What is the appropriate work‑up for a patient presenting with tingling and numbness?

Work-Up for Tingling and Numbness

Order nerve conduction studies and electromyography as the primary diagnostic test to confirm polyneuropathy and distinguish between axonal versus demyelinating patterns, while simultaneously screening for reversible metabolic causes with laboratory testing including glucose, HbA1c, vitamin B12, folate, TSH, HIV, and serum protein electrophoresis. 1

Initial Clinical Assessment

Determine the distribution pattern through focused history and examination:

• Distal symmetric pattern (stocking-glove distribution starting in toes/feet, progressing proximally) strongly suggests polyneuropathy and is the most common presentation 1
• Asymmetric or multifocal pattern affecting individual nerves suggests mononeuritis multiplex, requiring different diagnostic approach and often indicating vasculitis or inflammatory causes 1
• Proximal symptoms or symptoms that worsen with standing/walking may indicate radiculopathy or spinal stenosis rather than polyneuropathy 1

Key examination findings to document:

• Distal sensory loss to all modalities (pinprick, light touch, vibration, proprioception) 1
• Reduced or absent ankle reflexes, progressing to more proximal reflexes as severity increases 1
• Distal muscle weakness and atrophy if motor fibers are involved 1
• Wide-based, unsteady gait indicating proprioceptive sensory loss 1
• Autonomic symptoms including orthostatic hypotension, gastrointestinal dysmotility, urinary retention, or sexual dysfunction 1

Electrodiagnostic Testing Strategy

Nerve conduction studies are essential for:

• Documenting large fiber involvement and confirming the diagnosis of polyneuropathy 1
• Distinguishing axonal from demyelinating patterns, which narrows the differential diagnosis significantly 1
• Showing diffuse abnormalities with relatively uniform involvement across multiple tested nerves in polyneuropathy, versus focal abnormalities in mononeuropathies 1

Important timing consideration: Do not perform electrodiagnostic studies within the first week of acute symptom onset, as studies may be normal in 30-34% of patients with active disease; repeat testing 2-3 weeks later if initial studies are normal but clinical suspicion remains high 1

For small fiber neuropathy specifically:

• Conventional nerve conduction studies will be normal because small unmyelinated C-fibers are not assessed by standard techniques 1
• Order skin biopsy with intraepidermal nerve fiber density measurement to diagnose small fiber neuropathy 1
• Consider autonomic testing (heart rate variability, quantitative sudomotor axon reflex test) to document autonomic nervous system dysfunction 1

Essential Laboratory Screening

Order the following tests to identify reversible causes:

• Fasting glucose and HbA1c (diabetes is the leading cause in developed countries) 1
• Vitamin B12 and folate levels 1
• Thyroid-stimulating hormone (TSH) for hypothyroidism 1
• HIV testing 1
• Serum protein electrophoresis with immunofixation to screen for paraproteinemias and multiple myeloma 1
• Comprehensive metabolic panel to assess for chronic kidney disease and uremic neuropathy 1

When to Order Neuroimaging

Neuroimaging is indicated when:

• Any abnormal finding on neurologic examination beyond the expected distal symmetric sensory loss and reflex changes—this significantly increases likelihood of intracranial pathology 2
• History of numbness or tingling accompanied by headache, particularly if headache awakens patient from sleep, worsens with Valsalva, or is rapidly increasing in frequency 2
• Asymmetric presentation suggesting mononeuritis multiplex, which may require MRI to evaluate for nerve root enhancement or thickening 1
• Focal neurological deficits beyond the expected polyneuropathy pattern 2

Neuroimaging is NOT indicated for:

• Classic distal symmetric sensory loss in stocking-glove distribution with reduced ankle reflexes and known risk factors (e.g., diabetes)—the diagnosis can be made clinically 1
• Routine monitoring of stable, established polyneuropathy—serial neurologic examinations are preferred over repeated imaging 1

Common Pitfalls to Avoid

Do not order EMG for typical diabetic neuropathy with classic stocking-glove distribution and normal strength—this adds cost without changing management, as clinical examination is sufficient 1

Do not use EMG for routine serial monitoring of stable peripheral neuropathy—repeated EMG is only warranted when there is uncertainty about new or worsening neurological processes 1

Do not dismiss small fiber neuropathy because nerve conduction studies are normal—79.6-91.4% of peripheral nerve fibers are small fibers not assessed by conventional studies; skin biopsy is required for diagnosis 1

Do not perform electrodiagnostic studies too early—wait at least 1-2 weeks from symptom onset to avoid false-negative results, and repeat if initial studies are normal but suspicion remains high 1

Specific Diagnostic Patterns

For demyelinating polyneuropathy (e.g., Guillain-Barré syndrome):

• Look for reduced conduction velocities, prolonged distal motor latencies, abnormal temporal dispersion, partial motor conduction blocks, and prolonged or absent F-waves 1
• "Sural sparing" pattern (normal sural sensory response with abnormal median/ulnar responses) is highly characteristic of Guillain-Barré syndrome 1

For mononeuritis multiplex:

• Asymmetric sensory and/or motor deficits affecting multiple individual nerves with pain as prominent feature 1
• Consider vasculitis (polyarteritis nodosa is prototypical), infectious causes (HEV genotype 3), or inflammatory conditions 1
• Nerve biopsy may be valuable when vasculitis is suspected 1

Management Implications

Once polyneuropathy is confirmed:

• Treat underlying cause when identified (optimize glucose control, replace B12, treat hypothyroidism, etc.) 1
• For neuropathic pain: first-line medications include pregabalin, duloxetine, or tricyclic antidepressants; second-line options include gabapentin, tramadol, or SSRIs 1
• For autonomic symptoms: increased salt/fluid intake, fludrocortisone, midodrine, or droxidopa 1
• For immune-mediated polyneuropathies (e.g., Guillain-Barré): intravenous immunoglobulin or plasmapheresis 1