What is the differential diagnosis for a patient presenting with bilateral lower extremity (BLE) weakness and paresthesia?

Differential Diagnosis for Bilateral Lower Extremity Weakness and Paresthesia

The differential diagnosis for bilateral lower extremity weakness and paresthesia must immediately distinguish between life-threatening spinal cord emergencies (cauda equina syndrome, cord compression, aortic dissection) requiring emergency imaging and surgery within hours, versus peripheral nerve disorders (Guillain-Barré syndrome) requiring ICU monitoring and immunotherapy, versus vascular claudication requiring ankle-brachial index testing. 1

Immediate Life-Threatening Conditions Requiring Emergency Action

Cauda Equina Syndrome

• Progressive bilateral leg weakness with bladder/bowel dysfunction, perineal sensory changes, or saddle anesthesia mandates emergency MRI and surgical consultation within 12-72 hours to prevent permanent bladder dysfunction. 1
• Red flags include bilateral radiculopathy, progressive neurological deficits, impaired perineal sensation, and impaired anal tone. 1
• Patients with incomplete cauda equina syndrome who retain voluntary bladder control can avoid permanent dysfunction if treated urgently, whereas those with retention often have permanent impairment requiring catheterization. 1

Spinal Cord Compression

• Sharp sensory level, hyperreflexia, clonus, or extensor plantar responses indicate spinal cord pathology rather than peripheral nerve disease. 1
• Bladder/bowel dysfunction at onset suggests cord compression rather than Guillain-Barré syndrome. 1
• Emergency MRI of the entire spine is required when cord compression is suspected. 1

Aortic Dissection

• Acute aortic dissection can present with isolated bilateral lower extremity paralysis and paresthesia, caused by compression of the anterior spinal artery resulting in spinal cord ischemia. 2
• Examine for cold extremities with mottling, loss of pulses, and flaccid paralysis—this presentation comprises <2% of all aortic dissections but carries extremely high mortality. 2
• Computed tomography angiography is diagnostic when acute onset pain and pulselessness of lower extremities are present. 2, 3

Guillain-Barré Syndrome (Acute Inflammatory Polyneuropathy)

Diagnostic Features

• Progressive bilateral ascending weakness with areflexia developing over days to 4 weeks is the hallmark of GBS. 1
• Required diagnostic features include progressive bilateral weakness of legs and absent/decreased reflexes. 1
• Distal paresthesias or sensory loss often precede or accompany weakness. 4
• Recent infection history (within 6 weeks) is present in about two-thirds of patients and serves as an important diagnostic clue. 4

Critical Assessment Priorities

• Immediately assess respiratory function and autonomic stability, as 20% develop respiratory failure requiring mechanical ventilation. 1, 4
• Apply the "20/30/40 rule": patient is at risk of respiratory failure if vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O. 4
• Single breath count ≤19 predicts need for mechanical ventilation. 4
• Perform electrocardiography and continuously monitor heart rate and blood pressure for arrhythmias and blood pressure instability. 4

Variants to Recognize

• Classic sensorimotor GBS (30-85% of cases): Rapidly progressive symmetrical weakness and sensory signs with absent or reduced tendon reflexes, usually reaching nadir within 2 weeks. 5
• Pure motor variant (5-70% of cases): Motor weakness without sensory signs. 5
• Paraparetic variant (5-10% of cases): Paresis restricted to the legs. 5
• Bilateral facial palsy variant (<5% of cases): Bilateral facial weakness, paresthesias and reduced reflexes—this can be the presenting feature before limb weakness develops. 4

Diagnostic Testing

• Cerebrospinal fluid examination should be performed to look for albumino-cytological dissociation (elevated protein with normal cell count), though CSF protein can be normal in the first week. 4
• Electrodiagnostic studies should be performed to support diagnosis and classify the neuropathy pattern, looking for sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks. 4
• "Sural sparing pattern" (normal sural sensory nerve action potential with abnormal median/ulnar responses) is typical for GBS. 4
• Initial laboratory tests should include complete blood count, glucose, electrolytes, kidney function, liver enzymes to exclude metabolic or electrolyte dysfunction as causes of weakness. 4

Features That Should Prompt Reconsideration

• Marked persistent asymmetry, bladder dysfunction at onset, or marked CSF pleocytosis should prompt reconsideration of the diagnosis. 4

Peripheral Artery Disease (Vascular Claudication)

• Bilateral leg weakness with exertion that improves with rest within minutes is a symptom of peripheral artery disease. 1
• Absent or diminished lower extremity pulses (femoral, popliteal, dorsalis pedis, and posterior tibial) are signs of peripheral artery disease. 5, 1
• Atypical lower extremity symptoms related to PAD may include pain or discomfort that begins at rest but worsens with exertion, pain or discomfort that does not stop an individual from walking, and pain or discomfort that begins with exertion but is not alleviated within 10 minutes of rest. 5
• Ankle-brachial index testing is recommended when history or examination suggests peripheral artery disease, with ABI ≤0.90 being abnormal. 5, 1

Spinal Stenosis (Neurogenic Claudication)

• Bilateral buttocks and posterior leg pain/weakness with standing or walking is a symptom of spinal stenosis. 1
• Relief with lumbar spine flexion (sitting, leaning forward) distinguishes spinal stenosis from vascular claudication, which improves with standing still. 1
• Examine for sensory level and assess sphincter function to distinguish between spinal stenosis and other causes of bilateral leg weakness. 1

Metabolic and Endocrine Causes

Hypokalemic Periodic Paralysis

• Sudden onset bilateral lower extremity paralysis after consuming large amounts of carbohydrates and alcohol, with hypokalemia on laboratory testing. 6
• An abnormal electrocardiogram can immediately point to a likely systemic etiology in patients with acute bilateral lower extremity paralysis. 7

Thyrotoxic Periodic Paralysis

• Sudden onset paralysis with hyperthyroidism and hypokalemia—focus on treating and working up the hypokalemia instead of the paralysis. 6

Critical Diagnostic Algorithm

Step 1: Time Course Assessment

• Assess the time course of symptoms: hyperacute (minutes to hours) suggests vascular or metabolic causes; acute-subacute (days to 4 weeks) suggests GBS; chronic suggests degenerative causes. 1

Step 2: Reflex Examination

• Check reflexes immediately: areflexia indicates peripheral nerve disease (GBS); hyperreflexia indicates spinal cord pathology. 1

Step 3: Sensory Level and Sphincter Function

• Examine for sensory level: presence indicates spinal cord pathology requiring emergency imaging. 1
• Assess sphincter function: impairment at onset distinguishes cauda equina syndrome and cord compression from GBS. 1

Step 4: Vascular Examination

• Palpate lower extremity pulses and check for cold extremities with mottling—absence suggests vascular emergency. 2

Step 5: Respiratory and Autonomic Assessment

• If GBS is suspected, immediately measure vital capacity and assess autonomic stability. 4

Common Pitfalls to Avoid

• Do not dismiss GBS based on normal CSF protein in the first week—protein elevation may be delayed. 4
• Do not wait for antibody test results before starting treatment if GBS is suspected. 4
• Bilateral simultaneous facial weakness is extremely rare in Bell's palsy and should immediately raise suspicion for GBS. 4
• In patients presenting with sudden onset paralysis and hypokalemia, include thyrotoxic periodic paralysis in the differential diagnosis rather than focusing solely on neurological causes. 6
• Recognize that patients with GBS, even those with complete paralysis, usually have intact consciousness, vision, and hearing—explain procedures to reduce anxiety. 4