Week 2_1 Flashcards
what is the prevalence of seizures and epilepsy? what is the definition (2) of epilepsy?
seizure -> 10%
epilepsy -> <1%
epilepsy is:
- 2 unprovoked seizures
- 1 unprovoked seizure and abnormal EEG
what are the three types of seizure?
1) focal onset:
- aware or impaired awairness
- motor or non-motor onset
- focal to bilateral tonic-clonic
- effect depends on where in the brain the seizure is happening
2) generalized onset:
- motor or non-motor
- can be an absence seizure
3) unknown:
- motor or non-motor
3 phases of a tonic-clonic seizure
1) tonic (fast spikes in EEG)
2) clonic (slower wavesin EEG)
3) postictal (not really part of the seizure)
what is the aim of antiseizure treatment?
- seizure protection
- stabilization of hyperexcitability
- neuroprotection (brain maturation)
what is the pharmacoresistance in children VS adults? What do we need to know for a personalized antiseizure treatment?
15-20% in children, 30% in adults.
Know:
- seizure and epilepsy types
- etiology of epilepsy
- exact mechanism of action of the drug
- interactions and synergisms between drugs
- adverse effects (if it makes someone more agressive for example)
what are the 2 main mode of action of antiseizure drugs? what type of drugs do we not combine?
1) inhibitory (GABA)
2) excitatory (glutamate)
we don’t combine two drugs that have the same mode of action (too many side effects)
why are there more seizures at neonatal age? are GABA excitatory or inhibitory receptors at neonatal age?
insufficient postsynaptic mechanisms of inhibition
GABA receptors -> excitatory instead of inhibitory -> can’t give these drugs to neonatals
what is one problem when giving the drugs as tablets? what are some comorbidities and adverse effects?
Breaking tablets can lead to dosage changes.
Comorbidities: ADHD, ASD, mental retardation, aggressive behaviour, …
Adverse effects on sleep and cognition
what are the three levels of treatment? 6 etiologies?
1) seizure type-specific
2) epilepsy sydrome-specific
3) gene-specific
etiologies:
- structural
- genetic
- infectious
- metabolic
- immune
- unknown
which drug is used in first line for focal + generalized onset seizures? Why do we need to find an alternative?
valproate (VPA)
Adverse effects: sedation, hair changes and loss, tremor, liver enzyme elevation, teratogenicity (defect in foetus if taken by pregnant woman)
what are the treatment steps for Dravet syndrome?
VPA
VPA + other drug
Add keto diet, CBD, bromide
in the case of pharmacoresistance, what balance do we need to find?
balance between seizure control and as few sides effects as possible -> life quality is the main goal
name a few cognition comorbidities
- slow progressing speed
- fine motor dexterity difficulties
- working memory deficit
- autism
- behavioural problems
- …
what can be a biomarker for pharmacoresistance? how predictable is pharmacoresistance?
- EEG: we can see asymmetry, focal slowing, …
- 25% lack of efficiency with the first drug, 50% of these have a good response to second agent, 30% after two, 10% after 3
what are the 6 hypotheses of how pharmacoresistance works?
1) transporter hypothesis: increased activity of membrane transporters -> drug is taken out of the cell and can’t work anymore
2) target hypothesis: alteration of receptor subunit expression
3) intrinsic severity model: resistance dependant from severity of epilepsy through high frequency seizure
4) neuronal network hypothesis: neuroplasty adapts in a negative way
5) genetic
6) neuroinflammation: inflammation promotes and supports epilepsy
