CONCLUSIONS: BRAF V600E mutant papillary tumors represent a clearly distinct clinical-pathological entity of craniopharyngiomas. These are generally non-calcified suprasellar tumors that occur in adults. These distinct characteristics may someday lead to upfront chemotherapy. When surgery is necessary, EEA may be preferred over TCA.

Decision-making algorithm for minimally invasive approaches to anterior skull base meningiomas.

OBJECTIVE Anterior skull base meningiomas are benign lesions that cause neurological symptoms through mass effect on adjacent neurovascular structures. While traditional transcranial approaches have proven to be effective at removing these tumors, minimally invasive approaches that involve using an endoscope offer the possibility of reducing brain and nerve retraction, minimizing incision size, and speeding patient recovery; however, appropriate case selection and results in large series are lacking. METHODS The authors developed an algorithm for selecting a supraorbital keyhole minicraniotomy (SKM) for olfactory groove meningiomas or an expanded endoscopic endonasal approach (EEA) for tuberculum sella (TS) or planum sphenoidale (PS) meningiomas based on the presence or absence of olfaction and the anatomical extent of the tumor. Where neither approach is appropriate, a standard transcranial approach is utilized. The authors describe rates of gross-total resection (GTR), olfactory outcomes, and visual outcomes, as well as complications, for 7 subgroups of patients. Exceptions to the algorithm are also discussed. RESULTS The series of 57 patients harbored 57 anterior skull base meningiomas; the mean tumor volume was 14.7 ± 15.4 cm3 (range 2.2-66.1 cm3), and the mean follow-up duration was 42.2 ± 37.1 months (range 2-144 months). Of 19 patients with olfactory groove meningiomas, 10 had preserved olfaction and underwent SKM, and preservation of olfaction in was seen in 60%. Of 9 patients who presented without olfaction, 8 had cribriform plate invasion and underwent combined SKM and EEA (n = 3), bifrontal craniotomy (n = 3), or EEA (n = 2), and one patient without both olfaction and cribriform plate invasion underwent SKM. GTR was achieved in 94.7%. Of 38 TS/PS meningiomas, 36 of the lesions were treated according to the algorithm. Of these 36 meningiomas, 30 were treated by EEA and 6 by craniotomy. GTR was achieved in 97.2%, with no visual deterioration and one CSF leak that resolved by placement of a lumbar drain. Two patients with tumors that, based on the algorithm, were not amenable to an EEA underwent EEA nonetheless: one had GTR and the other had a residual tumor that was followed and removed via craniotomy 9 years later. CONCLUSIONS Utilizing a simple algorithm aimed at preserving olfaction and vision and based on maximizing use of minimally invasive approaches and selective use of transcranial approaches, the authors found that excellent outcomes can be achieved for anterior skull base meningiomas.

Radiation therapy rather than prior surgery reduces extent of resection during endonasal endoscopic reoperation for craniopharyngioma.

OBJECTIVE: Radiation therapy is often advocated for residual or recurrent craniopharyngioma following surgical resection to prevent local recurrence. However, radiation therapy is not always effective and may render tumors more difficult to remove. If this is the case, patients may benefit more from reoperation if gross total resection can be achieved. Nevertheless, there is little data on the impact of radiation on reoperations for craniopharyngioma. In this study, we sought to analyze whether a history of previous radiation therapy (RT) affected extent of resection in patients with recurrent craniopharyngiomas subsequently treated with reoperation via endoscopic endonasal approach (EEA). METHODS: The authors reviewed a prospectively acquired database of EEA reoperations of craniopharyngiomas over 13 years at Weill Cornell, NewYork-Presbyterian Hospital. All procedures were performed by the senior author. The operations were separated into two groups based on whether the patient had surgery alone (group A) or surgery and RT (group B) prior to recurrence. RESULTS: A total of 24 patients (16 male, 8 female) who underwent surgery for recurrent craniopharyngioma were identified. The average time to recurrence was 7.64 ± 4.34 months (range 3-16 months) for group A and 16.62 ± 12.1 months (range 6-45 months) for group B (p < 0.05). The average tumor size at recurrence was smaller in group A (1.85 ± 0.72 cm; range 0.5-3.2) than group B (2.59 ± 0.91 cm; range 1.5-4.6; p = 0.00017). Gross total resection (GTR) was achieved in 91% (10/11) of patients in group A and 54% (7/13) of patients in group B (p = 0.047). There was a near significant trend for higher average Karnofsky performance status (KPS) score at last follow-up for group A (83 ± 10.6) compared with group B (70 ± 16.3, p = 0.056). CONCLUSIONS: While RT for residual or recurrent craniopharyngioma may delay time to recurrence, ability to achieve GTR with additional surgery is reduced. In the case of recurrent craniopharyngioma, if GTR can be achieved, consideration should be given to endonasal reoperation prior to the decision to irradiate residual or recurrent tumor.

Endoscopic approach to the upper cervical spine and clivus: an anatomical study of the upper limits of the transoral corridor.

BACKGROUND: Recent advances in endoscopic techniques have allowed minimally invasive approaches to the cranio-vertebral junction (CVJ) through the oropharynx (ETA) in addition to the transnasal approach (EEA). These minimally invasive endoscopic techniques allow for increased surgical exposure using no visible incisions, with a potential less morbidity. The ability to know preoperatively the limit of the ETA is vital for the surgical planning in order to better address CVJ pathology. The aim of the present study is to determine the anatomical limits of endoscopic dissection of the skull base and upper cervical spine through the transoral corridor and the superior limit reached by adopting this approach. METHODS: Six fresh-frozen adult cadaver heads were dissected adopting ETA preserving the hard and soft palate. The most superior extent of the exposure was dissected. Post-operative CT scans were performed to confirm the superior extent. RESULTS: The superior most limit of dissection corresponded to the sphenoid-occipital junction, where the basilar portion of the occipital bone joins with the sphenoid bone's body. This ranged from 12.7 to 18.9 mm above the line of the hard palate. This was achieved without having to transgress any of the palatine structures. CONCLUSIONS: The sphenoid-occipital junction represents the rostral limit of endoscopic transoral approach to the lower skull base and CVJ area. This approach is limited superiorly by the orientation of the hard palate and mouth aperture and lower dentition due to the linear nature of the endoscope. Using the endoscope for this approach can allow for a more superior exposure than the traditional open transoral approach.

Primary central nervous system angiosarcoma: a case report and literature review.

Angiosarcoma is a rare vascular malignant neoplasm that mainly occurs in skin and soft tissues. Intracranial localization is very rare and only a few cases have been reported. This report intends to present the clinical, radiological and pathological pictures of a primary central nervous system angiosarcoma along with a review of the literature. A 35-year-old woman presented at our institution with weakness and sensory disturbances of her right hand. Neuroimaging revealed a roughly round, hemorrhagic and moderately enhancing lesion in the left frontal posterior region. The tumor was totally removed under awake anesthesia and continuous monitoring of motor and language functions. Histopathology revealed an epithelioid angiosarcoma. Radical removal, followed by adjuvant radiotherapy and chemotherapy, is able to completely control the disease for a relatively long period.

The rhinopalatine line as a reliable predictor of the inferior extent of endonasal odontoidectomies.

OBJECT: The endoscopic endonasal approach (EEA) provides a minimally invasive corridor through which the cervicomedullary junction can be decompressed with reduced morbidity rates compared to those with the classic transoral approaches. The limit of the EEA is its inferior extent, and preoperative estimation of its reach is vital for determining its suitability. The aim of this study was to evaluate the actual inferior limit of the EEA in a surgical series of patients and develop an accurate and reliable predictor that can be used in planning endonasal odontoidectomies. METHODS: The actual inferior extent of surgery was determined in a series of 6 patients with adequate preoperative and postoperative imaging who underwent endoscopie endonasal odontoidectomy. The medians of the differences between several previously described predictive lines, namely the nasopalatine line (NPL) and nasoaxial line (NAxL), were compared with the actual surgical limit and the hard-palate line by using nonparametric statistics. A novel line, called the rhinopalatine line (RPL), was established and corresponded best with the actual limit of the surgery. RESULTS: There were 4 adult and 2 pediatric patients included in this study. The NPL overestimated the inferior extent of the surgery by an average (± SD) of 21.9 ± 8.1 mm (range 14.7-32.5 mm). The NAxL and RPL overestimated the inferior limit of surgery by averages of 6.9 ± 3.8 mm (range 3.7-13.3 mm) and 1.7 ± 3.7 mm (range -2.8 to 8.3 mm), respectively. The medians of the differences between the NPL and NAxL and the actual surgery were statistically different (both p = 0.0313). In contrast, there was no statistically significant difference between the RPL and the inferior limit of surgery (p = 0.4375). CONCLUSIONS: The RPL predicted the inferior limit of the EEA to the craniovertebral junction more accurately than previously described lines. The use of the RPL may help surgeons in choosing suitable candidates for the EEA and in selecting those for whom surgery through the oropharynx or the facial bones is the better approach.

Predicting functional impairment in brain tumor surgery: the Big Five and the Milan Complexity Scale.

OBJECT The Milan Complexity Scale-a new practical grading scale designed to estimate the risk of neurological clinical worsening after performing surgery for tumor removal-is presented. METHODS A retrospective study was conducted on all elective consecutive surgical procedures for tumor resection between January 2012 and December 2014 at the Second Division of Neurosurgery at Fondazione IRCCS Istituto Neurologico Carlo Besta of Milan. A prospective database dedicated to reporting complications and all clinical and radiological data was retrospectively reviewed. The Karnofsky Performance Scale (KPS) was used to classify each patient's health status. Complications were divided into major and minor and recorded based on etiology and required treatment. A logistic regression model was used to identify possible predictors of clinical worsening after surgery in terms of changes between the preoperative and discharge KPS scores. Statistically significant predictors were rated based on their odds ratios in order to build an ad hoc complexity scale. For each patient, a corresponding total score was calculated, and ANOVA was performed to compare the mean total scores between the improved/unchanged and worsened patients. Relative risk (RR) and chi-square statistics were employed to provide the risk of worsening after surgery for each total score. RESULTS The case series was composed of 746 patients (53.2% female; mean age 51.3 ± 17.1). The most common tumors were meningiomas (28.6%) and glioblastomas (24.1%). The mortality rate was 0.94%, the major complication rate was 9.1%, and the minor complication rate was 32.6%. Of 746 patients, 523 (70.1%) patients improved or remained unchanged, and 223 (29.9%) patients worsened. The following factors were found to be statistically significant predictors of the change in KPS scores: tumor size larger than 4 cm, cranial nerve manipulation, major brain vessel manipulation, posterior fossa location, and eloquent area involvement (Nagelkerke R(2) = 0.286). A grading scale was obtained with scores ranging between 0 and 8. Worsened patients showed mean total scores that were significantly higher than the improved/unchanged scores (3.24 ± 1.55 vs 1.47 ± 1.58; p < 0.001). Finally, a grid was developed to show the risk of worsening after surgery for each total score: scores higher than 3 are suggestive of worse clinical outcome. CONCLUSIONS Through the evaluation of the 5 aforementioned parameters-the Big Five-the Milan Complexity Scale enables neurosurgeons to estimate the risk of a negative clinical course after brain tumor surgery and share these data with the patient. Furthermore, the Milan Complexity Scale could be used for research and educational purposes and better health system management.

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

OBJECT: Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. METHODS: The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. RESULTS: The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. CONCLUSIONS: Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

The Application of Sodium Fluorescein in Resection of Medulloblastoma Under YELLOW 560 Filter: Feasibility and Preliminary Results of a Monocentric Cohort and Systematic Review.

BACKGROUND: Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this tumor. Several dyes have been tested for improving tumor visualization; however, few reports with different protocols of fluorophores use are available and the results are inconsistent. Hence, we report our experience with sodium fluorescein in MB surgery, aiming to assess the role of this technique on the extent of resection. Furthermore, we performed a literature review of this topic. METHODS: Fluorescence characteristics, extent of resection, and clinical outcome were analyzed in 9 consecutively operated patients with MB. A comprehensive literature search and review for English-language articles concerning fluorescein application in MB was conducted. RESULTS: In our cohort, no side effect related to fluorescein occurred; all tumors presented with an intense or moderate yellow-green enhancement, and fluorescein was judged fundamental in distinguishing tumors from viable tissue in 7 of 9 cases. Gross total resection or near-total resection (i.e., a residual tumor volume <1.5 cm3) was achieved in 8 patients. The review explored the different techniques and surgical interpretations as well as surgical radicality; we did not find a homogenous protocol for fluorescein injection in the published articles. Fluorescence appeared moderate or intense in almost all cases, with a high percentage of usefulness and consensual achievement of a high rate of gross total resection. CONCLUSIONS: Based on these results, we can infer that fluorescein-guided surgical resection is a safe and valuable method for patients with MB.

Giuseppe Dagnini (1866-1928): Discoverer of the Trigemino-Cardiac Reflex and Practical Implications in Neurosurgery and Other Medical Specialties.

The authors present the life and art of Giuseppe Dagnini, a renowned Italian physician who was born in Bologna in 1866. He was the chief of the Maggiore Hospital in Bologna and authored valuable scientific works on the trigemino-cardiac reflex which is still applied in modern clinical practice. Dr. Dagnini firstly described the reflex in 1908 postulating that stimulation of one of the 3 branches of the trigeminal nerve triggers the afferent pathway in lowering heart rate. The authors also provide a modern outlook on the clinical implications of the TCR in neurosurgery, neuroanesthesia, and other medical specialties.