High p-mTOR expression is associated with recurrence and shorter disease-free survival in atypical meningiomas.

Due to their widely variable clinical behavior, the post-surgical treatment of atypical meningiomas is controversial. Therefore, prognostic factors able to identify high-risk cases, which may benefit from adjuvant treatments, are warranted. Mammalian target of rapamycin (mTOR) belongs to the PI3K-AKT pathway. Its phosphorylated form (p-mTOR Ser2448) is involved in cell growth, differentiation and tumorigenesis. The aim of this study was to evaluate p-mTOR Ser2448 expression and its eventual correlation with clinicopathological features, recurrence, or disease-free survival (DFS), in atypical meningiomas. p-mTOR immunohistochemical expression was analyzed in 48 atypical meningiomas and correlated with clinicopathological parameters and with DFS. Eighty-one percent of atypical meningiomas expressed p-mTOR Ser2448. High immuno-expression was significantly associated with recurrences (P = 0.01) and lower DFS (P = 0.01). The presence of brain invasion, high mitotic index plus sheeting, and Simpson grade were significant and independent prognostic variables at multivariate analysis. p-mTOR Ser2448 is expressed in atypical meningiomas. High expression predicts development of recurrences and shorter DFS in patients affected by these tumors. Since p-mTOR Ser2448 is a target of anti-neoplastic drugs, evaluation of its expression may be used, not only to identify atypical meningiomas at higher risk of recurrence, but also to select those to submit to adjuvant targeted chemotherapy.

Navigated Transcranial Magnetic Stimulation Motor Mapping and Diffusion Tensor Imaging Tractography for Diencephalic Tumor in Pediatric Patients.

Background. In deep-seated brain tumors, adequate preoperative planning is mandatory to assess the best surgical corridor to obtain maximal safe resection. Functional diffusor tensor imaging (DTI) tractography based on navigated transcranial magnetic stimulation (nTMS) motor mapping has proven to be a valid preoperative examination method in adults. The aim of this paper is to present the application of nTMS and functional DTI tractography in a series of pediatric diencephalic tumors. Material and methods. Three patients affected by thalamic (one) and thalamopeduncular tumor (two) were successfully examined with nTMS motor mapping and DTI tractography between October 2020 and October 2021 (F:M 3:0, mean age 12 years ± 0.8). Cortical representation of leg, hand and mouth were determined in the affected hemisphere and the positive stimulation spots were set as seeds point for tractography. Results. Mapping of the motor cortex and tracts reconstruction for leg and hand were successful in all patients, while facial function was properly mapped in one patient only. In all cases, the procedure was well tolerated and no adverse events were recorded. Spatial relationships between tumor and functional tissue guided the surgical planning. Extent of the resection varied from 96.1% to 100% with a postoperative new motor deficit in one patient. Conclusions. nTMS and DTI fiber tracking is a feasible, effective and well-tolerated method to identify motor pathway in deep-seated lesion in pediatric population.

Selective Stimulus Intensity during Hotspot Search Ensures Faster and More Accurate Preoperative Motor Mapping with nTMS.

INTRODUCTION: Navigated transcranial magnetic stimulation (nTMS) has emerged as one of the most innovative techniques in neurosurgical practice. However, nTMS motor mapping involves rigorous steps, and the importance of an accurate execution method has not been emphasized enough. In particular, despite strict adherence to procedural protocols, we have observed high variability in map activation according to the choice of stimulation intensity (SI) right from the early stage of hotspot localization. We present a retrospective analysis of motor mappings performed between March 2020 and July 2022, where the SI was only chosen with rigorous care in the most recent ones, under the guide of an expert neurophysiologist. MATERIALS AND METHODS: In order to test the ability to reduce inaccurate responses and time expenditure using selective SI, data were collected from 16 patients who underwent mapping with the random method (group A) and 15 patients who underwent mapping with the proposed method (group B). The parameters considered were resting motor threshold (%), number of stimuli, number of valid motor evoked potentials (MEPs), number of valid MEPs considered true positives (TPs), number of valid MEPs considered false positives (FPs), ratio of true-positive MEPs to total stimuli, ratio of true-positive MEPs to valid MEPs, minimum amplitude, maximum amplitude and mapping time for each patient. RESULTS: The analysis showed statistically significant reductions in total stimulus demand, procedural time and number of false-positive MEPs. Significant increases were observed in the number of true-positive MEPs, the ratio of true-positive MEPs to total stimuli and the ratio of true-positive MEPs to valid MEPs. In the subgroups analyzed, there were similar trends, in particular, an increase in true positives and a decrease in false-positive responses. CONCLUSIONS: The precise selection of SI during hotspot search in nTMS motor mapping could provide reliable cortical maps in short time and with low employment of resources. This method seems to ensure that a MEP really represents a functionally eloquent cortical point, making mapping more intuitive even in less experienced centers.

Ultrasound-assisted neuroendoscopic lavage for intraventricular hemorrhage in a newborn: illustrative case.

BACKGROUND: The optimal treatment for posthemorrhagic hydrocephalus in newborns has not been established yet. Moreover, despite many valid therapeutic alternatives, unfavorable neurodevelopmental outcomes are frequent. According to recent literature, these discouraging results could be related to secondary inflammatory damage of the white matter due to the gradual dissolution of the intraventricular hematoma, which should be removed. OBSERVATIONS: Neuroendoscopic lavage (NEL) has proven to be a safe and reliable procedure, able to adequately remove the intraventricular clots and the products of blood degradation. To increase surgical control of the entire ventricular system, the authors illustrated a case in which they associated real-time transfontanellar ultrasound monitoring with NEL. LESSONS: Coupling these two techniques, the authors performed a rapid ventricular wash and obtained intraoperative confirmation of complete and accurate clot removal.

Preoperative Repetitive Navigated TMS and Functional White Matter Tractography in a Bilingual Patient with a Brain Tumor in Wernike Area.

Awake surgery and intraoperative neuromonitoring represent the gold standard for surgery of lesion located in language-eloquent areas of the dominant hemisphere, enabling the maximal safe resection while preserving language function. Nevertheless, this functional mapping is invasive; it can be executed only during surgery and in selected patients. Moreover, the number of neuro-oncological bilingual patients is constantly growing, and performing awake surgery in this group of patients can be difficult. In this scenario, the application of accurate, repeatable and non-invasive preoperative mapping procedures is needed, in order to define the anatomical distribution of both languages. Repetitive navigated transcranial magnetic stimulation (rnTMS) associated with functional subcortical fiber tracking (nTMS-based DTI-FT) represents a promising and comprehensive mapping tool to display language pathway and function reorganization in neurosurgical patients. Herein we report a case of a bilingual patient affected by brain tumor in the left temporal lobe, who underwent rnTMS mapping for both languages (Romanian and Italian), disclosing the true eloquence of the anterior part of the lesion in both tests. After surgery, language abilities were intact at follow-up in both languages. This case represents a preliminary application of nTMS-based DTI-FT in neurosurgery for brain tumor in eloquent areas in a bilingual patient.

Histopathological features to define atypical meningioma: What does really matter for prognosis?

Atypical meningiomas are diagnosed in the presence of: (1) three or more of the following minor atypical criteria: increased cellularity, small cells with a high nuclear/cytoplasmic ratio, prominent nucleoli, sheeting, and foci of spontaneous or geographic necrosis; (2) mitotic count ≥ 4 mitoses per 10 HPF (high mitotic index); (3) brain invasion. The 5-year disease-free survival (DFS) is around 50%. Due to their heterogeneous behavior, the post-surgical treatment of atypical meningiomas is controversial. This study investigated the ability of histopathological features to predict recurrence risk of atypical meningiomas. Meningiomas classified as atypical only on minor atypical criteria had low recurrence risk. Brain invasion, high mitotic index and sheeting were significantly associated with shorter disease-free survival (DFS) (P = 0.001; P = 0.01; P = 0.01). The presence of brain invasion and the co-presence of sheeting and high mitotic index had the highest ability to identify recurring meningiomas (P = 0.0001) (sensitivity: 90.9%; specificity: 86.7%). Our results suggest reconsideration of classification of meningiomas as atypical based only on minor atypical criteria. The presence of brain invasion and the co-occurrence of sheeting and high mitotic count may be useful to identify high risk cases, which may benefit from adjuvant treatments.