What lab tests are used to diagnose axonal symmetric polyradiculopathy?

Laboratory Testing for Axonal Symmetric Polyradiculopathy

For axonal symmetric polyradiculopathy, the highest-yield screening laboratory tests are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis. 1

Core Screening Laboratory Panel

The American Academy of Neurology recommends the following tests with highest diagnostic yield for distal symmetric polyneuropathy 1:

First-Tier Tests (Highest Yield)

• Blood glucose - screens for diabetes and pre-diabetes, which are among the most common causes of axonal polyneuropathy 1
• Serum B12 with metabolites (methylmalonic acid with or without homocysteine) - more sensitive than B12 alone for detecting deficiency states 1
• Serum protein immunofixation electrophoresis (IFE) - superior to standard serum protein electrophoresis (SPEP) for detecting monoclonal gammopathies, identifying 17% of cases that SPEP misses, particularly small IgM gammopathies 1

Additional Glucose Testing

• Glucose tolerance test (GTT) should be considered when routine blood glucose is not clearly abnormal, especially in patients with painful sensory polyneuropathy, as 25-36% of patients with idiopathic distal symmetric polyneuropathy have impaired glucose tolerance versus 15% of controls 1

Additional Laboratory Tests Based on Clinical Context

Beyond the core panel, additional testing should be guided by specific clinical features 1:

Standard Additional Screening

• Complete blood count - evaluates for hematologic abnormalities 2
• Comprehensive metabolic panel - assesses renal function (uremic neuropathy) and electrolyte abnormalities 2
• Thyroid stimulating hormone (TSH) - screens for hypothyroidism as a reversible cause 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) - markers of inflammation 3

Specialized Testing for Specific Presentations

• HIV testing - particularly in at-risk populations 2
• Hepatitis B and C serologies - when vasculitic neuropathy suspected 2
• Antinuclear antibodies (ANA) and other autoimmune markers - if connective tissue disease suspected 2
• Creatine kinase (CK) - if concurrent myopathy suspected 3

Genetic Testing Considerations

Genetic testing may be considered only in patients with a classical hereditary neuropathy phenotype (early onset, family history, pes cavus, slowly progressive course) 1:

• CMT1A duplication testing yields 54-80% positivity in patients with demyelinating hereditary neuropathy phenotype 1
• Connexin 32 (GJB1) mutations account for approximately 12% of CMT cases and can present with either demyelinating or axonal patterns 1
• MFN2 mutations account for approximately 33% of axonal CMT2 cases 1

However, there is insufficient evidence to support routine genetic testing in cryptogenic polyneuropathy patients without a classical hereditary phenotype 1

Important Caveats

Monoclonal Gammopathy Detection

The use of immunofixation electrophoresis rather than standard protein electrophoresis is critical, as IFE detects 30% of small IgM monoclonal proteins (<5g/L) that SPEP misses 1. In referral center populations, 10% of patients with otherwise unexplained polyneuropathy have monoclonal gammopathy 1.

Pre-Diabetes Recognition

A common pitfall is failing to pursue glucose tolerance testing when fasting glucose is borderline or normal, particularly in patients with painful neuropathy. Impaired glucose tolerance is significantly more prevalent in painful versus painless sensory polyneuropathies 1.

Laboratory Abnormality Does Not Equal Causation

Finding a laboratory abnormality does not necessarily establish etiologic significance - the relationship between the abnormality and the neuropathy must be clinically plausible 1. For example, while impaired glucose tolerance is common in idiopathic polyneuropathy, whether this is truly causative remains uncertain 1.

Clinical Judgment Determines Additional Testing

Beyond the core screening panel, the specific clinical presentation should guide which additional specialized tests are pursued, as there is insufficient evidence for routine comprehensive testing in all cases 1.