Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

Aneurismal subarachnoid hemorrhage during the COVID-19 outbreak in a Hub and Spoke system: observational multicenter cohort study in Lombardy, Italy.

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.

Adult brainstem glioma: a multicentre retrospective analysis of 47 Italian patients.

BACKGROUND AND PURPOSE: Adult brainstem gliomas are rare primary brain tumours with heterogeneous clinical course. The low frequency of these tumours makes it difficult to achieve high-quality evidence regarding prognostic factors, adequate therapeutic approach and outcome in such patients. METHODS: In this retrospective study, we analysed clinical, radiological, molecular, prognostic and therapeutic factors in a series of 47 histologically proven adult brainstem gliomas recruited over a 20-year period (1998-2018). RESULTS: Twenty-two patients were male, 25 female with median age of 39 years. The tumour involved one brainstem segment in 20 cases and 2 or more segments in 27. Contrast enhancement was reported in 28 cases. Surgical procedures included biopsy in 26 cases and partial/total resection in the remaining 21. Histological diagnosis was of low-grade glioma in 23 patients, high-grade glioma in 22 and non-diagnostic in 2 cases. Data regarding molecular biology were available for 22 patients. Median overall survival was 35 months, in particular 16 months in high-grade glioma and 84 months in low-grade glioma. At univariate analysis, tumour grade was the only factor with a statistically significant impact on survival time (p = 0,003), whereas younger age, better performance status and total/subtotal resection showed a trend to more prolonged survival. This study also confirms safety of biopsy/surgery in adult brainstem glioma patients and shows a clear trend to a more frequent assessment of molecular biology data. CONCLUSIONS: Further prospective multicentre efforts, and hopefully clinical trials, are necessary to improve outcome in this neglected glioma patient population.

Concomitant cerebral aspergillosis and mucormycosis in an immunocompetent woman treated with corticosteroids.

We present the case of an immunocompetent 55-year-old woman, treated with corticosteroids, developing a cerebral fungal infection with autoptic ascertainment of aspergillosis and mucormycosis. This is the first report of cerebral co-infection by mucorales and aspergillus in an immunocompetent host. A possible explanation is that corticosteroids, even if taken for a short time, led to a transient lowering of immune function and contributed to negative outcome.

Stimulation-related intraoperative seizures during awake surgery: a review of available evidences.

Awake surgery is a well-defined procedure with a very low morbidity. In particular, stimulation-related intraoperative seizure (IOS) is a commonly discussed and serious complication associated with awake surgery. Here, we reviewed the literature on awake surgery and IOS and sought to obtain evidences on the predictive factors of IOS and on the effect of IOS on postoperative outcomes. We conducted a comprehensive search of the Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases to identify potentially relevant articles from 2000 to 2019. We used combinations of the following search terms: "intraoperative seizure awake craniotomy," "awake surgery seizures," and pertinent associations; the search was restricted to publications in English and only to papers published in the last 20 years. The search returned 141 articles, including 39 papers that reported the IOS rate during awake craniotomy. The reported IOS rates ranged between 0 and 24% (mean, 7.7%). Only few studies have assessed the relationships between awake surgery and IOS, and hence, drawing clear conclusions is difficult. Nevertheless, IOS does not cause permanent and severe postoperative deficits, but can affect the patient's status perioperatively and the hospitalization duration. Anterior tumor location is an important perioperative factor associated with high IOS risk, whereas having seizures at tumor diagnosis does not seem to influence. However, the role of antiepileptic drug administration and prophylaxis remains unclear. In conclusion, given the difficulty in identifying predictors of IOS, we believe that prompt action at onset and awareness of appropriate management methods are vital.

Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

OBJECTIVE: Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. METHODS: Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. RESULTS: Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76-0.81). CONCLUSIONS: The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Risk factors for intraoperative stimulation-related seizures during awake surgery: an analysis of 109 consecutive patients.

INTRODUCTION: During surgery for lesions in eloquent areas the goal is to achieve the widest resection possible, without loss of neurological function. Intraoperative seizures may lead to abandonment of the procedure or damages to the patient. Awareness regarding the predictors of IOS would help the surgeon. The aim of this retrospective study was to identify the factors associated with the occurrence of IOS in patients who underwent awake surgery for removal of gliomas in eloquent areas. METHODS: This was a retrospective analysis of prospectively collected data of 109 patients who underwent awake craniotomy between January 2010 and December 2017 for removal of gliomas. IOS were defined as tonic-clonic seizures or loss of consciousness resulting in communication difficulties with the patient occurring during cortical and subcortical mapping. RESULTS: A total of 109 patients were included in this study and IOS occurred in 9 (8.2%) patients. Demographic and clinical factors were comparable between patients with and without IOS. In the IOS group, 7 (77.8%) patients had seizures preoperatively and 4 (57.1%) were on more than one perioperative antiepileptic drugs (AED). CONCLUSIONS: The current series add some hints to the poorly studied IOS risk during awake surgery. The risk of IOS appears to be relatively higher in patients with anteriorly located tumors and in patients operated without intraoperative brain activity monitoring and different patterns of stimulation for language and sensory-motor mapping. Further studies are needed to clarify the role of intraoperative techniques.

A modified park bench position: the "Dormeuse" position.

BACKGROUND: Because of the restricted volume of the cisternal space, proper patient positioning on the operating table is of utmost importance during surgery by retrosigmoid approaches. Three positions are commonly used: supine, with the head rotated to the side contralateral to the lesion; the semi-sitting position; and the park bench position. Each position has advantages and disadvantages, and the surgeon should choose the one best suited to the individual patient and the pathology to be treated. METHODS: We describe a modified park bench position that we call the Dormeuse position. CONCLUSION: The Dormeuse position guarantees decrease in the posterior fossa pressure and allows optimal neural and vascular manipulation and control of any aspect of the cerebellopontine angle.

Mapping nouns and finite verbs in left hemisphere tumors: a direct electrical stimulation study.

Neurosurgical mapping studies with nouns and finite verbs are scarce and subcortical data are nonexistent. We used a new task that uses finite verbs in six Italian-speaking patients with gliomas in the left language-dominant hemisphere. Language-relevant positive areas were detected only with nouns in four patients, with both tasks yet in distinct cortical areas in one patient, and only with finite verbs in another patient. Positive areas and types of errors varied across participants. Finite verbs provide complementary information to nouns, and permit more accurate mapping of language production when nouns are unaffected by electrical stimulation.

Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis.

Intraoperative mapping and monitoring techniques for eloquent area tumors are routinely used world wide. Very few data are available regarding mapping and monitoring methods and preferences, intraoperative seizures occurrence and perioperative antiepileptic drug management. A questionnaire was sent to 20 European centers with experience in intraoperative mapping or neurophysiological monitoring for the treatment of eloquent area tumors. Fifteen centers returned the completed questionnaires. Data was available on 2098 patients. 863 patients (41.1%) were operated on through awake surgery and intraoperative mapping, while 1235 patients (58.8%) received asleep surgery and intraoperative electrophysiological monitoring or mapping. There was great heterogeneity between centers with some totally AW oriented (up to 100%) and other almost totally ASL oriented (up to 92%) (31% SD). For awake surgery, 79.9% centers preferred an asleep-awake-asleep anesthesia protocol. Only 53.3% of the centers used ECoG or transcutaneous EEG. The incidence of intraoperative seizures varied significantly between centers, ranging from 2.5% to 54% (p < 0.001). It there appears to be a statistically significant link between the mastery of mapping technique and the risk of intraoperative seizures. Moreover, history of preoperative seizures can significantly increase the risk of intraoperative seizures (p < 0.001). Intraoperative seizures occurrence was similar in patients with or without perioperative drugs (12% vs. 12%, p = 0.2). This is the first European survey to assess intraoperative functional mapping and monitoring protocols and the management of peri- and intraoperative seizures. This data can help identify specific aspects that need to be investigated in prospective and controlled studies.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

BACKGROUND: The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years. METHOD: A general survey on the managing of diffuse low-grade gliomas was answered by 21 centres in 11 European countries. Here we focused on specific questions regarding perioperative and intraoperative cognitive assessments. RESULTS: More centres referred to the same speech and language therapist and/or neuropsychologist across all assessments; a core of assessment tools was routinely used across centres; fluency tasks were commonly used in the perioperative stages, and object naming during surgery; tasks that tapped on attention, executive functions, visuospatial awareness, calculation and emotions were sparsely administered; preoperative assessments were performed 1 month or 1 week before surgery; timing for postoperative assessments varied; finally, more centres recommended early rehabilitation, whenever needed. CONCLUSIONS: There is an emerging trend towards following similar practices for the management of low-grade gliomas in Europe. Our results are descriptive and formalise current discussions in our group. Also, they contribute towards the development of a European assessment protocol.

Pattern of relapse of glioblastoma multiforme treated with radical radio-chemotherapy: Could a margin reduction be proposed?

To analyse the pattern of recurrence of patients treated with Stupp protocol in relation to technique, to compare in silico plans with reduced margin (1 cm) with the original ones and to analyse toxicity. 105 patients were treated: 85 had local recurrence and 68 of them were analysed. Recurrence was considered in field, marginal and distant if >80 %, 20-80 % or <20 % of the relapse volume was included in the 95 %-isodose. In silico plans were retrospectively recalculated using the same technique, fields angles and treatment planning system of the original ones. The pattern of recurrence was in field, marginal and distant in 88, 10 and 2 % respectively and was similar in in silico plans. The margin reduction appears to spare 100 cc of healthy brain by 57 Gy-volume (p = 0.02). The target coverage was worse in standard plans (pt student < 0.001), especially if the tumour was near to organs at risk (pχ2 < 0.001). PTV coverage was better with IMRT and helical-IMRT, than conformal-3D (pAnova test = 0.038). This difference was no more significant with in silico planning. A higher incidence of asthenia and leuko-encephalopathy was observed in patients with greater percentage of healthy brain included in 57 Gy-volume. No differences in the pattern of recurrence according to margins were found. The margin reduction determines sparing of healthy brain and could possibly reduce the incidence of late toxicity. Margin reduction could allow to use less sophisticated techniques, ensuring appropriate target coverage, and the choice of more costly techniques could be reserved to selected cases.

Intracranial and Spinal Dural Arterio-Venous Fistula (DAVF): A Surgical Series of 107 Patients.

INTRODUCTION: Dural arteriovenous fistulas (DAVFs) is a challenging condition in vascular neurosurgery. Development of new endovascular techniques has progressively modified treatment strategies; however, surgery is still considered a valid option of treatment of this pathology. MATERIALS AND METHODS: From a retrospective analysis of our database, we selected 107 patients who underwent surgical treatment for DAVFs. Patients were grouped into five categories according to the Borden and Cognard classifications. Patients and treatment characteristics/outcome is reported. RESULTS: At admission, 30 (28 %) patients presented with intracranial hemorrhage. Fifteen (14 %) had seizure, whereas nearly half of the patients presented with non-aggressive symptoms, including headache (10, 9.3 %), cognitive impairment (8, 7.5 %), gait disturbance, and imbalance (8, 7.5 %). The majority of patients underwent surgical treatment of fistulas; in some cases, we elected combined surgical-endovascular (obliteration) treatment. CONCLUSIONS: Management of DAVF requires a multidisciplinary assessment and treatment strategies including surgical, endovascular, and radiosurgical treatment. The data reported confirmed that surgical treatment of DAVFs is associated with a good clinical and radiological (complete occlusion of the fistula) outcome in all cases, with a low rate of complications.

Acute functional reactivation of the language network during awake intraoperative brain mapping.

Acute brain plasticity during resection of central lesions has been recently described. In the cases reported, perilesional latent networks, useful to preserve the neurological functions, were detected in asymptomatic patients. In this paper, we presented a case of acute functional reactivation (AFR) of the language network in a symptomatic patient. Tumor resection allowed to acutely restore the neurological deficit. Intraoperative direct cortical stimulation (DCS) and functional neuroimaging showed new epicentres of activation of the language network after tumor excision. DCS in awake surgery is mandatory to reveal AFR needful to improve the extent of resection preserving the quality of life.

Resection of supratentorial gliomas: the need to merge microsurgical technical cornerstones with modern functional mapping concepts. An overview.

Although surgery is not curative for the majority of intracranial gliomas, radical resection has been demonstrated to influence survival and delay tumor progression. Because gliomas are very frequently located in eloquent or more generally critical areas, surgeons must always balance the maximizing resection with the need to preserve neurological function. In this overview, we tried to summarize the recent literature and our personal experience about (1) the benefits and limits of using preoperative anatomical and functional neuroimaging (anatomical MRI, DTI fiber tracking, and functional MRI), (2) the issues to consider in planning the surgical strategy, (3) the need to thoroughly understand microsurgical techniques that enable a maximal resection (subpial dissection, vascular manipulation, etc.), (4) the importance of individualizing surgical strategy especially in patients with gliomas in eloquent areas (the role of neuropsychological evaluation in redefining eloquent and non-eloquent areas), and (5) how to use intraoperative mapping techniques and understand why and when to use them. Through this paper, the reader should become more familiar with a comprehensive panel of techniques and methodologies but more importantly become aware that these recent technical advances facilitate a conceptual change from classical surgical paradigms toward a more patient-specific approach.

Minimally invasive subfrontal route for the resection of medial temporal region intrinsic tumors.

BACKGROUND: The mesial temporal region (MTR) comprises important components of the limbic system, as well as vital neurovascular structures. Because of its important functional role, as much healthy brain tissue as possible must be preserved while targeting resection of MTR lesions. METHODS: A frontal minicraniotomy is used to access the MTR through a subfrontal approach. By opening the most medial part of the Sylvian fissure, the uncus-amygdala complex is exposed, and through this, the head of the hippocampus can be reached and removed as well. CONCLUSIONS: This approach is extremely suitable for MTR lesions, as it provides the advantage of sparing the most important functional structures of the temporal lobe, the temporal stem, and the limen insulae, as well as the optic radiations and the fronto-occipital connections.

Say "no" to spinal cord injury: is nitric oxide an option for therapeutic strategies?

PURPOSE: a literature review was made to investigate the role of nitric oxide (NO) in spinal cord injury, a pathological condition that leads to motor, sensory, and autonomic deficit. Besides, we were interested in potential therapeutic strategies interfering with NO mechanism of secondary damage. MATERIALS: A literature search using PubMed Medline database has been performed. RESULTS: excessive NO production after spinal cord injury promotes oxidative damage perpetuating the injury causing neuronal loss at the injured site and in the surrounding area. CONCLUSION: different therapeutic approaches for contrasting or avoiding NO secondary damage have been studied, these include nitric oxide synthase inhibitors, compounds that interfere with inducible NO synthase expression, and molecules working as antioxidant. Further studies are needed to explain the neuroprotective or cytotoxic role of the different isoforms of NO synthase and the other mediators that take part or influence the NO cascade. In this way, it would be possible to find new therapeutic targets and furthermore to extend the experimentation to humans.

Post-surgical therapeutic approaches to glioblastoma patients submitted to biopsy (BA) or "partial" resection (PR): the possibilities to treat also them without renunciations. Study from the Brescia Neuro-Oncology Group.

The extent of surgery predicts overall survival (OS) in patients treated for glioblastoma (GBM). The therapeutic approach after partial resection (PR) or biopsy alone (BA) is not clearly defined. This retrospective analysis was therefore planned to analyse clinical features, treatment and survival of patients undergoing PR or BA. We analysed the clinical/therapeutic features and the outcome of 232 patients submitted to BA/PR and treated with radiotherapy (RT) with/without chemotherapy. Two subgroups (pre- and post-Temozolomide-era) were identified. The BA/PR ratio did not change with the accrual periods. In the TMZ-era, 50 % of the patients had chemotherapy; "small" volume, hypo-fractionated and "low" dose RT (<54 Gy) were delivered to 93, 38 and 44 % of the patients; corresponding values for the previous period were 4, 28, 11 and 2 % (P < 0.001). Better two-year OS was evident in the TMZ-era (18 vs 7 %); PR and chemotherapy affected OS in patients treated with hypo-fractionated, low doses RT (P = 0.02, 0.04). Limited volume, more often MRI-based, and "short" RT treatments were given mostly to unfavourably selected patients, without compromising the results of the whole group. This strategy, combined with an increased use of chemotherapy, resulted in reduced treatment burden, in an improved 2-year OS rate and prospectively in better quality of life, even in this prognostically worse subset of glioma patients.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.