Jean-Michel Lemée

Intratumoral heterogeneity in glioblastoma: don't forget the peritumoral brain zone

Glioblastoma (GB) is the most frequent and aggressive primary tumor of the central nervous system. Prognosis remains poor despite ongoing progress. In cases where the gadolinium-enhanced portion of the GB is completely resected, 90% of recurrences occur at the margin of surgical resection in the macroscopically normal peritumoral brain zone (PBZ). Intratumoral heterogeneity in GB is currently a hot topic in neuro-oncology, and the GB PBZ may be involved in this phenomenon. Indeed, this region, which possesses specific properties, has been less studied than the core of the GB tumor. The high rate of local recurrence in the PBZ and the limited success of targeted therapies against GB demonstrate the need for a better understanding of the PBZ. We present here a review of the literature on the GB PBZ, focusing on its radiological, cellular, and molecular characteristics. We discuss how intraoperative analysis of the PBZ is important for the optimization of surgical resection and the development of targeted therapies against GB.

Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

Glioblastoma (GB) is the most frequent and aggressive type of primary brain tumor. Recurrences are mostly located at the margin of the resection cavity in the peritumoral brain zone (PBZ). Although it is widely believed that infiltrative tumor cells in this zone are responsible for GB recurrence, few studies have examined this zone. In this study, we analyzed PBZ left after surgery with a variety of techniques including radiology, histopathology, flow cytometry, genomic, transcriptomic, proteomic, and primary cell cultures. The resulting PBZ profiles were compared with those of the GB tumor zone and normal brain samples to identify characteristics specific to the PBZ. We found that tumor cell infiltration detected by standard histological analysis was present in almost one third of PBZ taken from an area that was considered normal both on standard MRI and by the neurosurgeon under an operating microscope. The panel of techniques used in this study show that the PBZ, similar to the tumor zone itself, is characterized by substantial inter-patient heterogeneity, which makes it difficult to identify representative markers. Nevertheless, we identified specific alterations in the PBZ such as the presence of selected tumor clones and stromal cells with tumorigenic and angiogenic properties. The study of GB-PBZ is a growing field of interest and this region needs to be characterized further. This will facilitate the development of new, targeted therapies for patients with GB and the development of approaches to refine the per-operative evaluation of the PBZ to optimize the surgical resection of the tumor.

Lessons to Be Remembered from a Dural Arteriovenous Fistula Mimicking Medulla and High Cervical Cord Glioma

The radiological signs of intracranial dural arteriovenous fistulas (ICDAVFs) are heterogenous. While it is commonly accepted that hyper intense T2 wedge magnetic resonance imaging of the brainstem and cervical cord mainly concern gliomas, it is so far uncommon and probably unknown that ICDAVFs can imitate similar radiological pattern, especially with gadolinium contrast enhancement and cord enlargement. Thus the angiography is poorly documented in the diagnostic workup. We report the unusual history of ICDAVFs, revealed by clinical and radiological features that mimicked a medulla or cervical spinal cord glioma. This observation provides information on the management of atypical lesions mimicking medulla or cervical cord glioma and arguments for a careful radiological study. Looking for dilated veins around the brainstem and the cord is mandatory in the workup of a supposed infiltrating brainstem or spinal cord lesion, in order to rule out an ICDAVF. Even if the hyperintense T2 images associated with contrast enhancement is in favor of a brainstem or spinal cord glioma, additional cerebral angiography should be mandatory. Moreover, this clinical case highlights the need for a multidisciplinary approach including neuroradiologist, oncologist and neurosurgeon.

Using a Virtual Reality Social Network During Awake Craniotomy to Map Social Cognition: Prospective Trial

Background In awake craniotomy, it is possible to temporarily inactivate regions of the brain using direct electrical stimulation, while the patient performs neuropsychological tasks. If the patient shows decreased performance in a given task, the neurosurgeon will not remove these regions, so as to maintain all brain functions. Objective The objective of our study was to describe our experience of using a virtual reality (VR) social network during awake craniotomy and discuss its future applications for perioperative mapping of nonverbal language, empathy, and theory of mind. Methods This was a single-center, prospective, unblinded trial. During wound closure, different VR experiences with a VR headset were proposed to the patient. This project sought to explore interactions with the neuropsychologist’s avatar in virtual locations using a VR social network as an available experience. Results Three patients experienced VR. Despite some limitations due to patient positioning during the operation and the limitation of nonverbal cues inherent to the app, the neuropsychologist, as an avatar, could communicate with the patient and explore gesture communication while wearing a VR headset. Conclusions With some improvements, VR social networks can be used in the near future to map social cognition during awake craniotomy. Trial Registration ClinicalTrials.gov NCT03010943; https://clinicaltrials.gov/ct2/show/NCT03010943 (Archived at WebCite at http://www.webcitation.org/70CYDil0P)