What is the diagnostic approach for a patient presenting with leg weakness, considering various potential causes including neurological and musculoskeletal conditions?

Diagnostic Approach to Leg Weakness

Begin by localizing the lesion anatomically through pattern recognition: unilateral weakness suggests stroke or focal nerve injury, bilateral distal weakness suggests peripheral neuropathy, bilateral proximal weakness suggests myopathy, and acute progressive ascending weakness suggests Guillain-Barré syndrome. 1, 2

Initial Clinical Assessment

Critical History Elements

• Onset and tempo: Acute onset (minutes to hours) suggests stroke, spinal cord compression, or acute vascular occlusion; subacute (days to weeks) suggests inflammatory or infectious causes; chronic (months) suggests degenerative or metabolic conditions 1, 2

• Distribution pattern:

  • Unilateral leg weakness with upper motor neuron signs points to contralateral hemispheric stroke (anterior cerebral artery territory if leg-predominant, internal capsule if leg and arm involved) 3
  • Bilateral symmetric distal weakness suggests peripheral neuropathy or toxic/metabolic causes 2
  • Bilateral proximal weakness suggests myopathy, endocrine disorders, or inflammatory muscle disease 2

• Associated symptoms:

  • Sensory changes, pain, or paresthesias suggest nerve root, peripheral nerve, or spinal cord involvement 2
  • Bowel/bladder dysfunction indicates cauda equina syndrome requiring emergent MRI 2
  • Diplopia, dysphagia, or ptosis suggest neuromuscular junction disorders (myasthenia gravis) 2

Targeted Physical Examination

Grade muscle strength objectively using the Medical Research Council scale (0-5) for each major muscle group to document severity and distribution. 2

• Upper motor neuron signs (hyperreflexia, Babinski sign, spasticity) localize to brain or spinal cord 1, 2

• Lower motor neuron signs (hyporeflexia, fasciculations, muscle atrophy) localize to anterior horn cell, nerve root, or peripheral nerve 2

• Vascular examination: Palpate femoral, popliteal, dorsalis pedis, and posterior tibial pulses; auscultate for femoral bruits; inspect for skin changes, hair loss, or ulcers suggesting chronic ischemia 4, 5

• Specific findings:

  • Chvosek sign suggests hypocalcemia 2
  • Hoarse voice suggests thyroid disorder or bulbar involvement 2
  • Asymmetric calf atrophy suggests chronic denervation or vascular insufficiency 5

Diagnostic Algorithm by Clinical Pattern

Acute Unilateral Leg Weakness (Stroke Pattern)

Obtain emergent brain MRI or CT to identify ischemic or hemorrhagic stroke, particularly if accompanied by upper motor neuron signs. 3, 2

• Leg-predominant weakness with arm sparing suggests anterior cerebral artery territory infarct affecting the medial precentral gyrus 3
• Severe leg weakness with mild proximal arm weakness suggests involvement of supplementary motor area and precentral gyrus 3
• Brainstem or internal capsule lesions may also present with leg-predominant weakness 3

Acute Bilateral Leg Weakness with Ascending Pattern

Consider Guillain-Barré syndrome and obtain lumbar puncture for albuminocytologic dissociation, nerve conduction studies, and monitor respiratory function. 1, 2

Chronic Bilateral Leg Weakness with Vascular Risk Factors

Measure ankle-brachial index (ABI) bilaterally as the initial diagnostic test; ABI ≤0.90 confirms peripheral artery disease. 4

• If ABI is normal (1.00-1.40) but symptoms suggest claudication, perform exercise treadmill ABI testing 4
• If ABI >1.40 (noncompressible vessels, common in diabetes), measure toe-brachial index (TBI) 4
• For confirmed PAD with lifestyle-limiting symptoms, obtain duplex ultrasound, CTA, or MRA to plan revascularization 4

Acute Leg Weakness with Absent Pulses (Acute Limb Ischemia)

Immediately initiate systemic anticoagulation with intravenous unfractionated heparin and obtain emergent CT angiography to define the level of occlusion and plan revascularization. 6

• Evaluate for the "6 Ps": pain, paralysis, paresthesias, pulselessness, pallor, and poikilothermia (cold extremity) 6
• Presence of motor weakness or sensory loss beyond the toes requires revascularization within 6 hours to prevent permanent damage 6
• ABI is insufficient for acute limb ischemia as it only confirms occlusion without providing anatomic detail needed for treatment planning 6

Bilateral Proximal Weakness Without Sensory Changes

Obtain creatine kinase, thyroid-stimulating hormone, electrolytes (calcium, potassium, magnesium), and consider inflammatory myopathy workup. 2

• Elevated CK suggests myopathy; obtain EMG and consider muscle biopsy 2
• Normal CK with abnormal TSH suggests thyroid myopathy 2
• Electrolyte abnormalities (hypokalemia, hypocalcemia) can cause reversible weakness 2

Bilateral Distal Weakness with Sensory Changes

Obtain EMG/nerve conduction studies to differentiate peripheral neuropathy from radiculopathy; check hemoglobin A1c, vitamin B12, and consider toxic exposures. 2

• Asymmetric weakness with pain suggests radiculopathy or plexopathy 2
• Symmetric stocking-glove distribution suggests length-dependent peripheral neuropathy 2

Common Pitfalls to Avoid

• Do not confuse subjective fatigue or pain-related motor impairment with true muscle weakness; always test strength objectively against resistance 2

• Do not obtain ABI for acute limb ischemia; proceed directly to CTA after initiating anticoagulation 6

• Do not delay imaging in suspected cauda equina syndrome (bilateral leg weakness with bowel/bladder dysfunction); obtain emergent MRI 2

• Do not miss bilateral piriformis syndrome in young patients with bilateral leg weakness and sciatica; consider MRI and EMG if standard workup is negative 7

• In older adults with vascular risk factors, do not attribute leg weakness solely to deconditioning; measure ABI to exclude PAD 4, 5

• In patients with diabetes or chronic kidney disease, do not rely on ABI alone; obtain TBI if ABI >1.40 due to arterial calcification 4

When to Obtain Specialist Consultation

• Vascular surgery: Acute limb ischemia, critical limb-threatening ischemia, or PAD requiring revascularization 6
• Neurology: Suspected stroke, Guillain-Barré syndrome, myasthenia gravis, or when diagnosis remains unclear after initial workup 1, 2
• Rheumatology: Suspected inflammatory myopathy with elevated CK and compatible EMG findings 2