What causes toe drop?

What Causes Toe Drop (Foot Drop)

The most common causes of foot drop are L5 radiculopathy and common peroneal nerve injury at the fibular neck, though any disruption along the motor pathway from the brain to the foot dorsiflexors can produce this symptom. 1, 2

Primary Neurological Causes

Peripheral Nerve Injuries

• Common peroneal nerve injury at the fibular neck is the most frequent peripheral cause, often from habitual leg crossing, direct trauma, or compression 3, 1
• Sciatic nerve injury can produce foot drop when affecting the peroneal division 3, 1
• Compartment syndromes of the lower leg can damage the deep peroneal nerve and lead to foot drop deformity 3

Radiculopathy and Plexopathy

• L5 radiculopathy is one of the two most common overall causes and should be evaluated with spine imaging 1, 2
• L4/L5 radiculopathy from spinal stenosis or disc herniation 3, 4
• Lumbar plexopathies affecting the motor pathways to foot dorsiflexors 3, 1

Central Nervous System Causes

• Anterior horn cell disease (motor neuron disease) 3, 1
• Brain tumors or metastases can present with foot drop as an unusual manifestation, requiring CNS investigation when peripheral workup is negative 4
• Stroke affecting the motor cortex or descending pathways 4

Metabolic and Systemic Causes

Diabetic Neuropathy

• Diabetes mellitus is the most common metabolic cause, presenting as distal symmetric polyneuropathy affecting both sensory and motor fibers 5
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic but still increases complication risk 6, 5
• Peripheral neuropathy is a component cause in 78% of diabetic foot ulcerations 6

Other Systemic Diseases

• Connective tissue diseases and vasculitides 4
• Hepatitis C infection with cryoglobulins 5
• Plasma cell dyscrasias (particularly POEMS syndrome) 5
• Amyloidosis from light chain deposits 5

Drug-Induced Causes

Multiple chemotherapeutic and other medications can cause motor neuropathy leading to foot drop:

• Vincristine causes motor neuropathy in approximately 10% of patients, ranging from mild distal weakness to rare life-threatening motor neurotoxicity 5
• Bortezomib causes predominantly sensory neuropathy, but motor impairment occurs in approximately 10% of cases 5
• Thalidomide is a major cause of treatment-related neuropathy in multiple myeloma patients 5
• Taxanes and platinum compounds primarily affect sensory fibers but can have motor components 5
• Metronidazole requires temporal association assessment and discontinuation when suspected 5
• Anti-TNF agents can cause peripheral neuropathy 5

Nutritional Deficiencies

• Vitamin B12 deficiency should be excluded in all patients with neuropathy 6, 5
• Vitamin E, thiamine, nicotinamide, and red-cell folate deficiencies, particularly with malabsorption or inflammatory bowel disease 5
• Copper deficiency can cause peripheral neuropathy 5

Hereditary Causes

• Charcot-Marie-Tooth type 1A should be ruled out, particularly in cases of severe motor involvement with distinct deformities (hollow foot, stork legs) 5
• Family or personal history of hereditary peripheral neuropathy predisposes to chemotherapy-induced neuropathy 5

Mechanical and Structural Causes

• Direct nerve compression (radicular or medullary) in multiple myeloma patients 5
• Surgical nerve injury from orthopedic or other procedures 4, 7
• Trauma to the dorsiflexor muscles or tendons 4

Risk Factors That Increase Susceptibility

Patients with the following conditions have increased risk for developing foot drop:

• Pre-existing diabetes mellitus 5
• Prior history of peripheral neuropathy 5
• Smoking 5
• Retinopathy and nephropathy (particularly dialysis or post-transplant patients) 5
• Foot deformities 5
• Prior ulceration or amputation 5

Clinical Pitfall

When peripheral workup fails to disclose the etiology, the central nervous system must be investigated to avoid diagnostic delays, as brain metastases or other CNS lesions can present with isolated foot drop. 4 A meticulous neurological examination localizing the lesion site is essential before imaging, with nerve conduction studies and electromyography useful for establishing injury degree and predicting recovery 1, 2