David Walk
- 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