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.

Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification.

Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.

Efficacy of neoadjuvant stereotactic radiotherapy in brain metastases from solid cancer: a systematic review of literature and meta-analysis.

Neoadjuvant stereotactic radiotherapy (NaSRT) is a novel strategy for brain metastasis (BM) treatment, promising to achieve good local control, improved survival, and low toxicity. This is a systematic review of available literature and meta-analysis of 8 articles eligible for inclusion after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases up to March 2023. A total of 484 patients undergoing NaSRT to treat 507 lesions were included. The median age was 60.9 (IQR 57-63) years, with a median tumor volume of 12.1 (IQR 9-14) cm3. The most frequent histology was non-small-cell lung cancer (41.3%), followed by breast (18.8%), and melanoma (14.3%). Lesions had a preferred supratentorial location (77.4%). Most of the studies used a single fraction schedule (91% of patients, n = 440). Treatment parameters were homogeneous and showed a median dose of 18 (IQR 15.5-20.5) Gy at a median of 80% isodose. Surgery was performed after a median of 1.5 (IQR 1-2.4) days and achieved gross-total extent in 94% of cases. Median follow-up was 12.9 (IQR 10-15.7) months. NaSRT showed an overall mortality rate of 58% (95% CI 43-73) at the last follow-up. Actuarial outcomes rates were 60% (95% CI 55-64) for 1-year overall survival (1y-OS), 38% (95% CI 33-43) for 2y-OS, 29% (95% CI 24-34) for 3y-OS; overall 15% (95% CI 11-19) for local failure, 46% (95% CI 37-55) for distant brain failure, 6% (95% CI 3-8) for radionecrosis, and 5% (95% CI 3-8) for leptomeningeal dissemination. The median local progression-free survival time was 10.4 (IQR 9.5-11.4) months, while the median survival without distant failure was 7.4 (IQR 6.9-8) months. The median OS time for the entire cohort was 17 (IQR 14.9-17.9) months. Existing data suggest that NaSRT is effective and safe in the treatment of BMs, achieving good local control on BMs with and low incidence of radionecrosis and leptomeningeal dissemination. Distant control appears limited compared to other radiation regimens.

Efficacy of radiotherapy and stereotactic radiosurgery as adjuvant or salvage treatment in atypical and anaplastic (WHO grade II and III) meningiomas: a systematic review and meta-analysis.

The role of radiotherapy (RT) and stereotactic radiosurgery (SRS) as adjuvant or salvage treatment in high-grade meningiomas (HGM) is still debated. Despite advances in modern neuro-oncology, HGM (WHO grade II and III) remains refractory to multimodal therapies. Published reports present aggregated data and are extremely varied in population size, exclusion criteria, selection bias, and inclusion of mixed histologic grades, making it extremely difficult to draw conclusions when taken individually. This current work aims to gather the existing evidence on RT and SRS as adjuvants following surgery or salvage treatment at recurrence after multimodality therapy failure and to conduct a systematic comparison between these two modalities. An extensive systematic literature review and meta-analysis were performed. A total of 42 papers were eligible for final analysis (RT n = 27; SRS n = 15) after searching MEDLINE via PubMed, Web-of-science, Cochrane Wiley, and Embase databases. Adjuvant regimens were addressed in 37 papers (RT n = 26; SRS n = 11); salvage regimens were described in 5 articles (RT n = 1; SRS n = 4). The primary outcomes of the study were the overall recurrence rate and mortality. Other actuarial rates (local and distant control, OS, PFS, and complications) were retrieved and analyzed as secondary outcomes. A total of 2853 patients harboring 3077 HGM were included. The majority were grade II (87%) with a mean pre-radiation volume of 8.7 cc. Adjuvant regimen: 2742 patients (76.4% RT; 23.6% SRS) with an overall grade II/III rate of 6.6/1. Lesions treated adjSRS were more frequently grade III (17 vs 12%, p < 0.001), and received subtotal resection (57 vs 27%, p = 0.001) compared to the RT cohort. AdjSRS cohort had a significantly shorter mean follow-up than adjRT (36.7 vs 50.3 months, p = 0.01). The overall recurrence rate was 38% in adjRT vs 25% in adjSRS (p = 0.01), while mortality did not differ between the groups (20% vs 23%, respectively; p = 0.80). The median time to recurrence was 1.5 times longer in the RT group (p = 0.30). Five-year local control was 55% in adjRT and 26% in adjSRS (p = 0.01), while 5-year OS was 73% and 78% (p = 0.62), and 5-year PFS was 62% and 40% in adjRT and adjSRS (p = 0.008). No difference in the incidence of complications (24% vs 14%, p = 0.53). Salvage regimen: 110 patients (37.3% RT; 62.7% SRS) with a grade II/III rate of 8.6/1. The recurrence rate was 46% in salRT vs 24% in salSRS (p = 0.39), time to recurrence was 1.8 times longer in the salRT group (35 vs 18.5 months, p = 0.74). Mortality was slightly yet not significantly higher in salRT (34% vs 12%, p = 0.54). Data on local and distant control were only available for salSRS. The 5-year OS was 49% and 83% (p = 0.90), and the 5-year PFS was 39% and 50% in salRT and salSRS (p = 0.66), respectively. High-grade meningiomas (WHO grade II and III) receiving adjuvant RT showed a higher overall recurrence rate than meningiomas receiving adjuvant SRS. The adjRT cohort, however, achieved higher 5-year LC and PFS rates, thus suggesting a potentially longer time to recurrence compared to adjSRS patients, who, meanwhile, experienced a significantly shorter follow-up. This result must also consider the higher number of grade III lesions and the smaller extent of resection achieved in the adjSRS group. Overall mortality did not differ between the two groups. No differences in outcome measures were observed in salvage regimens.

Meningioma and Other Meningeal Tumors.

Meningiomas develop from meningothelial cells and approximately account for more than 30 percent of central nervous system (CNS) tumors. They can occur anywhere in the dura, most often intracranially and at dural reflection sites. Half of the cases are usually at parasagittal/falcine and convexity locations; other common sites are sphenoid ridge, suprasellar, posterior fossa, and olfactory groove. The female-to-male ratio is approximately 2 or 3-1, and the median age at diagnosis is 65 years. Meningiomas are generally extremely slow-growing tumors; many are asymptomatic or paucisymptomatic at diagnosis and are discovered incidentally. Clinical manifestations, when present, are influenced by the tumor site and by the time course over which it develops. Meningiomas are divided into three grades. Grade I represents the vast majority of cases; they are considered typical or benign, although their CNS location can still lead to severe morbidity or mortality, resulting in a reported ten-year net survival of over 80%. Atypical (WHO grade II) meningiomas are considered "intermediate grade" malignancies and represent 5-7% of cases. They show a tendency for recurrence and malignant degeneration with a relevant increase in tumor cell migration and surrounding tissue infiltration; ten-year net survival is reported over 60%. The anaplastic subtype (WHO III) represents only 1-3% of cases, and it is characterized by a poor prognosis (ten-year net survival of 15%). The treatment of choice for these tumors stands on complete microsurgical resection in case the subsequent morbidities are assumed minimal. On the other hand, and in case the tumor is located in critical regions such as the skull base, or the patient may have accompanied comorbidities, or it is aimed to avoid intensive treatment, some other approaches, including stereotactic radiosurgery and radiotherapy, were recommended as safe and effective choices to be considered as a primary treatment option or complementary to surgery. Adjuvant radiosurgery/radiotherapy should be considered in the case of atypical and anaplastic histology, especially when a residual tumor is identifiable in postoperative imaging. A "watchful waiting" strategy appears reasonable for extremely old individuals and those with substantial comorbidities or low-performance status, while there is a reduced threshold for therapeutic intervention for relatively healthy younger individuals due to the expectation that tumor progression will inevitably necessitate proactive treatment. To treat and manage meningioma efficiently, the assessments of both neurosurgeons and radiation oncologists are essential. The possibility of other rarer tumors, including hemangiopericytomas, solitary fibrous tumors, lymphomas, metastases, melanocytic tumors, and fibrous histiocytoma, must be considered when a meningeal lesion is diagnosed, especially because the ideal diagnostic and therapeutic approaches might differ significantly in every tumor type.

Craniopharyngioma in Pediatrics and Adults.

Craniopharyngiomas are rare malignancies of dysembryogenic origin, involving the sellar and parasellar areas. These low-grade, epithelial tumors account for two main histological patterns (adamantinomatous craniopharyngioma and papillary craniopharyngioma), which differ in epidemiology, pathogenesis, and histomorphological appearance. Adamantinomatous craniopharyngiomas typically show a bimodal age distribution (5-15 years and 45-60 years), while papillary craniopharyngiomas are limited to adult patients, especially in the fifth and sixth decades of life. Recently, craniopharyngioma histological subtypes have been demonstrated to harbor distinct biomolecular signatures. Somatic mutations in CTNNB1 gene encoding ß-catenin have been exclusively detected in adamantinomatous craniopharyngiomas, which predominantly manifest as cystic lesions, while papillary craniopharyngiomas are driven by BRAF V600E mutations in up to 95% of cases and are typically solid masses. Despite the benign histological nature (grade I according to the World Health Organization classification), craniopharyngiomas may heavily affect long-term survival and quality of life, due to their growth pattern in a critical region for the presence of eloquent neurovascular structures and possible neurological sequelae following their treatment. Clinical manifestations are mostly related to the involvement of hypothalamic-pituitary axis, optic pathways, ventricular system, and major blood vessels of the circle of Willis. Symptoms and signs referable to intracranial hypertension, visual disturbance, and endocrine deficiencies should promptly raise the clinical suspicion for sellar and suprasellar pathologies, advocating further neuroimaging investigations, especially brain MRI. The optimal therapeutic management of craniopharyngiomas is still a matter of debate. Over the last decades, the surgical strategy for craniopharyngiomas, especially in younger patients, has shifted from the aggressive attempt of radical resection to a more conservative and individualized approach via a planned subtotal resection followed by adjuvant radiotherapy, aimed at preserving functional outcomes and minimizing surgery-related morbidity. Whenever gross total removal is not safely feasible, adjuvant radiotherapy (RT) and stereotactic radiosurgery (SRS) have gained an increasingly important role to manage tumor residual or recurrence. The role of intracavitary therapies, including antineoplastic drugs or sealed radioactive sources, is predominantly limited to monocystic craniopharyngiomas as secondary therapeutic option. Novel findings in genetic profiling of craniopharyngiomas have unfold new scenarios in the development of targeted therapies based on brand-new biomolecular markers, advancing the hypothesis of introducing neoadjuvant chemotherapy regimens in order to reduce tumor burden prior to resection. Indeed, the rarity of these neoplasms requires a multispecialty approach involving an expert team of endocrinologists, neurosurgeons, neuro-ophthalmologists, neuroradiologists, radiotherapists, and neuro-oncologists, in order to pursue a significant impact on postoperative outcomes and long-term prognosis.

Brain Tumors Affecting the Orbit Globe and Orbit Tumors Affecting the Brain.

Brain tumors affecting the orbit and orbital tumors affecting the brain are a heterogeneous group of lesions, with histological features, behaviors, diagnostic criteria, and treatments varying from each other. Dermoid cyst and cavernous hemangiomas are considered the most frequent benign lesions, while non-Hodgkin lymphoma is the most common malignant tumor in this region. Sharing the same anatomical region, clinical manifestations of orbital lesions may be often common to different types of lesions. Imaging studies are useful in the differential diagnosis of orbital lesions and the planning of their management. Lesions can be classified into ocular or extra-ocular ones: the latter can be further differentiated into extraconal or intraconal, based on the relationship with the extraocular muscles. Surgical therapy is the treatment of choice for most orbital lesions; however, based on the degree of removal, their histology and extension, other treatments, such as chemotherapy and radiotherapy, are indicated for the management of orbital lesions. In selected cases, chemotherapy and radiotherapy are the primary treatments. This chapter aimed to discuss the orbital anatomy, the clinical manifestations, the clinical testing and the imaging studies for orbital lesions, and the principal pathological entities affecting the orbit together with the principles of orbital surgery.

MIS removal of extraforaminal lumbar spine schwannoma using MAS-TLIF retractor: technical note.

BACKGROUND: To report the use of Nuvasive MAS-TLIF retractor for the removal of lumbar spine schwannomas. METHODS: A 47-year-old man with 1-year history of back pain with progressive left sciatica underwent surgical resection of a left extraforaminal lumbar schwannoma (type IV according to Eden's classification) using the MAS-TLIF retractor. RESULTS: The patient completely recovered from the preoperative symptoms and was discharged three days after surgery. The MRI acquired 6 months postoperatively showed complete tumour removal, with no signs of instability. The MAS-TLIF retractor allows for an optimal paraspinal tissues retraction, improving the area of exposure and the manoeuverability angle. Moreover, the stability of the retraction is guaranteed by the positioning of the two transpedicular screws. Spinal fusion is not necessary because the posterior tension band is not jeopardised. CONCLUSIONS: MAS-TLIF retractor allows for a minimally invasive and safe surgical removal of LSS maximising surgical exposure and avoiding spinal fusion.

Comparison between extended transsphenoidal and transcranial surgery for craniopharyngioma: focus on hypothalamic function and obesity.

PURPOSE: Patients suffering from craniopharyngiomas currently have good survival rates, but long-term sequelae, such as development of obesity, worsen their quality of life. Optimal treatment is still controversial and changed during the decades, becoming less aggressive. Transcranial (TC) surgery was the first approach to be used, followed by extended transsphenoidal (eTNS) access. This study aims to compare the two approaches in terms of risk of hypothalamic damage leading to obesity. METHODS: This is a monocentric retrospective analysis of post-puberal patients treated for primary craniopharyngioma. Postoperative obesity and percentual postsurgical BMI variation were considered proxy for hypothalamic function and used to fit regression models with basal BMI, type of surgery, tumor volume and hypothalamic involvement (anterior vs. anteroposterior). RESULTS: No difference in radicality was observed between the two approaches; eTNS was more effective in ameliorating visual function but was significantly associated with CSF leaks. The TC approach was associated with a higher incidence of diabetes insipidus. Regression analysis showed only tumor volume and basal BMI resulted as independent predictors for both postoperative obesity (respectively, OR 1.15, P = 0.041, and OR 1.57, P < 0.001) and percentual BMI variation (respectively, + 0.92%, P = 0.005, and - 1.49%, P = 0.001). CONCLUSIONS: Larger lesions portend a higher risk to develop postoperative obesity, independently of hypothalamic involvement. Interestingly, basal BMI is independent of lesional volume and is associated with postoperative obesity, but lesser postoperative BMI variation. The surgical approach does not influence the obesity risk. However, eTNS proves valid in managing large tumors with important hypothalamic invasion.

Local Pterional Advancement Flap: A Minimally Invasive Option to Reconstruct Spheno-Temporal Extracranial Soft Tissues Dehiscences in Fragile Patients.

BACKGROUND: Late-onset, extracranial soft tissues dehiscence in the spheno-temporal region after major neurosurgical procedures might represent a potentially life-threatening complication.Due to surgery-related galeal/pericranial and myofascial temporal atrophy, classical regional flaps are often unavailable, enforcing potential indication for free vascularized flaps.Nevertheless, in elderly multioperated patients, who are not eligible for major surgery, it becomes mandatory to consider less invasive options for reconstruction.Authors describe the application of a reconstructive option for late-onset, pterional soft tissues dehiscence in fragile patients, using a local pterional advancement flap. METHODS: Technique is stepwise described and illustrated in its clinical application. RESULTS: Local pterional advancement flap provides an excellent coverage, being extremely pliable, and flexible in contents and design. Vascular pedicle is independent from distal branches of the superficial temporal artery and provides adequate blood flow. Pedicle length enables a good arc of rotation, which facilitates its transposition. Flap preparation is very easy and minimally time consuming, due to its immediate regional availability and the easy harvesting technique. CONCLUSIONS: Local pterional advancement flap represents an effective option as regional flap for the reconstruction of late-onset, pterional soft tissues dehiscence in fragile patients.

MYD88 L265P mutation and interleukin-10 detection in cerebrospinal fluid are highly specific discriminating markers in patients with primary central nervous system lymphoma: results from a prospective study.

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.

Impact of C-shaped skin incision on surgical operability in the retrosigmoid approach: when a good start is half of the job.

BACKGROUND: The retrosigmoid approach (RSA) is one of the routes of choice to approach tumors and vascular lesions of the cerebellopontine angle. Among different types of skin incisions and soft tissue dissection techniques, the most widely used variants comprise the straight/lazy S-shaped and the C-shaped incisions. Several reports discuss advantages in terms of functional and clinical outcomes of the C-shaped incision, but scientific considerations about the critical impact of this kind of incision on surgical operability are still extremely limited. OBJECT: Authors comparatively analyze the advantage provided by C-shaped incision in RSA in terms of anatomic exposure and surgical operability, compared with straight/lazy S-shaped one. METHODS: A comparative microanatomical laboratory investigation was conducted. The operability score (OS) was applied for quantitative analysis of surgical operability. RESULTS: C-shaped incision, providing a significant reduction of the overall working distance (-13%) together with an overall increase of the maneuverability area (+ 204.9%), did improve the conizing effect on the surgical corridor. It optimized overall maneuverability of surgical instruments, in terms of angle of attack (+ 27.7%), as well as maneuverability arc (+ 122%), on the entire surgical field. C-shaped incision ensured good operability on all surgical targets (OS ranging from 2 to 3), most significantly improving surgical maneuverability at the porus trigeminus and internal acoustic meatus. CONCLUSION: C-shaped incision in the RSA significantly improves anatomic exposure and surgical operability as compared with straight/lazy S-shaped incision.

Microsurgical endoportal MRI/US-navigated approach for the resection of large intraventricular tumours: a 20-consecutive patients case series.

OBJECTIVES: Deep lesions located in lateral and third ventricles can be accessed thorough interhemispheric transcallosal or transcortical trans-ventricular approaches. Traditional brain retractors are made by 'non-cerebral engineered' spatulas, which do not equally distribute pressure on surrounding structures damaging brain. In this paper, we present a series of 20 intraventricular tumours resected through a MRI/US-navigated microscopic transcortical endoportal approach. PATIENTS AND METHODS: Between January 2014 and December 2017, 20 patients underwent US-MRI neuronavigated (Esaote®, Genova, Italy) transcortical endoportal (Vycor® Viewsite Brain Access System TC Model, Vycor® Medical Inc., Boca Raton, FL) surgery for intraventricular deep-seated lesions with the intent to reach maximal safe resection. RESULTS: Gross total removal was achieved in 14 patients (70%). The only prognostic factor that resulted in statistical significance related to surgical radicality from multivariate analysis was white matter infiltration (p = 0.043), regardless of other tumour (dimensions, origin and location inside ventricular system, histopathology) and patient (age, gender, clinical presentation) characteristics. The mean duration of surgery was 225.9 min (± 59). Neither critical events, nor major bleedings, nor intraoperative deaths occurred during surgery. One case of postoperative CSF infection (5%) was registered. Six patients (30%) required permanent CSF drainage system (Ommaya reservoir, VP shunt) in the postoperative period. The mean Functional Independence Measure (FIM) score at last follow-up was 105 (range: 65-124). CONCLUSIONS: Transcortical transventricular endoportal surgery seems to be a valuable alternative to transcallosal surgery, although further prospective multicentre studies with larger number of patients, evaluation of pre- and post-operative neuropsychological outcomes and achievement of postoperative DTI and f-MRI are needed to confirm our results.

Comparative Anatomical Study of Fronto-Orbito-Zygomatic and Fronto-Temporal Approach to the Central Skull Base.

ABSTRACT: Despite the advances in microsurgery and neuroanatomy, surgery of the central skull base still represents a challenge. Fronto-temporal approach has represented the mainstay of surgical approaches to this region. With advances in skull base surgery, orbital and zygomatic extensions were added to fronto-temporal approach to improve exposure minimizing brain retraction.The authors compared fronto-temporal and fronto-orbitozygomatic approaches to the central skull base by using the previously described operability score, to three different anatomical targets: the ipsilateral anterior clinoid process, the contralateral anterior clinoid process, and the ipsilateral posterior clinoid process.Based on the measurements taken, fronto-orbitozygomatic approache showed higher values at all 3 targets. The reported values were critically discussed.The operability score has been reported as an effective method to compare surgical approaches. The present study demonstrated the maximal possibility of exposure of the two approaches. Based on the strong variability of this anatomical region, especially because of the different pathologies, the authors suggest considering the operability score as a further tool to better define the best surgical approach to this anatomical region.

Enhanced SPARCL1 expression in cancer stem cells improves preclinical modeling of glioblastoma by promoting both tumor infiltration and angiogenesis.

Glioblastoma (GBM) is the most malignant brain tumor of adults and is characterized by extensive cell dissemination within the brain parenchyma and enhanced angiogenesis. Effective preclinical modeling of these key features suffers from several shortcomings. Aim of this study was to determine whether modulating the expression of extracellular matrix (ECM) modifiers in proneural (PN) and mesenchymal (MES) cancer stem cells (CSCs) and in conventional glioma cell lines (GCLs) might improve tumor invasion and vascularization. To this end, we selected secreted, acidic and rich in cysteine-like 1 (SPARCL1) as a potential mediator of ECM remodeling in GBM. SPARCL1 transcript and protein expression was assessed in PN and MES CSCs as well as GCLs, in their xenografts and in patient-derived specimens by qPCR, WB and IHC. SPARCL1 expression was then enforced in both CSCs and GCLs by lentiviral-based transduction. The effect of SPARCL1 gain-of-function on microvascular proliferation, microglia activation and advanced imaging features was tested in intracranial xenografts by IHC and MRI and validated by chorioallantoic membrane (CAM) assays. SPARCL1 expression significantly enhanced the infiltrative and neoangiogenic features of PN and MES CSC/GCL-induced tumors, with the concomitant activation of inflammatory responses associated with the tumor microenvironment, thus resulting in experimental GBMs that reproduced both the parenchymal infiltration and the increased microvascular density, typical of GBM. Overall, these results indicate that SPARCL1 overexpression might be instrumental for the generation of CSC-derived preclinical models of GBM in which the main pathognomonic hallmarks of GBMs are retrievable, making them suitable for effective preclinical testing of therapeutics.

Pediatric cerebellar pilocytic astrocytoma presenting with spontaneous intratumoral hemorrhage.

Pilocytic astrocytomas (PAs) are benign glial tumors and one of the most common childhood posterior fossa tumors. Spontaneous intratumoral hemorrhage in PAs occurs occasionally, in about 8-20% of cases. Cerebellar hemorrhages in pediatric population are rare and mainly due to head injuries, rupture of vascular malformations, infections, or hematological diseases. We have investigated the still controversial and unclear pathophysiology underlying intratumoral hemorrhage in PAs. Bleeding in low-grade tumors might be related to structural abnormalities and specific angio-architecture of tumor vessels, such as degenerative mural hyalinization, "glomeruloid" endothelial proliferation, presence of encased micro-aneurysms, and glioma-induced neoangiogenesis. The acute hemorrhagic presentation of cerebellar PA in childhood although extremely uncommon is of critical clinical importance and necessitates promptly treatment. We described a case of hemorrhagic cerebellar PA in a 9-year-old child and reviewed the English-language literature that reported spontaneous hemorrhagic histologically proven cerebellar PA in pediatric patients (0-18 years). According to our analysis, the mortality was not related to symptom onset, tumor location, hemorrhage distribution, presence of acute hydrocephalous, and timing of surgery, while the GCS at hospital admission resulted to be the only statistically significant prognostic factor affecting survival outcome. The abrupt onset of signs and symptoms of acute hydrocephalous and consequent raised intracranial pressure are life-threatening conditions, which need emergent medical and neurosurgical treatments. At a later time, the identification of posterior fossa hemorrhage etiology is crucial to select the appropriate treatment and address the surgical strategy, optimizing the postoperative results.

Combined Technique of Temporal Muscle Augmentation for Muscle Reconstruction in Case of Small to Medium Anatomic Defects.

Inadequate temporal muscle (TM) reconstruction after surgery may hesitate in potentially severe functional and aesthetic sequelae, making it of paramount importance to carefully consider TM reconstruction even in case of small deformities.The authors describe the combined temporal muscle augmentation technique (CTMA), an innovative technique for TM augmentation for muscle reconstruction in case of small to medium substance loss.A cadaver study was conducted as preclinical validation of the technique for the assessment of CTMA coverage capability. CTMA consists in a combination of 2 techniques for muscle surface coverage (MSC) increase: the radial (RA) and the longitudinal augmentation (LA), which enables to harvest a radial (RF) and a longitudinal flap (LF), respectively.Each flap derives from a different muscle-bundle, spearing TM segmentation and functional performance, and are supplied by a specific neuro-vascular peduncle, which makes flaps functionally independent.A surgical case is reported to demonstrate the feasibility of the technique.Combined temporal muscle augmentation technique provides an overall coverage surface of 6.5 ± 0.6 cm, which corresponds to a gap distance of 2.5 ± 0.2 cm, with RF providing a statistically significant larger surface of coverage compared to LF (×2.1; P = 0.0001).Combined temporal muscle augmentation technique is easy and fast to perform displaying a good reconstructive capability with complete preservation of temporal muscle anatomic compartmentalization and segmental vasculature. It might be considered as a safe and effective alternative in the reconstruction of small-to medium TM defects.

Comparative anatomical study on the role of zygomatic osteotomy in the extradural subtemporal approach to the clival region, when less is more.

PURPOSE: A great concern in performing the extradural subtemporal approach (ESTA) is the evaluation of the actual advantage provided by zygomatic osteotomy (ZO). Complications related to zygomatic dissection have been widely reported in the literature, making it of paramount importance to balance the actual need to perform it, against the risk of maneuver-related morbidity. Authors comparatively analyze the putative advantage provided by ZO in the ESTA in terms of anatomic exposure and surgical operability. Technical limits and potentials are critically revised and discussed. METHODS: A comparative microanatomical laboratory investigation was conducted. The operability score (OS) was applied for quantitative analysis of surgical operability. RESULTS: ZO was found to provide a weakly significant improvement in the surgical angle of attack (p value 0.01) (mean increase 3°). Maneuverability arch (MAC) increase related to ZO did not reach statistical significance (p value 0.09) (mean increase 2°). The variations provided by MAC increase on the conizing effect (CE) did not lead to an actual advantage in the real surgical scenario, modifying the vision area (VA) in terms of reduction of central vision area (CA) in favor of an increase of peripheral vision area (PA) only in the most caudal part of the surgical field. Ultimately, ZO did not influence the overall OS, scoring both ESTA-ZO+ and ESTA-ZO- 2 out of 3. CONCLUSION: In the ESTA, ZO does not provide an actual significant advantage in terms of surgical operability on clival and paraclival areas.

The emerging role of gamma knife radiosurgery in the management of glossopharyngeal neuralgia.

Glossopharyngeal neuralgia (GPN) represents a rare craniofacial disorder accounting for about 1% of all craniofacial pain syndromes. GPN shares several pathophysiologic and clinical features with the more common trigeminal neuralgia. Medical therapy and microvascular decompression, in case of vascular nerve compression, represented the mainstay of GPN management. Other ablative therapies have been reported to date; however, few data are available because of the rarity of this pain syndrome. Among the ablative procedures, gamma knife radiosurgery (GKRS) has been recently introduced in the management of GPN with good pain control and low complication rates. Authors performed a systematic review of the published literature about GKRS in the management of GPN. Radiosurgical treatment data, pain control and recurrence rate have been analysed and compared. GKRS represented a valuable and effective treatment option for the management of GPN. Pain control and complication rates are better than those reported by other ablative procedures and microvascular decompression; however, future studies should be focused on the long-term efficacy of GKRS.

Single fraction and multisession Gamma Knife radiosurgery for craniopharyngioma.

PURPOSE: The optimal management of residual or recurring craniopharyngioma is still a matter of debate even though adjuvant radiation therapy plays a crucial role. Aim of our study is to report the results of single fraction or multisession Gamma Knife radiosurgery (GKRS) in patients with craniopharyngioma. METHODS: We included 50 consecutive patients treated from 1994 to 2016. All patients had at least one post GKRS magnetic resonance imaging reviewed at our center. Vital status of all patients was assessed at the end of 2016. RESULTS: There were 29 males (58.0%) and 21 females (42.0%). Mean age was 41.5 ± 2.8 year. Single session GKRS was delivered in 29 patients (58.0%). The mean tumor volume was 2.15 ± 0.3 cm3 and the mean prescription dose to the tumor margin was 14.3 ± 0.3 Gy. During a mean follow-up of 74.6 ± 8.4 months, seven patients (14.0%) had recurrence of disease. The 5- and 10-year recurrence-free survivals were 90.3% (95% CI, 81.0-99.6%) and 78.4% (95% CI, 59.9-96.9%), respectively. Multisession GKRS was not less effective than single fraction GKRS. Eighteen of the 28 patients (64.3%) had a tumor volume decrease of at least 10%. No serious side effects occurred after GKRS treatment, except for one case of mild visual worsening. CONCLUSIONS: GKRS was effective for controlling the growth of residual or recurrent craniopharyngioma. Serious side effects were uncommon. Multisession GKRS seems a very promising tool to allow performing GKRS even in patients with large residual or recurrent craniopharyngioma.