David Walk
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Transcript of David Walk
Neurologic effects of cancer treatment
Survivorship conference 2013
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
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
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 bevacizumabo thalidomide
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
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
“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
risks of chemotherapy in the CNS
• encephalopathy usually resolves within days– 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
QuickTime™ and a decompressor
are needed to see this picture.
effects of radiation therapy in CNS
• can injure normal cells as well as tumor cells
• inflammation• interruption of BBB
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
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
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
• 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
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long-term CNS risks with radiation therapy
• 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
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