What is the appropriate work‑up for a patient presenting with numbness to the middle of the leg?

Work-up for Numbness to Middle of Leg

Begin with a focused history and neurological examination to determine whether this represents a dermatomal pattern (suggesting radiculopathy), a peripheral nerve distribution, or a systemic neuropathy, as the pattern of sensory loss will direct your entire diagnostic approach. 1, 2

Critical Initial Assessment

History - Key Questions to Ask

• Duration and progression: Acute onset over hours to days suggests vascular or inflammatory causes (including Guillain-Barré syndrome), while gradual onset over weeks to months suggests metabolic or compressive etiologies 1, 3

• Unilateral vs bilateral: Bilateral symptoms strongly suggest systemic disease (diabetes, vitamin deficiency, toxin) rather than focal nerve compression 1, 2

• Associated symptoms requiring urgent evaluation:

  • Bladder/bowel dysfunction, saddle anesthesia, or perineal numbness (cauda equina syndrome) 2
  • Ascending weakness with areflexia (Guillain-Barré syndrome) 2, 3
  • Back pain with progressive bilateral leg symptoms (spinal cord compression) 2

• Risk factors for systemic neuropathy: Diabetes history, alcohol use, vitamin B12 deficiency, thyroid disease, medications (chemotherapy, isoniazid), family history of neuropathy 1

• Vascular symptoms: Leg fatigue or numbness with exertion that improves with rest suggests peripheral arterial disease 4, 1, 2

Physical Examination - What to Check

Neurological examination priorities 4, 1:

• Reflexes first: Areflexia/hyporeflexia suggests peripheral nerve or root pathology (Guillain-Barré, radiculopathy), while hyperreflexia with upgoing toes indicates spinal cord pathology requiring emergency imaging 2, 3

• Sensory testing:

  • Pinprick and temperature (small fiber function) 1
  • Vibration with 128-Hz tuning fork (large fiber function) 4, 1
  • 10-g monofilament testing at multiple sites if diabetic neuropathy suspected 4, 1
  • Map the exact distribution: dermatomal (L2-S1), stocking pattern (length-dependent neuropathy), or patchy 1

• Motor examination: Test hip flexion, knee extension/flexion, ankle dorsiflexion/plantarflexion, and toe extension to identify weakness patterns 2

• Check for sensory level: A sharp cutoff at a specific spinal level indicates cord pathology and requires emergency MRI 2

• Sphincter function: Impaired anal tone or perineal sensation is a red flag for cauda equina syndrome 2

• Vascular assessment: Palpate pedal pulses; absent or diminished pulses suggest peripheral arterial disease 4, 1, 2

Laboratory Work-up

Order these tests for most patients with leg numbness 1:

• Hemoglobin A1c or fasting glucose (diabetes is the most common cause) 1
• Vitamin B12 level (deficiency causes sensory neuropathy) 1
• Thyroid function tests (hypothyroidism causes neuropathy) 1
• Complete blood count (screen for anemia, hematologic disorders) 1
• Comprehensive metabolic panel (assess renal function, electrolytes) 1

Additional testing if history suggests:

• Creatinine and eGFR if uremic neuropathy suspected 3
• CSF analysis if Guillain-Barré syndrome suspected (elevated protein with normal cell count) 3

Imaging Decisions

Emergency MRI of entire spine is indicated for 2, 3:

• Progressive bilateral leg weakness with bladder/bowel dysfunction 2
• Sensory level on examination 2
• Hyperreflexia with upgoing toes (cord compression) 2
• Suspected Guillain-Barré syndrome (to exclude cord pathology and assess for nerve root enhancement) 3

Imaging is NOT routinely indicated 1:

• Isolated sensory symptoms without weakness, normal reflexes, no red flags 1
• Suspected diabetic or metabolic neuropathy with typical stocking-glove pattern 1

Ankle-brachial index testing should be performed if peripheral arterial disease suspected (symptoms with exertion, diminished pulses) 4, 1, 2

Electrodiagnostic Testing

EMG/nerve conduction studies are rarely needed initially but reserve for 1:

• Atypical clinical features that don't fit a clear pattern 1
• Diagnosis remains unclear after initial work-up and 6-8 weeks of observation 1
• Need to distinguish between demyelinating vs axonal neuropathy (affects treatment in Guillain-Barré) 3

Critical Pitfalls to Avoid

• Don't assume mechanical causes without screening for diabetes, even in younger patients—diabetes is the most common cause of peripheral neuropathy 1

• Bilateral presentation suggests systemic disease, not focal compression; don't order lumbar spine MRI reflexively without considering metabolic causes first 1

• Don't miss cauda equina syndrome: Any bilateral leg symptoms with bladder/bowel changes require emergency MRI within hours, as surgery within 12-72 hours of retention improves outcomes 2

• Don't delay respiratory monitoring in suspected Guillain-Barré: 20% develop respiratory failure; check vital capacity and negative inspiratory force immediately 3

• Absent reflexes with ascending weakness is Guillain-Barré until proven otherwise—this requires urgent hospitalization, not outpatient work-up 2, 3

Management Based on Findings

If laboratory abnormalities identified 1:

• Optimize diabetes control if A1c elevated 1
• Supplement vitamin B12 if deficient 1
• Thyroid replacement if hypothyroid 1

If symptoms persist beyond 6-8 weeks despite normal initial work-up 1:

• Refer to neurology for electrodiagnostic studies 1
• Consider podiatry referral for custom orthotics and biomechanical assessment 1

If Guillain-Barré confirmed or highly suspected 3:

• Admit to monitored setting with respiratory monitoring capability 3
• Initiate IVIG 2 g/kg over 5 days or plasmapheresis urgently 3
• Monitor for dysautonomia 3