Neurologic effects of cancer treatment.

1. Neurologic effects of cancer
treatment
Survivorship conference 2013

2. introduction
• The arc of medical advance
– Supportive care
– Crude but sometimes effective
– Artful and often effective
• Survivor = courageous
– Not all of this will be encouraging
• Who I am
– Simple country neurologist
• Chemotherapy
– PNS
– CNS
• Radiation therapy
– PNS
– CNS

3. chemotherapy-induced
peripheral neuropathy
• pain, weakness, or imbalance can develop
• generally dose-dependent
• generally reversible, BUT
» symptoms can “coast”
» some irreversible neuropathy can occur
• risk is probably greater in people with pre-existing
neuropathy
• chemo affects structural & energy-producing elements in
nerve cells

4. chemotherapy induced
peripheral neuropathy
o vincristine
» weakness is prominent
» can cause autonomic and cranial nerve deficits
o cis-platinum
» accumulates in sensory nerve cells
» imbalance and loss of sensation is prominent
» can cause tinnitus, hearing loss
o oxaliplatin
» also accumulates in sensory nerve cells
» acutely, cold-induced pain and tingling in throat and limbs
» muscle cramps
» painful neuropathy
o taxanes
» sensory loss and some weakness
» can also cause autonomic dysfunction
o bevacizumab
o thalidomide

5. chemotherapy-induced
peripheral neuropathy
• no generally accepted prevention
• Ca/Mg infusions may have benefit (Oxaliplaten)
• several other treatments have been investigated
• glutathione
• N-acetylcysteine
• glutamine
• oxcarbazepine
• neurologic monitoring may help guide therapy
• neurologic examination
• QST
• bumps
• sweat testing

6. chemotherapy induced
peripheral neuropathy
• treatment of CIPN pain is difficult
– most drugs that have been proven beneficial in painful diabetic
neuropathy have had negative trials in CIPN
– recent modestly positive trial with Duloxetine
– topicals safe
» baclofen/amitriptyline/ketamine study marginally positive
» topical lidocaine
– reasonable to try other medications used for neuropathy pain

7. “chemobrain”
• a lot to learn yet; mechanisms under investigation
• affects concentration, processing speed, and
memory
– patient-specific factors may contribute
• treatment is symptomatic
– general health measures
– cognitive interventions
– treatment of sleep disruption, anxiety, depression if present
– consider medications

8. risks of chemotherapy in the CNS
QuickTime™ and a
decompressor
• encephalopathy usually resolves within days
are needed to see this picture.
– ifosfamide
– MTX
• PRES
• stroke (Bevacizumab, other VEGF inhibitors, L-asparaginase)
• aseptic meningitis (esp with MTX or ara-C given IT)
• spinal cord syndrome – ara-C
• cerebellar syndrome – ara-C
• paclitaxel acute pain syndrome – axial joints, days in duration
• oxaliplaten cold sensitivity
• ATRA (x-retinoic acid) pseudotumor-like syndrome
– chronic CNS effects
• leukoencephalopathy following MTX

9. effects of radiation therapy in
CNS
• can injure normal cells as well as tumor cells
• inflammation
• interruption of BBB

10. radiation-induced
peripheral nerve injury
– typically causes gradually progressive weakness
– develops months-years after radiation
– progresses for years
– blood thinners and steroids have been proposed
– Pentoclo (pentoxyphylline/tocopherol/clodronate-
prednisone)
– optic nerve and nerves of head and neck can be affected
after treatment of skull base or pituitary tumors
» intravitreal bevacizumab

11. Short-term CNS risks of
radiation therapy
• acute syndromes (days-weeks)
– acute encephalopathy
» breakdown of BBB
» swelling around brain tumors and exacerbation of
tumor symptoms
» headache, nausea
• subacute syndromes (2 weeks – 4 months)
– transient worsening of symptoms from brain tumors
– somnolence
– localized brain dysfunction affecting normal brain in field for
extracranial tumors
– subacute syndromes are due to transient demyelination
» can mimic tumor progression
» may improve with steroid therapy

12. long-term CNS risks with
radiation therapy
• radiation necrosis 3 mos – 2 years
– when related to radiation for brain tumors, can be
difficult to distinguish from tumor recurrence
– surgery, steroids, Bevacizumab
QuickTime™ and a
decompressor
are needed to see this picture.
• spinal cord syndrome (Brown-Sequard)
• cerebral atrophy, often with white matter change
– can be associated with cognitive/memory symptoms
• SMART syndrome
– stroke-like migraine attacks after RT

13. long-term CNS risks with
radiation therapy
QuickTime™ and a
decompressor
are needed to see this picture.
• delayed leukoencephalopathy
– white matter (deeper brain structures) affected
– can affect memory and personality
– commonly related to methotrexate with radiation
– attempts to treat with methylphenidate, donepizil
• radiation-induced vasculopathy (stroke)
– large blood vessels in neck (often head and neck
tumors)
– small blood vessels in brain (brain tumors)
– radiation-induced cavernous malformations and
aneurysms