Definition and Overview
The sudomotor function test is an autonomic nervous system assessment that evaluates the functional integrity of sympathetic cholinergic C fibers innervating the sweat glands. Sweating is one of the final effector responses of the autonomic nervous system and is among the first functions to show abnormalities in small fiber neuropathy.
Conventional nerve conduction studies can only evaluate large myelinated fibers (A-beta, A-delta), limiting their ability to diagnose small fiber (C fiber, A-delta fiber) lesions. Sudomotor function testing is a key examination that fills this diagnostic gap, demonstrating approximately 80% sensitivity in the diagnosis of small fiber neuropathy [1].
Types of Tests
Quantitative Sudomotor Axon Reflex Test (QSART)
QSART (quantitative sudomotor axon reflex test) is the standard sudomotor function test developed at the Mayo Clinic [1].
The test principle is as follows: acetylcholine is delivered to the skin via iontophoresis, stimulating sudomotor nerve terminals. Through the axon reflex, adjacent sweat glands are activated. Sweat output is quantitatively measured using a multicompartmental sweat cell.
The standard test sites are 4 locations: the forearm, proximal leg, distal leg, and foot. Sweat output (microL/cm2) is recorded over 5 minutes at each site and compared against age- and sex-specific normative values for interpretation.
Thermoregulatory Sweat Test (TST)
The thermoregulatory sweat test (TST) is an examination that visually assesses whole-body sweat distribution. After applying an indicator powder (alizarin red or starch-iodine powder) to the entire body surface, the temperature in a sealed testing room is raised to increase core body temperature by approximately 1 degrees C. Areas of sweating are revealed by color changes in the indicator, allowing photographic documentation of sweat distribution [2].
The advantage of TST is its ability to assess whole-body sweat distribution in a single examination, and anhidrosis patterns can help differentiate central (preganglionic) from peripheral (postganglionic) lesions.
Sympathetic Skin Response (SSR)
The sympathetic skin response (SSR) is a straightforward test that measures cutaneous electrical activity. It records skin potential changes in response to electrical stimulation, inspiratory stimulation, or psychological stimuli. While the test is simple and can be performed with standard electromyography equipment, it has limitations including poor reproducibility due to habituation and difficulty with quantification.
Quantitative Direct and Indirect Test of Sudomotor Function (QDIRT)
QDIRT (quantitative direct and indirect test of sudomotor function) is a method that quantitatively evaluates both direct and axon reflex responses at the individual sweat droplet level following acetylcholine iontophoresis [3]. It has been reported to provide accuracy comparable to QSART while being relatively simpler to perform.
Clinical Applications
Small Fiber Neuropathy
In patients with burning pain, tingling, and autonomic symptoms despite normal nerve conduction studies, abnormal sudomotor function testing is an important finding suggestive of small fiber neuropathy. The combination of QSART abnormalities and skin biopsy (reduced intraepidermal nerve fiber density) represents the diagnostic gold standard [5].
Diabetic Autonomic Neuropathy
Sudomotor dysfunction is one of the early signs of diabetic autonomic neuropathy. Abnormalities first appear distally (in the feet) and progress proximally with disease advancement. Regular sudomotor function testing is useful for monitoring the progression of autonomic neuropathy [1].
CRPS
In complex regional pain syndrome (CRPS), sweat abnormalities (either excessive or diminished) in the affected limb are part of the diagnostic criteria. QSART enables objective comparison of sweat output between the affected and unaffected limbs.
POTS and Other Conditions
Approximately 50% of patients with postural orthostatic tachycardia syndrome (POTS) demonstrate distal sudomotor reduction, suggesting peripheral sympathetic nerve dysfunction. Characteristic sudomotor abnormality patterns are also observed in multiple system atrophy, Parkinson's disease, and pure autonomic failure [4].
Interpretation of Results
QSART Result Interpretation
- Reduced sweat output: Suggests a peripheral lesion in the axon reflex pathway (postganglionic sudomotor failure).
- Increased sweat output: May indicate denervation supersensitivity or reinnervation processes.
- Selective distal reduction: A typical pattern of length-dependent small fiber neuropathy.
- Asymmetric findings: Suggestive of CRPS or focal nerve lesions.
TST Result Interpretation
- Distal anhidrosis: Peripheral autonomic neuropathy
- Segmental anhidrosis: Spinal cord lesion, sympathetic chain lesion
- Widespread anhidrosis: Central causes such as multiple system atrophy, pure autonomic failure
Limitations of the Test
Sudomotor function is influenced by age, sex, body temperature, ambient temperature and humidity, medications, and skin condition. Standardized testing environments and application of age- and sex-specific normative values are essential. Diagnosis should not be based on a single test result alone but rather on a comprehensive assessment integrating clinical findings and other autonomic function test results [2].