What are the possible causes of sudden lower extremity weakness?

Sudden Lower Extremity Weakness: Differential Diagnosis and Evaluation

Sudden lower extremity weakness is a medical emergency that requires immediate evaluation for vascular, neurologic, and metabolic causes, with acute limb ischemia being the most time-sensitive diagnosis requiring intervention within 4-6 hours to prevent permanent tissue damage and limb loss. 1

Immediate Bedside Assessment ("6 Ps" for Vascular Causes)

When evaluating sudden bilateral or unilateral leg weakness, immediately assess for acute limb ischemia using the "6 Ps" 1:

• Pain – sudden onset, severe, out of proportion to exam 1
• Pallor – white or mottled skin appearance 1
• Pulselessness – absent femoral, popliteal, dorsalis pedis, or posterior tibial pulses 2, 1
• Poikilothermia – cold extremity on palpation 1
• Paresthesia – new sensory loss distal to occlusion 1
• Paralysis – motor weakness or complete paralysis indicates immediately threatened limb 1

The presence of motor weakness (paralysis) indicates Rutherford Class IIb acute limb ischemia, requiring revascularization within 4-6 hours to prevent permanent damage. 1 Use handheld Doppler at bedside to assess arterial signals; absent arterial signals mandate emergent vascular surgery consultation. 1

Major Diagnostic Categories

1. Vascular Causes (Most Time-Sensitive)

Acute limb ischemia presents with sudden onset of the "6 Ps" and requires immediate anticoagulation with unfractionated heparin and CT angiography (CTA) of the entire lower extremity. 1 CTA is the preferred initial imaging because it provides rapid, comprehensive anatomic detail including occlusion level, atherosclerotic burden, and below-knee vessel patency essential for revascularization planning. 1

• Embolic occlusion – abrupt onset in patients with atrial fibrillation, recent MI, valvular disease, or LV thrombus; contralateral pulses typically normal 1
• Thrombotic occlusion – history of claudication or known peripheral artery disease; contralateral pulses often diminished 1
• Aortic dissection/occlusion – bilateral symptoms with absent femoral pulses 2

Critical pitfall: Do not delay anticoagulation or vascular surgery consultation while awaiting imaging. 1 If motor weakness or paralysis is present (Category IIb or III), proceed directly to operating room or catheter suite without prior imaging. 1

2. Neurologic Causes

Spinal cord pathology is the second most common cause of acute bilateral lower extremity weakness and requires urgent MRI. 3

• Spinal cord compression – from tumor, abscess, disc herniation, or hematoma; presents with sensory level, bowel/bladder dysfunction, and bilateral weakness 3
• Acute transverse myelitis – inflammatory process with ascending weakness and sensory changes 3
• Cauda equina syndrome – severe low back pain, saddle anesthesia, urinary retention, bilateral leg weakness 2
• Guillain-Barré syndrome – ascending weakness with areflexia, typically follows viral illness 4
• Acute stroke – bilateral leg weakness from anterior cerebral artery or basilar artery territory infarction 4

3. Metabolic/Endocrine Causes

Severe hypokalemia can present with acute bilateral lower extremity paralysis and characteristic ECG changes (U waves, flattened T waves, prolonged QT). 5 This diagnosis is confirmed by serum potassium <2.5 mEq/L and responds rapidly to potassium replacement. 5

• Hypokalemic periodic paralysis – sudden weakness upon awakening, often in young Hispanic or Asian men 5
• Thyrotoxic periodic paralysis – hypokalemia with hyperthyroidism 5
• Severe hypophosphatemia – weakness with serum phosphate <1.0 mg/dL 4

Key diagnostic clue: An abnormal ECG in a patient with acute bilateral leg weakness immediately suggests metabolic etiology and should prompt urgent electrolyte measurement. 5

4. Neuromuscular Causes

• Myasthenia gravis crisis – fluctuating weakness, ptosis, diplopia, bulbar symptoms 4
• Botulism – descending paralysis with cranial nerve involvement 4
• Acute inflammatory demyelinating polyneuropathy (AIDP) – in HIV patients with CD4 >200, responds to plasmapheresis or steroids 6

Diagnostic Algorithm

Step 1: Assess vital signs and perform focused cardiovascular exam including pulse palpation at all sites (brachial, radial, femoral, popliteal, dorsalis pedis, posterior tibial). 2, 1

Step 2: If any "P" of acute limb ischemia is present:

• Start IV unfractionated heparin immediately 1
• Obtain emergent vascular surgery consultation 1
• Order CTA lower extremity if limb is viable or marginally threatened (Category I or IIa) 1
• Proceed directly to OR/catheter suite if motor weakness present (Category IIb) 1

Step 3: If vascular exam is normal, obtain ECG immediately:

• Abnormal ECG → check electrolytes (potassium, phosphate, calcium, magnesium) stat 5
• Normal ECG → proceed to neurologic evaluation

Step 4: Perform detailed neurologic exam:

• Assess for sensory level, bowel/bladder dysfunction → urgent MRI spine if present 3
• Assess for ascending weakness, areflexia → consider Guillain-Barré, obtain CSF analysis 4
• Assess for cranial nerve involvement → consider myasthenia, botulism 4

Risk Factors to Elicit in History

For vascular causes: 2

• Age ≥70 years or ≥50 years with smoking or diabetes 1
• Atrial fibrillation (embolic source) 1
• Known coronary artery disease or prior MI 2
• History of claudication or prior vascular procedures 2
• Smoking (2-6 fold increased PAD risk) 2
• Diabetes (2-4 fold increased PAD risk) 2
• Hypertension, hyperlipidemia 2

For neurologic causes: 6, 3

• Recent viral illness (Guillain-Barré) 4
• HIV infection (multiple neuropathies possible) 6
• Cancer history (spinal metastases) 3
• Recent back trauma or procedures 3

Common Pitfalls to Avoid

1. Do not assume atherosclerosis is the only cause of lower extremity arterial disease. Consider popliteal artery entrapment syndrome in young adults with exercise-induced calf claudication, paresthesia, and swelling. 7 This is the most common surgically correctable vascular insufficiency in young adults. 7

2. Do not order ankle-brachial index (ABI) as the primary investigation for acute limb ischemia. ABI only confirms arterial occlusion but provides no information about location, cause, or treatment planning needed for emergency revascularization. 1 ABI is appropriate for screening chronic PAD, not acute presentations. 1

3. Do not delay treatment for echocardiography or extensive workup. Skeletal muscle tolerates ischemia for only 4-6 hours before permanent injury occurs. 1 Anticoagulation and vascular consultation must precede all diagnostic testing. 1

4. Do not rely solely on pulse palpation in high-risk patients. In patients with diabetes, advanced age, or prior vascular disease, palpable pulses are insufficient to exclude ischemia; objective vascular testing is required. 1

5. Do not assume bilateral weakness is always neurologic. Aortic occlusion or bilateral emboli can cause bilateral leg weakness with absent femoral pulses. 2