ICL 10.10: Fundamentals of Epileptogenesis & Epilepsy Pharmacology Flashcards
(41 cards)
what is a seizure?
a clinical (or electrographic) event associated with an abnormal, excessive and hypersynchronous electrical discharge in a group of cortical neurons
the fact that it’s cortical neurons specifically is important because that means epilepsy and seizures are a disfunction of the cerebral cortex – so disorders with the cerebellum or brainstem like Parkinson’s do not cause seizures!
but Alzheimer’s which effects the cerebral cortex can cause seizures!
what is epilepsy?
recurrent and unprovoked seizures
seizure = a clinical (or electrographic) event associated with an abnormal, excessive and hypersynchronous electrical discharge in a group of cortical neurons
what are the guidelines that would state that someone has epilepsy?
epilepsy is a disease of the brain defined by any of the following conditions:
- at least two unprovoked seizures occurring more than 24 hours apart.
- one unprovoked seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures (approximately 60% or more)
people who have had a single seizure but have underlying abnormalities on examination like Alzheimer’s or a cortical dysfunction or a stroke are at a higher risk and would qualify for having epilepsy
- Epilepsy Syndrome
what is epilepsy syndrome?
clinical and EG and MRI findings that signify a particular type of epilepsy
how does epilepsy effect the disability and death of those who have it?
of all the neurological problems, people with epilepsy comprise 5% of those who have disability that effects their life and work and 1-3% have shortened life span
what age range is more effected by epilepsy?
incidence of epilepsy is high in the neonatal group then it plateaus in young adults and starts to go back up after 50
so epilepsy is most common in older adults in their 80s
as people live longer and develop more neurological insults related to falls, trauma, alzheimer’s, heart disease etc. you’re more likely to see seizures in these older patients
what is an aura?
a premonition or an objective/subjective sensation of an impending seizure
they are localizable –> some people get a funny taste or smell which localizes to the frontal/temporal lobe while other people get anxious which localizes to the fight or flight part of the brain
it’s considered a simple partial seizure (focal aware seizure) and not all auras lead to a full blown seizure
what is the medical word for seizure?
ictus or ictal event
what state are people in after a seizure?
post-ictal state
patients will be sleepy, lethargic, somnolence or confusion due to the excessive release of GABA during the seizure
what are the 3 stages of a seizure?
- aura
- ictus
- post-ictual state
which types of seizures are not associated with epilepsy?
- metabolic like people with kidney disease
- traumatic brain injury
- drugs
- medications like penicillin
- alcohol
- systemic illness (autoimmune disorders like SLE)
what are the causes of epilepsy in children?
- cryptogenic (68%) aka we don’t know
- congenital abnormality (20%)
- trauma (5%) like shaken baby syndrome
babies don’t have generalized seizures because their brains aren’t developed enough yet so they just twitch in on like one side or one area of the body
what are absence seizures?
a type of epilepsy that is referred to as a generalized epilepsy and it happens in kids between 4-12 years old
the kids will have staring episodes for a few seconds and then they’re okay
there’s no aura or post-ictus confusion and they can have hundreds of episodes in a day
alkalosis makes the neuronal cells more excitable and it can provoke seizures which is why when you’re trying to catch a seizure on an EG, you ask them to blow on a windmill so they hyperventilate
what causes epilepsy in young adults?
- trauma (29%)
- congenital (22%)
- tumor (22%); usually low grade astrocytoma or meningioma
- infection (16%)
what causes epilepsy in adults?
- CVA (33%) like strokes and hemorrhages
- tumor (23%)
- trauma (22%); usually more malignant tumors
what are the types of seizures in adults?
- generalized seizures
2. complex partial seizures/focal seizures with impaired awareness
what causes epilepsy in the elderly?
- stroke from CVD (40.7%)
- unknown (33%)
- degenerative (16.5%)
this is the most common age group to get epilepsy!!
how do you classify seizures/epilepsy?
- based on phenomenology (seizure semiology)
generalized vs. partial/focal onset
- based on etiology
post-traumatic, post-stroke, tumor associated etc.
- based on pathophysiology
primary generalized epilepsy vs. secondarily generalized = involves both hemispheres or spreads from one to the other
- genetics
SCN1A mutation, GABRA1
- epileptic syndromes
Lennox Gastaut, Juvenile Myoclonic Epilepsy
we care about classification because certain medications only work on certain types of epilepsy
what’s the difference between a partial vs. generalized seizure?
FOCAL SEIZURES
1. simple partial seizures –> no alteration of awareness
- complex partial seizures –> there is alteration of awareness
GENERALIZED
1. primary generalized –> absence and JME seizure
- secondary generalized
slide 14
what are the various etiologies/causes behind epilepsy that are used to classify epilepsy?
- structural
- genetic
- infectious
- metabolic (inborn errors of metabolism like mitochondrial disorders)
- immune
- unknown
whatever the underlying cause may be, the management and treatment are pretty much the same!
what is the pathogenesis of a seizure?
first there is an insult and then there is a rapid response with inflammation, glial reaction and gene expression which increases excitability
this causes a decreasing seizure threshold due to epileptogenesis and allows a subthreshold stimulus to cause electrical activation and recurrent seizures
so brain tissues of epilepsy patients have more excitatory neurons than inhibitory neurons whether that be induced by stroke, trauma, infection etc – they all have a change in the cortical circuitry where there’s a group of abnormal neurons that are firing!
teacher explanation = epilepsy can be simplified as three stages: an initial insult, followed by epileptogenesis, and ultimately ending in a state of recurrent, spontaneous seizures(epilepsy). The initial insult can take several forms and is followed by both rapid and slower progressive changes with rapid and slower durations. Rapid changes in animal models include neuronal excitation and calcium influx, triggering a cascade of events that include second messenger and immediate early gene responses, modifications to pre-existing proteins, and protein synthesis. Within days, there can be cell death and proliferation as well as inflammatory, glia, and vascular responses. Slower responses include growth (eg, axon outgrowth, synapto-genesis, angiogenesis), leading to synaptic reorganization, and this may in turn cause other changes. Over time, seizure threshold is lowered by a growing increase in excitability, and the risk of a seizure increases. These changes may be sufficient to cause epilepsy or may stall until a second “hit” occurs. The second hit could be environmental, or it could be due to time-dependent gene expression or co-morbidity. Therefore, genes, development, and the responses to the initial insult are likely to act together to result in a state of chronic seizures.
what are the steps that occur building up to, during and after a seizure?
- epileptogenic lesion like head trauma, stroke, infection, etc. that causes neuronal injury
- latency period (epileptogenesis)
during this time there is reorganization such as neuronal loss, neurogenesis, gliosis, plasticity, inflammation and molecular reorganization which causes increased excitability
- seizure
- recurrent seizures
reorganization continues which allows for continued neuronal loss, neurogenesis, gloss etc.
if there is good seizure control though, there won’t be recurrent seizures and reorganization process will stop
which parts of the brain is most involved in focal seizures?
CA1 and CA3 of the hippocampus in the temporal lobe
they produce a lot of electrical activity that spreads to the rest of the cortex; they’re kind of the pacemakers of the brain so when there’s problems with them it can cause focal seizures!
focal epilepsy is the most common type of epilepsy and within that population, temporal and hippocampal are the most common
what is ictogenesis?
seizure generation
there are inhibitory neurons that shut down excitatory responses – but if you inhibit the inhibitory neurons then you get excitation and seizures!
if you inhibit multiple neurons, that’s what gives you epilepsy! this can effect many circuits in the brain, specifically the thalamic circuit that usually causes seizures due to abnormal excitation
