Epilepsy and Convulsants Flashcards
1
Q
What is epilepsy
A
- Sudden, excessive high frequency neuronal discharge
- Not random but highly synchronous- many neurons at once
- A disorder of the cerebral cortex
- May be loss of consciousness
- Behavioural changes related to site of discharge - focus
2
Q
Define Ictal
A
- Ictal (from Latin – a blow or stroke) – the actual seizure or convulsion
3
Q
Define interictal
A
- Interictal – quiescent state between seizures – some abnormal spike activity can be recorded
4
Q
Define epileptogenesis
A
- Epileptogenesis – the underlying process leading to development of epilepsy
5
Q
What are causes of epilepsy
A
- 70% idiopathic/cryptogenic - Unknown causes
- genetic - rare familial disorders
- congenital - structural abnormalities -dysplasia
- birth trauma - ischaemia
- neurological/neurodegenerative - elderly
- head trauma - penetrating or non-penetrating- rewiring of damaged brain tissue- leads to epilepsy
- metabolic - glucose/electrolyte imbalance
- disease - meningitis, tumour, abscess
6
Q
What are two methods to detect epilepsy
A
- Electro-EncephaloGraphy (EEG)
2. Magneto-EncepahloGraphy (MEG)
7
Q
Describe how to carry out Electro-EncephaloGraphy (EEG)
A
- Put on surface of head
- Can pinpoint activity in brain
- Record generalised seizure- every electrode shows it- synchronised
8
Q
Describe how to carry out Magneto-EncepahloGraphy (MEG)
A
- Look at magnetic fields rather than electrical activity
- continuous wave not discrete points- better picture of where it is occurring
- But more expensive
9
Q
What is used for imaging epilepsy
A
- PET – monitors local metabolism
- MRI – structure and volume
- fMRI – relates activity to structure
10
Q
What are invasive approaches to record epilepsy
A
- dural electrode arrays
- Expose surface of brain and put dural electrode array on surface of brain to pinpoint where seizure is - implanted depth electrodes
- Bands of insulation alternating with exposed bits
- Record depth of brain
11
Q
Describe EEG of normal
A
- normal- flat line with little synchronisation
12
Q
Describe EEG of Grand mal seizure
A
- Synchronisation
- Generalised seizure
- High frequency synchronisation-tonic phase
- Clonic- bigger amplitude and lower frequency
13
Q
Describe EEG of Petit mal
A
- Spike wave activity- 15 sec
2. Involved with brief period of loss of consciousness but no loss of posture
14
Q
Describe EEG of partial seizure
A
- Only on one side of brain
15
Q
Describe a Grand-mal seizure
A
- tonic phase- output from cortical areas is such a high frequency the limbs can tremor and stiffen but don’t move a lot
- Clonic phase- frequency falls and movement of muscles is much more obvious
- Post-ictal phase- relative lethargy and tiredness
16
Q
Where do seizure occur
A
- Anywhere
- subcortical rare
- mostly cortical - frontal, parietal, occipital, temporal
- Temporal most prevalent - 30-40%
a) Hippocampus, entorhinal cortex, amygdala
b) drug refractory
c) surgical resection
17
Q
What is a radical temporal lobectomy
A
- Removal of temporal lobe including entorhinal cortex and hippocampus- used to
- Less radical now
- Much more precision- only part that needs to be removed
18
Q
What is resective surgery
A
- Resective surgery for chronic epilepsy
- EEG identifies where seizure activity is arising
- MRI- structural correlation
19
Q
How do seizures arise
A
- Cortical activity - dynamic balance between inhibition and excitation
- Two levels
- Intrinsic - ion channels - Individual cells
- Network - synaptic transmission
- Disturbed balance - excessive synchrony and epilepsy
a) increase excitation, normal inhibition
b) decrease inhibition, normal excitation
c) decrease inhibition, increase excitation
20
Q
Describe basis of epilepsy discharge
A
- At start of seizure a sudden step in depolarisation
- Long train in prolonged depolarisation
- Paroxysmal shift- big shift at start
21
Q
Describe intrinsic balance - membrane ion channels
A
- Destabilising depolarising ion channel current in membrane of every neuron- sodium or calcium flowing into cell
- Balanced by stabilising/hyperpolarising currents- potassium leaving or chloride ions entering
- If balance lost then cells become hyperexcitable and more likely to coordinate activity abnormally
22
Q
Describe synaptic balance
A
- Glutamate is principle source of excitation
2. Balanced by inhibition by GABA
23
Q
Describe Synaptic excitation
A
- Synaptic excitation is controlled by synaptic inhibition in neuronal networks
- Excitatory glutamate neurons can excite each other
- Glutamate neurons also excite inhibitory GABA neurons
- GABA neurons control and limit excitation
- Loss of inhibition leads to runaway synchrony and epilepsy
24
Q
How can synaptic and intrinsic factors initiate and prolong a seizure
A
- In initial phase of epileptic event Ampa receptors are very important
- Excess activity causes depolarisation
- NMDA receptors- Contribute to excitation in prolonged way when cell is depolarised
- If membrane depolarises they become more important and activated
- Voltage gated ca2+ channels are opened by depolarisation
- Sub-threshold voltage gated Na+ channels are Opened by depolarisation- Not ones in charge of action potential
- All lead to continuation of depolarisation
25
Q
How do seizures stop
A
- Gluatamate depletion- Less to release
- Glutamate receptors desensitisation- Less effective over time
- K+ channel activation
- Na+ channel inactivation
26
Q
How can you treat epilepsy
A
- Block destabilizing currents- Sodium and calcium currents
- Increase stabilizing currents- Increases potassium current flow into cell
- Reduce synaptic excitation
a) Block glutamate release
b) Block glutamate receptors - Increase synaptic inhibition
a) Increase GABA release
b) Potentiate GABA receptors
27
Q
How can you block voltage gated Na-channels
A
- 3 states
a) Closed channel
b) Open channel
c) Inactivated state - Drugs that block Na-channels- bind to inactivated state so can’t return to closed channel
28
Q
What are some drugs that block Na-channels
A
- phenytoin (++)
- carbamazepine (++)
- lamotrigine (++)
- sodium valproate (+)
29
Q
How do you block voltage gated Ca-channels
A
- bind directly to stop them opening
30
Q
What are some drugs that block Ca-channels
A
- ethosuximide (++) - specifically, useful for absent seizures
- gabapentin
- phenytoin
31
Q
How can you block glutamate release
A
- Anticonvulsant blocks sodium channel activity
- Action potential arise by sodium channel opening, causing calcium channel opening, causes glutamate release
- Reducing action potential reduces glutamate release can also reduce glutamate release directly
- Drugs that reduce glutamate release
- Na-channel block
- Ca-channel block
- Reducing vesicle fusion - Levetiracetam
32
Q
How can drugs act at GABA synapses
A
- increase GABA levels in synaptic terminals
- GABA transaminase inhibitor- increase GABA present
- decrease GABA inactivation
- enhance postsynaptic response
33
Q
Which drugs increase GABA levels in synaptic terminals
A
- vigabatrin (++)
2. sodium valproate (+
34
Q
What do GABA transaminase inhibitors do
A
- blocks GABA breakdown
- increases GABA levels
- increases GABA release
35
Q
How can you decrease GABA inactivation
A
- tiagabine
- blocks GABA reuptake
- increases GABA in cleft
36
Q
How can you enhance postsynaptic response to GABA
A
- benzodiazepines
- barbiturates
- prolong channel open time
37
Q
What are some Alternative anticonvulsants
A
- felbamate - blocks NMDA receptors
- topiramate - blocks AMPA/kainate receptors
- retigabine - activates K-currents
- levetiracetam - modifies vesicle release machinery
- losigamone - blocks low threshold Na-currents
