Glymphatic system dysfunction in central nervous system malignancies: A narrative review

Abstract

The hypothesis of the glymphatic system as playing an important part in clearing waste from the brain has revolutionized our understanding of cerebrospinal and interstitial fluid dynamics in the brain. This review explores current knowledge of central nervous system (CNS) malignancies and their implications in the glymphatic system function. Here, we synthesize all available preclinical and clinical evidence on glymphatic dynamics in CNS malignancies. The human data evaluated (gliomas, meningiomas, peritumoral edema, and cerebral metastasis) constitute the total scope of current research. We conducted a systematic search in the PubMed database for studies published between 1 January 2015 and 1 January 2026. We selected 22 studies based on their relevance regarding brain tumors and their relationship to glymphatic system dysfunction. In contrast to animal studies that rely on contrast-enhanced imaging, human studies predominantly use the diffusion tensor imaging along perivascular spaces (ALPS) index due to its noninvasive nature and feasibility with multidirectional diffusion-weighted imaging, which is available on most clinical scanners. However, interpretation of the findings remains the subject of debate, particularly regarding the influence of microstructural factors and other parameters on index values. Consequently, current approaches increasingly assess the ALPS index as a potential indirect marker of glymphatic function alongside complementary MR-based techniques, including multiparametric mapping, volumetry, free water estimation, and DTI-derived microstructural measures. Further research in CNS tumors is required to clarify consistent patterns and address the variability of reported findings.