Epilepsy Flashcards
What groups are more likely to have a diagnosis of epilepsy?
Infants
Those over 50
High in those with learning difficulties
What is SUDEP?
Sudden unexpected death in epilepsy
often occurs at night
What are the risks for SUDEP?
- Not on anti-epileptic treatment
- Night time seizures
What are the possible causes of epilepsy?
2/3 is idiopathic = unknown cause
- Structural abnormalities in the brain
- Genetic mutation
- Infection- known infection e.g. TB, cerebral malaria
- Metabolic
- Immune- autoimmune mediated inflammation e.g. encephalitis
What are the risk factors for epilepsy?
- Premature birth
- Complicated febrile seizures- by a high temperature
- Brain development malformation
- Family history of epilepsy or neurological disease
- Head trauma
- Infection e.g. meningitis, encephalitia
- Tumour
- CVD/Stroke
- Dementia, Alzheimer’s disease
- drug and alcohol withdrawal
What investigations may be used to diagnose epilepsy?
- Patient history
- Eye witness of seizure
- ECG
- Blood tests, U&Es
- Neuroimaging e.g. MRI, CT- Identify structural abnormalities
- genetic testing
- antibody testing- if autoimmune encephalitis suspected
What is the gold-standard tool for diagnosis in neonates?
ECG
How is epilepsy classified?
- Seizure type
- Epilepsy type
- Epileptic syndrome
also co-morbidities, aetiology
What is a focal seizure?
Increased neuronal activity originating and remaining in one hemisphere of the brain.
Are sub0divided based on level of awareness:
- Simple focal seizures- no loss of consciousness
- Complex/focal dyscognitive seizures- impaired awareness
signs and symptoms depend on the area of the brain affected:
MOTOR ONSET:
- Physical movement e.g.
Jerking (clonic)
stiffness (tonic)
loss of muscle tone (catonic)
automatisms e.g. lip-smacking, pacing, repeating words
Hyperkinetic- big movements e.g. jumping, thrusting
epileptic spasms- flexing muscles in trunk
NON-MOTOR:
Autonomic: changes in HR, breathing, colour
Behavioural arrest- blank stare, stop talking to moving
confusion
slow-thinking
problems in understanding
sudden emotional change- fear, anxiety, pleasure
Sensory changes- hearing, vision, taste, pain, tingling
What are examples of symptoms of a motor seizure?
- Physical movement e.g.
Jerking (clonic)
stiffness (tonic)
loss of muscle tone (catonic)
automatisms e.g. lip-smacking, pacing, repeating words
Hyperkinetic- big movements e.g. jumping, thrusting
epileptic spasms- flexing muscles in trunk
What are examples of symptoms of a non-motor seizure?
Autonomic: changes in HR, breathing, colour
Behavioural arrest- blank stare, stop talking to moving
confusion
slow-thinking
problems in understanding
sudden emotional change- fear, anxiety, pleasure
Sensory changes- hearing, vision, taste, pain, tingling
What is a focal to bilateral tonic clonic seizure?
Begins with a focal onset but then spreads to other parts of the brain?
What is the name of a seizure that begins with a focal onset but then spreads to other parts of the brain
focal to bilateral tonic clonic seizure
What is a generalised seizure?
A seizure that has increased neuronal activity which is widespread across both hemispheres of the brain.
Sub-divided into motor and non-motor symptoms
- The level of awareness is less important in this type as MOST patients will have impaired awareness.
Motor symptoms:
Tonic- muscle contractions
myoclonus- muscle twitching
atonic- muscles become limp
clonic- rhythmic jerking movements
tonic clonic- starts clonic- rigid, loss of consciousness and then progresses into clonic- muscle twitching, loss of bladder/bowel control
Non-motor- vacant staring, no movement
What is tonic?
increases muscle contraction- tense and rigid
What is myoclonus?
Muscle twitching
What is atonic?
Muscles become limp
What is clonic?
Jerking rhythmic twitching movements
What is tonic-clonic?
Starts tonic- rigid, loss of consciousness but then progresses into clonic- muscle twitches, loss of bladder/bowel control
What is status epilepticus?
Prolonged convulsive seizure lasting 5 minutes or longer
OR
Recurrent seizures without recovery in-between
What should you do if you witness a patient having a seizure in the community?
- Note time of onset of seizure
- Protect from injury- move harmful objects out of way
- Do NOT obstrain
- When/if seizure stops, check airways, and place in recovery position
if lasts 5 minutes+
ACT FAST
secure airways and respiratory and cardiac function
- Buccal Midazolam or rectal diazepam
Call 999 if
- seizure lasts 5 minutes after emergency meds given
- if history of seizures who has status epilepticus or this is first time requiring emergency treatment
- concerns regarding patients airways and respiratory and cardiac function
What are possible triggers for status epileptics?
head injury
metabolic disturbance e.g. hypoglycaemia
cerebrovascular event e.g. stroke
alcohol withdrawal
What emergency medicines can be given for epilepsy in the community?
Buccal midazolam (1st line)
Rectal diazepam
What are the procedure should a patient have a seizure in hospital?
0-5 mins:
Time it
establish IV access for quick treatment- difficult when fitting
secure airways
monitor rest and cardiac function
give high conc oxygen
high potency thiamine e.g. pabrinex (esp if suggested alcohol abuse)
glucose if hypoglycaemic
5-20 mins:
more info about patient- med, drug history, epilepsy history
chest x-ray, CT scans
- IV lorazepam (0.1mg/kg - max 4kg)
or IV diazepam
Alternatively- buccal midazlolam if no iv access
20-40 mins:
alert anaesthetist and ICU
2nd line IV anti-epileptic e.g. Phenytoin, phenobarbital, levtericatem
40-60 mins:
Transfer to ICU
administer general anaesthesia- midazolam, propvol, thiopental
What is the aim of management of epilepsy?
Monotherapy!
Decreases the likelihood of interactions and adverse effects
What is the usual procedure should the first anti-epileptic drug (AED) fail?
If 1st fails, switch to another AED- add 2nd, uptitrtte dose to therapeutic before tapering and stopping first
- If 2nd AED fails, consider combination therapy
What counselling points are important when prescribing AEDs?
- Patient may get suicidal thoughts
- Anti-epileptic hypersensitive syndrome- rare but fatal- can be seen within 1-8 weeks of starting drugs- STOP drug immediately
- Patient may need vitamin D supplements if immobile for long periods, inadequate sun exposure, inadequate dietary intake
What is the major risk of sodium valproate?
Risk of birth defects and developmental disorders if taken while pregnant.
1 in 9 babies have birth defects e.g. spina bifida
4 in 10 risk of developmental disorder e.g. low intelligence, poor speech or language
According to the MHRA, who should not be started on sodium valproate and what are the exceptions to this rule?
Anyone under 55 years old- male or female
- UNLESS, two specialists independently consider and document other treatments to be ineffective
or compelling reasons that reproductive risks do not apply e.g. had histrectomy
What must be done annually with patients on sodium valproate?
Review the annual risk acknowledgement form.
If treatment is to continue a 2nd opinion and signature is required.
What is the PPP?
This is the pregnancy prevention programme that must be put in place for patients on sodium valproate.
- Pregnancy must be ruled out on initiation
- And highly effective contraception should be used throughput
When is sodium valproate used?
1st line: Offer SV to patients with myoclonic/tonic-clonic/atonic/tonic seizures, not of childbearing potential e.g. Men (not under 55 though?), under 10 year olds, those who can’t have children
2nd line: Absence seizures
- also used in Dravet’s syndrome, Lennox-gaut syndrome
- Unlicensed use in migraine prophylaxis
- Is used in mania in bipolar
What are the potential side effects of epilepsy?
Nausea
Weight gain
Transient elevation LFTs
Blood dycrasias- anemia, thrombocytopenia
Alopecia
Liver toxicity
Pancreatitis (rare)
need to shcek what this is meant to be because it doesnt make sense
What monitoring is required for patients on sodium valproate?
LFTs: Before starting and within 6 months
FBC- before
Monitoring for blood dyscrasias- report bleeding, bruising, mouth ulcers, fever
Liver disorders- jaunduice, tiredness, abdominal pain, lethargy, swelling
Pancreatitis- N+V, acute abdominal pain
When is carbamazepine used?
Carbamazepine is recommended 2nd line in focal seizures
- As an adjunct in focal seizures
- BUT is considered last-line in generalised tonic-clonic and unsuitable in myoclonic, tonic/atonic and absence seizures = exacerbates seizures
ALSO used in
- prophylaxis of Bipolar if unresponsive to lithium
- Trigeminal neuralgia- nerve pain in face
- Adjunct in scute alcohol withdrawal (unlicensed)
- Diabetic neuropathy
What are the potential side effects of carbamazepine?
Drowsiness
nausea
vision disorders
blood- leukopenia, eoisionphilia, thrombocytopoenia
hyponatraemia
skin disorders
- nausea, ataxia, dizziness is often dose-related but can limit a patients tolerability
What effect does carbamazepine have on CYP enzymes?
Carbamazepine is a CYP P450 inducer
- note clearance can be affected by enzyme inducers and inhibitors and it can cause auto induction of its own metabolism
Are formulations of carbamazepine bioequivalent?
NO- Cant just switch directly between tablets, liquid etc
What pre-treatment screening is required for carbamazepine?
In patients of a Han-chinese or Thai origin- need to check for the HLA-B*1502 allele- this allele increases the risk of Steven-Johnson syndrome
What AED requires pre-screening for the HLA-B*1502 allele?
Carbazepine - In patients of a Han-chinese or Thai origin- need to check for the HLA-B*1502 allele- this allele increases the risk of Steven-Johnson syndrome
What does having the HLA-B*1502 allele increase your risk of?
Steven-Johnson syndrome
What monitoring is required for carbamazepine?
- Pre-treatment screening: In patients of a Han-chinese or Thai origin- need to check for the HLA-B*1502 allele- this allele increases the risk of Steven-Johnson syndrome
- Plasma concentration - looks at response, optimum: 4–17 mg/L after 1-2 weeks
- FBC
- LFTs
- Renal function
- Monitor for blood dyscrasia- fever, bleeding, rash, bruising, mouth ulcers
What is oxcarbazepine?
A pro-drug of carbamazepine
- is a weak enzyme inducer of CYP 3A4/5 and inhibitor of CYP-2C19
If a patient has a hypersensitivity to carbamazepine, what is the chance they will have the same reaction to oxcarbazepine?
25-30%
What is preferable about oxcarbazepine over carbamazepine?
It doesn’t cause self-induction of metabolism
When is ethosuximide used?
- Offer ethosuximide as first-line treatment for absence seizures
- 3rd line for epilepsy with myoclonic-atonic seizures
What are the side effects of ethosuximide?
GI- N+V, Diarrhoea, constipation
anxiety, sleep disturbances, ataxia
blood disorders
Steven-johnson syndrome (rash)
- monitor for suicidal behaviour and blood dyscrasia e.g. fever, rash, bleeding, bruising
When is lamotrigine used?
- 1st line for and as an adjunct in focal, generalised Tonic-clonic, absence (If Ethosuximide or SV not suitable), tonic or atonic seizures
- also inidicated in bi-polar, neuropathic pain (unlicensed)
What are the side effects of lamotrigine?
Dizziness, drowsiness
dry mouth
headache
double vision (diplopia)
hypersensitivity
suicidal thoughts
blood disorders
Monitor for skin reactions-rash, hypersensitivity
Bone marrow failure- bruising, bleeding, anaemia
What must you be cautious with lamotrigine?
If given with hepatic enzyme inducers or inhibitors, the half life will be altered and a dose adjustment may be needed.
Note, lamotrigine can induce its own metabolism
When is levetiracetam used?
1st line: Generalised tonic-clonic seizures, focal, myoclonic idiopathic generalised seizures
2nd line: absence, myoclonic, idiopathic generalised seizures, epilepsy syndromes
What are the possible side effects of levetericetam?
Drowsiness, dizziness, GI, nsomia, rash
rare- suicidla thoughts, thrombocytopenia, leukopenia
When is phenobarbitol used?
- Has NO 1st line indications
- Add on 2nd line in generalised tonic-clonic
add-on 3rd line in focal and myoclonic seizures - is licensed for all epilepsy types EXCEPT absence seizures
What are the potential side effects of phenobarbitol?
Hypersensitivity- Stevenjohnson syndrome
bone fractures and dosrders
folate deficiency
drowsiness
suicidal behabiours
hepatic disorders
Is phenobarbitol a cyp inducer or inhibitor?
Inducer
What monitoring is recommended for phenobarbitol?
Optimum plasma conc- 15-40 mg/L
Monitor for suicidal behaviours
Skin reactions- report rash, hypersensitivity
When is phenytoin used?
- NO first line indicatons
- Adjunctive add-on 3rd line in focal seizures
- Prevention of seizures following neurosurgery and head injury
- unlicensed use in trigeminal neuralgia
What are the possible side effects of phenytoin?
Drowsy
confusion
hirsutism
gingival hyperplasia
cerebellar dysfunction
bone and bone marrow disorders
What are the symptoms of phenytoin toxicity?
Nystagmus- involuntary eye movement
diplopa
slurred speech
ataxia
confusion
hyperglycaemia
What is different about the pharmacokinetics of phenytoin?
It is cleared by the liver (like most AEDs), but it follows non-linear kinetics meaning saturation of the clearance pathway can occur at therapeutic doses- will have a knock on effect on the half-life of the drug
What monitoring is recommended for phenytoin?
- Screen for HLA-*B1502 in chinese- Han/tai origin patients- allele increases risk of Steven-johnson syndrome
- Monitoring needed in patients where protein binding may be decreased (As Phenytoin is 90% protein bound) e.g. pregnancy, elderly, interacting drugs
- blood dyscrasias, fever, rash, bruising,bleeding, mouth ulcers
- With IV use- monitor ECG and BP
What are 3 categories of AEDs according to the MHRA when prescribing AEDs?
CATEGORY 1: These drugs MUST be kept on a specific brand as there are clinically relevant differences between products and can lead to ADRs and loss of seizure control:
Carbamazepine
Phenobarbitol
Phenytoin
Primidone
CATEFORY 2: Need for continuous brand based on clinical judgement and patient/ carer (clinical and non-clinical factors):
Clobazepam
C,lonazepam
Eslicarbazepine
lamotrigine
perampane;
topiramate
sodium valproate
CATEGORY 3: Unnecessary for patient to be maintained on specific brand as there is therapeutic equivalence. Can still consider non-clinical factors though:
Ethosuximide
Levetiracetam
pregablin
tiagabine
vigabatran
gabapentin
CLINICAL FACTORS; Seizure frequency, potential implications to patient having a breakthrough seizure, treatment history
NON-CLINICAL: Dosing errors, anxiety, confusion, decreased adherence
What is the involvement of a ketogenic diet in epilepsy?
This is a non-pharmacological treatment that may be used in difficult to treat epilepsy.
- This diet is high fat, low protein and low carbohydrate diet
- NICE recommends this only under tertiary care epilepsy specialist
- Mimics the state of starvation for the brain, forcing the body to breakdown fat instead of carbohydrates to produce energy. Breakdown of fats = ketones = have anti-convulsive properties.
There are 3 types:
- Classical
- Modified
- Medium-chain triglyceride
What drugs can exacerbate/trigger seizures?
- Alcohol
- prescription drugs
- illicit drugs
- Drugs that induce or inhibit hepatic enzymes- alter the pharmacokinetics and plasma cones of AEDs
- Secondary effects of other drugs e.g. drugs that cause a decrease in sodium ions
- Drugs that affect dose/conc of AED e.g. renal/hepatic impairment, interacting drugs e.g. ciprofloxacin, theophylline
When may AEDs be withdrawn?
AEDs may be withdrawn in patients who have been seizure-free for at least 2 years:
- Slowly withdrawn over 3 months
- Patients on barbiturates and benzodiazepines - withdrawal is slower = over 6 months due to withdrawal symptoms and potential seizure recurrence
- if on multiple AEDs, withdraw one at a time
List the AEDs that are enzyme inducers and those that are non-enzyme inducers ?
Inducers:
carbamazepine
escicarbazepine
oxcarbazepine
perampanal (doses over 12mg daily)
phenobarbitol
phenytoin
primidone
topiramate (over 200mg)
non-enzyme inducers:
acetozolamide
clobazepam
clonazepam
ethosuximide
gabapentin
lacosamide
lamotrigine
levetiracetam
perampanal (doses under 12mg daily)
prcegablin
Sodium valproate
Tiagbine
Topiramate (less than 200mg daily)
vigabatran
zonisamide
What drug do combined oral contraceptives (COCs) affect the metabolism of?
Lamotrigine
Patients on enzyme-inducing AEDs may affect the metabolism of COCs making them less effective. What contraceptions can be recommended instead?
- Progesterone only depot injection
- Levonorgestrel IUD
- Copper IUD
- The COC may be sued only in exceptional circumstances as a last resort. BNF states that if ethinylestradiol dose is 50mcg daily and uses a tricycling regimen followed by a shortened break ( 4 days instead of 7) = use of COCs can be used unlicensed- effectiveness is unknown
What contraception methods are not appropriate on patients on enzyme-inducing AEDs?
- Oral progesterone only pills
- Progesterone only implants
- COCs with less than 50mcg of Ethinylestradiol
note- AED is withdrawn, the inducing effects persist for 4 weeks so continue contraceptives!
What emergency hormonal contraception can be used in patients taking enzyme-inducing AEDs?
- Copper IUD
- Levonorgestrel 1.5mg tablets- need a double dose (1.5mg x 2 tablets)- only if copper IUD unsuitable. Effectiveness of this dose is unknown
- Ullipristal acetate 30mg tablet (EllaONE) - effectiveness is unknown. Double dose is NOT appropriate with this tablet.
What contraceptive methods can be used in patients on AEDs that are NOT enzyme inducers?
Normal contraceptive methods can be used (Same as if not on any AEDs)
EXCEPT LAMOTRIGINE:
- This is because the COC decreases the efficacy of lamotrigine by inducing glucoronidation and decreasing the serum levels of Lamotrigine and increasing the risk of seizures during days 1-21 days of the cycle. Then during the COC-free period, there is an increased risk of toxic due to increased exposure to lamotrigine.
- Can have a no pill-free regimen
- Progesterone-only (Desogestrel) is also thought to increase lamotrigine risk so requires careful monitoring
- When on Lamotrigine, advise barrier methods as well.
What are the contraception precautions/recommendations in patients on lamotrigine?
Normal contraceptive methods can be used in non enzyme-inducing AEDs (Same as if not on any AEDs)
EXCEPT LAMOTRIGINE:
- This is because the COC decreases the efficacy of lamotrigine by inducing glucoronidation and decreasing the serum levels of Lamotrigine and increasing the risk of seizures during days 1-21 days of the cycle. Then during the COC-free period, there is an increased risk of toxic due to increased exposure to lamotrigine.
- Can have a no pill-free regimen
- Progesterone-only (Desogestrel) is also thought to increase lamotrigine risk so requires careful monitoring
- When on Lamotrigine, advise barrier methods as well.
What are the safest anti-epileptics for use during pregnancy?
Lamotrigine
Levetiracetam
these are safer in pregnancy than other AEDs as don’t increase the risk of birth abnormalities.
What AEDs can increase risk of physical birth abnormalities?
Carbamazepine
Phenobarbitol
Phenytoin
Topiramate
What must be done in patients planning pregnancy?
AEDs should be monitored during pregnancy and antenatal care as they are considered at risk of seizures worsening. If they have any dose changes, they should return to pre-conception doses after birth.
Obtain a baseline conc
What should be recommend for mothers to take before falling pregnant?
Folic acid supplements- help prevent neural tube defects, which are one of the most common defects associated with AEDs especially sodium valproate
- 5mg of Folic avid for at least 1st trimester (often longer)
What are the recommendations/procedures given to patients with epilepsy that fall pregnant and after pregnancy?
During pregnancy:
- Encouraged to notify UK epilepsy and pregnancy register
- Detailed ultrasound scan at 18-20 weeks- screen for structural abnormalities
- Genetic counselling- consider is known his factors or fear of inheritance of epilepsy- esp in idiopathic epilepsy and family history
After birth:
- babies born to mothers on enzyme-inducing AEDs are given a 1mg Vitamin K parentally st delivery
- encourage to breastfeed- consult SPC of individual AEDs
- Discuss safety precautions to reduce harm to infant and mum
What are the risk of seizures during pregnancy birth like?
- Unlikely to experience an increased risk of seizures. However, patients with generalised tonic-clonic seizures are at higher risk of damaging a foetus during a seizure.
- Risk of seizures during labour is low but is recommended patient give birth in hospital- close observation and NOT in a room alone- risk of SUDEP.
why should patients with epilepsy not be in hospital rooms alone?
Risk of sudep- need close monitoring in the presence of others
What is given to babies born to mothers on enzyme-inducing AEDs
Parenteral 1mg Vitamin K
What safety precautions should you give to a mother to reduce harm to them and their baby?
- Bathing: if home alone, go in the shower- less risk of drowning as the water is drained away immediately. If bathing have someone nearby
- Feeding: when feeding baby, sit on the floor with the back against the wall and cushions either side to protect baby
- Changing- change on floor not on changing table
- going out- have a rod attached to pram and mums wrist so the pram can’t roll away e.g. into traffic
- never sleep with baby in same bed
- limit how often you need to carry baby up and down the stairs- keep nappies, clothes etc on ground floor
- carry in strapped carseat up and down stairs. avoid carrying them attached to you
Can mums with epilepsy breastfeed?
- You can safely breastfeed while you’re taking your epilepsy medication. There are very few exceptions. For example, benzodiazepines (like clobazam and clonazepam) or barbiturates (like phenobarbital) may cause sedation in newborns.
What is the effect of AEDs on bone health?
Long-term use of AEDs can increase the likelihood of decreased bone density, increased risk of osteoporosis and fractures.b
What is the mechanism by which AEDs can affect bone health?
Though to be due to metabolism of vitamin D by CYP450 enzymes induced by AEDs- but not fully understood.
enzyme inducers- carbamazepine, phenytoin, primidone
- risk of decreased bone health increases if on multiple AEDs or for long periods of time. Vitamin D levels should be monitored in patients on these drugs via DEXA scans- they monitor bon mineral density or FRAX tool- fracture risk assessment tool.
Hoe is bone mineral density monitored in patients on AEDs?
Vitamin D levels should be monitored in patients on these drugs (enzyme inducers) via DEXA scans- they monitor bon mineral density or FRAX tool- fracture risk assessment tool.
What counselling should be given to patients regarding their bone health?
- Need good diet- adequate vitamin D and calcium
- Good sun exposure
- Exercise- strengthen bones and joints
- Smoking cessation
- Decrease alcohol intake
What should patients diagnosed withe epilepsy do in terms of driving?
inform DVLA if have seizures or blackouts and STOP driving immediately.
- if don’t inform can be fines £1000 and be prosecuted
- Done online or via FEP1 form
