2025 American Academy of Neurology Abstract Website

Objective:

In this review, we focus on the recent developments exploring the ultrastructural pathology of gliomas.

Background:

Gliomas arise from glial cells making up to 40% of the brain tumors and contributing up to 85% of the malignant tumors of the brain. Gliomas are a heterogeneous group of tumors classified based on various factors such as genetics, molecular profiles, etc. Glioblastoma, an aggressive form of gliomas, has poor survival of only 15 months suggesting that thorough research is needed to enhance the outcomes for patients with gliomas. This requires a critical analysis of the microenvironment of gliomas to understand the pathophysiology at play. Ultrastructural analysis (UA) using high-resolution electron microscopy offers crucial insights into the cellular and subcellular characteristics of gliomas, revealing organelle abnormalities and confirming molecular alterations.

Design/Methods:

We review recent studies describing ultrastructural abnormalities found in gliomas’ microenvironment and review the literature to describe the potential pathophysiology and implications of these findings.

Results:

UA shows a detailed microenvironment of gliomas to reveal the abnormal presence of lipids in the intra- and extracellular environment of gliomas accompanied by the disrupted structure of the cellular membranes and organelles. The disruptions were also noted in the blood vessels of the tumors displaying intriguing details regarding the formation of neovasculature and the absence of typical contents of vessel walls like endothelial cells. A comparative survey of the mitochondrial ultrastructure of gliomas with or without Isocitrate Dehydrogenase 1 (IDH1) mutations also reveals the role of UA in deciphering the impact of different mutations on the microenvironment level. Here, we also discuss the major implications of these findings regarding the research direction, diagnostic modalities, and therapeutic options.

Conclusions:

Ultrastructural analysis of gliomas displays distorted cellular structures with excessive lipid deposition and disruptions of the blood vessel components.