What is the recommended work-up for neuropathy?

Recommended Work-up for Neuropathy

The recommended work-up for neuropathy should include screening for reversible causes through comprehensive laboratory testing, neurological examination, and specialized testing based on clinical presentation.

Initial Evaluation

• History and targeted neurological examination to determine the pattern of symptoms (stocking-glove distribution, symmetric vs. asymmetric, sensory vs. motor, small vs. large fiber involvement) 1
• Screen for common reversible causes with initial laboratory tests:
  • Complete blood count 1, 2
  • Comprehensive metabolic profile 1, 2
  • Fasting blood glucose and HbA1c 1
  • Vitamin B12 level 1, 2
  • Thyroid-stimulating hormone (TSH) 1, 2
  • Serum protein electrophoresis with immunofixation 1, 2

Clinical Assessment of Neuropathy

• Small-fiber function assessment using pinprick and temperature sensation tests 1
• Large-fiber function assessment using:
  • Vibration perception testing 1
  • 10-g monofilament testing 1
  • Lower extremity reflexes 1
• Protective sensation assessment using 10-g monofilament 1

Additional Testing Based on Clinical Suspicion

• Electrodiagnostic studies (nerve conduction studies and electromyography) to differentiate between axonal and demyelinating neuropathies 1, 2
• Specialized laboratory tests when clinically indicated:
  • Antiganglioside antibody tests for Guillain-Barré syndrome and its variants 1
  • Paraneoplastic workup (e.g., ANNA-1 antibody testing) 1
  • Autoimmune panels (ANA, ESR, CRP, ANCA, anti-smooth muscle, SSA/SSB, RNP, anti-dsDNA) 1
  • Vitamin B6, folate levels 1
  • Lyme disease, hepatitis B/C, and HIV testing 1, 2
  • Flow cytometry in patients with hematologic malignancies 1

Imaging and Advanced Diagnostics

• MRI of the spine with/without contrast if radiculopathy or spinal cord involvement is suspected 1
• MRI of the brain if cranial nerve involvement is present 1
• MRI of the plexus if plexopathy is suspected 1
• Lumbar puncture with CSF analysis for cell count, protein, glucose, cytology, and cultures when inflammatory neuropathies are suspected 1, 2

Autonomic Neuropathy Assessment

• Cardiovascular autonomic testing for heart rate variability with deep breathing 1
• Orthostatic vital signs to detect orthostatic hypotension 1
• Gastrointestinal evaluation if symptoms present:
  • Gastric emptying scintigraphy for suspected gastroparesis 1
  • 13C octanoic acid breath test as an alternative 1
• Genitourinary evaluation for patients with recurrent urinary tract infections, incontinence, or palpable bladder 1

Special Considerations

• Diabetic neuropathy work-up should include assessment of glycemic control, blood pressure, and lipid management 1
• Immune checkpoint inhibitor-related neuropathy requires additional monitoring of pulmonary function (NIF or VC) and frequent neurological checks 1
• Guillain-Barré syndrome requires immediate hospitalization with capability for ICU transfer and specialized testing 1

Common Pitfalls to Avoid

• Failure to identify treatable causes of neuropathy, which account for a significant percentage of cases 2
• Overlooking non-diabetic causes in patients with diabetes, as other etiologies may coexist 1
• Incomplete evaluation of small fiber neuropathy, which may be missed by conventional nerve conduction studies 3
• Neglecting autonomic symptoms which can significantly impact morbidity and mortality 1
• Premature attribution to idiopathic causes before completing a thorough evaluation 4, 2

Remember that approximately 25-46% of peripheral neuropathy cases remain idiopathic despite comprehensive evaluation 2, but identifying treatable causes is essential for improving patient outcomes and quality of life.