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.

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.

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.

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.