Chapter 4 - Epilepsy Flashcards
What does the ILAE define epilepsy as?
> 2 unprovoked seizures >24h apart
Or
One unprovoked seizure and a 60% probability of having another within 10 years
What is seizure freedom?
12 months without a seizure
What is a good therapeutic effect of an AED?
3 times the longest previous interval between seizures
Does glutamate cause an excitatory or inhibitory response?
Excitatory
Does GABA cause an excitatory or inhibitory response?
Inhibitory
What are the two types of focal seizures?
Simple - remain aware
Complex - lose consciousness
What are the five main types of motor generalised seizures?
Tonic-clonic Tonic Clonic Myoclonic Atonic
What are some signs and symptoms that may be seen in a focal seizure?
Kicking Rocking Altered vision Numbness or tingling Muscles stiffening in one area Smelling, tasting, hearing or seeing things Behavioural changes
There may be an aura
What is an example of a non-motor generalised seizure?
Absence
What happens during a tonic-clonic seizure?
Muscles contract and the body becomes rigid
Loss of consciousness and falling to the floor
Violent muscle contractions
How long to tonic-clonic seizures last for?
Usually 1-3 mins
>5 mins is a medical emergency
Do people always recover straight away after a tonic-clonic seizure?
No, it can take a while to recover
The person may feel confused, tired, agitated etc
If a person has bitten their tongue/cheek during a seizure, what type of seizure does this usually indicate?
Generalised tonic-clonic
What is a myoclonic seizure?
Brief jerks of a muscle/group of muscles
Does a person usually lose consciousness during a myoclonic seizure?
No, they are usually too short to affect consciousness
What age group do absence seizures usually occur in?
Children
How long do absence seizures usually last?
A few seconds
What is an absence seizure?
A brief seizure that causes a lapse in awareness, e.g. the child may stare at something
What groups of people are atonic and tonic seizures seen in?
Children
Epilepsy syndromes
What are tonic and atonic seizures?
Tonic - rigidity/stiffness, usually happens I’m in sleep
Atonic - the body goes limp e.g. head may drop, eyelids mag drop, the person may drop items that they are holding
What is a febrile seizure?
A seizure in a child caused by a high fever
How are febrile seizures managed?
Usually with antipyretics e.g. paracetamol
> 5 mins is a medical emergency (status epilepticus)
What is reflex epilepsy?
Seizures triggered by the environment
E.g. due to noises, chewing, flashing lights, sleep deprivation
How is epilepsy diagnosed?
Speak to the patient and any witnesses (especially if they were unconscious)
ECG - but don’t use this alone to diagnose epilepsy
Why isn’t an ECG used alone to diagnose epilepsy?
It can sometimes give false positive or false negative results
What is status epilepticus?
A seizure lasting >5 mins
Or
Multiple seizures where the person doesn’t regain consciousness in between
In a person with status epilepticus, what should also be given if alcohol abuse is suspected?
Thiamine
What would you give for status epilepticus in the community?
Rectal diazepam
Buccal midazolam
What is the first treatment for status epilepticus in hospital?
When should this be repeated if it fails or if seizures reoccur?
IV lorazepam IV diazepam (carries a high risk of thromboplebitis)
Repeat after 10mins if necessary
In status epilepticus, if seizures are still occur 25mins after giving IV lorazepam/diazepam, what would you do?
Either:
IV phenytoin
IV fosphenytoin
IV phenobarbital
In status epilepticus, if seizures are still occur 45 mins after giving IV lorazepam/diazepam, what would you do?
Refer to ICU
Give thiopental sodium, midazolam, or propofol
What are the indications of lorazepam?
Status epilepticus
Febrile convulsions
Convulsions due to poisoning
Anxiety
Panic attacks
Sedation
If lorazepam is used for sedation, how long shouldn’t the patient drive for afterwards?
Minimum 24h
Why shouldn’t people have benzodiazepines and alcohol?
Both are CNS depressants
What are the indications of midazolam?
Status epilepticus
Febrile convulsions
Convulsions in palliative care
Sedation
Does midazolam have a short or long duration of action compared to other benzodiazepines?
Shorter duration of action
And so faster recovery time
After a first unprovoked seizure, how long can’t a person drive for?
When can they start driving again?
6 months
Can restart if they have been assessed by a specialist and have been declared fit to drive at a low risk of another seizure
After an AED has been changed or stopped, how long can’t someone drive for?
Minimum 6 months (as long as there have been no seizures within this time)
What are the first line and alternative options for focal seizures?
First line
Lamotrigine
Carbamazepine
Alternatives
Sodium valproate
Levetiracetam
Oxcarbazine
What are the first line and alternative options for generalised tonic-clonic seizures?
First line
Sodium valproate
Alternatives
Lamotrigine
Carbamazepine or oxcarbazine (may worsen myoclonic or absence seizures)
When is adjunct therapy used in focal seizures?
When two first line AEDs haven’t worked
What are the first line and alternative options for absence seizures?
First line
Ethosuximide
Sodium valproate
Alternatives
Lamotrigine
What are the first line and alternative options for myoclonic seizures?
First line
Sodium valproate
Alternatives
Lecetiracetam
Topirmate (consider poor side effect profile)
What are the first line and alternative options for tonic and atonic seizures?
First line
Sodium valproate
Alternatives
Lamotrigine
What AEDs can worsen myoclonic, absence, tonic and atonic seizures?
Carbamazepine Oxcarbazine Gabapentin Phenytoin Pregabalin Tiagabine Vigabatrin
What are the first line and alternative options for Dravet Syndrome?
First line
Sodium valproate
Topiramate
Alternatives
Cannabinol and clobazam
What are the first line and alternative options for Lennox-Gastaut syndrome?
First line
Sodium valproate
Alternatives
Sodium valproate + lamotrigine
Cannabidol + clobazam
How effective do cannabidol and clobazam need to be in order to be continued in epilepsy syndromes?
Need to reduce seizure frequency by 30% in 6 months
When are antiepileptic drugs usually initiated?
After the second unprovoked seizure
How are AEDs initiated?
- Monotherapy - titration to the lowest effective dose/maximum tolerated dose
- Monotherapy with an alternative AED
- Combination therapy
What is the MRHA advice regarding AEDs and suicidal thoughts/behaviour
All AEDs are associated with a small increase in suicidal thoughts or behaviour
How soon can suicidal thoughts or behaviour occur as a result of AEDs?
Within 1 week
How frequently are most AEDs usually taken?
What are the exceptions?
Twice a day
Exceptions include lamotrigine, phenytoin and phenobarbital - these have a longer half life
What is an advantage of giving AEDs more frequently?
Peak drug concentration will be reduced, which will reduce the adverse effects
Why interactions do many AEDs have in common?
Most are hepatic
enzyme inhibitors or inducers
If a patient is on multiple AEDs, how should these be withdrawn?
Gradually and one at a time
Why should AEDs be withdrawn gradually?
Which AEDs is this particularly important for?
Because withdrawing them quickly increases the risk of rebound seizures, which may be severe
Take particular care with benzodiazepines and barbiturates
What is refractory epilepsy?
When two AED schedules have failed to achieve seizure freedom
Which AEDs do you do routine TDM for?
Phenytoin
Carbamazepine
When is the risk of teratogenicity increased with the use of AEDs?
When AEDs are used in the first trimester
When multiple AEDs are being taken
What are the implications of using sodium valproate in pregnancy?
Congenital malformations (10%) Neurodevelopmental disorders (30-40%) Increased risk of intra-uterine growth restriction
When used in pregnancy, which AEDs can cause:
Congenital malformations
Neurodevelopmental disorders
Increased risk of intra-uterine growth restriction?
Sodium valproate
Phenytoin
Phenobarbital
When used in pregnancy, which AEDs can cause:
Congenital malformations
Carbamazepine
Topiramate
Sodium valproate
Phenytoin
Phenobarbital
When used in pregnancy, which AEDs can cause:
Increased risk of intra-uterine growth restriction?
Topiramate
Zonisamide
Sodium valproate
Phenytoin
Phenobarbital
When can sodium valproate be given to females of a child bearing potential?
When they have met the conditions of the pregnancy prevention programme
When alternative treatments are not effective or not tolerated
Which AEDs are safest in pregnancy?
Lamotrigine
Levetiracetam
If a patient on sodium valproate finds out she’s pregnant, should she stop taking her sodium valproate?
No - seek urgent medical advice first
Which AEDs are hepatic inducers?
Carbamazepine
Phenytoin
Phenobarbital
Which AEDs are hepatic inhibitors?
Sodium valproate
Why is folate supplementation given in pregnancy when a person is also taking AEDs?
To prevent neural tube defects
Pregnancy can change the concentrations of AEDs, which two AEDs can be particularly affected?
Lamotrigine
Phenytoin
When switching between AEDs, what drugs are in category 1?
Carbamazepine
Phenytoin
Phenobarbital
When switching between AEDs, what drugs are in category 2?
Clobazam Clonazepam Lamotrigine Oxcarbazepine Topiramate Valproate Zonisamide
When switching between AEDs, what drugs are in category 3?
Pregabalin
Gabapentin
Levetiracetam
Ethosuximide
What is antiepileptic hypersensitivity syndrome?
A rare but potentially fatal type of anaphylactic reaction
What AEDs is antiepileptic hypersensitivity syndrome associated with?
Carbamazepine Lamotrigine Oxcarbazine Phenytoin Phenobarbital
How soon does antiepileptic hypersensitivity syndrome usually occur after exposure to an AED?
1-8 weeks
What are some signs and symptoms of antiepileptic hypersensitivity syndrome?
Rash Fever Hepatic dysfunction Renal dysfunction Pulmonary abnormalities Multi organ failure
What is sudden unexpected death in epilepsy?
A non traumatic death
With or without evidence of a seizure
In the absence of status epilepticus
What are some risk factors for sudden unexpected death in epilepsy?
Young age Refractory epilepsy Nocturnal seizures Long duration of epilepsy Frequent convulsions
When should an ambulance be called if a person is having a seizure?
Duration >5 minutes First seizure Difficult to wake up afterwards Difficulty breathing Person is injured
How can you prevent injury duri bf a seizure?
Remove glasses/anything that could cause harm
Put something soft under the persons head
Don’t restrain them
What should you do once a persons seizure has stopped?
Check their airways
Put them in the recovery position
Monitor for injuries and manage as appropriate
When does liver dysfunction occur with use of sodium valproate?
Within the first 6 months
If sodium valproate is used in pregnancy, how should it be used?
Lowest dose possible
Prescribe m/r
Prescribe less than 1g - doses higher than this are associated with an increased risk of teratogenicity
When dispensing sodium valproate to women of a child bearing potential, what should you do if you can’t dispense in whole packs?
Ensure that a pregnancy warning label is either on the box or as a sticker
If a patient on lamotrigine develops a rash, what could this be?
Stevens-Johnson syndrome
Antiepileptic hypersensitivity syndrome
If a patient on lamotrigine develops a rash, what should be done?
Discontinue lamotrigine
If a patient on lamotrigine develops a rash, factors increase the risk of a serious skin reaction?
Concomitant use of valproate
Starting at high doses
Titrating quickly
Can lamotrigine be given in pregnancy and breastfeeding?
Yes
What is the interaction between lamotrigine and oestrogen containing contraceptives?
Oestrogen containing contraceptives may reduce the plasma concentration of lamotrigine, which may result in a loss of seizure control
Can levetiracetam be given in pregnancy and breastfeeding?
Pregnancy - yes
Breastfeeding - no
What is the brand name of levetiracetam?
Keppra
Does levetiracetam interact with hepatic enzymes?
Not as much as other AEDs - it is not extensively metabolised by the liver
Should carbamazepine be titrated quickly?
No
How long does it take for carbamazepine to reach a steady state?
About 2 weeks
What types of seizures can carbamazepine worsen?
Myoclonic
Absence
Tonic
Atonic
Does carbamazepine cause hypernatraemia of hyponatraemia?
Hyponatraemia
What are the optimal plasma concentrations of carbamazepine?
4-12 mg/litre
20-50 micromol/litre
What is the brand name of carbamazepine?
Tegretol
Is phenytoin base and phenytoin salt bioequivalent?
No
Phenytoin salt 100mg = phenytoin base 92mg
Why is phenytoin not commonly used?
Poor side effect profile
Narrow therapeutic window (requires lots of monitoring)
Lots of drug interactions (hepatic enzyme inducer)
Unpredictable kinetics
How is phenytoin given in patients who have enteral feeding?
Interrupt enteral feeding 2hours before and after the phenytoin dose
Can phenytoin be given IM?
No - absorption is slow and erratic
What type of seizures can phenytoin exacerbate?
Absence
Myoclonic
What are some symptoms of phenytoin toxicity?
Confusion Slurred speech Hyperglycaemia Ataxia Loss of balance Muscle weakness
What is the optimal phenytoin concentration in:
a) adults
b) children <3 years
c) children 3-18 years
a) adults 10-20mg/litre (40-80 micromol/litre)
b) 6-15mg/litre (25-60micromol/litre)
c) 10-29mg/litre (40-80 micromol/litre)
When might you want to measure free plasma phenytoin concentration?
When there is reduced protein binding e.g. in pregnancy and neonates
What increase the risk of respiratory depression in patients taking gabapentin?
Elderly
Renal impairment
Compromised respiratory function
What was gabapentin and pregabalin reclassified from and to in 2019
POM to schedule 3 CD
Why were gabapentin and pregabalin reclassified?
Risk of abuse - can be mixed with other drugs e.g. methadone
Is gabapentin renally or hepatically excreted?
100% renal excretion
At what CrCl does the dose of gabapentin need to be reduced?
<79ml/min
What Pre-treatment screening may be required for some patients due to the risk of Stevens-Johnson syndrome?
Test for the allele HLA-B*1502 in Han Chinese and Thai patients
These patients are at an increased risk of Stevens-Johnson syndrome
Which AEDs are associated with a risk of Stevens-Johnson syndrome?
Carbamazepine
Lamotrigine
Phenytoin
Phenobarbital
Which AEDs are associated with a risk of blood disorders?
Carbamazepine Lamotrigine Phenytoin Phenobarbital Sodium valproate Ethosuximide
Which AEDs are associated with a risk of hepatic disorders?
Sodium valproate
Carbamazepine
What are the symptoms of heparins disorders?
Jaundice Dark urine Abdominal pain Vomiting Anorexia
Why is folate supplementation used in pregnancy?
To prevent neural tube defects
