Neurological problems in advanced cancer - oxford Flashcards
1
Q
Intracranial hypertension
A
- tumour, asbcess, hematoma
- disruption of BBB –> increased volume in vault
- slow accumulation has compensation:
- reduced intracranial blood volume
- increased drainage via circulatory system
2
Q
Clinical features of raised ICP
A
- altered LOC
- headache
- diffiuse
- worse supine, cough, valsalva
- worse in AM
- vomiting
- projectile in posterior fossa lesions
- papilledema
- non sensitive
- focal signs
- CN VI ABDUCENS ***
- diplopia
- Seizure
3
Q
Acute raised ICP clinical features : Pressure Waves
A
- Pressure waves
- seconds to minutes
- agitation, delirium
- focal or general seizures
- opisthotonus
- decerebration
- amauraosis fugax
- II, IV, VI palsy (gaze deviation)
- nystagmus, tinnitus
- myoclonus
- dysarthria
- pyramidal sx
- hyperthermia, cyanosis, flushing
- sweating
- nausea, vomiting, diarrhea, incontinence
4
Q
Brain edema
A
- loss of osmotically active substances albumin from circulation into brain interstitial tissue
- caused by disruption of BBB by tumour
Vasogenic edema:
- increased extracellular space
- increased capillary permeability
- pathogenesis for tumour induced brain edema
5
Q
Treatment of raised ICP
A
- goal to maintian CPP and reduce vasogenic edema
- Euvolemia
Positioning - head at 30 degrees
Hypertonic saline
- usually used if refractory to mannitol
Mannitol
- increased blood blow, improved cerebral perfusion
- osmotic gradient between blood and CSF
- diuretic effect
Steroids
- blocks outflow of blood from capillary bed into brain tissue at BBB
- Dexamethasone does not reduce water content in brain tissue
- 48-72 hours to see improvement
- Dex 4-8 mg po q6h
- Children 1 mg / kg initial dose
6
Q
Seizures : definition
A
- transient occurence of sx due to abnormal excessive neuronal activity in brain
- caused by structural disease (primary and metastatic)
- non structural disease (metabolic and drugs)
7
Q
Seizure classification
A
- Simple Partial
- normal level of consciousness
- selective area of cortex involved –> focal symptoms
- Complex partial seizures
- altered LOC with focal symptoms
- motor automatisms
- awake, eyes fixed
- post ictal phase
- Generalized abscence seizures
- Generalized tonic clonic seizures
- sudden LOC
- muscle rigidity –> cyanosis TONIC
- myclonus, fasciculations CLONIC
- post ictal phase
8
Q
AED (Antiepileptic drugs) : Phenobarbital
A
- partial and tonic clonic
- liver CYP450 metabolism
- slow clearance 4-5 days
- SE:
- drowsiness, ataxia
- Stevens Johnson syndrome
- TEN
- 1.5 mg /kg adult
- 3-8 mg/kg children
9
Q
AED : Phenytoin and fosphenytoin
A
- first line
- simple and complex partial seizures and tonic clonic
- not sedating
- SE:
- ataxia
- GI
- hirsutism
- osteporosis
- megaloblastic anemia
- Qtc prolongation
- hypotension
- drug drug interactions common:
- CYP 450, 3A4 inducer
- significant interaction with DEXAMETHASONE
- can reduce phenytoin plasma levels by 50%
- Contraindications:
- diabetes
- megaloblastic anemia
- pancytopenia
- thrombocytopenia
- neutropenia
Fosphenytoin
- prodrug of phenytoin
- water soluble
- faster infusion
- IM admin
- lower cardiac related adverse effects
- less local skin irritation
10
Q
AED : Sodium Valproate
A
- broad spectrum and status epilipticus
- SE :
- tremors
- sedation
- ataxia
- GI sx
- thrombocytopenia
- sodium channel blockade, GABA, glutamate, NMDA inhibition
- liver toxicity
- hyperammonemia
- metabolism by glucuronidation
- 250-500 mg /day
- children 10-15 mg/kg/day
11
Q
AED : Levetiracetam (Keppra)
A
- broad spectrum and status
- well tolerated
- SE:
- sedation
- asthenia
- dizziness
- psychosis
- IV/po
- MOA unknown
- does not undergo extensize metabolism
- NO DRUG INTERACTIONS
- metabolites not active
- NO CYP450
- eliminated through kidneys
12
Q
Status epilepticus : definition
A
- seizure that lasts 30 minutes or more
- two or more seizures without complete recovery inbetween
- likelihood of spontaneous resolution after 5 minutes is small –> treat as status
- Non-convulsive status:
- EEG seizure activity without convulsive activity
- confusion, psychotic behaviours, automatisms
- Convulsive status epilepticus
- continuous or frequent abnormal motor movements plus altered LOC
- risk of cerebral damage, acidosis, rhabdo
13
Q
Which AEDs can be given rectally?
A
- phenobarbital
- carbamazepine
- valproic acid
- lamotrigine
- diazepam
14
Q
Status epilepticus : treatment
A
- ABC, sugar, labs, reversible causes
- Lorazepam 4-8 mg IV adult, 0.1-0.15 mg/kg children
- half life 10-15 hours
- onset 3 min
- Midazolam IV or atomized nasal preparation, IM, SC
- water soluble
- short half life
- 3 minute onset
- Diazepam IV, rectal (0.2 mg/kg or 10-20 mg)
- PREFERRED RECTAL BENZO
- high lipid solubility
- redistributes rapidly to body tissues, and brain concentration falls.
- needs re-dosing within 20 min
- AED:
- Levatiracetam 20-30 mg/kg IV load over 30 min
- Phenytoin 20 mg/kg IV load over 60 min
15
Q
Seizure management
A
- check for reversible causes : hypoglycemia
- ABC
- if self limited, no treatment, but consider AED
- Acute seizure:
- IV lorazapeam first line
- Clonazepam / midaz subcutaneous
- If no response, see status treatment
16
Q
AED : phenobarbital
A
- 10-15 mg/kg
- 1-3 mg/kg/day IV or IM, can go in PEG tube
- 60-90 mg sc tid
- for refractory EOL status or recurrent seizures
17
Q
Brain metastases
A
- lung cancer (multiple lesions)
- breast cancer (1 lesion)
- melanoma
- cause sx by compression, destruction, irritation, edema and bleeding
- Sx:
- headache (night, morning, moderate-severe)
- nausea/vx
- decreased LOC
- Focal signs
- seizures
18
Q
Treatment of brain metastases
A
- Surgery if single met with limited or no systemic disease
- WBRT but cog impairment and survival 4-6 months
- stereotactic rt
- Steroids :
- all symptomatic patients with mets or primary brain tumour
- imrpovement with reduction in peritumoural edema and restoration of BBB
- Peri-radiation 8-16 mg po od then tapered to lowest effective dose
- Taper 2-4 mg q5days
