Epliepsy Flashcards
what is the epidemiology of epilepsy
75 million worldwide
3rd most common neurological disease
0.7% incidence in UK
what is the definition of epilepsy and seizure
epilepsy = tendency to have recurrent seizures
seizure = episodes of altered consciousness
what is ictogenesis
the development of a seizure
brain state transition
what is epileptogenesis
the development of epilepsy
what does interictal mean
between seizures
what does paroxysmal mean
sudden, violent outburst
how do people die of epilepsy
rare occasions where the seizure doesnt stop
if the brain is locked in a persistent epileptic state, it becomes a neurological emergency -> increase of 50% mortality even with medical care
what is SUDEP in epilepsy
sudden unexpected death in epilepsy
someone with epilepsy goes to sleep alone, in morning they are dead
telemetry units show when people have seizure it is common to stop breathing briefly, and seizure can also affect cardiac, respiratory and brain systems
what is epilepsy incidence distribution associated with
socioeconomic factors
driving, reduced employment opportunities
14% are unemployed
epilepsy is a drive for downward social mobility
people also get judged
outline interictal activity ( between seizures)
transient abnormal focal neural discharges seen on EEG
basis for most diagnoses
- not in hope of catching seizure but to assess whether brain is ‘twitchy’
evidence of hyperexcitability
outline interictal cognitive deficits
Kleen et al.
epileptic rat trained to chose between 2 levers depening on where light comes on
the longer the pause the more rat gets door wrong
performance declines with time
but if rat has epilepsy, performance remains good
if they have a discharge at time when they choose door, performance drops
what are co-morbidites associated with epilepsy
excess mortality
memory deficits
schizophrenia - 7 fold increase, common pathophysiologies
depression, stress, anxiety
downward social movement
outline the causes of epilepsy
genetic - dont have full penetrance,
brain injury - trauma, stroke
brain infection - HPV = calcified lesions in brain associated with HPV infection in utero, evidence is strong, measles - since MMR vaccine in 70s, temporal lobe epilepsy has dropped
brain tumours
drugs (alcohol)
are there currently any anti-epileptogenic drugs
no
what are some causes of seizures
drugs (alcohol)
electrical stimulation (ECT)
sensory triggers - flashing lights, - rare
metabolic imbalance - pH (can stop seizure by making someone acidotic e.g breathing in and out of paper bag)
hormonal state - menstrual cycle, cluster patterns
brain state - transitions, absence seizure discharges dont happen during sleep, some happen only during sleep
temperature, fatigue, stress
what is the spotlight of attention
at any given moment, only a small proportion of nerve cells are active
most information coming into the brain is suppressed e.g like out clothes
brain processes things serially not in parallel
what is an absence seizure
blank out
stare into space for a few seconds
what did Liu et al show through compromised computation
absence seizures likely compromise brain function by blocking flow of activity through thalamus and also interictal events
recently suggested these discharges also alter intellectual performance
what are the cells like during a seizure
all cells active at the same time, only one possible combination of doing that, then they are all turned off, so seizure represents catastrophic reduction in number of possible ways brain can work
when does the maximal number of possibilities exist in neurones
when half the neurons are active
these are called ‘ensembles’
what do optical illusions do in terms of neuronal ensembles
brain flips from one ensemble to another
outline brain associations
good for leaping and thinking about one thing to make a connection with another - like if they look similar
this is the essence of invention
outline pattern completion
comes from the way the brain is wired
arises from recurrent connections
when two cells are coactive their connection strengthens
what are synchronising influences to the cortex
sensory input
glia
intrinsic bursting
what causes synchronised activity in the cortex
LTP/LTD - basis for memory
binding problem
signal transfer - requires a lot of input, info passes through quickly - can fail?
what is meant by ‘up’ states?
working memory
what is recurrent connectivity in the cortex
memory completion
attractor dynamics
positive feedback at cellular level
why do we have persistent short term activity in the brain
basis of short term memory, brain is in semi persistent activity, has ability to flip, happens in recurrent connective networks, crucial for pattern completion
what is normal neuronal function kept in check by
neuronal inhibition
if all inhibition is removed - disinhibition = single cells may trigger epileptiform events
what did the brain slide study show about single neurones
they can initate synchronised population discharge in the hippocampus
the study blocked all synaptic inhibition, quickly saw large discharges, every single nerve cell discharged at that moment
shows the entire network is activated in these field events
with 3 iterations, entrained entire network to be activated from single cell
how can we see activity in nerve cells
Ca2+ network imaging
dying Ca2+ as it enters active cells
outline the spatial profile of a seizure
core territory where seemingly every neuron is active, this projects forward huge glutaminergic activity onyo this territory - leads to rapid recruitment of interneurons in this territory, then rapid feedforward restraint of pyramidal activity
people describe auras before seizure - preferential activation of inhibitory neurons, there is discrepancy between activation of e/i - protective firing
what is the next spatial profile of seizure after ictal
penumbral
what is the balance between excitation and inhibition
either no activity or epileptiform activity - all a balance
is the brain defined by balances?
not by balances but by TIPPING POINTS
how does the all or nothing response come about
through positive feedback mechanism, paired up with negative feedback mechanisms pushing it back to normal
the threshold is the LEAST STABLE POINT
happens because of Na+ channels - depolarising , as more open, more posiitve feedback
what is an attractor state
whenever we have an ‘aha’ moment or memory suddenly pops into out head , if Na channels didnt close automatically, neurons would get stuck in this attractor
energy sink, systems converge toward these states from multiple starting points
means brain heads towards certain stable patterns of activity
how do attractor states show the epileptic brain is different to normal brain?
has pathological state that is a little bit easier to enter as it has a reduced protective barrier
what are bifurcations
transitions between ictal and interictal states
what happens immediately prior to seizure onset
all or nothing switch
outline what Graham et al. found about what happens before seizure onset
optogenetics - nerve cells fire when iron channels open and ions move across membrane - energy helf there by big ion gradients
bacterial proteins expressed in nerve cell illuminates tissue using light
stimulated pyramidal cells and recorded output
all or nothing allows brain to leap from one state to another
mediated by Ca2+ channels too - depolarising
what is the basic mechanism of antiepileptic drugs
suppress excitation
enhance inhibition
what does AED Phenytoin do
stabilises inactive state of Na channels
what do benzos and barbiturates do as AEDs
benzo = e.g diazepam, elongates opening time of GABAA channels
barb = increased GABAA current
what does Ethosuximide do
target voltage-dependant Ca2+ channels for treatment of absence seizures
outline the success of antiepileptic drugs
half of peoples seizures were controlled on 1st drug
1/6th on second drug
1/3 rd remained refractory to medication (epilepsy maintained)
what are other treatment options for epilepsy?
neurosurgical resection - only if drugs dont work, identifiable focus of pathology,, irreversible
brain stimulation - now use of optogenetics, with no irreversible damage - want to find out when to stimulate to stop a seizure onset
gene therapy - genes can trigger inhibitory potassium channel, more then cell reduces excitability, epileptic seizure triggers gene expression to make more K+ channels - dampen down cells in seizure
what are tipping points created by
multiple synergistic positive feedback mechanisms
what is a seizure?
brain state, usually reverses, without ostensible long term damage
typically very intense (hypersynchronous) network activation
typically profound neuronal suppression post-ictally
how are auras defined
the ‘right’ processing at the ‘wrong’ time
