Abstract
IntroductionDiffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as ‘passive’ consequences of the tumor. However, seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal activity causes faster glioma growth. It is unclear whether the same holds true in patients. Here, we investigate whether lower levels of oscillatory brain activity relate to lower NLGN3 expression and predict longer progression free survival (PFS) in diffuse glioma patients.MethodsTwenty-four newly diagnosed patients with diffuse glioma underwent magnetoencephalography and subsequent tumor resection. Oscillatory brain activity was approximated by calculating broadband power (0.5–48 Hz) of the magnetoencephalography. NLGN3 expression in glioma tissue was semi-quantitatively assessed by immunohistochemistry. Peritumor and global oscillatory brain activity was then compared between different levels of NLGN3 expression with Kruskal–Wallis tests. Cox proportional hazards analyses were performed to estimate the predictive value of oscillatory brain activity for PFS.ResultsPatients with low expression of NLGN3 had lower levels of global oscillatory brain activity than patients with higher NLGN3 expression (P < 0.001). Moreover, lower peritumor (hazard ratio 2.17, P = 0.008) and global oscillatory brain activity (hazard ratio 2.10, P = 0.008) predicted longer PFS.ConclusionsLower levels of peritumor and global oscillatory brain activity are related to lower NLGN3 expression and longer PFS, corroborating preclinical research. This study highlights the important interplay between macroscopically measured brain activity and glioma progression, and may lead to new therapeutic interventions in diffuse glioma patients.
Highlights
Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as ‘passive’ consequences of the tumor
Inclusion criteria were (1) age over 17 years old, (2) histopathologically confirmed World Health Organization (WHO) 2007 grade II, III or IV diffuse glioma [17], (3) at least one seizure, and (4) ability to complete neuropsychological testing
Lower peritumor oscillatory brain activity was associated with lower NLGN3 expression and was predictive of longer progression free survival (PFS) in a cohort of newly-diagnosed diffuse glioma patients
Summary
Diffuse gliomas have local and global effects on neurophysiological brain functioning, which are often seen as ‘passive’ consequences of the tumor. Seminal preclinical work has shown a prominent role for neuronal activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal activity causes faster glioma growth It is unclear whether the same holds true in patients. We investigate whether lower levels of oscillatory brain activity relate to lower NLGN3 expression and predict longer progression free survival (PFS) in diffuse glioma patients. Conclusions Lower levels of peritumor and global oscillatory brain activity are related to lower NLGN3 expression and longer PFS, corroborating preclinical research. Most gliomas in adult patients are characterized by diffuse infiltration of tumor cells in the surrounding brain parenchyma These so-called diffuse gliomas have widespread effects on neurophysiological functioning as measured with magnetoencephalography (MEG) and electroencephalography (EEG): both increased low frequency.
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