What is the initial workup and treatment for unilateral foot neuropathy?

Unilateral Foot Neuropathy Workup

When a patient presents with unilateral foot neuropathy, immediately suspect Charcot neuro-osteoarthropathy (CNO) if they have diabetes and the foot is red, warm, and swollen—this requires urgent knee-high immobilization while diagnostic workup proceeds to prevent devastating complications including fracture, dislocation, deformity, ulceration, and amputation. 1

Critical Initial Assessment

Rule Out Charcot Neuro-Osteoarthropathy First

• Always suspect active CNO when a diabetic patient with neuropathy presents with a unilateral red, warm, swollen foot with intact skin and no ulceration history 1
• Initiate knee-high immobilization/offloading immediately while performing diagnostic studies—do not wait for imaging confirmation given the catastrophic consequences of delayed treatment 1
• Exclude other acute diagnoses: infection, gout, deep venous thrombosis 1
• Pain may be absent or mild due to sensory neuropathy, so lack of pain does not rule out CNO 1

Temperature Assessment

• Use infrared thermometry to measure skin temperature comparing the affected foot to the contralateral foot at identical anatomic points 1
• A temperature difference ≥2°C between feet suggests active CNO 1
• The site of maximum temperature difference correlates with radiographic abnormalities in 92% of cases 1

Comprehensive Neurological Evaluation

Clinical History

• Characterize symptoms: numbness, tingling, burning, pain distribution 2, 3
• Assess for diabetes mellitus (most common cause), alcohol use, toxin exposure, medication history (chemotherapy), vitamin deficiencies 2, 3, 4
• Determine onset and progression: acute (days) suggests Guillain-Barré syndrome; chronic (months-years) suggests metabolic or compressive causes 5, 6

Physical Examination

• 10-g monofilament testing: Most useful test to diagnose loss of protective sensation (LOPS); perform at multiple plantar sites 1, 7
• 128-Hz tuning fork: Assess vibration perception for large fiber function 1, 7
• Pinprick and temperature sensation: Evaluate small fiber function 7
• Ankle reflexes: Absent reflexes suggest peripheral neuropathy 1
• Inspect for skin integrity, deformities, ulcers, calluses 1
• Palpate pedal pulses and assess for peripheral arterial disease 1

Laboratory Workup

Initial Testing (All Patients)

• Fasting blood glucose and HbA1c: Screen for diabetes mellitus 2, 3, 4
• Vitamin B12 level: Common treatable cause 2, 3, 4
• Thyroid-stimulating hormone (TSH): Rule out hypothyroidism 2, 3, 4
• Complete blood count and comprehensive metabolic profile: Assess for systemic disease, renal dysfunction 3, 4
• Serum protein electrophoresis with immunofixation: Screen for paraproteinemia 3
• Erythrocyte sedimentation rate: Evaluate for inflammatory conditions 4

Additional Testing (If Indicated)

• Hepatitis B, C, and HIV serology if risk factors present 2
• Anti-ganglioside antibodies if Guillain-Barré syndrome suspected 2
• Lumbar puncture if acute inflammatory demyelinating polyneuropathy considered 4

Imaging Studies

For Suspected Charcot Neuro-Osteoarthropathy

• Plain radiographs of the affected foot and ankle 1
• Consider MRI or bone scan if radiographs inconclusive but clinical suspicion remains high 1

For Vascular Assessment

• Ankle-brachial index (ABI) if peripheral arterial disease suspected 1
• Urgent vascular imaging if ABI <0.5, toe pressure <30 mmHg, or transcutaneous oxygen pressure <25 mmHg 1

When to Refer to Neurology

Refer for electrodiagnostic studies (nerve conduction studies and electromyography) if:

• Initial evaluation is inconclusive 3, 4
• Pattern suggests mononeuropathy multiplex, demyelinating neuropathy, or motor predominant neuropathy 6, 8
• Rapid progression or asymmetric presentation without clear compressive etiology 6, 8
• Consideration of nerve biopsy needed 4, 8

Common Pitfalls

• Failing to immobilize immediately when CNO is suspected—waiting for imaging confirmation allows irreversible bone destruction 1
• Assuming unilateral presentation rules out diabetic neuropathy—CNO and compressive neuropathies can present unilaterally in diabetics 1
• Not excluding other causes of neuropathy (B12 deficiency, hypothyroidism, toxins) before attributing symptoms solely to diabetes 7, 3
• Missing up to 50% of diabetic neuropathy cases that are asymptomatic but still increase ulceration and amputation risk 7
• Overlooking peripheral arterial disease, which requires urgent revascularization if severe 1