What are the differentials and management for sudden onset upper and lower extremity weakness?

Differential Diagnosis for Sudden Onset Upper and Lower Extremity Weakness

For sudden onset weakness affecting both upper and lower extremities, immediately assess for acute limb ischemia (particularly aortic saddle embolus), Guillain-Barré syndrome, and spinal cord pathology—these are the three life-threatening emergencies that require recognition within minutes to hours. 1, 2, 3

Immediate Life-Threatening Differentials

Acute Limb Ischemia (Aortic Saddle Embolus or Bilateral Arterial Occlusion)

Check the "5 Ps plus temperature" immediately: Pain, Paralysis, Paresthesias, Pulselessness, Pallor, and Polar (cold extremities). 2, 3

• Absent or severely diminished femoral pulses bilaterally with cool extremities indicates aortic saddle embolus until proven otherwise 2, 3
• History of atrial fibrillation, recent myocardial infarction, or cardiac disease strongly supports embolic etiology 1, 2
• Time is tissue: delays beyond 4-6 hours dramatically increase risk of permanent damage and limb loss 1, 2, 3
• Obtain CT angiography of the aorta and bilateral lower extremities with IV contrast immediately if pulses are absent 2, 3
• Start unfractionated heparin bolus and infusion immediately while awaiting imaging to prevent thrombus propagation 1, 2, 3
• If paralysis or motor weakness is present, call vascular surgery immediately—surgical intervention may be needed before imaging is complete 2, 3

Guillain-Barré Syndrome (GBS)

Progressive bilateral weakness ascending from legs to arms over days to 4 weeks (usually <2 weeks) with absent or decreased reflexes is the hallmark of GBS. 1

• Relative symmetry of weakness is typical, though mild asymmetry can occur 1
• Sensory symptoms are relatively mild or absent in pure motor variants 1
• Bilateral facial palsy, autonomic dysfunction, and back/limb pain strongly support the diagnosis 1
• Features that cast doubt on GBS include: fever at onset, sharp sensory level, hyperreflexia or clonus, extensor plantar responses, bladder/bowel dysfunction at onset, or nadir <24 hours 1
• Obtain lumbar puncture for CSF analysis (elevated protein with normal cell count supports diagnosis) and nerve conduction studies 1
• More than 50 mononuclear cells/μL in CSF should prompt consideration of alternative diagnoses like CNS infection 1

Spinal Cord Pathology (Acute Transverse Myelitis, Compression, Infarction)

A sharp sensory level, hyperreflexia, extensor plantar responses, or bladder/bowel dysfunction at onset indicates spinal cord pathology, not peripheral nerve disease. 1

• Acute cervical spinal cord injury causes greater proximal than distal upper extremity weakness (central cord syndrome pattern) 4
• Obtain urgent MRI of the entire spine if any upper motor neuron signs are present 1
• Saddle anesthesia with bowel/bladder dysfunction represents cauda equina syndrome requiring emergency neurosurgical consultation 5

Secondary Differentials Based on Tempo and Pattern

Metabolic/Electrolyte Disorders

Hypokalemia, hypophosphatemia, hypomagnesemia, or thyrotoxic periodic paralysis can cause acute flaccid weakness without sensory changes. 1

• Check basic metabolic panel, magnesium, phosphate, and thyroid function immediately 1
• These conditions typically cause flaccid weakness with preserved or diminished reflexes, distinguishing them from upper motor neuron lesions 1

Inflammatory Myositis or Acute Rhabdomyolysis

Proximal muscle weakness with elevated creatine kinase and myoglobinuria suggests muscle pathology rather than nerve or vascular disease. 1

• Check CK, aldolase, and urinalysis for myoglobin 1
• Recent statin use, colchicine, or chloroquine exposure increases suspicion for drug-induced toxic myopathy 1

CNS Inflammation or Infection

Brainstem or spinal cord inflammation from sarcoidosis, Sjögren syndrome, neuromyelitis optica, or infectious causes can mimic peripheral neuropathy. 1

• Obtain MRI brain and spine with contrast if cranial nerve involvement, altered consciousness, or upper motor neuron signs are present 1
• Lumbar puncture with cell count, protein, glucose, oligoclonal bands, and infectious workup is essential 1

Critical Diagnostic Algorithm

1. Within 5 minutes: Assess pulses, temperature gradient, motor strength, reflexes, sensory level, and bladder function 2, 3

2. If absent pulses or cold extremities: Start heparin, obtain CTA aorta/lower extremities, call vascular surgery emergently 2, 3

3. If normal pulses with ascending weakness and hyporeflexia: Obtain lumbar puncture and nerve conduction studies for GBS 1

4. If hyperreflexia, sensory level, or bladder dysfunction: Obtain urgent MRI spine for cord pathology 1

5. If none of the above: Check electrolytes, CK, thyroid function, and consider inflammatory or metabolic causes 1

Common Pitfalls to Avoid

• Do not delay vascular imaging or anticoagulation while obtaining a "complete neurological workup" if pulses are diminished—acute limb ischemia requires intervention within 6 hours 1, 2, 3
• Do not dismiss GBS because CSF protein is normal early in the disease course—protein elevation may not occur until after the first week 1
• Do not attribute weakness to "functional disorder" until all life-threatening causes are excluded with appropriate imaging and laboratory studies 1, 3
• Do not assume peripheral nerve injury if reflexes are hyperactive or plantar responses are extensor—these indicate CNS pathology requiring different imaging 1