Seizures and psychogenic non-epileptic seizures Flashcards
Seizure definition
Seizure classification
Epilepsy definition
Seizure semiology
How a seizure starts and progresses, as reflection of area of brain involved in the abnormal electric activity giving rise to the seizure.
I.e.
The semiology of epileptic seizures reflects activation, or dysfunction, of areas of brain (often termed the symptomatogenic zone) as a seizure begins and evolves.
What is the most common inter-ictal EEG finding in adult with focal seizures?
Anterior temporal lobe spike discharge
Types of epileptiform tracings on EEG
Spikes (shorter duration)
Sharp waves (longer duration)
Different patterns of these on BG activity correspond to different epilepsy syndromes
Why would you try to avoid use of Carbamazepine and Lamotrigine in a patient with epilepsy of Chinese origin?
Han Chinese populations have high rate of HLAB1502 mutations which are associated with Stevens Johnson reaction to Carbamazepine and Lamotrigine
Special consideration for patients taking hormonal therapies (incl OCP, HRT), with regards to AEDs?
Should be warned of interaction between Topiramate and Lamotrigine with hormonal treatments - e.g. Topiramate > 100mg od induces metabolism of OCP -> renders the OCP ineffective
If patient is pregnant or taking OCP on Lamotrigine, this reduces its effectiveness -> need to increase the dose of Lamotrigine
Considerations when adding AED
Pharmacologically redundant to add a drug that has the same mechanism of action to the current one - need to exploit different mechanism
Choice of AED based on seizure type
Depends on type of epilepsy
- Focal seizures -> usually best to use Na+ channel blockers e.g. Carbamazepine, Lamotrigine, Lacosamide
- Generalised -> sodium valproate, levetiracetam, Lamotrigine, Ethosuximide (reserved for use in childhood absence seizures), Zonisamide, Perampanel
AED to avoid in those with mood issues
Levetiractam
AED to avoid in those with PCOS, obesity
Na valproate
AED to avoid in those with bone marrow/haematological issue
Na valproate - known to cause thrombocytopenia
AED to avoid in those with hyponatratemia
Carbamazepine
AED to avoid in those with movement disorders
Na valproate
AED to avoid in those with cognitive issues
Topiramate and phenobarbital
AED to avoid in those with kidney stones
Topiramate, Zonisamide
AED to avoid in those with insomnia
Lamotrigine - or at least make sure take all dose in morning so no evening peak to cause insomnia
AED to avoid in those with liver impairment
Na valproate
AED to avoid in those with renal impairment
Levetiracetam, pregabalin, gabapentin
Which AEDs are Na+ channel blockers
Carbamazepine
Lamotrigine,
Lacosamide
Phenytoin
Oxcarbazepine
Eslicarbazepine
Rufinamide*
Zonisamide*
Felbamate*
Topiramate*
- have other mechanisms of action aside from being Na ch blockers
AED to avoid in those with myoclonus
Na+ channel blockers i.e. Carbamazepine, Lamotrigine, Lacosamide
Which AEDs have mood stabilising effects?
Na valproate, Lamotrigine
Which AEDs should not be given together as they induce each others’ metabolism and therefore cancel out each others’ effectiveness?
Phenytoin and Carbamazepine
Which AEDs are GABA enhancers?
Phenobarbital
Primidone (prodrug of phenobarbital)
Clobazam
Clonazepam
Na valproate
Topiramate
Vigabatrine
Tiagabine
Felbamate
These drugs are more likely to cause sedation
Which AEDs are Ca channel blockers?
T type - used in treatment of epilepsy
Na valproate
Ethosuximide
Zonisamide
Others (A2D of VGCC) - used more in treatment of neuropathic pain
Gabapentin
Pregabalin
What is the mechanism of action of Levetiracetam and Brivaracetam?
Binds to synaptic vesicle protein SV2A thus modulating synaptic neurotransmitter release
- a novel mechanism of action
Mechanism of action of Perampanel
AMPA receptors
- a novel mech of action
Mechanism of action of Retigabine
K+ channel opener
- a novel mech of action
Mechanism of action of Felbamate
NMDA receptors
- a novel mech of action
What are two AED of last resort due to their significant adverse effects?
Vigabatrin - irreversible visual field contraction
Felbamate - significant bone marrow suppression
These are reserved for palliation in those with refractory seizures who are not candidates for surgery
What are the broad spectrum AEDs?
Na valproate
Levetiracetam
Lamotrigine
Topiramate
Zonisamide
Perampanel
Brivaracetam
Which AEDs have non-linear pharmacokinetics?
Phenytoin
Gabapentin
Which AEDs induce liver enzymes and thereby can lower the effectiveness of other drugs e.g. warfarin, OCP?
Phenytoin
Na valproate
Phenobarbital
Carbamazepine
Oxcarbazepine
Explain the non-linear pharmacokinetics of Phenytoin
Beyond 300mg per day, Phenytoin saturates its own metabolism so that ANY even small increase beyond this dose leads to a disproportionately large increase in the drug serum concentration. That is why there is a NARROW THERAPEUTIC RANGE - easy to go into toxic level
- interestingly, Phenytoin is a strange AED as it causes increase in frequency of seizures if serum concentrations go beyond 30g/L (i.e. in toxic high range)
- with this in mind, once in therapeutic range but seizures still not controlled and need to uptitrate the drug this must be done in small increments 30-60mg
- In practice, many clinicians use 300mg/day as the ceiling maintenance dose of Phenytoin for patients for the above reasons
What is meant by ‘non-linear kinetics?’
Usually, we expect that as you increase drug dose, you thereby proportionately increase the concentration of the drug in the blood
However, this does not occur for some drugs e.g Phenytoin and Gabapentin
Explain the non-linear kinetics of Gabapentin
It is opposite to that of Phenytoin
As dose of Gabapentin is increased, it saturates its own absorption mechanism from the gut so serum concentration does not rise proportionately to the increase in dose and serum level actually starts to fall
Summary of AEDs and types of epilepsy they are used in
What is the criteria for ‘refractory epilepsy’?
When seizures are not adequately controlled despite 2x AEDs at adequate levels
- this is the time to refer to a Specialist
How do psychogenic non-epileptic seizures (PNES) differ from epileptic seizures?
Their aetiology is psychological rather than neuronal (abnormal brain discharge)
Epidemiology of PNES
- occur 3x more in women than men
- less prevalent than epilepsy (33/100,000 vs 638/100,000) but more health burden
- 2.5 x higher mortality rate than general population = comparable to mortality rate of people with drug-resistant epilepsy
- comorbidity with epilepsy common - 20-30% of those with PNES also have a confirmed dx of epilepsy
- as is comorbidity with psychiatric conditions - 57-85% of people with PNES also have a dx of depression or anxiety disorder (including PTSD, dissociative disorders, personality disorders, pain disorders)
- commonly also suffer from other medically unexplained sx
Aetiology of PNES
What are the models that seek to explain how PNES manifests physically?
What is the diagnostic gold standard for PNES?
Video EEG + neuropsychiatric evaluation
How to you clinically tell a seizure apart from a PNES?
Epileptic seizures tend to be stereotypical i.e. tend to happen in the same way for a similar period of time each episode, whereas in PNES there is considerable variation in the characteristics of the attacks within and between each episode
PNES - tend to retain some awareness of surroundings/things said to them during the attack
PNES - tend to close eyes during a tonic event whereas epileptic seizures more likely for eyes to stay open/roll backwards
What is the gold standard treatment for PNES?
Currently there is none as per a recent Cochrane review
However, patient - doctor dynamics very important including how the diagnosis is communicated to the patient - affects their recovery, long term outcomes
Also, recent pilot trial at the Alfred shows promising results
Re -PROGRAM trial
What are the patient and clinician factors which can delayed dx of PNES, inadequate patient-centred care and significant healthcare burden (i.e. through re-admissions)
Re-PROGRAM pilot results
