1. Chemotherapy and radiation therapy can both cause neurologic side effects, including peripheral neuropathy, "chemobrain", and damage to the central nervous system. 2. Chemotherapy-induced peripheral neuropathy commonly causes pain, weakness, or imbalance and is generally dose-dependent and reversible, though some neuropathies may persist. Radiation-induced peripheral neuropathy typically causes gradually progressive weakness months to years later. 3. Radiation therapy carries risks of acute and chronic effects in both the central and peripheral nervous systems, including encephalopathy, leukoencephalopathy, vascular injuries like stroke, and spinal cord syndromes. Long-term risks include radiation necrosis, cerebral atrophy, and delayed leukoencephalopathy

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