From:  Biomarkers in small fiber neuropathy

Clinically available autonomic and small fiber function tests

Clinically available autonomic and small fiber function testsWhat they measureModalitiesAdvantagesDisadvantagesSensitivity/specificityReference
VMAssesses the reduction in cardiac preloadCardiovascular adrenergicProvides quick results for analysisPatients may experience increase in blood pressure80% Sensitivity, 80% specificity[56, 59, 67]
Tilt table testChanges in blood volume due to gravity redistribution in the transition to an upright postureCardiovascular adrenergicProvides quick results for analysisLarge range of long-term reproducibility (50–85%)The sensitivity and specificity are difficult to establish[56, 111]
SSW testDegree of wrinkling, which reflects vasoconstriction controlled by sympathetic nerve fibers in the glabrous handSudomotor

  • Simple to perform

  • Cost-effective

  • Does not require specialized equipment

Limited to the hands, because wrinkling in the feet is unreliable

  • - EMLA wrinkling: 81.6% sensitivity, 74.7% specificity

  • - Water wrinkling: 71.4% sensitivity, 73% specificity

[60–63]
QSARTQuantitative assessment of postganglionic sudomotor function controlled by autonomic nerve fibers that cause sweatingSudomotorAble to assess the distribution of sudomotor impairment

  • Moderate test- retest reliability with a large standard error of measurement

  • Norms only established for ≥ 10 years of age

Sensitivity of 80%[16, 64–66]
QSTPsychophysical thresholds for cold and warm sensationsThermal sensation

  • Non-invasive

  • Easily performed

  • More reproducible than QSART

  • High inter- operator, inter- patient and inter- test variability

  • Cannot differentiate between central and peripheral causes

-[69, 70, 72, 73]
Thermoregulatory sweat test (TST)Percentage of anterior body surface anhidrosisSudomotor

  • Able to detect abnormality at any point along the sudomotor neuraxis

  • Greater sensitivity than tests confined to sampled sites

Patients experience thermal discomfort of the heat stimulus which makes them reluctant to undergo repeat testing80% Sensitivity[56]
Sympathetic skin response (SSR)Momentary changes in electrical potentials associated with induced sweating in palms and solesSudomotorSimple to implement

  • Highly variable response

  • Does not reflect degree of dysfunction

87.5% Sensitivity
88.2% Specificity		[56]
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