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5 aminolevulinic acid fluorescence guided resection


The introduction of fluorescence guided resection (FGS) represents one of the most important advances in the neurosurgical treatment of brain tumors.

5 aminolevulinic acid fluorescence guided resection permits the intraoperative visualization of malignant glioma tissue and supports the neurosurgeon with real-time guidance for differentiating tumor from normal brain that is independent of neuronavigation and brain shift.

The 5 aminolevulinic acid has been used in glioma surgery and recent studies applied in Sylvian and spinal meningiomas 1) 2).

see 5 aminolevulinic acid fluorescence guided resection of glioma

see 5 aminolevulinic acid fluorescence guided resection of intracranial meningioma

see 5 aminolevulinic acid fluorescence guided resection in children

see 5 aminolevulinic acid fluorescence guided resection and intraoperative monitoring

see 5 aminolevulinic acid fluorescence guided resection of high grade glioma.

see 5 aminolevulinic acid fluorescence guided resection of low grade glioma.

Meningeal sarcoma

First case published in the literature of meningeal sarcoma in a child in which intraoperative fluorescence with 5-ALA was used to achieve a complete resection 3).


Metabolic imaging tools such as 5-ALA fluorescence-guided resection and navigated FET-PET were helpful for the resection of complex-shaped, recurrent skull base meningioma. 5-ALA fluorescence was useful to dissect the adherent interface between tumor and brain. Furthermore, it helped to delineate tumor margins in the nasal cavity. FET-PET improved the assessment of bony and dural infiltration. We hypothesize that these imaging technologies may reduce recurrence rates through better visualization of tumor tissue that might be left unintentionally. This has to be verified in larger, prospective trials 4).

Tumor fluorescence can occur in benign meningiomas (WHO grade I) as well as in WHO grade II and WHO grade III meningiomas. Most of the reviewed studies report fluorescence of the main tumor mass with high sensitivity and specificity. However, different parts of the same tumor can present with a different fluorescent pattern (heterogenic fluorescence). Quantitative probe fluorescence can be superior, especially in meningiomas with difficult anatomical accessibility. However, only one study was able to consistently correlate resected tissue with histopathological results and nonspecific fluorescence of healthy brain tissue remains a confounder. The use of 5-ALA as a tool to guide resection of intracranial meningiomas remains experimental, especially in cases with tumor recurrence. The principle of intraoperative fluorescence as a real-time method to achieve complete resection is appealing, but the usefulness of 5-ALA is questionable. 5-ALA in intracranial meningioma surgery should only be used in a protocolled prospective and long-term study 5).

Spinal tumor

The application of 5-ALA has also been described in spinal tumors.

Three hours before the induction of anesthesia, 5-ALA was administered to patients with different intra- and extradural spinal tumors. In all patients a neurosurgical resection or biopsy of the spinal tumor was performed under conventional white-light microscopy. During each surgery, the presence of Protoporphyrin IX fluorescence was additionally assessed using a modified neurosurgical microscope. At the end of an assumed gross-total resection (GTR) under white-light microscopy, a final inspection of the surgical cavity of fluorescing intramedullary tumors was performed to look for any remaining fluorescing foci. Histopathological tumor diagnosis was established according to the current WHO classification.

Fifty-two patients with 55 spinal tumors were included in this study. Resection was performed in 50 of 55 cases, whereas 5 of 55 cases underwent biopsy. Gross-total resection was achieved in 37 cases, STR in 5, and partial resection in 8 cases. Protoporphyrin IX fluorescence was visible in 30 (55%) of 55 cases, but not in 25 (45%) of 55 cases. Positive PpIX fluorescence was mainly detected in ependymomas (12 of 12), meningiomas (12 of 12), hemangiopericytomas (3 of 3), and in drop metastases of primary CNS tumors (2 of 2). In contrast, none of the neurinomas (8 of 8), carcinoma metastases (5 of 5), and primary spinal gliomas (3 of 3; 1 pilocytic astrocytoma, 1 WHO Grade II astrocytoma, 1 WHO Grade III anaplastic oligoastrocytoma) revealed PpIX fluorescence. It is notable that residual fluorescing tumor foci were detected and subsequently resected in 4 of 8 intramedullary ependymomas despite assumed GTR under white-light microscopy.

In this study, 5-ALA-PpIX fluorescence was observed in spinal tumors, especially ependymomas, meningiomas, hemangiopericytomas, and drop metastases of primary CNS tumors. In cases of intramedullary tumors, 5-ALA-induced PpIX fluorescence is a useful tool for the detection of potential residual tumor foci 6).


Stummer et al. showed that 5–ALA guided resections carry a higher risk of post-operative neurological deterioration than conventional resections (26% vs 15%, respectively), even though the difference vanished within weeks 7).

Just as tumour tissue is often indiscernible from normal brain tissue, functionally critical tissues are indistinguishable from tissues with less clinically relevant functions.

Thus, knowing when to stop a resection due to proximity to areas of crucial neurological functions is of obvious and utmost importance. Detailed knowledge of the normal brain anatomy and distribution of function is not sufficient during glioma resection. Interindividual variability and functional relocation (i.e., plasticity) induced by the presence of an infiltrating tumour 8) requires an exact functional brain map at the site of surgery in order to spare areas involved in crucial (so-called eloquent) functions. Preoperative localisation of function, either with functional MRI (fMRI) or navigated transcranial magnetic stimulation (nTMS), provides an approximate map 9) 10).

Furthermore, intra-operative direct cortical and subcortical electrical stimulation (DCS) for functional analysis of the tissue in the tumour’s infiltration zone is required for accurate identification of areas that need to be spared in order to retain the patient’s functional integrity 11) 12). Motor evoked potentials (MEP) provide real-time information on the integrity of the primary motor cortex and the corticospinal tract 13). Direct cortical mapping and phase reversal identify the primary motor and sensory cortices. Subcortical mapping can estimate the distance to the pyramidal tract, acting as guidance close to functionally critical areas 14). When integrated into the existing surgical tools, continuous and dynamic mapping enables more extensive resection while simultaneously protecting motor function 15). Using these techniques and a detailed electrophysiological “Bern-concept”, a group achieved complete motor function protection in 96% of patients with high-risk motor eloquent tumours 16). Furthermore, localisation of cortical and subcortical regions relevant to language function is essential for speech preservation during resection of gliomas in proximity to presumed speech areas 17) and requires the patient to be awake during the brain mapping part of surgery. Similarly, intra-operative mapping of visual functions may contribute to increased resections while avoiding tissue essential for vision within the temporal and occipital lobes 18).

Chae MP, Song SW, Park SH, Park CK. Experience with 5- aminolevulinic Acid in fluorescence-guided resection of a deep sylvian meningioma. J Korean Neurosurg Soc. 2012;52:558–60.
Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: A prospective study in 52 consecutive patients. J Neurosurg. 2000;93:1003–13.
Bernal García LM, Cabezudo Artero JM, Royano Sánchez M, Marcelo Zamorano MB, López Macías M. Fluorescence-guided resection with 5-aminolevulinic acid of meningeal sarcoma in a child. Childs Nerv Syst. 2015 Apr 12. [Epub ahead of print] PubMed PMID: 25863951.
Cornelius JF, Slotty PJ, Stoffels G, Galldiks N, Langen KJ, Steiger HJ. 5-Aminolevulinic Acid and (18)F-FET-PET as Metabolic Imaging Tools for Surgery of a Recurrent Skull Base Meningioma. J Neurol Surg B Skull Base. 2013 Aug;74(4):211-6. doi: 10.1055/s-0033-1342918. Epub 2013 Apr 1. PubMed PMID: 24436914.
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Millesi M, Kiesel B, Woehrer A, Hainfellner JA, Novak K, Martínez-Moreno M, Wolfsberger S, Knosp E, Widhalm G. Analysis of 5-aminolevulinic acid-induced fluorescence in 55 different spinal tumors. Neurosurg Focus. 2014 Feb;36(2):E11. doi: 10.3171/2013.12.FOCUS13485. PubMed PMID: 24484249.
Stummer W1, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, et al. ALA-Glioma Study Group. Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5–aminolevulinic acid glioma resection study. J Neurosurg. 2011;114(3):613–23. doi: 10.3171/2010.3
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Krieg SM, Shiban E, Buchmann N, Gempt J, Foerschler A, Meyer B, et al. Utility of presurgical navigated transcranial magnetic brain stimulation for the resection of tumors in eloquent motor areas. J Neurosurg. 2012;116(5):994–1001. doi: 10.3171/2011.12.JNS111524
11) , 17)
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Seidel K, Beck J, Stieglitz L, Schucht P, Raabe A. The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors. J Neurosurg. 2013;118(2):287–96.
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Schucht P, Seidel K. Beck J, Murek M, Jilch A, Wiest R, et al. Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome. Neurosurg Focus. 2014;27(6):E16.
Gras-Combe G, Moritz-Gasser S, Herbet G, Duffau H. Intraoperative subcortical electrical mapping of optic radiations in awake surgery for glioma involving visual pathways. J Neurosurg. 2012;117(3):466–73.
5_aminolevulinic_acid_fluorescence_guided_resection.txt · Last modified: 2018/07/29 13:46 by administrador