epilepsy Flashcards
what is epilepsy?
- 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)
what percentage of the population does epilepsy affect?
~1% of the population (70 million people)
how common are seizures?
approximately 1 in 5 people will have a seizure at some point in their life
what are the types of seizures?
partial (affects only one hemisphere)
generalised (affects both hemispheres)
what are the types of partial seizures?
simple (maintain consciousness)
complex (loss of consciousness)
what are the types of generalised seizures?
atonic (loss of muscle tone)
tonic (increased muscle tone)
myoclonic (jerking movement)
tonic-clonic (stiffness and jerking)
absence (loss of awareness)
what is epilepsy characterised by?
increased excitability of networks in different parts of the brain
epilepsy and plasticity
change in neurons leading to enhances response which is continued (similar to LTP)
where does plasticity occur?
- synapses (external stimulus)
- whole cells (change in cellular response)
- networks (change in network activity)
what happens if plasticity becomes excessive?
- synapses (external stimulus)
- excessive cellular response
- networks=epileptiform activity!
what leads to epilepsy?
excessive plasticity in networks leads to epileptiform activity
(epileptogenisis)
epilepsy- effect of synchrony
- lots of neurons have to fire to generate a wave of excitability
- e.g 5 neurons synapse with target neuron (convergent network)
role of synchronous firing in brain function
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
what is it that generates seizures?
both increased neuronal excitation and synchronous firing are required
summation and neuronal activity
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
what is temporal lobe epilepsy (TLE)?
- 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
hippocampal trisynaptic network
- input from perforant path to mossy fibres through dentate
- mossy fibres from CA3 to CA1 to schaffer collateral path
- CA1 to subiculum
what pathway is CA3-CA1?
schaffer collateral pathway
what is hippocampal sclerosis (HS)?
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
neuronal loss and epilepsy
glutamate-mediated excitotoxicity via NMDA receptors or potentially calcium permeable AMPA receptors
what cell types are most vulnerable to excitotoxicity?
inhibitory interneurons eg. neuropeptide gamma-, somatostatin- and paravalbumin expressing of the dentate hilus are lost in HS
debates of HS
does HS cause epilepsy or does epilepsy cause HS?
mechanisms of absence epilepsy
essentially falling asleep without loss of muscle tone
- neurons in the reticular nucleus around thalamus
steps of absence epilepsy
- cortical hyperexcitability (especially in layer 5/6 pyramidal neurons)
- excessive excitation sent to thalamic relay neurons
- relay neurons activate reticular neurons (nRT)
- nRT sends inhibitory GABAergic bursts back to relay neurons → rebound bursts via T-type calcium channels
- creates a reverberating loop → generates 3 Hz spike-and-wave discharges.
- network synchronization leads to behavioral arrest (typical absence seizure)
