Neuro-psycho-oncology Flashcards
How do rates of mental disorders in cancer patients compare to the general population?
They are much higher, especially as first recurrence
What mental health problems are most common in cancer patients?
▪️Mood problems
▪️Anxiety
▪️Insomnia and sleep disturbance
▪️Cognitive difficulties
▪️Body image and self-esteem
What mental health problems are common during treatment?
▪️Insomnia
▪️Cognitive difficulties
Which types of cancer are associated with worse mental health?
▪️Head and neck
▪️Lung
▪️Pancreas
▪️Haemotological
What factors predict worse mental health outcomes in cancer patients?
▪️Young age
▪️Lower SES
▪️Poor functioning
▪️Pain
▪️Comorbidities
▪️Severity of illness
▪️Prognosis
What did the 2017 KCH audit find about the key concerns of haemotology patients?
▪️30% of concerns were emotional
▪️Half of the top 10 concerns were psychological (e.g. anxiety, fatigue, intimacy, sadness)
How might cancer cause psychiatric effects?
▪️Mass effect or destruction of tissue
▪️Systemic depletion of substance
▪️Hormone secretion by tumour
▪️Paraneoplastic hormone secretion
▪️Onconeuronal antibodies
▪️Pro-inflammatory action
What cancer treatment might psychiatric effects?
All of them!
Both directly to the CNS and indirectly via distant sites
What is Cushings Syndrome?
A syndrome of chronic, low level, hypercortisolaemia caused by too much cortisol
How is corticol produced?
▪️Corticotrophin releasing factor (CRF) is produced in the hypothalamus
▪️CRF stimulates the pituitary gland to produce ACTH
▪️ACTH stimulates the adrenal gland to produce cortisol
Which types of tumours actively secrete ACTH?
▪️Active pituitary tumours
▪️Thyroid medullary tumours
Which tumours secrete glucocorticoids (e.g. cortisol) ?
Adrenocortical tumours
BUT rare
How might tumours cause Cushing Syndrome (too much cortisol)?
▪️Active secretion of ACTH or cortisol
▪️Paraneoplastic secretion (ACTH provokes adrenal glands to produce cortisol)
What cancer is associated with paraneoplastic ACTH secretion?
Small cell lung cancer
How do you treat Cushings Syndrome?
Corticosteroids
(Most commonly for GBM and Haemotological cancers)
What are the neuropsychiatric symptoms of Cushing Syndrome?
▪️Severe depression
▪️Cognitive difficulties
▪️Emotional instability
▪️Sleep disorders
▪️Fatigue
What neuropsychiatric sequelae might be seen with high doses of steroids?
Severe psychosis or mania
What neuropsychiatric sequelae might be seen with low doses of steroids?
▪️Depressed mood
▪️Anxiety
▪️Insomnia
▪️Agitation
▪️Euphoria
How might hypothyroidism occur as a consequence of cancer?
▪️Destruction of the hypothalamus or pituitary gland by tumour
▪️Thyroid damage from surgery or radiation
▪️Molecular treatments and monoclonal antibodies
How might hyperthyroidism occur as a consequence of cancer?
bHCG secreted by some testicular cancers can mimic TSH, stimulating the thyroid
(Much more rare!)
What are the neuropsychiatric symptoms of hypothyroidism?
▪️Fatigue
▪️Mood change
▪️Memory change
What are the neuropsychiatric symptoms of hyperthyroidism?
▪️Agitation
▪️Anxiety
▪️Mania
▪️Psychosis
How might cancer cause oestrogen deficiency?
▪️Pelvic irradiation
▪️Oestrogen-receptor blockers
▪️Hypothalamus or pituitary surgery or irradiation
What is the main role of oestrogen in the brain?
▪️Neuroprotection
▪️Increases serotonin synthesis
▪️Promotes neuroplasticity
What neuropsychiatric sequelae may be seen with oestrogen deficiency?
▪️Depression
▪️Increased later dementia risk
What hormone deficiencies might occur after pituitary or hypothalamus surgery or irradiation?
▪️Oestrogen
▪️Growth hormone
What are the neuropsychiatric symptoms of growth hormone deficiency?
▪️Depression
▪️Anxiety
▪️Subtle cognitive deficits in attention and memory
What are onconeuronal antibodies?
Antibodies produced by tumour cells that bind to targets in the CNS
What type of cancer is associated with anti-Hu antibodies and what neurological consequences might they cause?
▪️Small lung cell carcinomas
▪️Encephalitis
What type of cancer is associated with anti-Yo antibodies and what neurological consequences might they cause?
▪️Aggressive breast cancer
▪️Paraneoplastic cerebellar degeneration
▪️Cerebellar symptoms, cognitive deficits, disinhibition, visuospatial problems
What type of cancer is associated with NMDAr antibodies and what are the symptoms?
▪️Teratomas (particularly ovarian)
▪️Acute schizophrenia-like psychosis
What are the two main routes to deficiency and how do they relate to cancer and cancer treatment?
▪️Poor absorption (from surgery or radiotherapy)
▪️Poor appetite (chemo sickness, cytokine production, precursor to cancer)
What is methotrexate and how does it work?
A form of chemotherapy that deprives the body of folate, preventing cells from replicating thus stopping cancerous growth
What might cause folate (B12) deficiency in cancer?
▪️Impaired absorption from stomach/upper bowel surgery or radiation
▪️Methotrexate
What is folate/B12 needed for?
▪️DNA replication and cell growth
▪️Myelin synthesis
▪️Red cell production
How might cancer cause anaemia?
Bone marrow suppression either by invasion (blood cancer) or treatment (chemotherapy)
How might anaemia present neuropsychiatrically?
Depression symptoms
How do carcinoid tumours lead to serotonin deficiency?
–> Produce too much peripheral serotonin
–> Depletion of tryptophan (negative feedback loop)
–> Reduces the amount of serotonin that reaches the brain
How do pancreatic adenocarcinoma lead to serotonin deficiency?
Produce an inflammatory reaction which depletes tryptophan
What percentage of people experience cognitive deficits after brain irradiation?
50-90% (dose dependent)
(Particularly memory, attention, and IQ)
How is radiation thought to impact cognition?
Likely through its neuroinflammatory effect (microglia activation and decreased neurogenesis)
What are risk factors for worse cognitive reactions to radiotherapy?
▪️Young age (brain still developing)
▪️Intrathecal chemo (methotrexate)
▪️Pituitary radiation (hormone effects)
What is chemo brain?
‘Brain fog’ and subjective cognitive difficulties commonly reported after or alongside chemotherapy.
What factors may underlie chemo brain?
▪️Effect of cancer
▪️Radiation and other treatments
▪️Psychological stress
▪️Insomnia
▪️Some evidence for APOE e4 gene
What parts of the brain appear to be affected by chemo brain?
Everywhere except the occipital lobe
How might chemotherapy directly induce cognitive impairment?
▪️BBB penetration leading to neurotoxocity, axonal damage, demyelination etc
▪️Oxidative stress response
▪️Hormone changes
▪️Immune dysregulation and inflammation
▪️Altered LTP
▪️Cerebral vascular alteration
(Or all of the above?)
What is CICI?
Chemotherapy-Induced Cognitive Impairment
(contraversial!)
What is PML?
Progressive Multifocal Leukoencephalopathy (PML)
A disease caused by the JC virus, which targets myelin producing cells, leading to demyelination and white matter abnormalities
What are the symptoms of PML?
▪️Progressive weakness
▪️Speech problems
▪️Loss of coordination
▪️Cognitive deficits
▪️Seizures
▪️Death
How might cancer treatments cause PML?
Immunosuppression can reactivate the JC virus which is usually harmless. The virus then invades oligodendrocytes causing irreversible demyelination.
(Usually monoclonal antibodies or chemotherapy)
How does CAR T-cell therapy work?
▪️CAR T-cell are made in lab from patients T-cells
▪️Infused back into patients
▪️CAR T-cells bind to cancer cells and prompts massive inflammatory response
What symptoms do you get with CAR T-cell therapy and why?
Massive inflammatory response and release of cytokines causes a severe influx of symptoms including:
▪️CAR-related encephalopathy syndrome (CRES) (headaches, confusion, weakness, seizures, hallucinations, aphasia etc)
▪️Sepsis-like symptoms
When are CAR T-cell therapy patients most at risk?
During the first few days.
Severe symptoms are usually temporary and reversible but have ICU bed ready just in case
