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Background: Neuroimaging differentiation of glioblastoma, primary central nervous system lymphoma (PCNSL) and solitary brain metastasis (BM) remains challenging in specific cases showing similar appearances or atypical features. Overall, advanced MRI protocols have high diagnostic reliability, but their limited worldwide availability, coupled with the overlapping of specific neuroimaging features among tumor subgroups, represent significant drawbacks and entail disparities in the planning and management of these oncological patients. Objective: To evaluate the classification performance metrics of a deep learning algorithm trained on T1-weighted gadolinium-enhanced (T1Gd) MRI scans of glioblastomas, atypical PCNSLs and BMs. Materials and Methods: We enrolled 121 patients (glioblastoma: n=47; PCNSL: n=37; BM: n=37) who had undergone preoperative T1Gd-MRI and histopathological confirmation. Each lesion was segmented, and all ROIs were exported in a DICOM dataset. The patient cohort was then split in a training and hold-out test sets following a 70/30 ratio. A Resnet101 model, a deep neural network (DNN), was trained on the training set and validated on the hold-out test set to differentiate glioblastomas, PCNSLs and BMs on T1Gd-MRI scans. Results: The DNN achieved optimal classification performance in distinguishing PCNSLs (AUC: 0.98; 95%CI: 0.95 - 1.00) and glioblastomas (AUC: 0.90; 95%CI: 0.81 - 0.97) and moderate ability in differentiating BMs (AUC: 0.81; 95%CI: 0.70 - 0.95). This performance may allow clinicians to correctly identify patients eligible for lesion biopsy or surgical resection. Conclusion: We trained and internally validated a deep learning model able to reliably differentiate ambiguous cases of PCNSLs, glioblastoma and BMs by means of T1Gd-MRI. The proposed predictive model may provide a low-cost, easily-accessible and high-speed decision-making support for eligibility to diagnostic brain biopsy or maximal tumor resection in atypical cases.

Purpose Transsphenoidal surgery (TSS) for pituitary adenomas can be complicated by the occurrence of intraoperative cerebrospinal fluid (CSF) leakage (IOL). IOL significantly affects the course of surgery predisposing to the development of postoperative CSF leakage, a major source of morbidity and mortality in the postoperative period. The authors trained and internally validated the Random Forest (RF) prediction model to preoperatively identify patients at high risk for IOL. A locally interpretable model-agnostic explanations (LIME) algorithm is employed to elucidate the main drivers behind each machine learning (ML) model prediction. Methods The data of 210 patients who underwent TSS were collected; first, risk factors for IOL were identified via conventional statistical methods (multivariable logistic regression). Then, the authors trained, optimized, and audited a RF prediction model. Results IOL reported in 45 patients (21.5%). The recursive feature selection algorithm identified the following variables as the most significant determinants of IOL: Knosp's grade, sellar Hardy's grade, suprasellar Hardy's grade, tumor diameter (on X, Y, and Z axes), intercarotid distance, and secreting status (nonfunctioning and growth hormone [GH] secreting). Leveraging the predictive values of these variables, the RF prediction model achieved an area under the curve (AUC) of 0.83 (95% confidence interval [CI]: 0.78; 0.86), significantly outperforming the multivariable logistic regression model (AUC = 0.63). Conclusion A RF model that reliably identifies patients at risk for IOL was successfully trained and internally validated. ML-based prediction models can predict events that were previously judged nearly unpredictable; their deployment in clinical practice may result in improved patient care and reduced postoperative morbidity and healthcare costs.

5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence is used by neurosurgeons to identify the tumor cells of high-grade gliomas during operation. However, the issue of whether 5-ALA-induced PpIX fluorescence consistently stains all the tumor cells is still debated. Here, we assessed the cytoplasmatic signal of 5-ALA by fluorescence microscopy in a series of human gliomas. As tumor markers, we used antibodies against collapsin response-mediated protein 5 (CRMP5), alpha thalassemia/mental retardation syndrome X-linked (ATRX), and anti-isocitrate dehydrogenase 1 (IDH1). In grade III–IV gliomas, the signal induced by 5-ALA was detected in 32.7–75.5 percent of CRMP5-expressing tumor cells. In low-grade gliomas (WHO grade II), the CRMP5-expressing tumor cells did not fluoresce following 5-ALA. Immunofluorescence with antibodies that stain various components of the blood–brain barrier (BBB) suggested that 5-ALA does not cross the un-breached BBB, in spite of its small dimension. To conclude, 5-ALA-induced PpIX fluorescence has an established role in high-grade glioma surgery, but it has limited usefulness in surgery for low-grade glioma, especially when the BBB is preserved.

Meningiomas are mostly benign tumors that, at times, can behave aggressively, displaying recurrence despite gross-total resection (GTR) and progression to overt malignancy. Such cases represent a clinical challenge, particularly because they are difficult to recognize at first diagnosis. SOX2 (Sex-determining region Y-box2) is a transcription factor with a key role in stem cell maintenance and has been associated with tumorigenesis in a variety of cancers. The purpose of the present work was to dissect the role of SOX2 in predicting the aggressiveness of meningioma. We analyzed progressive/recurrent WHO grade 1–2 meningiomas and WHO grade 3 meningiomas; as controls, non-recurring WHO grade 1 and grade 2 meningioma patients were enrolled. SOX2 expression was evaluated using both immunohistochemistry (IHC) and RT-PCR. The final analysis included 87 patients. IHC was able to reliably assess SOX2 expression, as shown by the good correlation with mRNA levels (Spearman R = 0.0398, p = 0.001, AUC 0.87). SOX2 expression was an intrinsic characteristic of any single tumor and did not change following recurrence or progression. Importantly, SOX2 expression at first surgery was strongly related to meningioma clinical behavior, histological grade and risk of recurrence. Finally, survival data suggest a prognostic role of SOX2 expression in the whole series, both for overall and for recurrence-free survival (p < 0.0001 and p = 0.0001, respectively). Thus, SOX2 assessment could be of great help to clinicians in informing adjuvant treatments during follow-up.

Lumbosacral chordoma is a slow-growing but locally aggressive tumor, resistant to adjuvant treatments and endowed with dismal prognosis. Surgery is the mainstay of treatment but the choice of surgical approach (the posterior-only approach or the combined anterior–posterior approach) remains an open question due to the need of both pursuing a surgical radicality and preserving the neurologic function. The aim of the study was to compare the surgical and clinical outcomes of these approaches in the management of lumbosacral chordomas. A systematic review and meta-analysis in agreement with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines of papers comparing the outcomes of the two approaches was performed. Ten papers met the inclusion criteria. The combined anterior–posterior approach was more frequently performed for tumors with an upper level beyond S2 (p = 0.012). The 5-year progression-free survival was significantly higher in posterior-only approach compared with the combined anterior–posterior approach (44.7% vs 27.1%, p = 0.049). Adjuvant radiotherapy was added more frequently after a posterior-only approach (p = 0.036) and the rate of complications was significantly lower after a posterior-only approach (p = 0.040). No significant differences in sex, age, tumor diameter, entity of resection, and overall survival were observed. Posterior-only surgical approach may be a reasonable option for lumbosacral chordoma, being associated with comparable entity of surgical resection, reduced complication rate and increased 5-year progression-free survival rate as compared with combined anterior–posterior approach.

Decompressive craniectomy (DC) is effective in controlling increasing intracranial pressure determined by a wide range of conditions, mainly traumatic brain injury (TBI) and stroke, and the subsequent cranioplasty (CP) displays potential therapeutic benefit in terms of overall neurological function. While autologous bone flap (ABF) harvested at the time of DC is the ideal material for skull defect reconstruction, it carries several risks. Aseptic bone flap resorption (BFR) is one of the most common complications, often leading to surgical failure. The aim of our study was to systematically review the literature and carry out a meta-analysis of possible factors involved in BFR in patients undergoing ABF cranioplasty after DC. A systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. Different medical databases (PubMed, Embase, and Scopus) were screened for eligible scientific reports until April 30th 2021. The following data were collected for meta-analysis to assess their role in BFR: sex, age, the interval time between DC and CP, the presence of systemic factors, the etiology determining the DC, CP surgical time, CP features, VP shunt placement, CP infection. Studies including pediatric patients or with less than 50 patients were excluded. Fifteen studies were included. There was a statistically significant increased incidence of BFR in patients with CPF > 2 compared to patients with CPF ≤ 2 (54.50% and 22.76% respectively, p = 0.010). TBI was a significantly more frequent etiology in the BFR group compared to patients without BFR (61.95% and 47.58% respectively, p < 0.001). Finally, patients with BFR were significantly younger than patients without BFR (39.12 ± 15.36 years and 47.31 ± 14.78 years, respectively, p < 0.001). The funnel plots were largely symmetrical for all the studied factors. Bone flap fragmentation, TBI etiology, and young age significantly increase the risk of bone resorption. Further studie

Objective: Ability to thrive after invasive and intensive treatment is an important parameter to assess in patients with glioblastoma multiforme (GBM). Karnofsky Performance Status (KPS) is used to identify those patients suitable for postoperative radiochemotherapy. The aim of the present study is to investigate whether machine learning (ML)-based models can reliably predict patients' KPS 6 months after surgery. Methods: A cohort of 416 patients undergoing surgery for a histopathologically confirmed GBM were collected from a multicentric database and split into a training and hold-out test set in an 80:20 ratio. Worsening of KPS at 6 months after surgery (compared with preoperative KPS) occurred in 138 patients (33.2%). Relevant preoperative, intraoperative, and immediately postoperative variables were selected by a recursive features selection algorithm (Boruta) and used to build 2 ML-based predictive models. Results: A random forest classifier and a random forest regressor were trained to predict 6 months postoperative KPS as a categorical (worsening vs. stable/improving) and continuous variables; they achieved, respectively, an area under the curve of 0.81 (95% confidence interval, 0.76–0.84) and a mean absolute error of 4.4 (95% confidence interval, 4.0–4.7). Leveraging the predictive value resulting from the combination of independent variables, the random forest classifier outperformed conventional statistics (area under the curve improvement of +21%). Conclusions: Two robust ML-based prediction models were successfully trained and internally validated. Considerable effort remains to improve the interpretation of the results when these predictions are used in a patient-centered care context.

Background: A recent trend of looking for health-related conditions on the Internet has been described, with up 70% of searchers stating that online sources have affected their medical decision-making. Patients with vestibular schwannomas (VS) use online sources, including videos, to seek information about treatment alternatives and outcomes and surgeons experience. Our study investigates the reliability and quality of VS-related online videos. Methods: In April 2020, a search was launched on YouTube for the key terms ‘vestibular schwannoma,’ ‘acoustic neuroma,’ ‘eighth cranial nerve schwannoma,’ and ‘eighth cranial nerve neuroma.’ Results were screened for possible inclusion. Three authors independently used the DISCERN instrument to evaluate the reliability and quality of the included videos. Factors possibly influencing popularity were investigated. Results: The initial search yielded 6416 videos. 38 videos were included in the final analysis. The average DISCERN score was 2.76, indicating overall poor quality and reliability of information. Only 5% scored 4.0 or more (unbiased videos that offer evidence-supported information); 31% scored between 3.0 and 3.99, and 63% scored 2.99 or less. Videos describing symptoms or the patient’s clinical presentation were slightly more popular than videos without these characteristics. Surgical videos (videos containing clips of surgical procedures) were significantly more popular than non-surgical videos (p =.024) despite being of similarly poor quality (DISCERN score 2.85 vs. 2.74, respectively). Conclusions: Available patient educational videos for VS are of mixed quality and reliability: the authors describe the strengths and pitfalls of existing YouTube videos. Considering that VS is a pathology with multiple available management modalities, and that patients’ decision-making is affected by the information available on the Internet, it is of great importance that good-quality informative material be released by medical, a

Brain biopsy is the gold standard in order to establish the diagnosis of unresectable brain tumors. Few studies have investigated the long-term outcomes of biopsy patients. The aim of this single-institution-based study was to assess the concordance between radiological and histopathological diagnoses, and the long-term patient outcome. Ninety-three patients who underwent brain biopsy in the last 5 years were analyzed. We included patients treated with stereotactically guided needle, open, and neuroendoscopic biopsies. Most patients (86%) received needle biopsy. Gliomas and primary brain lymphomas comprised 88.2% of cases. The diagnostic yield was 95.7%. Serious complication and death rates were 3.2% and 2.1%, respectively. The concordance rate between radiological and histological diagnoses was 93%. Notably, the positive predictive value of radiological diagnosis of lymphoma was 100%. Biopsy allowed specific treatment in 72% of cases. Disease-related neurological worsening was the main reason that precluded adjuvant treatment. Adjuvant treatment, in turn, was the strongest prognostic factor, since the median overall survival was 11 months with vs. 2 months without treatment (p = 0.0002). Finally, advanced molecular evaluations can be obtained on glioma biopsy specimens to provide integrated diagnoses and individually tailored treatments. We conclude that, despite the huge advances in imaging techniques, biopsy is required when an adjuvant treatment is recommended, particularly in gliomas.

Spontaneous intracranial hypotension (SIH) is an often misdiagnosed condition resulting from non-iatrogenic cerebrospinal fluid (CSF) hypovolemia, typically secondary to spinal CSF leakage. Patients commonly present with posture-related headache, nausea, and vomiting. Following failure of conservative measures, epidural blood patching (EBP) is the most commonly performed intervention for spinal CSF leaks. The authors performed a systematic review and meta-analysis of existing literature to evaluate the role of different factors possibly affecting the efficacy of the EBP procedure. In accordance with the PRISMA guidelines, PubMed/Medline and SCOPUS databases were searched. Six eligible articles were retrieved. Five hundred patients were treated for SIH with EBP, of which 300 reported good response defined as complete remission of symptoms within 48 h after the first EBP requiring no further invasive treatment. Among the factors available for meta-analysis, none was found to be statistically significant in affecting the efficacy of the EBP procedure. A largely symmetrical funnel plot is reported for all the variables evaluated, indicating that publication bias did not play a significant role in the observed effects. The current knowledge about SIH and the EBP is scarce. The existing literature is contradictory and insufficient to aid in clinical practice. More studies are needed to draw significant conclusions that may help in the identification of patients at higher risk of EBP failure, who may benefit from different approaches.

The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.

A major complication in cranial and spinal surgery is the post-operative occurrence of a cerebrospinal fluid (CSF) leak. Here we reported a technical note firstly describing the use of Hemopatch® with fibrin glue as a dural sealant in cranial and spinal neurosurgical procedures. Moreover we carried out a review of the literature. Further to the best of our knowledge this was the first series including patients submitted to different spinal surgeries in whom Hemopatch® was used as dural sealant. We prospectively collected the data of 22 patients. In all procedures, fibrin glue was applied after Hemopatch®. The mean age was 59.68 ± 10.79 years and the mean follow-up (FU) was 3.63 ± 1.46 months, respectively. Overall, Hemopatch® with fibrin glue was used in 8 cranial procedures (36.36%; all were retrosigmoid craniotomies) and 14 spinal procedures (63.64%). 9/14 spinal cases (64.28%) were incidental durotomies during a spinal decompression procedure. No CSF leak, no postoperative infection, no adverse reaction were observed during the FU in all cases. The literature search revealed only two retrospective series, reporting only patients submitted to cranial surgery for a total of 56 patients and a CSF leak occurring in 3 patients (5.35%). In conclusion, we firstly reported the feasibility and the safety of using Hemopatch® with fibrin glue as dural sealant in cranial surgery and different spinal procedures. Further larger comparative studies are needed to confirm our initial encouraging results.

Background: Osteoblastomas are rare primary bone tumors with a predilection for the spine. The extraosseous growth pattern is rare, and to our knowledge, only 2 cases of fully extraosseous osteoblastomas have been previously reported. Case Description: A man aged 36 years presented with a 7-month history of low back pain radiating to the gluteal area. On examination, a typical L5 radiculopathy was noted. The radiologic examinations conducted in the previous months pointed out the rapid growth of an extraosseous mass occluding the right L5-S1 foramen. Partial laminectomy was performed to achieve gross total resection. Histological analysis was consistent with osteoblastoma. Conclusions: Osteoblastomas with extraosseous extension are uncommon, and an exclusively extraosseous presentation is anecdotal. This can lead to preoperative misdiagnosis when typical radiologic characteristics of bone-forming tumors are missing. We describe the case of an extraosseous lumbar osteoblastoma whose clinical and radiologic presentation was suggestive of malignancy.