Epilepsy (1) Flashcards
1
Q
Brain size and neuron count
A
- Elephant has huge cerebellum- more complicated movements (trunk)
- All speicies show epilepsy
- Head trauma, stoke can increase risk of species
2
Q
What do brain cells do?
A
- Neurones in the brain are rhythmic- around 300 times per second
- Beta rhythm- rhythm for the posture
- Gamma rhythm- rhythm for movement
- Epilepsy is when the rhythms go wrong
3
Q
What don’t neurons all fire at once
A
- Excitation v Inhibition
- They are in balance between synaptic excitation and inhibition
- Many synapses on the same neurone- many excitation and inhibition therefore different neurones are kept at different levels from the threshold
- Anything that changes that balance can cause epilepsy- Strychine; Kainic acid
- There are 30,000 synapses on a typical cell, a mix of Glu and GABA
- No 2 cells will have the same balance of synaptic activity so they are all at a different distance from firing threshold
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4
Q
Spiking activity is STOPPED by GABA inhibition
A
- When GABA is applied to a neurone, AP firing slows down- the cells then fire at a set rhythm
- GABA not only slows neurones from firing, it also tells neurones when to fire
5
Q
Epilepsy
A
- 0.5-1% of the population suffers from epilepsy i.e. 450,000 people in the UK
- 2% suffer at least one seizure in their lifetime
- 30,000 new cases each year in the UK
- 30% are refractory to drug treatment
- Lots of them respond at the Beginning and then stop after a while
- 20-30% not improved by surgery
- 1000 epilepsy-related deaths per year
- 50% of deaths are SUDEP
- 60-90% Undiagnosed or untreated in developing countries
6
Q
The basis of the ECG
A
- If these 6 neurones fire randomly you end up with a relatively flat line
- If they fire at the same time- you see a rhythm as you get additive effect
- When a seizure occurs there is widespread excessive spiking on an EEG- all brain cells are synchronised when they shouldn’t be
7
Q
Pathological synchronization
A
8
Q
Classification of epilepsies
A
- Generalised whole cortex bilateral
- Tonic-clonic motor seizures- (grand-mal)
- Absence few motor signs- (Petit mal)
- If you have either of these types you lose consciousness
- Partial/focal/localised- you do not lose consciousness
- Auras (can be any of these)
- Visual hallucinations
- Deja vu
- Specific motor symptoms (Jacksonian twictch)
- Sometimes partial seizure can spread over a greater area you can lose consciousness
9
Q
Reflex epilepsy
A
- About 7% of people with epilepsy
- Seizures are triggere: TV; Sunlight through leaves; strobe light; sunlight on water
- 0.001% of suffers have musicogenic seizures
- Other triggers: eating, tooth brushing, smells, chess, reading, sums
10
Q
Why do seizures happen
Neuronal networks
A
- Brain is a small world network
- Regular you have to pass through every neurone to get across
- Small world you can skip neurones out
- Random- No telling how long how many neurones are connected
- Connections all excitatory- Additive effect occurs
- Some inhibitory connections
11
Q
Small world neuronal networks with excitation AND inhibition produce oscillation
A
- These connected networks with excitatory and inhibitory cells have the elements required to create rhthyms
- GABA cells tell neurones when they can fire
12
Q
Neuronal network oscillations- EEG (electroencephalography)
A
- Different rhythms have different functions
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13
Q
Human EEG in temporal lobe epilepsy
A
- Tonic phase- everywhere is active- muscle ridge (muscles are stiff)
- Clonic phase- rhythm will slow down
- This lasts around 30s-1 minutes
- Psychogenic seizures- psychological seizure not as many physiological signs- often shown by very long seizures
- Seizures can go straight into another seizure- this is life-threatening and patients need to be comatose
14
Q
Synchronisation of 2 PCs by an interneurons
A
15
Q
So- why do seizures happen
A
- Imbalance between excitation and inhibition
- Damage to network and maladaptive response
17
Q
Modeling epilepsy
A
- Induce seizures in a rat
- Leave them for around 3-4 weeks (latent period- this period they are on there way to becoming epileptic)
- They start having many seizures and are epileptic
- These models are bad because 80% of rats die
- This often causes the rats to have strokes
19
Q
Reduced intensity status Epilepticus (RISE) induced epileptogenesis
A
- This takes around 3 months
- Because this is slow we can monitor changes in brain structure
- There is greater variability in rats in terms of number of seizures
21
Q
Epileptogenesis- questions
A
22
Q
The number of synapses is not changed
A
- There are no changes in the number of synapses in the brain
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23
Q
The number of AMPA receptors in massively reduced by seizures
A
- The results show that it is the number of excitatory receptors in the brain decrease
- In the 3 months, it takes to become epileptic the hippocampus will not be able to stimulate- No seizures= no excitation
24
Q
Latent period CA3 is hypoexcitable when challenged with 100 nM KA
A
25
Q
Epileptogenic involved homeostatic synaptic scaling
A
- When a memory is made new receptors are inserted into the synapses- therefore strengthening the synapse
- Alcoholics- lots of GABA meaning the brain puts lots of excitation within the synapses
- On acute cessation of alcohol, we lose GABA potentiation leaving lots of excitation= seizure
- In the rat model, the excessive excitation- lots of inhibitory receptors- as they normalise epilepsy then sets in
