Diagnostic and Therapeutic Recommendations for Symmetric Sensorimotor Axonal Neuropathy

Diagnostic Workup

Perform targeted laboratory screening that includes fasting blood glucose (or HbA1c), serum vitamin B12 with methylmalonic acid ± homocysteine, and serum protein immunofixation electrophoresis, as these tests provide the highest diagnostic yield for symmetric sensorimotor axonal neuropathy. 1
Fasting blood glucose testing is the single most valuable initial screen because diabetes and pre‑diabetes are highly prevalent among patients with distal symmetric polyneuropathy. 1
Serum vitamin B12 with metabolite measurements should be obtained routinely, since B12 deficiency represents a common, reversible cause of axonal neuropathy. 1
Serum protein immunofixation electrophoresis is more sensitive than standard SPEP and identifies monoclonal gammopathies in roughly 10 % of otherwise unexplained cases. 1
When routine glucose results are borderline or inconclusive, a glucose tolerance test should be added, particularly in patients whose neuropathy is painful. 1

Order genetic testing when a family history suggests a hereditary neuropathy; current panels achieve 100 % specificity and high sensitivity for pathogenic mutations in Charcot‑Marie‑Tooth disease and related disorders. 1

Treat any underlying metabolic or hematologic abnormalities uncovered by the workup—e.g., optimize glycemic control for diabetes, provide vitamin B12 supplementation for deficiency, and address clinically significant monoclonal gammopathies. 1

Skin biopsy for intra‑epidermal nerve‑fiber density may be considered when clinical features point to small‑fiber involvement. 2
Nerve biopsy is not routinely indicated for typical symmetric sensorimotor axonal neuropathy; reserve it for specific indications such as suspected amyloid neuropathy, vasculitic mononeuropathy multiplex, or atypical chronic inflammatory demyelinating polyneuropathy. 2

Autonomic testing can be employed to document dysautonomia when patients report sweating abnormalities or circulatory instability. Age‑adjusted reference values are required to achieve high specificity (≈ 97.5 %) and avoid false‑positive results from intrinsic cardiac disease. 2