Punch (skin) biopsy – IENFD

What it is: A 3-mm skin punch biopsy used to quantify intraepidermal nerve fiber density (IENFD).

Evidence and Role: “Distal leg skin biopsy… is a reliable and efficient technique to assess the diagnosis of SFN.”

(Level A)Safety: “3-mm skin biopsy at the ankle is a safe procedure… [with] 0.19% incidence of non-serious side effects.”

Comparison: Highly specific and objective, but invasive and less practical for frequent monitoring.
SUDOSCAN, being non-invasive, is better suited for regular screening or follow-up.

QSART (Quantitative Sudomotor Axon Reflex Test)

What it is: Uses cholinergic iontophoresis to measure postganglionic sudomotor function.

Core physiology: “QSART measures the postganglionic sudomotor response.”

Limitations: “QSART is also time-consuming, requires special equipment and is not widely available.”

Comparison: QSART is physiologically precise but resource-intensive. 

SUDOSCAN offers a faster, clinic-friendly sudomotor test.

SSR (Sympathetic Skin Response)

What it is: Measures evoked electrodermal potentials reflecting sympathetic cholinergic activation.

Sensitivity caveat: “Considering its low sensitivity, SSR should not be used as the only test to confirm sensory small fibre neuropathy.”

Comparison: SSR is easy to perform but less sensitive. 

SUDOSCAN delivers an objective, quantitative, reproducible sudomotor measurement.

QST (Quantitative Sensory Testing)

What it is: Assesses thermal and mechanical detection thresholds through patient response.

Limitations: “Quantitative sensory tests are psychophysical in nature, requiring cooperation from the patient.” And: “QST is a psychophysical test and lacks the objectivity of NCS.”

Comparison: QST helps characterize sensory gain/loss but is subjective.

 SUDOSCAN is objective, operator-independent, and less influenced by patient variability.

EMG (Electromyography)

What it is: Measures the electrical activity of muscles at rest and during contraction, typically via needle electrodes, to evaluate motor nerve and muscle health.

Clinical role: “Electromyography (EMG) is used to assess the health of muscles and the nerve cells that control them (motor neurons).”

Limitations for SFN: EMG primarily detects large fiber or motor involvement; “EMG and nerve conduction studies are often normal in patients with small fiber neuropathy.”

Comparison: EMG is valuable for ruling out other neuropathies and neuromuscular disorders but has low sensitivity for SFN. 

SUDOSCAN directly evaluates small autonomic fibers, making it complementary rather than competitive.