78 Abstract Introduction - Several recent studies of diagnosing small fiber neuropathy (SFN) have shown a lack of uniformity in thermal threshold testing (TTT)/quantitative sensory testing (QST) which makes it a challenge to compare the data. It is known that the chance of finding an abnormality increases with increasing number of measurements. With this study we first wanted to investigate whether TTT could benefit from a new approach focusing on the balance between the number of measurements, depending on the selection of parameters and measuring sites, and on number of abnormalities (NOAs). Second, we wanted to address the role of the method of levels (MLe) in possible desensitization during TTT measurements. Methods - Onehundredseventeen participants were included (48 sarcoidosis patients with probable SFN, 49 without SFN, 20 healthy controls). TTT measurements and small fiber neuropathy screening list (SFNSL) questionnaire were used to assess SFN. Results - A combination of measuring all thermal threshold parameters at both feet except for MLe, showed the best diagnostic performance. Increasing TTT NOAs correlates with the severity of SFN. Adding the SFNSL questionnaire further improves diagnostic performance. Discussion - Looking at TTT NOAs in all TTT parameters except for MLe at both feet should be considered as new approach to improve the consistency and balance between the selection of TTT parameters, measuring sites and definition of “abnormal QST”. Moreover, the SFNSL questionnaire is a valuable tool to quantify SFN symptoms and could improve SFN diagnosis. Introduction Sarcoidosis is a complex immune-mediated granulomatous disease of unknown cause, which can affect various organs, such as the lungs, skin, eyes and heart. Non-organ related symptoms such as fatigue, cognitive failure and symptoms associated with small fiber neuropathy (SFN) may, however, also have a large impact on the quality of life 1. Up to 86% of patients with sarcoidosis experience symptoms associated with SFN.2 The exact prevalence, however, remains unknown. Symptoms include neuropathic pain, paresthesia, diminished heat and cold sensation, bedsheet intolerance or autonomic dysfunction.3,4 Diagnosis of SFN is currently based on clinical signs of SFN in combination with decreased intraepidermal nerve fiber density (IENFD) and/or abnormal quantitative sensory testing (QST).5–7 QST assesses both small and large nerve fibers.8 Since performing the full test is time-consuming, thermal threshold testing (TTT) has been selected to test the small nerve fibers,9–11 while nerve conduction studies are recommended to test large nerve fibers.12 TTT measures the cold detection threshold (CDT), warm detection threshold (WDT), thermal sensory limen (TSL), paroxysmal heat sensation (PHS), cold pain threshold (CPT) and heat pain threshold (HPT). CDT and WDT can be measured using the method of limits (MLi) and the method of levels (MLe). The MLi is time-dependent and requires the participant to respond as soon as they feel a change in temperature. MLe applies standardized temperature changes and requires feedback with a yes or no button to determine whether the next stimulus is higher (after no) or lower (after yes). No clear agreement has been reached on the superiority between the two methods and results are conflicting.7,11 For example, the DFNS protocol,13 the most widely recognized and standardized 5 82 5
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