14.8 (14.1) neurological problems in advanced cancer

Question 1

List SEVEN features of intracranial pressure waves (aka inc ICP).

Answer 1

◆ altered state of consciousness, agitation, delirium

◆ focal/generalized seizures
◆ cerebellar fits (opisthotonus - WP: think tetanus posture)
◆ decortication or decerebration posture

◆ amaurosis (transcient vision loss), anisocoria (unequal pupil size)
◆ II, IV, VI nerve paralysis, conj. eye deviation (WP: conj. = both)
◆ nystagmus, tinnitus

◆ myoclonus of face and limb
◆ dysarthria, dysphagia
◆ headache, neck pain

◆ pyramidal signs, paraesthesiae

◆ CV/Resp disturbances, yawning, hiccup

◆ hyperthermia, face cyanosis, flushing, pallor, sweating
◆ nausea, vomiting, sialorrhoea, diarrhea, incontinence

Question 2

List FOUR features of a HA that would make you concerned about increased ICP

Answer 2

◆ Progressive, severe, diffuse
◆ More intense in the supine position*
◆ Worse in AM immediately after awakening *
◆ Worsen w/ head movement, cough, Valsalva*
◆ Accompanying N/V*
- projectile vomiting in children -> post fossa lesions

FS:
- morning headache
- worse supine + valsalva (2)
- comes with N/V

Question 3

List four types of brain edema that can cause increased ICP and their mechanisms. Which is the most common type in advanced cancer?

Answer 3

Vasogenic edema - increase of extracellular fluid caused by increased capillary permeability (due to lesions that damages the blood brain barrier)

osmotic edema - increase of extracellular fluid caused by plasma hypoosmolarity (ie. SiADH)

Interstitial edema - increase of extracellular fluid caused by blockade of csf resorption at any level

cytoxic edema - increase in intracellular fluid due failure of intracellular ion pump ( caused by ischemic or hypoxic cellular damage)

*vasogenic edema most common in advanced cancer

FS: VOIC

Question 4

List three interventions for reducing ICP and maintaining cerebral perfusion pressure

Answer 4

Positioning - neutral head position at least 30 degrees above heart

Infusion of hypertonic solutions (mannitol, hypertonic saline) - works only if blood brain barrier intact

Corticosteroids

Question 5

List 8 side effects of corticosteroids (box 14.1.2 + 14.8.3)

Answer 5

◆ BRAINZ
- pseudotumor cerebri

◆ Cutaneous
- delay in wound healing
- thinning of skin
- easy bruising
- epidural lipomyotosis

◆ Endo
- hyperglycemia
- adrenal suppression
- immunosuppression

◆ GI
- PUD
- perineal burning sensation

◆ Muscular
- myopathy
(impacts pelvic girdle, head flexors & shoulder)

◆ Bone
- osteoporosis
- aseptic necrosis of the fem head

◆ Psych
- dysphoria
- aggressiveness/irritability
- psychosis/hallucination/delirium

◆ Ocular
- glaucoma
- cataract

FS:
Insomnia
Delirium
Agitation

PUD
GI bleed

Hyperglycaemia
Adrenal insufficiency
Hypogonadism

Proximal muscle weakness
Osteoporosis
Skin changes (easy bruising)

Question 6

What is the role of seizure prophylaxis in patients with brain mets (no seizure hx)

Answer 6

Not utilized

Question 7

List three antiseizure meds that induce CYP 3A4

Answer 7

Antiepileptic agents that can induce CYP3A4 are carbamazepine, phenobarbital, phenytoin, and primidone

Question 8

List 2 features of status epilepticus

Answer 8

≥5 minutes of continuous seizures

≥2 discrete seizures between which there is incomplete recovery of consciousness

WP: used Uptodate def because 5th/6th answers suck

Question 9

You are on the PCU when a patient develops status epilepticus. The patient has no IV access. List three medications and their routes that can be used to a treat a seizure

Answer 9

Phenobarbital - subcutaneous
midazolam - subcutaneous
lorazepam - subcutaneous, sublingual

Question 10

List the three most common cancers associated with brain mets

Answer 10

Lung
breast
melanoma

Question 11

List 3 ways by which brain mets cause symptoms

Answer 11

Local destruction  
compression
brain edema
bleeding

irritation of surrounding brain tissue

Question 12

How do corticosteroids reduce edema from brain mets

Answer 12

reduction in peritumoral edema due to partial restoration of the blood brain barrier

Question 13

What 3 factors determine the functional outcome of a patient with epidural spinal cord compression

Answer 13

degree of neurlogical impairment at diagnosis

promptness of treatment

response to treatment

Question 14

List 4 features of pain that suggests spinal cord compression

Answer 14

crescendo pattern
worse with cough or valsalva
pain lying down
longstanding pain that changes characteristics
radicular pain
+ Lhermitte’s (barber’s chair sign)

FS:
L - radicular pain
O - Acute worse I g
P - valsalva, lying down
Q - sharp stabbing
R - radicular
S
T - crescendo pain

Question 15

List 3 treatments for underlying epidural spinal cord compression

Answer 15

surgery
radiation
steroids

Question 16

List four indications for surgery in the setting of spinal cord compression

Answer 16

site of primary tumor unknown

spinal instability or vertebral displacement*

plegia of rapid onset*

neurological symptoms progress during radiotherapy*
relapse after xrt
tumor not likely radiosensitive*

Question 17

Leptomeningeal disease represents dissemination of tumour cells in what space

Answer 17

subarachnoid space

Question 18

Leptomeningeal disease is most commonly seen in what four cancers

Answer 18

Lung*
Breast *
Melanoma *
lymphoma
leukemia

Question 19

List four common symptoms of leptomeningeal disease

Answer 19

Headache* 
change in mental status*

Seizure 

radicular type pain*

Cauda equina

cranial nerve involvement
polyradiculopathy

*most common

Question 20

List four findings of leptomeningeal disease in csf

Answer 20

high opening pressure
high protein content
increased white cell count
low glucose
\+/- malignant cells

Question 21

List three treatments for leptomeningeal disease

Answer 21

corticosteroids
radiotherapy
intrathecal or intraventricular chemo
systemic chemo

Question 22

A patient develops numbness in the chin but no pain. What nerve is likely involved?

Answer 22

Mental nerve

Question 23

A patient has pain in the neck and throat which radiates to the ear. Pain is aggravated by swallowing.

What nerve is likely involved?
Severe pain may be associated with what other cardiac feature?

Answer 23

glossopharyngeal nerve

syncope

Question 24

A patient with breast ca develops pain in the shoulder, elbow, hand and 4th & 5th fingers.

What complication is occurring?

Which malig is it common in?

Answer 24

◆ brachial plexopathy

◆ breast, lung, lymphoma

Question 25

List 4 reasons a patient with cancer may develop a peripheral neuropathy or polyneuropathy

Answer 25

◆ myeloma associated neuropathies
◆ paraneoplastic sensory neuropathy
◆ sensory motor peripheral neuropathy
◆ nutritional factors (cachexia-ass neuromyopathy)
◆ vitamin deficiency (B12, folate)
◆ cancer related metabolic dysfunction (hepatic, renal)
◆ direct infiltration of peripheral nerves (lymphoma, leukemias)
◆ vascular nerve injury (hemorrhagic or ischemic)

◆ cytotoxic treatments
~~~

FS:
Ca -> Infiltration of peripheral nerve

Ca -> vascular nerve injury

Ca -> Paraneoplastic neuropathy

Ca -> metabolic dysfunction

Chemo

Question 26

List FOUR chemo drugs that cause peripheral neuropathy.

Each one must be from a different class.

Answer 26

◆ Sensory or sensory/motor or autonomic
- Vinca alkaloids (vincristine)
- Taxanes (paclitaxel)
- Platinum-derivate agents (oxaliplatin)
- Antibodies (trastuzumab)
- Immunomodulatory drugs (thalidomide)
- Proteasome inhibitor (bortezomib)
- Rarely: anti-metabolites (5-FU)
- Rarely: immune checkpoint inhibitors (pembrolizumab)

◆ Guillain-Barre
- Immune checkpoint inhibitors (pembrolizumab)
- Tyrosine kinase inhibitors (imatinib)
- Antibodies (rituximab)

◆ Myasthenia gravis
- Immune checkpoint inhibitors (pembrolizumab)

Box 14.8.6

FS:
COP - TV

Question 27

What are the two most common paraneoplastic neurological syndromes? What cancers are they associated with?

Answer 27

Lambert eaton myasthenic syndromes -> SCLC

Myasthenia gravis -> thymoma

Question 28

List FOUR features of ICP in children

Answer 28

◆ Non-specific findings
◆ irritability
◆ labile mood*
◆ negativity
◆ aggressive or hostile behaviour*
◆ sunset sign
- downward ocular deviation, eyelids retract due to compression of quadrigeminal plate*
◆ projectile vomiting w/ post fossa lesions

Question 29

List FIVE signs of central herniation syndrome*

Answer 29

◆ starts with:
- dec LOC
- Cheyne-Stokes resp
- miotic but light reactive pupils
- “doll’s eyes” phenomenon/oculovestibular caloric response (warm/cold water in ext ear canal) preserved
- paratonic rigidity
- pyramidal signs

◆ progresses to:
- coma
- resp rhythm changes
- fixed pupils
- oculovestibular abnormalities
- decerebrate rigidity
- limb flaccidity
- loss of brainstem reflexes

Question 30

List FIVE signs of uncal herniation*

Answer 30

◆ starts with:
- ipsilateral pupil to lesion mydriatic + non-reactive to light
- sometimes contralateral pupil changes (w/ brainstem displacement)
- ipsilateral to lesion visual field defects

◆ progress to:
- dec LOC
- Cheyne-Stokes resp
- oculomotor paralysis
- oculovestibular abnormalities

Question 31

List THREE signs of cerebellar herniation*

Answer 31

◆ starts with:
- occipital/frontal headache
- hiccups
- vomiting

◆ progress to:
- dec LOC
- abnormal breathing
- “cerebellar fits” - opisthotonus + decerebration

Question 32

Dex dosing suggestion in 6th Ed for inc ICP*

Answer 32

dexamethasone 96 mg IV (!!) immediately then 24 mg IV q6hr

Question 33

Suggested lorazepam + midaz dosing in status epilepticus

Answer 33

◆ Loraz
- Adult: 4-8 mg IV/IM/SC
- Children: 0.1 mg/kg IV/IM/SC

◆ Midaz
- 0.2 mg/kg initial dose then 0.05-0.5 mg/kg/h IV infusion
- no specification child vs adult
- initial dose 0.05 mg/kg if frail, concurrent opioids/other benzos

Question 34

Suggested TWO alternatives to benzos to seizures management

Answer 34

◆ sodium valproate
◆ levetiracetam
◆ lacosamide

Question 35

Name THREE common side effects of sodium valproate*

Answer 35

◆ tremors
◆ sedation
◆ ataxia
◆ GI sym
◆ thrombocytopenia
◆ severe liver tox (rare; in children under 3 yo on other anticonvulsants)

Question 36

Name TWO common side effects of levetiracetam

Answer 36

◆ somnolence
◆ asthenia (abN weakness)
◆ dizziness

Question 37

Peds dosing dex in brain mets

Answer 37

initial dose of 1 mg/kg
then 0.4-1 mg/kg in one or more dose

Question 38

Name SIX cancers associated with lumbosacral plexopathy

Answer 38

◆ colorectal
◆ breast
◆ lung
◆ cervical
◆ melanoma
◆ pelvic
- bladder
- uterus
- prostate
◆ retroperitoneal
- sarcoma
- met nodal tumours
- sarcoma
- lymphoma

Question 39

Name THREE symptoms of lumbosacral plexopathy

Answer 39

◆ pain (can precede other sym by weeks/months)
◆ numbness
◆ paraesthesia
◆ weakness
◆ leg edema

Question 40

Name THREE symptoms and therapies that cause posterior reversible encephalopathy syndrome (PRES)*

Answer 40

◆ Symptoms
- headache
- confusion
- visual disturbances
- seizures

◆ Therapies
- sunitinib
- sorafenib
- pembrolizumab
- bevacizumab