The Use of 5-Aminolevulinic Acid in Glioma Surgery: From Intracranial to Spinal Applications

A Narrative Review of Intracranial and Spinal Applications

Abstract

Fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) has become an important adjunct in glioma surgery, with the aim of maximizing the extent of resection while preserving neurological function. After oral or intravenous administration, 5-ALA is metabolized to protoporphyrin IX (PpIX), which preferentially accumulates in tumor cells and fluoresces under blue light, thereby improving intraoperative visualization of malignant tissue. This narrative review summarizes the current indications, evidence, challenges, and future directions of 5-ALA in intracranial and spinal cord glioma surgery. Randomized and observational studies have demonstrated that 5-ALA FGS increases gross total resection rates and improves progression-free and overall survival in intracranial high-grade glioma. Although its role in low-grade glioma is less established, focal fluorescence may identify anaplastic foci and serve as a prognostic marker. In spinal cord gliomas, 5-ALA appears particularly useful for ependymomas, in which high fluorescence rates and favorable resection outcomes have been reported. Its application in spinal astrocytomas requires caution because robust evidence of benefit remains limited and over-resection may cause substantial neurological harm. Overall, 5-ALA has a favorable safety profile, with mostly mild and transient adverse effects. Beyond resection guidance, 5-ALA-based photodynamic and radiodynamic approaches are being explored as adjuvant therapies. Current evidence strongly supports its use in high-grade intracranial gliomas and selected spinal ependymomas, while emerging theranostic applications may further expand its role in multimodal neuro-oncology.