Thermal threshold testing: call for a balance between the number of measurements and abnormalities in the diagnosis of sarcoidosis-associated small fiber neuropathy

Abstract

Introduction: Several recent studies of diagnosing small fiber neuropathy (SFN) have shown a lack of uniformity in thermal threshold testing (TTT) or 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.

Objectives: 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: One hundred seventeen participants were included (48 patients with sarcoidosis with probable SFN, 49 without SFN, and 20 healthy controls). Thermal threshold testing 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 a 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.

Keywords: Diagnosis; Method of levels; Quantitative sensory testing; Small fiber neuropathy; Temperature threshold testing.

Figure 1.

One patient showed a decreased vitamin B₁₂ level, 4 patients showed decreased nerve conduction velocity, and 1 patient was diagnosed with neurosarcoidosis during the process. In the end, 117 participants were eligible for inclusion. SFN, small fiber neuropathy.

Figure 2.

Principal component analysis of thermal threshold testing (TTT) parameters for the test foot. Patients with sarcoidosis without small fiber neuropathy (SFN) are displayed as blue dots and patients with sarcoidosis with probable SFN are displayed as yellow triangles. Overall, results overlapped between participants with probable SFN and those without SFN. When 2 vectors are close, with a small angle between them, the 2 variables represent a positive correlation. An example is CDT MLe and HPT. If they are at an angle of 90° to each other, they were not likely to be correlated. An example is PHS and WDT MLi. When they diverged and formed a large angle (close to 180°), they are negatively correlated. An example is CPT and WDT MLi. CDT, cold detection threshold; CPT, cold pain threshold; HPT, heat pain threshold; MLe, method of levels; MLi, method of limits; WDT, warm detection threshold.

Figure 3.

Distribution of abnormalities measured with both the method of levels (MLe) and the method of limits (MLi), with only MLe, with only MLi, or both detected as normal for (A) the cold detection threshold (CDT) and (B) the warm detection threshold (WDT).

Figure 4.

(A) Total number of abnormal thermal threshold test parameters (TTT NOA) was higher in patients with sarcoidosis and probable small fiber neuropathy (Prob. SFN) compared with patients without SFN (No SFN) and healthy controls (HCs). (B) SFNSL questionnaire also shows higher scores in the group with probable SFN. Note that there is a large dispersion in the group of patients with sarcoidosis without SFN. (C) Correlation was found between the number of abnormalities in thermal threshold testing (TTT NOAs) and the number of symptoms based on the SFNSL questionnaire.