What are the causes and differentials of foot drop in patients with a history of stroke, multiple sclerosis, peripheral neuropathy, diabetes, or vitamin B12 deficiency?

Foot Drop: Causes and Differential Diagnosis

Foot drop results from disruption anywhere along the motor pathway from the brain to the dorsiflexor muscles, with the most common causes being L5 radiculopathy and common peroneal nerve injury at the fibular head. 1, 2

Anatomical Localization Framework

The key to diagnosing foot drop is determining the precise lesion site through systematic neurological examination, as this directly determines treatment options and prognosis. 1, 2

Central Nervous System Causes

Upper Motor Neuron Lesions:

• Stroke affecting the motor cortex or corticospinal tract produces spastic foot drop with associated upper motor neuron signs (hyperreflexia, positive Babinski, spasticity) 1
• Multiple sclerosis can cause foot drop through demyelinating lesions in the brain or spinal cord, often with other CNS manifestations 3
• Brain tumors affecting motor pathways 4

Spinal Cord and Nerve Root Causes

L5 Radiculopathy:

• One of the two most common causes of foot drop 1, 2
• Presents with weakness of ankle dorsiflexion AND toe extension, plus sensory loss over the dorsum of the foot extending to the great toe 2
• Often accompanied by low back pain radiating down the leg 2
• May show weakness in hip abduction (gluteus medius) which helps distinguish from peroneal neuropathy 2

Lumbar Plexopathy:

• Less common but important differential 2, 4
• Broader distribution of weakness beyond just foot dorsiflexion 2

Peripheral Nerve Causes

Common Peroneal Neuropathy at the Fibular Head:

• The most frequent peripheral cause of foot drop 1, 2, 5
• Habitual leg crossing is the most common etiology and most patients improve when they stop this habit 2
• Other causes include: direct trauma, compression during prolonged immobilization (especially in critically ill or surgical patients), tight casts or braces, mass lesions 2, 6
• Presents with weakness of ankle dorsiflexion and eversion, with sensory loss over the dorsum of the foot but SPARING the first web space (supplied by saphenous nerve) 2
• Inversion strength is preserved (posterior tibial nerve) 2

Sciatic Nerve Injury:

• Occurs at the sciatic notch or along its course 4, 5
• Produces foot drop PLUS weakness of ankle plantarflexion and toe flexion (distinguishing feature from peroneal neuropathy) 2, 5
• Sensory loss extends beyond peroneal distribution to include sole of foot 2

Anterior Horn Cell Disease:

• Motor neuron disease (ALS) can present with foot drop 1, 4
• Look for fasciculations, widespread weakness, and absence of sensory findings 1

Metabolic and Systemic Causes

Diabetic Peripheral Neuropathy:

• Diabetes is the most common metabolic cause of peripheral neuropathy 7
• Typically presents as distal symmetric polyneuropathy affecting sensory fibers predominantly, but can contribute to foot weakness and deformity 3, 8, 7
• Up to 50% may be asymptomatic yet still at high risk for complications 7
• The American Diabetes Association recommends comprehensive foot examination at least annually with neurological assessment using 10-g monofilament testing plus at least one additional test (pinprick, temperature, or vibration) 3

Vitamin B12 Deficiency:

• Causes both symptomatic and asymptomatic peripheral neuropathy with small fiber loss 7
• Should be excluded in all patients with peripheral neuropathy, particularly those with malabsorption or inflammatory bowel disease 7
• Can cause distal sensory neuropathy that may contribute to foot weakness 3

Other Nutritional Deficiencies:

• Vitamin E, thiamine, nicotinamide, copper, and folate deficiencies should be considered 7

Compartment Syndrome

Anterior Compartment Syndrome:

• Can lead to foot drop through ischemic injury to muscles and deep peroneal nerve 4
• Acute presentation with severe pain, tense compartment, and progressive weakness 4

Hereditary Causes

Charcot-Marie-Tooth Disease:

• Inherited neuropathy presenting with progressive foot weakness and deformities (hollow foot, stork legs) 8, 7
• Family history is key diagnostic clue 7
• Patients are at increased risk for chemotherapy-induced neuropathy 7

Tethered Cord Syndrome:

• Can cause progressive muscle weakness, gait disturbances, and foot deformities including foot drop in children and adults 8

Critical Diagnostic Examination Elements

Motor Examination Must Include:

• Ankle dorsiflexion strength (tibialis anterior - deep peroneal nerve, L4-L5) 2
• Ankle eversion (peroneus longus/brevis - superficial peroneal nerve, L5-S1) 2
• Ankle inversion (tibialis posterior - tibial nerve, L4-L5) - preserved in peroneal neuropathy 2
• Ankle plantarflexion (gastrocnemius - tibial nerve, S1-S2) - weak in sciatic neuropathy 2
• Toe extension (extensor hallucis longus - deep peroneal nerve, L5) - weak in L5 radiculopathy 2
• Hip abduction (gluteus medius - superior gluteal nerve, L4-L5) - weak in L5 radiculopathy, normal in peroneal neuropathy 2

Sensory Examination:

• Dorsum of foot (superficial peroneal nerve) 2
• First web space (deep peroneal nerve) 2
• Lateral foot (sural nerve - spared in peroneal neuropathy) 2
• Sole of foot (tibial nerve - affected in sciatic neuropathy) 2

Reflexes:

• Ankle jerk (S1) - reduced in S1 radiculopathy or sciatic neuropathy 2
• Knee jerk (L4) - may be reduced in L4 radiculopathy 2
• Pathological reflexes (Babinski) - present in upper motor neuron lesions 1

Inspection:

• Foot deformities (pes cavus in CMT, Charcot foot in diabetes) 3, 8
• Muscle atrophy patterns 8
• Skin changes, ulcers, calluses (diabetic neuropathy) 3

Diagnostic Testing Strategy

Electrodiagnostic Studies:

• Nerve conduction studies and EMG are essential for localizing the lesion, establishing severity, and predicting recovery 1, 2
• Important caveat: Conventional nerve conduction studies will miss early small fiber-predominant disease, as small fibers constitute 70-90% of peripheral nerve fibers and are damaged earliest in diabetic neuropathy 7

Imaging:

• MRI of lumbar spine for suspected radiculopathy 2
• MRI of brain/spinal cord for suspected central lesions (stroke, MS, tumor) 2
• Ultrasound, CT, or MRI along the course of peripheral nerves for suspected nerve compression or mass lesions 2

Laboratory Evaluation for Metabolic/Systemic Causes:

• Hemoglobin A1c and fasting glucose (diabetes screening) 7
• Vitamin B12 level 7
• Thyroid function, vitamin E, thiamine, copper, folate 7
• Serum protein electrophoresis, immunofixation (plasma cell dyscrasias) 7
• Cryoglobulins, hepatitis C (if clinically indicated) 7
• HIV testing in at-risk populations 7

High-Risk Populations Requiring Vigilance

Diabetic Patients:

• Require comprehensive foot examination at least annually, or every 1-3 months if high-risk (history of ulcer/amputation, loss of protective sensation, peripheral artery disease) 3
• Peripheral neuropathy is present in 78% of diabetic foot ulcerations 3

Critically Ill Patients:

• At risk for foot drop from prolonged immobilization, nerve compression from positioning, or critical illness polyneuropathy 6

Surgical Patients:

• Peroneal nerve compression at fibular head from positioning is a recognized perioperative complication 9
• Prevention requires avoiding pressure on the fibular head and using appropriate padding 9

Common Pitfalls to Avoid

• Assuming all foot drop is peroneal neuropathy - L5 radiculopathy is equally common and requires different management 1, 2
• Missing central causes - Always assess for upper motor neuron signs 1
• Overlooking habitual leg crossing - The most common reversible cause of peroneal neuropathy 2
• Relying solely on nerve conduction studies in diabetics - Will miss early small fiber disease 7
• Failing to examine hip abduction - Key to distinguishing L5 radiculopathy from peroneal neuropathy 2
• Not checking ankle plantarflexion - Essential to rule out sciatic neuropathy 2