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Peripheral Nervous System

 

Vincristine Related Neuropathy

 

Vincristine neuropathy is a distal symmetric sensory and motor neuropathy². 

It generally begins 4 to 5 weeks after treatment start.  However, impaired ankle jerks can be seen as early as 2 weeks following onset of therapy.

Very common - affects almost all patients given this drug to some extent

Vinblastine can also cause peripheral neuropathy. Peripheral neuropathy is rarely caused by vinblastine, but a distal dose-dependent axonal sensorimotor polyneuropathy has been described after treatment with vinorelbine.

 

Etiology:

• Neurotoxicity is the dose limiting toxicity of vincristine³
• Due to disruption of microtubule formation and axoplasmic transport - leads to axonal degeneration.

 

Signs and Symptoms:

Initially - paresthesias in the fingers and feet and loss of Achilles reflexes.

Symptoms	Signs
Wrist and foot “drop”– wrist and foot “drop”2   Neuritic pain and muscle cramps   Paresthesias Initially in fingers, followed by feet Impaired vibration sense Proprioception is spared   Constipation - quite common to have autonomic symptoms2.	Loss of deep tendon reflexes (absent ankle jerks2)   Motor weakness involving: Extensor muscles of the fingers Wrists Toes and dorsiflexors of the feet.
Less frequently causes: Paralytic ileus Postural hypotension Cranial nerve palsies Bilateral ptosis (commonest cranial problem) Transient cortical blindness Oculomotor nerve dysfunction paralytic strabismus Jaw pain Facial palsy Sensorineural hearing loss Laryngeal nerve paresis (hoarseness)

If vincristine therapy continues, sensory symptoms in the limbs progress proximally and distal weakness occurs in more severely affected cases².

 

Investigation:

EMG studies show:

• Denervation with fibrillation
• Reduced amplitude of sensory nerve potentials and prolonged distal motor latencies with normal or mildly slowed conduction velocities, indicating a primary axonal degeneration
• Decreased numbers of motor units in the distal muscles

 

Risk Factors:

• Risk is dose related:
  • Incidence and severity are related to the cumulative drug dose
  • Observed after cumulative total dose of 6-8 mg
• Significant toxicities occur above 15-20 mg
• Severe Vincristine related neuropathy associated with:
  • Underlying peripheral neuropathy
    • Patients with type 1 Charcot-Marie-Tooth hereditary neuropathy can develop rapidly progressive, severe neuropathy after low cumulative doses of vincristine⁴
  • Bedridden patients
  • Hepatic insufficiency
  • Administration of concurrent granulocyte- or granulocyte-macrophage-colony stimulating factor

 

Prognosis:

• Slowly reversible upon removal of the drug.  Symptoms may worsen for a few months after vincristine is discontinued, and then improve slowly.
• Usually mostly resolved 4 months or so after the end of therapy
• Charcot-Marie-Tooth can be associated with a severe exacerbation after Vincristine therapy²
• Drop foot can be prevented in bedridden patients with the use of bilateral foot braces to keep the foot dorsiflexed².

 

 

 

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