Session 13: Epilepsy Flashcards
Define seizure.
A transient occurrence of signs or symptoms due to abnormal electrical activity in the brain which leads to a disturbance of conscious, emotion, behaviour, motor function and sensation.
What happens if you stimulate glutamate and NMDA receptors?
They are channels that let Na+ and Ca2+ in and K+ out leading to depolarisation and increased excitation of the neurons.
This means the neuron is more likely to fire and action potential.
Explain what happens if you stimulate GABA and GABAa receptors?
They open channels that let Cl- in which will hyperpolarise the membrane and lead to a less likelihood of an action potential firing.
Give general causes of a seizure.
Genetic differences in brain chemistry and receptor structure i.e. genetic epilepsy syndrome.
Drugs that stimulate receptors
Drug withdrawal or metabolic changes leading to an acquired change in brain chemistry.
Strokes/Tumours
Signs and symptoms of a seizure
Often an aura before seizure begins.
Shaking
Loss of consciousness with changes in muscle tone and biting (generalised seizure)
In a tonic-clonic seizure there is an initial hypertonic phase followed by rapid clonus (shaking/jerking)
Post-ictal phase which can last from minutes to hours.
Defintion of epilepsy.
Seizure does not mean epilepsy
It is diagnosed by a specialist.
At least two unprovoked seizures occurring more than 24 hours apart.
One unprovoked seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures.
What is a reflex seizure?
A seizure brought on by stimulus.
Give examples of reflex seizures.
Photogenic
Phonogenic/Musicogenic
Thinking
Eating
Hot water immersion
Reading
Orgasm
Movement
What type of onsets of seizures are there?
Focal onset
Generalised onset
Unknown onset
How can focal onset be subdivided?
Aware focal onset
Impaired awareness focal onset
Motor onset or nonmotor onset
How can generalised onset be subdivided?
Motor onset (tonic-clonic)
Or nonmotor onset (absence)
What is focal to bilateral tonic-clonic?
A focal onset seizure that becomes a generalised tonic-clonic seizure.
Which types of generalised motor onset seizures are there?
Tonic-clonic
Myoclonic
Atonic
and many more…
Explain the spread of a generalised seizure.
Originate at some point within and rapidly engage bilaterally distributed networks.
This can include cortical and subcortical structures but not necessarily the entire cortex.
Explain the origin and spread of a focal seizure.
Originate within networks limited to one hemisphere.
May be discretely localised or more widely distributed.
What is a grand mal?
A generalised seizure
What is a petit mal?
An absence seizure
What is a partial seizure?
A focal seizure
Give examples of provoked seizures.
Drug use or withdrawal
Alcohol withdrawal
Head trauma and intracranial bleeding
Hyponatraemia/hypoglycaemia
Meningitis and encephalitis
Febrile seizures in infants
Uncontrolled hypertension
Differential diagnoses of seizures
Vasovagal syncope
Reflex anoxic seizures
Arrhythmias
Parkinson’s
Huntington’s
TIAs
Migraines
Non-epileptic attack disorders
Initial management of a seizure.
A-E assessment
Airways
Breathing - sats reading
Circulation (expect a high HR and be wary of the BP as drugs might drop BP)
Disability - consciousness state
Exposure
Why should you set a timer for 5 minutes at the onset of a seizure?
Because the majority of seizures will self-terminate without the use of drugs.
Therefore a timer is set for 5 minutes and if it is still going give seizure terminating drugs.
Define status epilepticus.
A seizure lasting more than 5 minutes or more, or multiple seizures without a complete recovery between them.
Has a mortality of around 20% after 30 days.
Explain the pharmacological approach to a seizure.
Wait 5 minutes.
Give benzodiazepines
If that doesn’t work give benzodiazepines again.
If that doesn’t work give a loading dose of phenytoin or levetiracetam.
If that doesn’t work call intensive care/anaesthetics to give thiopentone or other anaethesia. This must be done by a specialist.
Explain the mechanism of action of benzodiazepines.
GABAa agonist.
Increases the Cl- conductance leading to a more negative resting potential and the neuron less likely to fire.
No firing nuerones = no seizure.
Benzos work best when membrane positive like in a seizure.
Other uses for benzos.
Anxiolytics
Sleep aids
Alcohol withdrawal
ADRs of benzos
Addiction
Cardiovascular collapse
Airway issues
Give benzodiazepine options and what to give in status epilepticus.
Intravenous lorazepam
Rectal diazepam (can be difficult)
Buccal or intranasal midazolam - beware of biting - might be easier to give if no cannula.
Investigations of epilepsy
EEG - Electroencephalography
Imaging such as MRI
Explain how EEGs are performed.
Record of electrical pattern of activity in the brain.
It relies on catching an episode in the act or an abnormal pattern.
Also a lot of people without epilepsy have abnormal EEGs.
Usually done by a sleep deprived EEG
Give examples of Anti-Epileptic drugs.
Carbamezapine
Phenytoin
Valproate
Lamotrigine
Levetiracetam
Benzodiazepines (for seizure termination)
Why are anti-epileptic drugs important?
Because of sudden unexplained death in epilepsy (SUDEP)
Explain the mechanism of action of carbamezepine.
Sodium channel blocker (also used in bipolarity and sometimes in chronic pain)
Side-effects of carbamezepine.
Suicidal thoughts
Joint pain
Bone marrow failure
Explain the mechanism of action of phenytoin.
Sodium channel blocker used mainly in status epilepticus or as an adjunct in generalised seizures.
Side effects of phenytoin
Bone marrow suppression
Hypotension
Arrhythmias
Why is it important to monitor the administration of phenytoin?
Because it exhibits zero order kinetics meaning that it doesn’t decrease via half-life but linearly instead.
This means that giving a larger dose will exhibit the same metabolism.
Explain the mechanism of action of sodium valproate.
A mix of GABAa effects and sodium channel blockade.
The 1st line for generalised epilepsies.
Specific side effects of sodium valproate.
Liver failure
Pancreatitis
Lethargy
Explain the action of lamotrigine
Sodium channel blocker and also affects calcium channels.
It is especially good for focal epilepsy and often used where valproate is contraindicated in generalised epilepsy.
Explain mechanism of action of levetiracetam.
Synaptic vesicle glycoprotein binder that stops the release of neurotransmitters into the synapse and reduces neuronal activity.
This is a good option for focal seizures and generalised seizures.
Safe in pregnancy
Side effects of anti-epileptic drugs.
Tiredness/Drowsiness
Nausea and vomiting
Mood changes and suicidal ideation
Osteoporosis
Steven-Johnson syndrome/Rashes
Anaemia, thrombocytopenia, bone marrow failure
Carbamezepine and phenytoin DDIs.
May decrease the effectiveness of oral contraceptive pills.
May decrease the effectiveness of some antibiotics
Valproate DDIs
Can increase the plasma concentration of other AEDs.
AEDs that are inducers of CYP 450 enzymes
Phenytoin
Carbamazepine
Barbituates
AEDs that are inhibitors of CYP 450 enzymes
Valproate
How do you start someone on AEDs?
Look at guidelines.
Start at a low dose and build up.
Trial of drug and see how patient responds. Look for the efficacy of the drug and the side effects.
Aim for the patient to be seizure free with minimal or acceptable side-effects.
Transition to a new agent should be done carefully.
What are the risks of AEDs and especially valproate in pregnancy?
Risk of congenital malformations (10%)
Valproate should not be prescribed to any woman of childbearing age unless they meet the conditions of a pregnancy prevention programme.
Which are the safest AEDs in pregnancy?
Lamotrigine and particularly levetiracetam.
