Various shades of red-a systematic analysis of qualitative estimation of ALA-derived fluorescence in neurosurgery

5-Aminolevulinic acid (5-ALA)-fluorescence-guided resection is well established in many neuro-oncologic centers. Different classifications of 5-ALA-induced fluorescence have been reported. The aim of the systematic analysis was to evaluate the frequency of graduations, definitions, and designations of 5-ALA-induced fluorescence qualities. A systematic database search of PubMed was performed to identify studies reporting (1) on 5-ALA fluorescence-guided either spinal or cranial surgery, (2) on qualitative estimation and/or categorization of 5-ALA-induced fluorescence, (3) in English, and (4) were published as peer-reviewed original studies. Totally, 93 studies were identified. Different classification systems of 5-ALA-induced fluorescence were found. Over 60 % of the included studies used a dichotomized categorization of 5-ALA-induced fluorescence and 27.5 % of studies distinguished two different intensities of 5-ALA fluorescent tissue in addition to non-fluorescing tissue. More than 50 % of studies explicitly defined criteria for categorization of 5-ALA-induced fluorescence. The major limitation of the present analysis might be that it mainly comprises data from retrospective, uncontrolled, non-randomized trials. However, a precise definition of each 5-ALA-induced fluorescence quality is essential. Although dichotomized classification is the most common and simple graduation system, it may not be suitable for every clinical or scientific task. A three-level 5-ALA-induced fluorescence classification with precise definition of each fluorescence quality and their correlation with histological features would be more useful and reproducible in these cases.