epilepsy

Question 1

what is epilepsy?

Answer 1

• characterised by excessive, synchronous firing of neurons
• expresses behaviourally as recurrent, episodic seizures
• seizures may be spontaneous or they may be triggered by scpecific stimuli (e.g light)

Question 2

what percentage of the population does epilepsy affect?

Answer 2

~1% of the population (70 million people)

Question 3

how common are seizures?

Answer 3

approximately 1 in 5 people will have a seizure at some point in their life

Question 4

what are the types of seizures?

Answer 4

partial (affects only one hemisphere)
generalised (affects both hemispheres)

Question 5

what are the types of partial seizures?

Answer 5

simple (maintain consciousness)
complex (loss of consciousness)

Question 6

what are the types of generalised seizures?

Answer 6

atonic (loss of muscle tone)
tonic (increased muscle tone)
myoclonic (jerking movement)
tonic-clonic (stiffness and jerking)
absence (loss of awareness)

Question 7

what is epilepsy characterised by?

Answer 7

increased excitability of networks in different parts of the brain

Question 8

epilepsy and plasticity

Answer 8

change in neurons leading to enhances response which is continued (similar to LTP)

Question 9

where does plasticity occur?

Answer 9

1. synapses (external stimulus)
2. whole cells (change in cellular response)
3. networks (change in network activity)

Question 10

what happens if plasticity becomes excessive?

Answer 10

1. synapses (external stimulus)
2. excessive cellular response
3. networks=epileptiform activity!

Question 11

what leads to epilepsy?

Answer 11

excessive plasticity in networks leads to epileptiform activity
(epileptogenisis)

Question 12

epilepsy- effect of synchrony

Answer 12

• lots of neurons have to fire to generate a wave of excitability
• e.g 5 neurons synapse with target neuron (convergent network)

Question 13

role of synchronous firing in brain function

Answer 13

when you have synchronous firing, action potentials fire together so you have a longer tail of activity in the target neuron
this means you get action potentials for a much longer time
this enhances excitability of the target cell
if you combine increased firing rate and synchrony there is a massive increase of activity in the target neuron=seizure

Question 14

what is it that generates seizures?

Answer 14

both increased neuronal excitation and synchronous firing are required

Question 15

summation and neuronal activity

Answer 15

increased excitability makes neurons more likely to fire repeatedly in a short amount of time
- this could lead to excessive temporal summation, where postsynaptic potentials from the same neuron add up too quickly and trigger seizure-like activity
excessive or synchronous firing from multiple presynaptic neurons could lead to too much depolarization at the postsynaptic site, causing spatial summation to push the neuron to threshold.
- this type of summation may be particularly relevant in epileptic networks

Question 16

what is temporal lobe epilepsy (TLE)?

Answer 16

• most common cause of partial seizures (60% of partial account for all)
• often hard to treat and AEDs have low efficacy and extensive side effects
  medial/mesial TLE is often associated with hippocampal sclerosis

Question 17

hippocampal trisynaptic network

Answer 17

1. input from perforant path to mossy fibres through dentate
2. mossy fibres from CA3 to CA1 to schaffer collateral path
3. CA1 to subiculum

Question 18

what pathway is CA3-CA1?

Answer 18

schaffer collateral pathway

Question 19

what is hippocampal sclerosis (HS)?

Answer 19

hippocampus becomes scarred and atrophied (shrunken) due to loss of neurons and gliosis
particularly in CA1 where S-C projects to but also subiculum and dentate
also associated with alzheimers/mild-to-severe dementia
CA1 in hippocampus is critical to learning mechanisms

Question 20

neuronal loss and epilepsy

Answer 20

glutamate-mediated excitotoxicity via NMDA receptors or potentially calcium permeable AMPA receptors

Question 21

what cell types are most vulnerable to excitotoxicity?

Answer 21

inhibitory interneurons eg. neuropeptide gamma-, somatostatin- and paravalbumin expressing of the dentate hilus are lost in HS

Question 22

debates of HS

Answer 22

does HS cause epilepsy or does epilepsy cause HS?

Question 23

mechanisms of absence epilepsy

Answer 23

essentially falling asleep without loss of muscle tone
- neurons in the reticular nucleus around thalamus

Question 24

steps of absence epilepsy

Answer 24

1. cortical hyperexcitability (especially in layer 5/6 pyramidal neurons)
2. excessive excitation sent to thalamic relay neurons
3. relay neurons activate reticular neurons (nRT)
4. nRT sends inhibitory GABAergic bursts back to relay neurons → rebound bursts via T-type calcium channels
5. creates a reverberating loop → generates 3 Hz spike-and-wave discharges.
6. network synchronization leads to behavioral arrest (typical absence seizure)