What are the possible causes of acute bilateral lower‑extremity weakness with loss of ambulation and a normal serum potassium level?

Acute Bilateral Lower Extremity Weakness with Normal Potassium: Differential Diagnosis

Despite normal serum potassium, acute bilateral lower extremity weakness with inability to ambulate requires immediate consideration of life-threatening conditions including acute limb ischemia, spinal cord compression, Guillain-Barré syndrome, and thyrotoxic periodic paralysis (which can present with normal potassium during the recovery phase). 1

Immediate Life-Threatening Causes to Exclude

Acute Limb Ischemia

• Look for the "6 Ps": pain, pallor, pulselessness, poikilothermia (coolness), paresthesias, and paralysis to diagnose acute limb ischemia, which threatens limb viability and requires urgent revascularization 1
• Motor weakness with sensory loss beyond the toes indicates Class IIb acute limb ischemia requiring urgent intervention 1
• Complete motor paralysis with anesthesia indicates Class III acute limb ischemia with irreversible damage 1
• Perform comprehensive vascular examination including pulse palpation at femoral, popliteal, dorsalis pedis, and posterior tibial sites, assess skin temperature and color, and obtain ankle-brachial index (ABI) 2

Spinal Cord Compression

• Acute bilateral weakness with sensory level, bowel/bladder dysfunction, or back pain suggests spinal cord pathology requiring emergent imaging 1
• This represents a neurosurgical emergency requiring immediate MRI spine 1

Metabolic and Endocrine Causes

Thyrotoxic Periodic Paralysis

• This condition can present with severe bilateral lower extremity weakness and inability to walk even when serum potassium appears normal or is normalizing 3, 4
• Classically presents after high carbohydrate meals or alcohol intake with acute onset weakness 3
• Critical pitfall: Potassium supplementation alone may not improve weakness; beta-blockers (propranolol 20-60 mg orally) can produce dramatic improvement within 30 minutes 3
• Look for small, smooth goiter on examination and obtain thyroid function tests (TSH, free T4, free T3) 4
• More common in Asian males but can occur in any population 3, 4

Other Electrolyte Disturbances

• Hypermagnesemia can cause arreflexic weakness and quadriplegia with respiratory insufficiency 5
• Hypophosphatemia produces arreflexic weakness 5
• Severe hypocalcemia causes mixture of encephalopathy and weakness or paresthesias 5
• Obtain comprehensive metabolic panel including magnesium, phosphorus, and calcium 5

Neurologic Pattern Recognition

Inflammatory Myopathy

• Objective symmetric proximal lower extremity weakness that is progressive over weeks to months suggests idiopathic inflammatory myopathy 1
• Neck flexors relatively weaker than extensors strongly supports this diagnosis 1
• Obtain creatine kinase, LDH, AST, ALT (elevated in myositis) 1
• Consider anti-Jo-1 antibody testing 1

Guillain-Barré Syndrome

• Ascending paralysis with areflexia, typically following respiratory or gastrointestinal infection 1
• May have normal potassium but requires urgent evaluation with lumbar puncture and nerve conduction studies 1

Vascular Causes with Normal Potassium

Peripheral Arterial Disease

• Bilateral lower extremity PAD can cause weakness and inability to ambulate due to ischemia-related pathophysiologic changes in calf skeletal muscle, including smaller muscle area, increased fat content, impaired leg strength, and impaired metabolic function 6
• Poorer peroneal nerve conduction velocity occurs with severe PAD 6
• Functional impairment is common even in asymptomatic PAD 6
• Obtain ABI; value ≤0.90 confirms PAD 7, 8

Diagnostic Algorithm

Step 1: Assess acuity and vascular status

• Examine for acute limb ischemia signs (6 Ps) 1
• Palpate all lower extremity pulses bilaterally 2
• Obtain ABI immediately if vascular etiology suspected 1, 7

Step 2: Obtain targeted laboratory studies

• Complete metabolic panel including potassium, magnesium, phosphorus, calcium 5
• Thyroid function tests (TSH, free T4, free T3) - essential even with normal potassium 4
• Creatine kinase, LDH, AST, ALT 1
• Consider arterial blood gas if acidosis suspected 5

Step 3: Perform neurologic examination

• Assess pattern: proximal vs. distal, symmetric vs. asymmetric 1
• Check reflexes (areflexia suggests GBS or severe electrolyte disturbance) 5
• Evaluate sensory level for spinal cord pathology 1

Step 4: Obtain appropriate imaging

• Emergent MRI spine if any concern for cord compression 1
• Lower extremity arterial Doppler/ABI for acute onset with vascular symptoms 1
• CTA abdomen/pelvis with bilateral lower extremity runoff if PAD confirmed and intervention considered 7

Critical Management Priorities

If Thyrotoxic Periodic Paralysis Suspected

• Administer beta-blocker (propranolol 20-60 mg orally) immediately - can produce dramatic improvement within 30 minutes 3
• Cautious potassium repletion (aggressive repletion can cause rebound hyperkalemia) 3, 4
• Initiate anti-thyroid therapy once diagnosis confirmed 3

If Acute Limb Ischemia Confirmed

• Urgent revascularization for Class IIb or higher 1, 7
• Immediate anticoagulation to reduce thrombus propagation 7

If PAD Without Acute Ischemia

• Cardiovascular risk reduction: antiplatelet therapy, ACE inhibition, smoking cessation, lipid management 1, 7

Common Pitfalls to Avoid

• Do not assume normal potassium excludes thyrotoxic periodic paralysis - the potassium may be normalizing or the weakness may persist despite correction 3
• Do not rely on potassium supplementation alone in thyrotoxic periodic paralysis - beta-blockers are essential 3
• Do not overlook vascular examination in bilateral weakness - PAD causes functional impairment through ischemic muscle and nerve damage 6
• Rapid correction of electrolyte abnormalities can cause complications (central pontine myelinolysis with hyponatremia, cardiac arrhythmias with potassium) - correct cautiously 5