36 Figure 5 AUC overview of several diagnostic methods. It determines the diagnostic accuracy of each method. The size of each bubble represents the study size. Unmyelinated axon-Schwann ration is calculated based on biopsies and not further reviewed in this article. Clinical applicability Not all methods are ready for routine use. Table 4 sums up the limitations for each method and their clinical applicability level. The classification is designed for this review and based on the Dutch healthcare system, which consists of 4 hospital levels. Level 1: Clinical applicable in general hospitals Level 2: Clinical applicable in top clinical hospitals Level 3: Clinical applicable in academic hospitals Level 4: Only used in research setting or not yet applicable for routine use Each technique is labeled based on current applicability. Diagnostic workflow Since small nerve fibers are part of both the somatic and autonomic nervous system, the location of the neuropathy influences the type of symptoms. Therefore phenotyping SFN into “small fiber sodium channel dysfunction”, “small fiber mediated painful neuropathy”, “small fiber mediated widespread 2 38 2
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