What is the most likely cause of lower limb neuropathy in a 14-year-old girl with Acute Lymphoblastic Leukemia (ALL) after receiving induction chemotherapy?

Chemotherapy Neurotoxicity as the Cause of Lower Limb Neuropathy in ALL

The patient's lower limb neuropathy with axonal sensory neuropathy of the peroneal nerve is most likely caused by chemotherapy neurotoxicity (option A) from vincristine used during induction therapy for ALL.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy in ALL

Vincristine is the most likely causative agent in this case, as it is:

• A standard component of ALL induction regimens 1
• Known to cause peripheral neuropathy through axonal damage
• Associated with a predominantly sensory neuropathy that follows a "stocking-glove" distribution 1

The pathophysiological mechanism involves:

1. Disruption of microtubule assembly and axonal transport in peripheral nerves
2. Axonal sensory damage with reduced amplitude of sensory nerve action potentials
3. Length-dependent neuropathy affecting distal extremities first (explaining lower limb symptoms)
4. Predominantly sensory symptoms rather than motor involvement 1

Evidence Supporting Chemotherapy Neurotoxicity

Several factors support chemotherapy neurotoxicity as the diagnosis:

• Temporal relationship: Symptoms developed after receiving induction chemotherapy
• Pattern of involvement: Axonal sensory neuropathy of peroneal nerve is consistent with vincristine toxicity
• High prevalence: Up to 78% of children with ALL develop vincristine-induced peripheral neuropathy 2
• Electrophysiological findings: NCS/EMG showing axonal sensory neuropathy matches the pattern seen in vincristine toxicity

Why Other Options Are Less Likely

1. Hereditary neuropathy (B):

   • No mention of family history
   • Acute onset after chemotherapy exposure (hereditary neuropathies typically present gradually)
   • While vincristine can unmask underlying Charcot-Marie-Tooth disease 3, this would be rare and would typically present with more severe symptoms than expected

2. Tumor-related neuropathy (C):

   • Direct tumor infiltration of nerves is uncommon in ALL
   • Timing of symptoms after chemotherapy rather than at diagnosis argues against this

3. Immune system activation (D):

   • Immune-mediated neuropathies typically have different clinical and electrophysiological features
   • Temporal relationship with chemotherapy strongly suggests direct neurotoxicity

Clinical Characteristics of Vincristine-Induced Neuropathy in ALL

• Predominantly sensory symptoms (numbness, tingling, pain) 1
• Distal to proximal progression in a "stocking-glove" distribution
• More prominent in lower extremities than upper extremities 1
• Can persist for months to years after completion of therapy 4, 2
• Severity varies, with some patients (approximately 10%) experiencing severe neuropathy 2

Risk Factors for Chemotherapy-Induced Neuropathy

• Age: Older children tend to experience worse vincristine-induced peripheral neuropathy 2
• Cumulative dose of vincristine
• Treatment schedule and dose intensity
• Pre-existing neuropathy or genetic predisposition

Clinical Implications

This understanding has important implications for management:

• Monitoring for progression of neuropathy during continued treatment
• Potential need for dose modifications if symptoms are severe
• Consideration of supportive care measures for symptom management
• Recognition that symptoms may persist even after treatment completion 4, 2

Despite attempts to reduce vincristine frequency in some protocols, evidence suggests that chemotherapy-induced peripheral neuropathy can persist for at least 12 months after completion of therapy 4.