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Peripheral Nervous System

 

Vincristine Related Neuropathy

 

Vincristine neuropathy:

• Distal symmetric sensory and motor neuropathy⁶
• Generally begins 4-5 weeks after treatment start
• Impaired ankle jerks can be seen as early as 2 weeks following onset of therapy
• This neurotoxicity is very common, affecting 70-90% of all patients³ given this drug

Vincristine more frequently causes severe peripheral neuropathy than other vinca alkaloids (vinblastine, vindesine)¹.

Vinblastine can also cause peripheral neuropathy. Peripheral neuropathy is rarely caused by vinblastine.

A distal dose-dependent axonal sensorimotor polyneuropathy has been described after treatment with vinorelbine.

 

Etiology:

• Vinca alkaloids disrupt microtubule formation and axoplasmic transport which leads to axonal degeneration and neuropathy of peripheral nerve fibres⁵

 

Signs and Symptoms:

First symptoms are usually paresthesias in the fingers and feet, and loss of ankle jerks.

Symptoms	Signs
Paresthesias (57% of patients)3 Initially in fingers, followed by feet Impaired vibration sense Proprioception is spared   Wrist and foot “drop”6   Neuritic pain and muscle cramps   Autonomic symptoms (constipation, ileus) in up to 33% of patients.5	Loss of deep tendon reflexes (absent ankle jerks6) (22-34% of patients)3   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)

 

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:

• Incidence and severity of symptoms is related to the cumulative dose:
  • Peripheral neuropathy in vincristine treatment is seen when the cumulative dose rises above 6 mg/m²
  • Significant toxicities occur above 15-20 mg total³
• 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 vincristine⁷
  • 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, but may take up to 2 years

• Charcot-Marie-Tooth can be associated with a severe exacerbation after Vincristine therapy⁶
• Drop foot can be prevented in bedridden patients with the use of bilateral foot braces to keep the foot dorsiflexed⁶

 

If vincristine therapy continues, sensory symptoms in the limbs progress proximally and distal weakness occurs in more severely affected cases⁶.

Neurotoxicity is the dose limiting toxicity of vincristine³

 

 

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