Epilepsy Flashcards
Seizure clinical definition
Abnormally excessive and hypersynchronous activity of neurones located mainly in cerebral cortex
Classification of seizures
Generalised (both hemispheres)
Partial (one hemisphere)
Secondary generalised (partial that spreads to general)
Generalised can cause what movements
Absence Myoclonic Tonic-clonic Tonic Atonic
Partial seizure can cause
Simple
Complex
With secondary general
Partial seizure of parietal lobe
Tingling/jerking of leg, arm, face
Partial seizure of occipital lobe
Flashing lights or spots, vomiting
Partial seizure of temporal lobe
Strange smell or taste
Altered behaviour
Deja vu
Lip smacking/ jaw movements
Partial seizure of frontal lobe (front)
Adversive seizures
Eyes or head turn to one side
Partial seizure of frontal lobe (back)
Jacksonian seizure
Tingling feeling in hand or arm
What is an EEG?
Electroencephalography
Uses scalp electrodes to record the electrical activity along the scalp produced by the firing of neurones within the brain.
Spike-wave discharges analysed
Status epilepticus - what is it?
SE
Life-threatening condition in which the brain is in persistent seizure.
Medical emergency
Status epilepticus - time scales
> 30 mins of continuous seizure
Two or more sequential seizures spanning this period without full recovery
Status epilepticus - treatment
GABAa receptor agonist
Epilepsy - what is it?
A condition in which seizures recur, usually spontaneously
Basic mechanisms for seizures
Excitation - ionic: Na+, Ca2+ influx; neurotrans: glutamate, aspartate release
Inhibition: ionic: Cl- influx, K+ efflux; neurotrans - GABA release
What is done to keep brain waves flowing in one direction?
Inhibitory interneurones allow activity to spread in one direction, but not sideways.
They release GABA
What are interneurones?
10%-20% of neurones
How initially localised hyperexcitability spreads into surrounding neuronal networks.
Are counter balanced by inhibitory mechanisms.
What is GABA?
y-aminobutyric acid Major inhibitory neurotrans Found at 30% of synapses GABAa and GABAb Pentameric protein The composition of subunits affect affinity for diazepam or zolpidem
GABAa receptor type
Ligand-gated chloride channel receptor
GABAb receptor type
G protein-coupled receptor
GABAa subunit mutations causes which types of epilepsies
CAE (childhood absence epilepsy)
FS (pure febrile seizures)
GEFS+ (generalized epilepsy with febrile seizures plus)
JME (juvenile myoclonic epilepsy)
DS (Dravet syndrome – also know as SMEI (severe myoclonic epilepsy in infancy))
History of dravet syndrome
First at 3 months, reported at 26 yo.
Febrile seizures, tonic-clonic seizures, myoclonic seizures, absence seizures, complex partial seizures and tonic seizures
Post-status epilepticus model results
The modulation of GABAa receptors subunit composition by gene transfer is one approach that may prevent epileptogenesis
What do antiepileptic drugs do?
Treat symptoms of seizures not epileptic condition
Antiepileptic drugs - modes of action
Suppress APs - via Na blockers or K openers
Enhance GABA transmission - via GABA uptake inhibitors or mimetics
Suppression of excitatory transmission - glutamate receptor antagonist
Anticonvulsant drugs - main mechanisms of action
Enhance GABA transmission
Inhibition of Na channels
Combinations of the above
Anticonvulsant drugs - seizure type = partial simple & partial complex - which drug?
Carbamazepine
Phenytion
Valproic acid
Anticonvulsant drugs -
seizure type = generalised tonic clonic
Carbamazepine
Phenytoin
Valproic acid
Anticonvulsant drugs -
seizure type = absence
Ethosuximide
Valproic acid
Anticonvulsant drugs -
seizure type = atypical abscence, atonic, myoclonic
Valproic acid
Anticonvulsant drugs -
seizure type = febrile seizures
Diazpam, rectal
Mechanisms of action of benzodiazepines
Increase affinity of GABA for its receptor
by:
- increasing Cl- current
- suppresses seizure by raising AP threshold
Unwanted side effects of benzodiazepines
Main = sedation
Tolerance and dependency issues
Also, resp. depression if used IV
Inhibition of Na+ channels uses which drugs
Phenytoin
Carbamazepine
Oxcarbamazepine
Lamotrigine
Phenytoin mechanism of action
- Na+ channel opens
- Na+ channel closes
- Hyperpolarised state
Phenytoin binds in the hyperpolarised state and slows recovery
Mixed actions - which drugs
Gabapentin
Valproate - main
Levetiracetam
Mixed actions - their uses
Effective vs tonic-clonic and abscence
Can also be used in bipolar depressive illness
Oral
Well-absorbed
Mechanism of action of valproate
Inhibits Na+ channels weakly
Decreased GABA turnover via inhibiting enzymes = more synaptic GABA
Blocks neurotransmitter release by blocking T-type Ca2+ channels
Antiepileptics and pregnancy
Seizures are very harmful in pregnancy
Monotherapy prefered
Folic acid supplements recommended
Phenytoin, valproic acid are absolutely contraindicated - the others are better
Foetal hydantoin syndrome - % of women on … drug
30% of mothers on phenytoin drug
Foetal hydantoin syndrome - clinical presentation
Intrauterine growth restriction w/ microcephaly
Minor dysmorphic craniofacial features and limb defects
Small population has growth problems and developmental delay or mental retardation
Heart defects, cleft lip
Foetal valproate syndrome
limb deformities
Valproic acid exposure
How effective are these anti-epileptic drugs?
70% seizure free with one drug
5 to 10% seizure free with 2 or more
20% still have seizures
