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Perth Haematology :: Dr Steven Ward

Neuropathy

 

Peripheral Neuropathy


Grading  

Scale / Grade
0
1
2
3
4
WHO
None
Paraesthesia / dec tendon reflexes Severe paraesthesia / mild weakness
Intolerable paraesthesia / marked motor loss
Paralysis
NCIC-CTC  sensory
None
Mild paraesthesia, loss of tendon reflexes
Mild/mod objective sensory loss, mod paraesthesia
Severe objective sens loss or parasesthesia interferes with function
 -
NCIC-CTC  motor
None
Subjective weakness
Mild objective weakness, normal function
Objective weakness with impaired function
Paralysis


Vinca Alkaloids (Vincristine, Vindesine, Vinblastine, etc)

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Most common with Vincristine, least with Vinblastine

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Dose related

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 Close monitoring required before each dose

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Cease therapy if problems (clinical decision)

 

Vincristine

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Sequence:

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sensory impairment , paraesthesia

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 neuritic pain

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motor difficulty (fine motor skills)

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If continue therapy can become permanent

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Pre-existing neurological disorders may be exacerbated by Vincristine therapy

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 Loss of tendon reflexes, foot drop, wrist drop, ataxia, paralysis  have been reported with continued administration

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 Cranial nerve palsies can occur (eg oculomotor, laryngeal, jaw pain)

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 Autonomic neuropoathy is common (constipation)

 

Vindesine

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Peripheral neuropathy, autonomic neuropathy, cranial nerve palsy

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Liver dysfunction increases the neurotoxicity

 

Vinblastine

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Peripheral neuropathy

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 Craninal nerve palsy

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 Autonomic neuropathy: constipation, abdo pain, urinary retention, paralytic ileus. GI symptoms especially when high-dose (>20mg).

 

 

Thalidomide

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Peripheral neuropathy due to axonal degeneration without demyelination

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Affects lower limbs especially; glove and stocking distribution

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Can be painful

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Paraesthesia, burning, muscle cramps

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Motor disability is rare and late

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Cease therapy early in onset of neuropathy as sensory changes may not be reversible if therapy continues.

 

Velcade Neuropathy

Small fibre affected. Usually painful axonal sensory distal neuropathy. Tendon reflexes are diminished, proprioception affected and a mild motor neuropathy can occur.

Risk factors are the cumulative dose of Velcade, route of administration (sc<iv) and pre-existing neuropathy.

Recent studies show neuropathy is common with up to 22-50% experiencing mild Grade 1 symptoms, and 13-30% grade 2. More severe Grade 3 and 4 disease in less common, occurring in 7-15% of newly treated patients.

Dose reduction was needed in 12% of patients due to neuropathy, and 5% had to cease therapy. Improvement usually occurs in around 3 months, but can take much longer.

 

Dose modifications:

         Grade 1: no change

         Grade 1 with pain or Grade 2: reduce to 1.0mg/m2

         Grade 2 with pain or Grade 3: Stop and restart when improved at 0.7mg/m2

         Grade 4: Stop therapy

Some regimes now advocate weekly injections (rather than twice a week).