I have unilateral leg numbness with hyperesthesia over the dorsum of the foot; what evaluation and management steps should I take?

Unilateral Leg Numbness with Dorsal Foot Hyperesthesia: Evaluation and Management

This presentation requires urgent evaluation to exclude acute limb ischemia and nerve compression syndromes, followed by systematic assessment for peripheral neuropathy, radiculopathy, and local nerve entrapment.

Immediate Life-Threatening Conditions to Rule Out

First, assess vascular status immediately by palpating dorsalis pedis and posterior tibial pulses bilaterally. 1

• Absent or significantly diminished pulses with unilateral symptoms constitute a vascular emergency requiring immediate vascular surgery consultation within 6 hours to prevent irreversible tissue loss 1
• Acute limb ischemia presents with the "6 P's": pulselessness, pallor, paresthesias, paralysis, coolness (poikilothermia), and pain 1
• If pulses are uncertain, use handheld continuous-wave Doppler at bedside to assess arterial signals—loss of Doppler signal indicates a threatened limb 1
• Start systemic anticoagulation with unfractionated heparin immediately if acute limb ischemia is suspected, unless contraindicated 1

Second, assess for progressive motor weakness or rapidly ascending sensory loss, which may indicate Guillain-Barré syndrome or acute myelopathy. 2

• Check for areflexia/hyporeflexia, ascending weakness pattern, and history of preceding infection within 6 weeks 2
• Immediate MRI of the entire spine is required if you suspect cord compression or transverse myelitis 2
• Admission to a monitored setting with respiratory monitoring capability is necessary if Guillain-Barré syndrome is suspected 2

Focused History Elements

Obtain specific details about symptom distribution, temporal pattern, and aggravating factors:

• Distribution pattern: Determine if numbness follows a dermatomal pattern (suggesting radiculopathy), involves the entire leg distal to a certain level (suggesting peripheral neuropathy), or is localized to the dorsum of the foot (suggesting local nerve entrapment) 3, 4
• Temporal course: Acute onset (<6 hours) with pain/weakness suggests arterial occlusion or aortic dissection; subacute progression over days to weeks suggests inflammatory or compressive etiology; chronic progression over months suggests metabolic or hereditary neuropathy 1, 5
• Exacerbating factors: Symptoms that worsen with walking, running, or squatting suggest superficial peroneal nerve entrapment; symptoms worse with standing and extending spine suggest spinal stenosis; symptoms worse with hip flexion suggest sciatic nerve involvement 6, 3
• Associated symptoms: Back pain radiating down the leg suggests radiculopathy; rest pain worse when supine and improved with limb dependency suggests critical limb ischemia; autonomic symptoms (orthostatic hypotension) suggest diabetic neuropathy 3, 5

Medication review is crucial:

• Metformin (especially ≥2g daily) causes vitamin B12 deficiency leading to peripheral neuropathy 7
• Chemotherapy agents (cisplatin, paclitaxel, vincristine), amiodarone, and HIV nucleotide reverse transcriptase inhibitors cause toxic neuropathy 5
• Statins rarely cause neuropathy but should be considered 7

Physical Examination Priorities

Vascular examination:

• Palpate femoral, popliteal, dorsalis pedis, and posterior tibial pulses bilaterally and rate as 0 (absent), 1 (diminished), 2 (normal), or 3 (bounding) 3
• Presence of all four distal pulses (bilateral dorsalis pedis and posterior tibial) is associated with low likelihood of PAD 3
• Assess for elevation pallor/dependent rubor, asymmetric hair growth, and calf muscle atrophy 3
• Measure ankle-brachial index (ABI)—absolute systolic blood pressure ≤50 mmHg at the ankle or ≤30 mmHg at the toe suggests amputation risk without revascularization 1

Neurological examination:

• Sensory testing: Use 10-g monofilament at multiple plantar sites to detect loss of protective sensation; test pinprick, vibration with 128-Hz tuning fork, and light touch 7, 3
• Pattern recognition: Symmetric "stocking-glove" distribution suggests peripheral neuropathy; dermatomal pattern suggests radiculopathy; isolated dorsal foot involvement suggests superficial peroneal nerve entrapment 4, 6
• Motor testing: Assess ankle dorsiflexion, plantar flexion, toe extension, and hip flexion strength—distal weakness suggests peripheral neuropathy; proximal weakness suggests radiculopathy or myopathy 4
• Reflexes: Check ankle reflexes—suppression/reduction proportional to sensory loss suggests peripheral neuropathy 3
• Special tests for superficial peroneal nerve entrapment: Look for soft tissue bulge over anterolateral leg approximately 10 cm above lateral malleolus; check for Tinel sign over the bulge; observe if bulge increases with resisted ankle dorsiflexion or weight bearing; assess for tenderness over the bulge or distally over terminal sensory branches 6, 8

Musculoskeletal examination:

• Assess for "flattened" midfoot appearance suggesting Charcot arthropathy in diabetic patients 3
• Evaluate hip range of motion—limited range with pain suggests hip arthritis rather than neuropathy 3
• Check for lumbar spine tenderness and range of motion—pain with extension suggests spinal stenosis 3

Initial Diagnostic Testing Algorithm

If pulses are normal and no acute vascular emergency is suspected, proceed with laboratory evaluation:

First-tier mandatory tests: 2, 4, 5

• Fasting blood glucose and HbA1c (diabetes is the most common cause, affecting >50% of peripheral neuropathy cases) 5
• Complete blood count and comprehensive metabolic panel (assess for renal disease, electrolyte abnormalities) 2, 4
• Vitamin B12 level with methylmalonic acid ± homocysteine (especially if on metformin) 7, 5
• Thyroid-stimulating hormone (hypothyroidism is a reversible cause) 2, 4
• Serum protein electrophoresis with immunofixation (detect monoclonal gammopathy) 2, 4, 5

Second-tier tests if initial workup is unrevealing: 7, 4

• Erythrocyte sedimentation rate/C-reactive protein if vasculitis is suspected (asymmetric pattern suggests vasculitic neuropathy) 7
• HIV testing in appropriate clinical context 7
• Hepatitis C serology (up to 50% of HCV-infected patients develop peripheral neuropathy) 7

Imaging studies:

• Plain radiography of the foot if diabetic to assess for Charcot arthropathy or osteomyelitis 3
• MRI of lumbar spine if radiculopathy is suspected (back pain radiating down leg, dermatomal pattern) 2
• Arterial duplex ultrasound if ABI is abnormal (<0.9 or >1.4) or if pulses are diminished 3

Electrodiagnostic studies:

• Refer to neurology for nerve conduction studies and electromyography if diagnosis remains unclear after initial evaluation 4, 5
• Nerve conduction studies can differentiate axonal from demyelinating neuropathy and confirm superficial peroneal nerve entrapment (unrecordable evoked response or prolonged distal latency) 6, 8

Management Based on Etiology

Diabetic peripheral neuropathy (most common cause): 5

• Target HbA1c <7% to prevent progression—tight glycemic control is the only convincingly proven strategy 2, 7
• First-line medications for neuropathic pain: duloxetine 30mg daily for one week, then increase to 60mg daily (provides 30-50% pain reduction) 7, 5
• Alternative agents: pregabalin, gabapentin 1200mg daily (38% achieve ≥50% pain reduction), tricyclic antidepressants (amitriptyline, nortriptyline), or venlafaxine 7, 5
• Physical activity has been shown to improve neuropathy symptoms 7
• Educate patients to conduct daily foot inspections to identify early skin breakdown or ulceration 7

Vitamin B12 deficiency (metformin-induced or dietary): 7

• Continue vitamin B12 supplementation at 2500 mcg daily 7
• Recheck B12 levels in 3 months to ensure repletion 4

Superficial peroneal nerve entrapment: 6, 8

• Surgical decompression by fasciotomy at the site of nerve herniation through fascial defect provides complete symptomatic relief 6, 8
• Refer to neurosurgery or orthopedic surgery for definitive treatment 8

Lumbar radiculopathy: 2

• Conservative management including physical activity and NSAIDs for initial treatment 2
• Surgical referral for progressive neurological deficits or severe symptoms refractory to conservative management 2

Vasculitic neuropathy (if asymmetric/multifocal pattern with elevated inflammatory markers): 7

• Combined nerve-and-muscle biopsy rather than nerve biopsy alone markedly increases diagnostic yield 7
• For severe vasculitic neuropathy with motor involvement: high-dose glucocorticoids (IV methylprednisolone 500-1000 mg/day for 3-5 days, followed by oral prednisone 1 mg/kg/day, max 80 mg) together with cyclophosphamide 7
• For non-severe vasculitic neuropathy (sensory-only): steroid-sparing immunosuppressant (azathioprine, methotrexate, or mycophenolate mofetil) combined with moderate-dose oral prednisone (0.25-0.5 mg/kg/day) 7

Critical limb ischemia (if ABI ≤0.5 or toe pressure ≤30 mmHg with rest pain): 1

• Urgent vascular surgery consultation for revascularization 1
• Continue anticoagulation and optimize cardiovascular risk factors 1

Follow-Up and Monitoring

Schedule reassessment in 2-4 weeks to: 2

• Review laboratory results and adjust treatment accordingly 2
• Assess response to initial interventions (pain reduction, functional improvement) 2
• Determine need for specialist referral (neurology, vascular surgery, pain management) 2

For confirmed peripheral neuropathy: 7

• Serial neurologic examinations every 6 months to assess disease activity 7
• Monitor for progression of symptoms and adjust treatment as needed 2
• Routine repeat electromyography is unnecessary unless new or worsening symptoms arise 7

Common Pitfalls to Avoid

• Do not dismiss unilateral symptoms as "just neuropathy"—unilateral presentation should prompt evaluation for structural causes (nerve entrapment, radiculopathy, mass lesion) or vascular disease 1, 6
• Do not overlook medication-induced neuropathy—metformin is extremely common and often missed as a cause of B12 deficiency 7
• Do not rely solely on ABI in diabetic patients—calcified vessels can produce falsely elevated ABI (>1.4); use toe pressures instead 3, 1
• Do not perform superficial skin punch biopsy for suspected vasculitic neuropathy—deep-skin biopsy reaching medium-sized vessels or combined nerve-muscle biopsy is required for adequate diagnostic yield 7
• Do not delay vascular surgery consultation if pulses are absent—skeletal muscle tolerates ischemia for only 4-6 hours before irreversible damage occurs 1