What is the differential diagnosis for a patient presenting with foot drop?

Differential Diagnosis of Foot Drop

Foot drop results from weakness of ankle and toe dorsiflexors and requires systematic evaluation from central nervous system to peripheral nerve, with common peroneal nerve injury at the fibular head being the most frequent cause, but central etiologies including stroke, spinal cord lesions, and lumbar radiculopathy must be excluded before attributing symptoms to peripheral pathology. 1, 2

Anatomic Localization Framework

The diagnostic approach must proceed systematically along the neuroanatomical pathway from brain to muscle:

Central Nervous System Causes

Cortical lesions can produce isolated foot drop despite their rarity:

• Stroke affecting the precentral gyrus at high convexity (leg motor area) presents with sudden onset foot drop, particularly in elderly patients 3
• Parasagittal meningiomas compressing the motor cortex can cause progressive contralateral foot drop over weeks to months 2
• These central causes are underappreciated and often missed because they mimic peripheral nerve lesions 2, 3

Spinal cord pathology must be considered when peripheral workup is negative:

• Cervical spinal stenosis (C4-C7) can present with bilateral progressive foot drop due to pyramidal tract compression 2
• Thoracic stenosis (T11-T12) may also manifest as lower extremity weakness including foot drop 2
• Central lesions occur where pyramidal tract connections are condensed and somatotopically organized 2

Nerve Root and Plexus Level

L5 radiculopathy from lumbar pathology:

• Disc herniation, spinal stenosis, or degenerative disease at L4-L5 or L5-S1 4, 1
• Typically accompanied by back pain radiating down lateral leg, though pain may be absent in some cases 1

Sciatic nerve injury at the sciatic notch:

• Trauma, hip surgery, prolonged compression, or intramuscular injections 1
• Affects both peroneal and tibial divisions, producing foot drop plus plantar flexion weakness and sensory loss extending beyond peroneal distribution 1

Peripheral Nerve Level

Common peroneal nerve injury at the fibular head (most common cause):

• Compression from leg crossing, prolonged squatting, tight casts, or fibular fractures 1
• Direct trauma or surgical injury 4, 1
• Presents with isolated dorsiflexion and eversion weakness, sensory loss over dorsum of foot and lateral leg 1

Deep peroneal nerve injury (anterior compartment):

• Compartment syndrome, anterior tibial artery injury, or direct trauma 4, 1
• Produces isolated toe and ankle dorsiflexion weakness with minimal sensory loss (first web space only) 1

Systemic and Medical Causes

Peripheral neuropathies:

• Diabetic neuropathy (though typically bilateral and symmetric) 4
• Vasculitis affecting vasa nervorum 4
• Drug toxicities (chemotherapy agents) 4
• Connective tissue diseases 4

Critical illness-related:

• Nerve compression from prolonged immobilization, positioning during surgery, or ICU stay 5
• Vascular compromise in critically ill patients 5
• Muscular dysfunction from critical illness myopathy 5

Key Distinguishing Clinical Features

Unilateral vs. bilateral presentation:

• Unilateral: favors peripheral nerve injury, stroke, or unilateral radiculopathy 1, 2, 3
• Bilateral progressive: suggests central cord pathology, bilateral radiculopathy, or systemic neuropathy 2

Onset pattern:

• Sudden (hours): stroke, acute nerve compression, compartment syndrome 3
• Subacute (days to weeks): progressive nerve compression, tumor 2
• Chronic (months): degenerative spine disease, chronic neuropathy 2

Associated findings that localize the lesion:

• Upper motor neuron signs (hyperreflexia, spasticity, Babinski): central cause 2, 3
• Sensory loss distribution: determines nerve root vs. peripheral nerve 1
• Weakness beyond foot dorsiflexors: sciatic nerve or L5 root involvement 1
• Plantar flexion weakness: sciatic nerve (not isolated peroneal) 1

Diagnostic Algorithm

Initial evaluation must include:

• Detailed motor examination of hip flexors, knee flexors/extensors, ankle dorsiflexors/plantarflexors, toe extensors, and ankle evertors to distinguish nerve levels 1
• Sensory examination mapping dermatomal vs. peripheral nerve distributions 1
• Reflex testing (ankle jerk absent in S1 radiculopathy, preserved in peroneal nerve injury) 1
• Upper motor neuron signs (if present, mandate brain/spinal cord imaging) 2, 3

When peripheral examination suggests peripheral cause:

• Electromyography and nerve conduction studies to localize lesion and assess severity 1, 2
• Lumbar spine MRI if radiculopathy suspected 1, 2

When peripheral workup is negative or central signs present:

• Brain MRI with diffusion-weighted imaging to exclude stroke, especially in elderly with sudden onset 3
• Cervical and thoracic spine MRI to exclude cord compression if bilateral or upper motor neuron signs present 2

Critical Pitfalls to Avoid

Never assume peripheral cause without excluding central pathology when:

• Electromyography suggests preganglionic lesion 2
• Bilateral progressive symptoms develop 2
• Upper motor neuron signs are present 2, 3
• Elderly patient with sudden onset (stroke until proven otherwise) 3

Never delay imaging in patients with:

• Rapidly progressive weakness (compartment syndrome, acute cord compression) 5, 4
• Bilateral symptoms (central cord pathology more likely) 2
• Minimal symptomatology that seems disproportionate to findings (may indicate central process) 4

Recognize that small central lesions can mimic peripheral nerve injuries, particularly in elderly patients, and maintain high suspicion for stroke when onset is acute 3