Lecture 23- Epilepsy Flashcards
Seizures
“Transient occurrence of signs or symptoms due to abnormal electrical activity in the brain, leading to a disturbance of consciousness, behaviour, emotion, motor function or sensation
Pathology of seizures
- The brain is a complicated network of neurones
- These are either excitatory, inhibitory or interneurons
- The most important excitatory neurotransmitter is glutamate via the NMDA receptor
- The most important inhibitory neurotransmitter is GABA, via the GABAa receptor
- In a normal brain the inhibitory and excitatory sides are in balance
Therefore in a seizure..
- Abnormal and excessive excitation and synchronisation (all neurones acting at once) of a group of neurones within the brain
- Loss of inhibitory (GABA mediated) signals
- Or too strong an excitatory (NMDA/glutamate) one
- This imbalance can happen in any part of the brain, and local changes can lead to generalised effects
- In a normal brain the inhibitory and excitatory sides are in balance
Seizures: What causes the imbalance?
- Genetic differences in brain chemistry/receptor structure – genetic epilepsy syndromes
- By exogenous activation of receptors- drugs
- Acquired changes in brain chemistry- drug withdrawal, metabolic changes
- Damage to any of these networks- strokes, tumours
Signs and symptoms of seizure
signs of generalised seizure
loss of consciousness often with changes in muscle tone and tongue biting
signs of tonic clonic seizure
initial hypertonic phase, followed by rapid clonus (shaking/jerking) of the limbs
what is post-ictal period
less alert and more vacant after seizure
Defining epilepsy
- Epilepsy is a tendency toward recurrent seizures unprovoked by a systemic or neurological insult
- Not everyone who has a seizure has epilepsy
- An epilepsy diagnosis is life changing, and therefore should only be made by a specialist, in an epilepsy or first fit clinic
- Note not just a disease of the young, over 60s almost as common and incidence increases with age
epilepsy diagnosis
- At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
- One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures (at least 60% over the next 10 years)
Types of Reflex Seizure
Seizure brought on by a particular stimulus (not provoked e.g. taking drugs )
- Photogenic (strobe lights)
- Musicogenic
- Thinking
- Eating
- Hot water immersion
- Reading
- Orgasm
- Movement
grand mal
generalised seizure
petit mal
absence seizure
partial seizure
focal seizure
clinical classification of seizure
Classification of seizure
-
Focal onset
- Aware
- Impaired awareness
- Motor onset
- Non motor onset
-
Generalised onset
- Always lose consciousness
- E.g. tonic-clonic, myoclonic, atonic, nonmotor
-
Unknown onset
- Motor
- unclassified
generalised seizure
- Originate at a specific place in the brain and rapidly engage both hemispheres
Focal seizures
- Originate within networks limited to one hemisphere
- May be discretely localized or more widely distributed….
- Usually don’t lose consciousness due to usually affecting one side of the brain
why dont focal seizure make you lose consciousness
Usually don’t lose consciousness due to usually affecting one side of the brain
Provoked Seizures
- Seizure as a result of another medical condition
- Examples include:
- Drug use or withdrawal
- Alcohol withdrawal
- Head trauma and intracranial bleeding
- Metabolic disturbances e.g hyponatraemia, hypoglycaemia
- CNS Infections: meningitis and encephalitis
- Febrile seizures in infants
- Uncontrolled hypertension
- Key is to treat both the seizure and the underlying condition. Unlikely to need ongoing AED treatment if cause treated
Differential diagnosis of seizures
- Syncopal episodes e.g vasovagal syncope
- Cardiac issues including reflex anoxic seizures, arrythmias
- Movement disorders e.g Parkinsons, Huntingtons
- TIAs
- Migraines
- Non-epileptic attack disorders (formerly pseudo-seizures)
case - outline intiial management of a seizure
- Primary Survey/A to E assessment
- Airway- Is it patent? Can you do anything about it it?/Adjuncts
- Breathing- Sats reading, Apply Oxygen
- Circulation- Expect a high HR, wary of BP
- Disability- Will have reduced consciousness in generalised seizures, may be awake in partial. Check GLUCOSE
- Everything else- May want to get them into recovery position if able
- Do something for the ABC problems if you can
- Look at a clock/start a timer
- Get some help
status epilepticus
a seizur eof any variety lasdting more than 5 minures or more or multiple seizures without a compelte recovery between them
MEDICAL EMERGENCY
20% mortality
treatment of most seizures doesnt include
drugs
- The majority of seizures will self terminate without the use of drugs
- Wait for 5 minutes and if still going then give seizure terminating drugs à this is called Status Epilepticus (also series of seizures that take place for more than 5 minutes)
- Be aware of how long it takes to get and prepare drugs
Pharmacological treatment for status
1) Full dose of benzodiazepine (5 mins)
2) Full 2nd dose of “ (0-15 mins)
3) Consider IV thiamine if alcohol use
4) 2nd line anti-epileptic if still in seizure (15-45) e.g. phenytoin, levetiracetam
5) 45+ = thiopentone/anaesthesia (will need ventilating)
benzodiazepines drug class
GABAa agonists
benzodiazepines end in
–apam, come in various flavours
- Intravenous lorazepam
- Diazepam rectally
- Buccal or intranasal midazolam (don’t lose a finger)
Uses of GABAa agonist se..g benzos
- Status epilepticus
- Also used as anxiolytics, sleep aids, alcohol withdrawal
Mode of action of benzos
- GABAa agonists
- Increased Cl- conductance, = more negative resting potential, less likely to fire.
- Work best when membrane positive i.e in seizures
- No firing neurones=no more seizure
Adverse drug response of benzos
- Be wary of addiction
- cardiovascular collapse
- airway issues
*remember you can always put more in but you cant take it out so go slowly*
Diagnosis of Epilepsy
- Epilepsy diagnosis should be made by a specialist, in a dedicated first fit or epilepsy clinic
- Largely based on history from patient and eyewitnesses to attacks
- Video can be very helpful in determining this
inevstigations
EEG and Imagging e.g. MRI
electrocephalogram (EEG)
- Electroencephalography:
- Record of electrical pattern of activity in the brain
- Can be very useful, especially if an attack is caught while being recorded- Can make this more likely with sleep deprived EEG
- But relies on either capturing an episode or an abnormal pattern
- Many people without epilepsy have an abnormal EEG
- A single EEG may show abnormalities in as few as 30% of adults with epilepsy
Imaging
- MRI is the imaging of choice
- May detect vascular or structural abnormalities that can account for epilepsy
- Generally not required when there is a degree of confidence that there is a generalised epilepsy syndrome e.g generalised seizures in a young person, associated with sleep deprivation
But why treat epilepsy?
- Sudden Unexplained Death in Epilepsy (SUDEP)
- Occurs in 0.1% adults with epilepsy per year
- More frequent in people with poor seizure control
- Massive burden- can impact ability to drive, swim, have a bath, time out of school or university
Anti-Epileptic Drugs (AEDs)
- There are numerous AEDs, with varying mechanisms of action
- We will concentrate on 6:
- Carbamazepine
- Phenytoin
- Valproate
- Lamotrigine
- Levetiracetam
- Benzodiazepines for seizure termination (already done)
- I will refer to trade names too where applicable, generally patients should stay on the same formulation
- NB it is not required of you to know these trade names
How do anti-epileptic drugs work?
- sodium channel blockade
- calcium channel blockade
- GABA agonist
- SV2 vesicle inhibition
Sodium Channel Blockade
- Blocking of Na channels in central neurones
- This slows recovery of neurones from inactive to closed state
- Reduces neuronal transmission
name 5 sodium channel bloackades
sodium valproate
carbamazepines
Lamotrigine
Phenytoin
sodium valproate uses
generalsied epilepsies
sodium valproate MOA
Mode of action
- Probably a mix of GABAa effects and sodium channel blockade
- Blocking of Na channels in central neurones
- This slows recovery of neurones from inactive to closed state
- Reduces neuronal transmission
Adverse drug response of sodium valproate
- Liver failure
- Pancreatitis
- Lethargy
carbamazepine uses
- Anti-epileptic
- Bipolar
- Chronic pain e.g. trigeminal neuralgia
Mode of action of carbamazepine
- Blocking of Na channels in central neurones
- This slows recovery of neurones from inactive to closed state
- Reduces neuronal transmission
Adverse drug response of carbamazepine
- Suicidal thoughts
- Joint pain
- Bone marrow failure
lamotrigine uses
-
Focal epilepsies
- Used often where valproate contraindicated in generalised epilepsy
Mode of action of iamotrigine
-
Primarily a sodium channel blocker, may also affect calcium channels
- Blocking of Na channels in central neurones
- This slows recovery of neurones from inactive to closed state
- Reduces neuronal transmission
phenytoin uses
- Used mainly in status epilepticus or as an adjunct in generalised seizures
MOA of phenytoin
- Blocking of Na channels in central neurones
- This slows recovery of neurones from inactive to closed state
- Reduces neuronal transmission
Adverse drug response of Phenytoin
Exhibit zero order kinetics- care when adjusting doses
- Bone marrow suppression
- Hypotension
- Arrythmias (IV use)
levetiracetam is a
anticonvulsant
levetiracetam uss
- Option for focal seizures and generalised seizures
- Anecdotally being used more frequently, easy dosing and well tolerated
- Safe in pregnancy
Mode of action of Levetiracetam
- Novel mechanism of action
- Synaptic vesicle glycoprotein binder.
- Stops the release of neurotransmitters into synapse and reduces neuronal activity
Side Effects of AEDs
- Largely common across all drugs:
- Tiredness/drowsiness
- Nausea and vomiting
- Mood changes and suicidal ideation
- Osteoporosis
- Rashes, including Steven Johnson syndrome can be caused by all. Most likely in carbamazepine or phenytoin (1 in 1000)
- Many can cause anaemia, thrombocytopenia or bone marrow failure
drug drug interactions of anti-epileptis
- AEDs can be both inducers and inhibitors of CYP enzymes
- They therefore interact with a wide variety of drugs, including each other
Practically what does AED drug drug interactions mean?
- Patients on anti-epileptics and warfarin will need close monitoring
- Ideally patients on AEDs should not consume alcohol
- Carbamazepine and phenytoin may decrease the effectiveness of oral contraceptive pills
- Carbamazepine and phenytoin may decrease the effectiveness of some antibiotics
- Valproate can increase the plasma concentration of other AEDs
- Newer AEDs have less side effects, or are metabolised in other ways (levetiracetam)
How to start someone on AEDs?
- Pick a drug- There are guidelines for this for various types of epilepsy (they will have changed by the time you have to know)
- Start at a low dose and build up
- Trial of drug and see how patient responds- look for efficacy and tolerable side effects
- Aim for all anti-epileptic treatment is to be seizure free with minimal or acceptable side effects
- Plasma levels can be monitored, but should not necessarily be done regularly without reason (e.g patient becomes pregnant, loses seizure control, issues with adherence)
- Transition to a new agent should be done carefully
- Should be overseen by epilepsy specialist
family planning and AEDs
- There is some risk of congenital malformations with all AEDs
- The risk is greatest with Valproate (as high as 10% risk of a major malformation)
- Valproate should not be prescribed to any woman of childbearing age unless they meet the conditions of a pregnancy prevention programme
- Lamotrigine and particularly Levetiracetam are the safest
which drug should not be prescribed to a women of childbirthing age
sodium valproate
- The risk is greatest with Valproate (as high as 10% risk of a major malformation)
- Valproate should not be prescribed to any woman of childbearing age unless they meet the conditions of a pregnancy prevention programme
whcih AEDs are safest for women of childbearing age
- Lamotrigine and particularly Levetiracetam are the safest
Epilepsy and driving
- Need to ask all patients with seizures about driving
- Will temporarily lose license and need to be seizure free for one year before reapplying
- For bus lorry or coach drivers you need to be seizure free for 5 years off medication for a single seizure, or 10 years if had multiple
- Patients responsibility to inform DVLA
- A 26 year old arrives in resus fitting. The ambulance crew state this began 10 minutes ago, she has received a single dose of IV lorazepam.
- What is the first step in your management?
Further dose of lorazepam (benzodiazepam)
-
You have treated her with further a further dose of lorazepam, and given a loading dose of phenytoin. It is 30 minutes later and she continues to fit. What do you do next?
- A. Give thiopentone
- B. Wait a further 5 minutes
- C. Give levetiracetam
- D. Call intensive care
- E. Hide in a cupboard and pretend its not happening
- A. Give thiopentone
- B. Wait a further 5 minutes
- C. Give levetiracetam
- D. Call intensive care
- E. Hide in a cupboard and pretend its not happening
-
She has now stopped seizing, and you see her in 2 weeks later in the epilepsy clinic. She is not on any contraception. Which of the following drugs should be avoided?
- A. Levetiracetam
- B. Valproate
- C. Lamotrigine
- D. Carbamazepine
- E. I’m still hiding in the cupboard from question
valproate
