Diagnostic Evaluation and Management of Axonal Sensorimotor Polyneuropathy

Diagnostic Evaluation

• Conduct electrodiagnostic studies to confirm the diagnosis and determine the pattern (axonal vs. demyelinating) of axonal sensorimotor polyneuropathy in patients with bilateral leg symptoms 1, 2
• Consider skin biopsy with intraepidermal nerve fiber (IENF) density measurement, particularly if small fiber involvement is suspected in patients with axonal sensorimotor polyneuropathy, as it has moderate to good sensitivity (45-90%) and very good specificity (95-97%) for polyneuropathy 1, 2, 3
• IENF density measurement has moderate to good sensitivity (45-90%) and very good specificity (95-97%) for diagnosing polyneuropathy in patients with axonal sensorimotor polyneuropathy 2

Monitoring and Follow-up

• Regularly assess the development of complications (autonomic dysfunction, falls, skin breakdown) in patients with axonal sensorimotor polyneuropathy, as recommended by the guidelines from Nature Reviews Neurology 4, 5
• Consider referral to specialized centers for patients with severe neuropathy of unidentified cause or atypical presentation, as suggested by the guidelines from Nature Reviews Neurology 4, 5

Special Considerations

• In cases resembling Guillain-Barré syndrome (GBS) with acute/subacute onset, consider urgent hospitalization and monitoring of respiratory function, and evaluate for potential triggers (infections, toxins), as recommended by the guidelines from Nature Reviews Neurology 4, 5
• For small fiber involvement, standard nerve conduction studies may be normal, but skin biopsy with IENF density measurement is particularly valuable for diagnosis, as noted in the guidelines from PM&R (The Journal of Injury Function & Rehabilitation) 1, 2, 3

Skin Biopsy Findings and Diagnostic Implications for Small‑Fiber Neuropathy

Diagnostic Value of Intraepidermal Nerve Fiber Density (IENF)

• In patients with suspected peripheral neuropathy, a skin biopsy that shows reduced IENF density has very high specificity (≈95‑97 %) for confirming a polyneuropathy, although its sensitivity is moderate (≈45‑90 %)【6】【7】.
• The presence of reduced IENF density markedly raises the probability that a polyneuropathy is present, but a normal IENF count does not rule out the disease【8】【7】.
• When standard nerve‑conduction studies are normal, a low IENF density is especially useful for diagnosing small‑fiber neuropathy【9】.

Axonal Swellings as a Prognostic Marker

• Detection of axonal swellings on skin biopsy predicts progression of neuropathy and reflects active axonal degeneration in patients with small‑fiber disease【6】【7】【10】.

Functional Testing for Small‑Fiber Neuropathy

• The Quantitative Sudomotor Axon Reflex Test (QSART) identifies distal small‑fiber loss with a sensitivity of 75‑90 % in the evaluated population【8】【10】.
• Comprehensive autonomic testing is recommended when patients exhibit symptoms suggestive of autonomic involvement, to further characterize small‑fiber dysfunction【9】【7】.

Ancillary Laboratory Evaluation

• A basic metabolic panel (including renal function and electrolytes) is part of the essential first‑line laboratory work‑up for patients with suspected small‑fiber neuropathy【6】.