Lecture 23- Epilepsy Flashcards
(63 cards)
1
Q
Seizures
A
“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
2
Q
Pathology of seizures
A
- 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
3
Q
- In a normal brain the inhibitory and excitatory sides are in balance
A
4
Q
Seizures: What causes the imbalance?
A
- 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
5
Q
Signs and symptoms of seizure
A
6
Q
signs of generalised seizure
A
loss of consciousness often with changes in muscle tone and tongue biting
7
Q
signs of tonic clonic seizure
A
initial hypertonic phase, followed by rapid clonus (shaking/jerking) of the limbs
8
Q
what is post-ictal period
A
less alert and more vacant after seizure
9
Q
Defining epilepsy
A
- 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
10
Q
epilepsy diagnosis
A
- 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)
11
Q
Types of Reflex Seizure
Seizure brought on by a particular stimulus (not provoked e.g. taking drugs )
A
- Photogenic (strobe lights)
- Musicogenic
- Thinking
- Eating
- Hot water immersion
- Reading
- Orgasm
- Movement
12
Q
grand mal
A
generalised seizure
13
Q
petit mal
A
absence seizure
14
Q
partial seizure
A
focal seizure
15
Q
clinical classification of seizure
A
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
16
Q
generalised seizure
A
- Originate at a specific place in the brain and rapidly engage both hemispheres
17
Q
Focal seizures
A
- 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
18
Q
why dont focal seizure make you lose consciousness
A
Usually don’t lose consciousness due to usually affecting one side of the brain
19
Q
Provoked Seizures
A
- 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
20
Q
Differential diagnosis of seizures
A
- 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)
21
Q
case - outline intiial management of a seizure
A
- 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
22
Q
status epilepticus
A
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
23
Q
treatment of most seizures doesnt include
A
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
24
Q
Pharmacological treatment for status
A
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)
25
benzodiazepines drug class
**GABAa agonists**
26
benzodiazepines end in
–apam, come in various flavours
* Intravenous lorazepam
* Diazepam rectally
* Buccal or intranasal midazolam (don’t lose a finger)
27
**Uses of GABAa agonist se..g benzos**
* **Status epilepticus**
* Also used as anxiolytics, sleep aids, alcohol withdrawal
28
**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
29
**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\*
30
**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
31
inevstigations
EEG and Imagging e.g. MRI
32
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
33
**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
34
**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
35
**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
36
**How do anti-epileptic drugs work?**
- sodium channel blockade
- calcium channel blockade
- GABA agonist
- SV2 vesicle inhibition
37
**Sodium Channel Blockade**
* Blocking of Na channels in central neurones
* This slows recovery of neurones from inactive to closed state
* Reduces neuronal transmission
38
name 5 sodium channel bloackades
sodium valproate
carbamazepines
Lamotrigine
Phenytoin
39
sodium valproate uses
generalsied epilepsies
40
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
41
**Adverse drug response of sodium valproate**
* Liver failure
* Pancreatitis
* Lethargy
42
carbamazepine uses
* Anti-epileptic
* Bipolar
* Chronic pain e.g. trigeminal neuralgia
43
**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
44
**Adverse drug response of carbamazepine**
* Suicidal thoughts
* Joint pain
* Bone marrow failure
45
lamotrigine uses
* **Focal epilepsies**
* **Used often where valproate contraindicated in generalised epilepsy**
46
**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
47
phenytoin uses
* Used mainly in status epilepticus or as an adjunct in generalised seizures
48
MOA of phenytoin
* Blocking of Na channels in central neurones
* This slows recovery of neurones from inactive to closed state
* Reduces neuronal transmission
49
**Adverse drug response of Phenytoin**
Exhibit zero order kinetics- care when adjusting doses
* Bone marrow suppression
* Hypotension
* Arrythmias (IV use)
50
levetiracetam is a
anticonvulsant
51
levetiracetam uss
* Option for focal seizures and generalised seizures
* Anecdotally being used more frequently, easy dosing and well tolerated
* Safe in pregnancy
52
**Mode of action of** Levetiracetam
* Novel mechanism of action
* Synaptic vesicle glycoprotein binder.
* **Stops the release of neurotransmitters into synapse and reduces neuronal activity**
53
**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
54
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
55
**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)
56
**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
57
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
58
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**
59
whcih AEDs are safest for women of childbearing age
* Lamotrigine and particularly Levetiracetam are the safest
60
**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
61
* **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)
62
* **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
63
* **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
