Epilepsy Flashcards
(118 cards)
1
Q
What does convulsion mean?
A
Muscles contract and relax in a rapid cycle
2
Q
What is a seizure?
A
Paroxysmal (attack) events that may involve motor, sensory systems or are related to consciousness: brain involvement
3
Q
What is Epilepsy?
A
A set of disorders that have recurrent, (unprokoved) seizures
4
Q
What are disorder components involved in epilepsy?
A
- Muscle rigidity
- Convulsions
- Psychic (changes in sensory perception, anxiety or deja vu)
- Loss of consciousness
5
Q
In what age groups is epilepsy most common?
A
Children and elderly
6
Q
What percentage of people have epilepsy at a singular given time?
A
0.5-1% of the population
7
Q
What percentage of the population will experience epilepsy in thier lifetime?
A
5%
8
Q
What factors increase the risk of epilepsy in old age?
A
- Causes to brain structure via….
- Stroke
- Dementia
- Tumours
9
Q
What is a Myoclonic (myoclonus) seizure?
A
Involuntary twitching of muscle or muscle group
Can occur in everyday life such as hiccups or jolts when we fall asleep
Does not normally have a rhythm
10
Q
What is a clonic (clonus) seizure?
A
Rhythmic muscle contractions
Normally involve large movements
11
Q
What is a tonic seizure?
A
A phase in which there is sustained muscle contraction (initial rigidity)
12
Q
What is an atonic seizure?
A
Loss of muscle tone
Usually a brief loss of consciousness
13
Q
What is a common name for an atonic seizure?
A
Drop seizure
14
Q
What is an absence seizure?
A
A short lapse in consciousness
Doesn’t have a motor component
Normally has rapid recovery
15
Q
What is an Ictal seizure?
A
Anything pertaining to a seizure
Sometimes this term can also be used for strokes
16
Q
What are the three first ILAE system seizure classes?
A
- Focal onset
- Generalised onset
- Unknown onset
17
Q
In the focal onset category of the ILAE system, what are the following elements of a seizure?
A
- Aware/ impaired awareness
- Motor onset/ Non-motor onset
- Focal/ bilateral tonic-clonic
18
Q
In the Generalised onset and unknown categories of the ILAE system, what are the following elements of a seizure?
A
- Motor (tonic-clonic/ other motor)
- Non motor (absence)
19
Q
What are the two groups of seizure categorisation for the old system (most common)?
A
- Partial: simple/complex
- Generalised: grand mal (tonic-clonic)/petit mal (absence)
20
Q
What are the four epilepsy syndromes as disclosed by the ILAE system?
A
- Focal
- Generalised
- Combined generalised and focal
- Unknown
21
Q
What are five electroclinical ways of classifying epilepsy?
A
- Neonatal
- Infancy
- Childhood
- Adolescence/Adult
- Not age related
22
Q
How can we classify epilepsy based on brain areas, give examples (3)?
A
- EEG can identify the particular brain region involved
- This may be included in the naming:
- ADNFLE (autosomal dominant nocturnal frontal lobe epilepsy)
- Temporal lobe epilepsy
- Occipital lobe epilepsy
23
Q
What is a focus?
A
- A group of neuronns generating high frequency acitivity
- The initial problem stems from this focal area
- There may be a single focus, or multiple foci
- Can spread
- Symptoms depend on the areas of the brian involved
24
Q
What are four possible causes of a focus?
A
- Paroxysmal depolarizing shift (neurons undergo periodic changes in the resting membrane potential)
- Synchronization of activity (generation of the high frequency activity)
- Remodelling (of synaptic connectivity and neuronal loss because of seizures may feed in and worsen it)
- Kindling
25
What is Kindling?
An animal model where an animal is given a repeated low level stimulation to a particualr brain region
Makes this area more sensitive and then a small stimulation can cause seizures
Eventually, spontaneous seizures occur
26
What are the triggers of epilepsy?
- Most occur spontaneously
- Stress can increase frequency
- Some have particular triggers:
- Photosensitive (most common, still only 3% of epileptic patients)
- Reading
- Music
- Hot water
27
What are four ways of diagnosing epilepsy?
- Electroencephalography (scalp recordings)
-Video EEG (can be combined with video recording to correlate with the change in consciousness or motor activity)
- CT/MRI scans (to see underlying causes)
- PET scans (are there regions of the brain that function differently)
28
What are three main animal models that are used as a model of human disease?
- Genetic models
- Chemically induced models
- Electrically induced models
29
What is the aetiological classification of epilepsy?
- Direct **genetic** inheritance
- **structural/metabolic** such as brain trauma which predisposes a person to epilepsy
- Unknown causes
30
What percentage of epilepsy is thought to be of genetic origin?
40%
31
How do genetic epilepsies occur?
- Due to mutations in ion channels and receptors
- "channelopathies"
- May cause more epilepsies than identified by inheritance patterns
32
What proteins are most likely to be involved in genetic epilepsies?
- GABAA receptors
- neuronal nAChR
- VS channels
33
What is autosomal dominant nocturnal frontal lobe epilepsy?
- "Channelopathy"
- Seizures happen at night during sleep
- Frequently misdiagnosed as nightmares
- Linked to mutations in neuronsal nAChR alpha and beta subunits (important in regulation of other CNS neurotransmitters)
- Causes the receptors to change sensitivity to ACh and desensitization altered
34
What is Hyperekplexia?
- "Channelopathy" **NOT** an epilepsy
- Startle syndrome
- EEG generally normal
- Mutations in proteins associated with glycinergic transmission in the spinal cord such as:
- Glycine receptor subunits
- Glycine transporters
- Cytoskeletal proteins
35
What are the legal driving implications of having epilepsy?
- Driving licence removed after a seizure
Unless
- Seizure free for one year
- Three years of seizures only at night
36
What are four social implications of Epilepsy?
- Employment may be difficult for people with severe epliepsy
- Pregnancy may be difficult
- Some people with epilepsy feel a sense of shame (stigma
- There is still a fear of epilepsy in society
37
What is a tonic-clonic seizure's classification name?
Grand Mal
38
What type of seizure is regarded as the 'classic' epileptic seizure?
Tonic-clonic
39
What are the three stages of a tonic-clonic seizure?
- (prodromal phase (20%))
- Aura
- Tonic phase
- Clonic phase
40
What is the aura phase of a tonic-clonic seizure?
- Altered sensory perception and psychic symptoms such as deja vu, anxiety and hallucinations
- May be a valuable warning that they are about to have a seizure
- Is a form of seizure activity- type of focal seizure with maintained consciousness
41
What is the tonic phase of a tonic-clonic seizure?
The patients will lose consciousness and their muscles will become rigid, they may make strange sounds during this part of the seizure
42
What is the clonic phase of a tonic-clonic seizure?
The seizure will progress into convulsions and the patient may suffer from incontinence. This phase can last several minutes
43
What is the prodromal phase of the tonic-clonic seizure?
- Only happens in 20% of epileptic patients
- A sensation which starts hours or days before the seizure which can serve as a further warning sign
- This is not a form of epileptic acitvity
44
What are absence seizure's classification name?
Petit Mal
45
What age group are absence seizures most common in?
Children
46
What is an absence seizure?
- Involve a siggen, brief lapse in consciousness
- Have very rapid recovery
- Can happen frequently during the day
- Some people have a brief motor component (more subtle than a proper motor seizure)
- Usually the person has no memory of what has happened.
47
What is Juvenile Myoclonic Epilepsy?
- Very common type of epilepsy (10% of all epilepsies)
- Frequently inherited
- Myoclonic jerks of the arms or legs
48
What percentage of people with JME experience a myoclonic component?
- 17%
- In other cases, the person will also experience tonic-clonic seizures or absence seizures
49
What are the triggers for JME?
- Sleep deprivation
- Fatigue
- Alcohol consumption
50
What are the four mutations associated with JME?
- GABAAR alpha subunit
- GABAAR delta subunit
- EFHC1 (role unknown but associated with calcium channels)
- CACNB4 (calcium channel beta subunit)
51
What is a Gelastic seizure?
- A 'laughing seizure'
- There is also a dacrystic seizure type ('crying seizure')
52
What is Status Epilepticus?
- Single epileptic seizures that lasts longer than five minutes
- Or repeated seizures within 5 minutes of each other
- It can involve all types of generalised seizure
53
What is the fatality rate for status epilepticus?
20% of people who have status epilepticus will die within 30 days of the seizure
Others will be left with a permanent disability due to brain damage and oxygen deficiency
54
What is often the cause of status epilepticus?
- Underlying medical reason
- Stroke
- brain tumour
- Head injury
55
What drug type is used to treat status epilepticus and give examples
- **benzodiazepines**
- Lorazepam
- Midazolam
- Diazepan
56
If status epilepticus cannot be bought under control what can be used to stop it?
- General anaesthetics
such as
- Barbiturates
- Propofol
57
How do doctors choose which anti-epileptic drug to prescribe?
- Some work better than other for particular types of epilepsy
- Some will make certain kinds of epilepsy worse
- NICE guidelines
- Simplified guidance in BNF
58
What are the 3 main targets for anti-convulsants?
- Calcium channel inhibition
- GABAergic potentiation (receptor potentiation, uptake inhibition, metabolism inhibition)
- Sodium channel inhibition
59
What drug is phenytoin structurally related to?
Barbiturates
60
What is phenytoin's trade name?
Dilantin
61
What does Phenytoin do?
- Stabalises voltage- gated sodium channels in inactivated state
- Effective against tonic-clonic and partial seizures (can worsen absence and myoclonic seizures)
62
What are some side-effects of phenytoin?
- Teratogenic
- Risk of lupus
- Cerebeller atrophy (changes in brain structure)
- Acne, hirsuitism (extra hair growth)
- Gingival overgrowth (gum growth)
63
What is a major issue with Phenytoin's pharmacokinetics?
- Different people's plasma levels react in different ways to changes in the dose
- Once the dose gets to a certain amount, the plasma levels no longer increase proportionally
- There is a small therapeutic range which is hard to keep individuals in
64
What does Carbamazepine do?
-Blocks voltage-gated sodium channels
- Secondary action of GABAA receptors
- First line treatment for focal seizures, useful in tonic-clonic
- Also used as a mood stabalizer and neuropathic pain treatment
65
What are two related drugs to carbamazepine?
- Oxycarbazepine
- Eslicarbazepine
(have better side-effect profiles)
66
What enzyme is carbamazepine metabolised by?
CYP3A4
67
Why is the fact that carbamazepine metabolised by CYP3A4 a problem?
- Takes a while to reach a steady plateu because carbamazepine auto-induces the enzyme (when patient takes more drug, means more enzyme is produced)
- Interaction with grapefruit juice
- Because of induction of CYP, there are many interactions as this enzyme metabolises a range of drugs (auto-induction means other drugs will be metabolised quickly and there will be competition between these and carbamezapine).
68
What are some side-effects of carbamazepine?
- Tetratogenic
- Risk of lupus
- Worsens JME and absence seizures
- Cognitive problems and mood changes
69
What is Lamorigine?
- Sodium channel blocker
- First line treatment for tonic-clonic seizures
- Second line for absence
- Can exacerbate myoclonic seizures at higher doses
- Also used to treat bipolar disorder
70
What are the side-effects of Lamotrigine?
- Sedation
- Sleep disturbances
- Rash
- Binds to eye pigment
- Steven Johnson's disease
71
How can we effect the GABAergic presynaptic terminal in order to treat epilepsy?
- Have the GAT1 GABA transmitter on the presynaptic nerve terminals
- If inhibit this, we will boost GABA in the synapse
- This increases inhibition
- Combats epilepsies excitatory effects
72
How can we effect the GABAergic post-synaptic terminal to treat epilepsy?
- If we potentiate the GABAA receptor in the post-synaptic membrane
- More inhibitory actions occur such as chloride flux
- Combats epilepsies excitatory effects
73
How can we effect the GABAergic reuptake in order to treat epilepsy?
- The enzyme GABA transaminase is an enzyme in the astrocyte (recycles GABA) and the presynaptic nerve terminal
- This enzyme metabolises GABA
- If we inhibit this enzyme, we will cause more GABA in the cleft and therefore boost inhibition
- This combats the excitatory effect of epilepsy
74
What do Benzodiazepines do?
Potentiate the actions of GABAA receptors by binding to the allosteric site
74
What are 3 benzodiazepines?
- Clobazam
- Clonazepam
- Diazepam
75
What is Clobazam used for?
- Adjunct medication for epilepsy
- Also treats anxiety
76
What is Clonazepam used for?
- Refractory epilepsy
- Also acts on calcium channels
- Can only be prescribed by specialists in special circumstances
77
What is Diazepam used for?
- Status epilepticus
- Only used for serious epilepsies as can become tolerant very quickly
78
What are the side-effects of the benzodiazepines?
- Sedation
- Tolerance/dependance
- Seizures on withdrawal
79
What is a similar acting class of drugs to the benzodiazepines?
- Barbiturates
- Similar action but worse side effects
- Listed in BNF but mostly prescribed by specialists
- Allosteric potentiates GABAAR
- Directly acts on the GABAAR so it is easy to overdose
80
What is Tiagabine?
- GAT1 inhibitor (transporter inhibitor)
- Adjuvant medication
- Partial seizures (focal seizures)
- Panic attacks
- Neuropathic pain
81
What is Tiagabine's trade name?
Gabatril
82
What are the side-effects of tiagabine?
- Sedation
- Dizziness
- Paraesthesias (pins and needles)
- Provokes seizures in non-epileptic patients
- When overdose: amnesia and confusion also
83
What is Vigabatrin?
- Irreversible GABA transaminase inhibitor
- Adjuvant medication
- Addictions
- Panic attacks
84
What is vigabatrin's trade name?
Sabril
85
Why can vigabatrin be taken only once a day?
- Has a short plasma half life
but
- This doesn't matter becasue it is irreversible, if take once a day, will have actions as it covalently modifies the enzyme
- So will have a continued effect once it has been metabolised
86
What are the side-effects of vigabatrin?
- Visual disturbances
- Depression
- Psychosis
- Sedation
- Teratogenic actions
87
What are the three forms of Sodium valproate?
- Sodium valproate
- Valproic acid
- Mixture: valproate semisodium
(no difference in the actions of these drug formations)
88
What is sodium valproate?
- First line treatment for a range of epilepsies
- Also used in bipolar disorder and migraine's
89
What are the potential mechanisms for sodium valproate (4)?
- GABA transaminase inhibitor (most likely)
- Enhances post-synaptic GABA function
- Inhibits sodium channels
- Inhibits calcium channels
90
What are sodium valproate's trade names?
- Epilim
- Depakote
91
What are the side-effects of valproate?
- Liver toxicity (can be sudden onset)
- Teratogenic (folic acid antagonist)
- ASD
- Cleft palate
- Limb defects
- Cognitive changes and brain structure changes with long term use (could be reversible when the drug is withdrawn)
92
What are the characteristic facial structures of foetal valproate syndrome?
- High forehead
- Flat nasal bridge
- Broad base of nose
- Shallow philtrum
- Long upper lip
93
What are gabapentin and pregabalin trade names?
- Neurontin
- Lyrica
93
What are the two main Gabapentinoids?
- Gabapentin
- Pregabalin
94
How do gabapentin and pregabalin act?
- Bind to a alpha2delta subunit of a neuronal calcium channel
- Has a physiological role with the natural ligands leucine and isoleucine
- Normally, when one amino acid is bound, the calcium channel complex is transported to the cell surface
- If a gabapentinoid binds , the channel is retained in the cell and is broken down, reducing the calcium channels on the cell surface
95
What does pregabalin increase the levels of?
- GAD
- GABA
96
What are gabapentin and pregabalin used for?
- Adjunct medication for focal seizures
- Pregabalin also as a monotherapy and for anxiety
- Used for neuropathic pain
97
What are the side-effects of gabapentin and pregabalin?
- Sedation
- Diziness
- Suicidal thoughts
- Abuse potential
- Seizures upon withdrawal
98
What are the gabapentinoids street drug names?
- Gabbies
- Johnnies
- Budweisers
99
Where is there a particular problem with gabapentinoids as a street drug?
- Prisons- double the rate of prescriptions here
- 19/96- 20% of prescrptions were not in the possesion of the person who was prescribed them
- Can be fatal when combined with methadone (problem when prescribed for withdrawal in prisons)
100
What class are the gabapentinoids?
Class C controlled substance under schedule 3
101
What is Ethosuximide?
- Blocks T type calcium channels
- First choice drug for absence seizures (can exacerbate other types of epilepsy)
- Lacks the liver toxicity seen with valproate
102
What are the side-effects of ethosuximide?
- Sedation
- Nausea
- Mood changes
103
What seizures is Leviteracetam (Keppra) used to treat?
- Focal
- Myoclonic
- Tonic-clonic
104
What is the mechanism of leviteracetam?
- Bit of a mystery
- Likely inhibits presynaptic calcium channels
- or binds to SV2A which is a protein involved in the release of neurotransmitter
- inhibiting this and the channels will cause the same overall effect of a reduce in neurotransmitter release
105
What are the side-effects of leviteracetam?
- Depression
- Agitation
- Aggression
- Suidide ideation
- Psychosis (rare)
- Stevens-Johnson syndrome (v. rare)
106
What drugs is Stevens-Johnson syndrome seen with?
- Lamotrigine
- Phenytoin
- Valproate
- Oxcarbazepine
- Ethosuximide
- Carbamazepine
107
What are the two forms of Stevens-Johnson syndrome?
- Skin blisters, peeling and lesions around the mouth
- Toxic epidermal necrolysis which is where the top layer of the skin comes off and looks like burn damage
108
What is topiramate used for?
- Adjunct treatment for focal seizures and tonic-clonic seizures
- Migraines
- Bipolar disorder
- Alcoholism
109
What are the side-effects of topiramate?
- Sedation
- Cognitive problems
- Psychiatric
- Teratogenic
110
What is the ketogenic diet used for?
- The 30% of epileptic patients where antiepileptic drugs do not work
111
What is the ketogenic diet?
- An extreme version of the Atkins diet
- Very high in fat
- Very low in carbohydrates
- Controlled protein
112
What percentage of children will see an improvement in symptoms when on the ketogenic diet?
- 50% of children will see a significant decrease in the number of seizures
- Some even become seizure free
113
What is a hemispherectomy and what is it used to treat?
-Treats Rasmussen's encephalitis which is an inflammatory condition that results in frequent and severe seizures
- The removal of one hemisphere of the brain occurs
114
What is a corpus callosotomy and what is it used to treat?
- Treats intractable epilepsy
- Severs the corpus callosum
- This prevents seizures from spreading to the other hemisphere
- Can have adverse effects such as cognitive impairment, language difficulty and hand syndrome (hand has a mind of its own)
115
What are optogenetics?
- Use light gated channels or pumps to modify the behaviour of neurons
- Can be used for the treatment of epilepsy in the future
116
What are DREADDs?
- Designer receptors exclusively activated by designer drugs
- An engineered form of receptor is introduced into the target cells
- This receptor is mutated so it no longer responds to its nornal endogenous ligand, but only the synthetic drug
- A possible future method for treating epilepsy
