Epilepsy Flashcards
define seizures
the clinical manifestation of an abnormally excessive and hyper synchronous activity of neurones located predominantly in the cerebral cortex
what does the abnormal neurone activity cause in muscles and in the brain
muscles=twitch
brain=seizures
what are 3 classifications of tumours
generalised- neuronal activity in both hemispheres.
Partial (aka focal seizures)- initial activation of neurones in both hemispheres
secondary generalised- a partial seizure that later spreads to involve the majority of the 2 cerebral hemispheres.
what are some of the main clinical fetters of a partial seizure
absence- starting and blinking without thinking.
Myoclonic- jerking movements of the body
what are the some of the main clinical features of a generalised seizure
tonic clonic-stiffening, falling and jerking of the body.
tonic/ atonic- falling heavily to the ground.
in which type of seizure complex or simple are you more alert or aware
simple.
which lobe of the brain does the Jacksonian seizure effect and what are it’s clinical symptoms
frontal
tingling in hand or arm
which lobe of the brain does the adversive seizure effect and what are its clinical symptoms
frontal
eyes or head both turn to one side
what are the clinical manifestations of a temporal lobe seizure
strange smell or taste altered behaviour- déjà vu feeling, lip smacking or chewing movements.
what are the clinical manifestations of the occipital lobe seizures
Flashing lights or spots vomiting
what are the clinical manifestations of the parietal lobe seizures
Tingling in or jerking of leg, Arm and Face.
what device is used to diagnose epilepsy and how is it used
EEG- electroencephalogram.
scalp electrodes are used to monitor the firing of neurones within the brain.
define status epilepticus
Brian is in a persistent seizure
seizure more than 30 mins long
2 sequential seizures without recovery in between.
what effect to a seizure have if it affects the brainstem
affects the body’s autonomic functions e.g. breathing.
what is the treatment for status epilepticus.
GABA receptor antagonist + diazapem
define epilepsy
Conditions were seizures recur, usually spontaneously.
2 or more unprovoked seizures
How do too little inhibition and too much excitation cause seizures.
(think about what ions go in and out and the neurotransmitters involved)
excitation- too much
influx sodium and calcium
neurotransmitter- glutamate and aspartate are released.
Inhibition- too little
efflux- chlorine and potassium.
neurotransmitter released GABA
what is the function of inhibitory interneurones
allow activity to spread in one direction, but not to spread out sideways
what inhibitory neurotransmitter do inhibitory interneurones release
GABA.
what % of the brains neurones are interneurones
10–20% of the total number of neurones
Is GABA a inhibitory neurotransmitter
Yes
what type of chemical molecule is GABA
Y aminobutyric acid
GABA is penatmeric what is it’s composition (alpha, beta, delta and gamma)
2 alpa, 2 beta and one gamma or delta subunit.
what are some examples of epilepsy causes by mutation in the GABA subunits
CAE (Childhood absence epilepsy)
FS (pure febrile seizures)
GEFS- (Generalised epilepsy with febrile seizure plus)
JME (juvenile myoclonic epilepsy
DS (Dravet syndrome- also known as SMEI (severe myoclonic epilepsy in infancy)
patients with dravet’s syndrome typically have what form of mutation.
GABRG2 (Q390X)- a truncated subunit with the loss of 78 –C terminal amino acids.
what type of seizures do people with dravet’s have
Can have different types of seizures over years
Febrile, tonic-clonic, myoclonic, absence, complex partial seizures and tonic seizures
what is the pathogenesis behind the mutation in the GABA sub unit
changing the subunit from a trans membrane protein to a globular cytosolic protein.
what type of drug is pilocarpine
proconvulsant.
which subunits of GABA are increased and which are decreased in status epileptics
A4 increased
A1 decreased.
How does the change in GABA subunits lead to epilepsy.
The change in receptor subtype from α1βγ2 to α4βγ2 may have dramatic effects on brain inhibition.
α4 containing GABARs have been shown to desensitize rapidly, especially when assembled with β3 subunits
what effect does the induction of α1 subunit viral vector have
increased latency time and decreased rates of seizure development,
what are the modes of action of antieplieptics
1. Suppress action potential • Sodium channel blocker or modulator • Potassium channel opener 2. Enhance GABA transmission • GABA uptake inhibitor • GABA mimetics 3. Suppression of excitatory transmission • Glutamate receptor antagonist
what are the main anti epileptics for a partial simple or parietal complex seizure or generalised seizure
carbamazepine
phenytoin
Valproic acid
what are the main anti epileptics for febrile seizures
diazepenem rectal
what are the main anti epileptics for absence seizures
ethosuximide
Valproic acid
what are the main anti epileptics for atypical absence or atonic, myoclonic acid
valproic acid.
what drugs enhance the action of GABA receptors
barbiturates e.g. phenobarbital, benzodiazepines e.g. clonazepam.
what are the main drugs which inhibit GABA transminase receptors
vigabatrin
which drug prevents GABA uptake
tiagabine
which drug is effective against status epileptics
diazapam (valium and lorazepam)
what are the 3 main benzodiazepines
clonazepam
clorazpate
Diazepam
mechanism of action of benzodiazepines.
Increase affinity of GABA for its receptor.
– Increases Cl- current (opening frequency)
– Suppresses seizure focus by raising action potential threshold
– Strengthens surround inhibition – prevents spread
side effects of benzodiazepines
sedation
respiratory depression.
which anti epileptics work by inhibiting sodium channels
- Phenytoin
- Carbamazepine and oxcarbamazepine
- Lamotrigine
mechanism of action of phenytoin
Phenytoin binds to the inactivated state of an action potential and slows down its recovery.
what are the uses of valproic acid
Effective against tonic-clonic and absence.
Bipolar illness
Mechanism of action of valproate
More than 1 mechanism
Inhibits Na+ channels but weaker than phenytoin
Decreased GABA turnover
• Inhibition of succinic semialdehyde dehydrogenase and thereby indirectly inhibiting GABA transaminase
• May lead to increased synaptic GABA levels
Blocks neurotransmitter release by blocking T-type Ca2+ channels
What is often given to pregnant women with epilepsy
folic acid
what drug causes foetal hydantoin syndromes
phenytoin.
what are the clinical symptoms of foetal hydantoin syndrome
- intrauterine growth restriction with microcephaly
- minor dysmorphic craniofacial features and limb defects including hypoplastic nails and distal phalanges (birth defects)
- a smaller population will have growth problems and developmental delay, or mental retardation
- Heart defects and cleft lip may also be featured
what types of seizures does optogenetic stimulation work for
partial seizures
mechanism of action of optogenetic stimulation
halorhodopsin hyperpolarize the neurones in reaction to yellow light
Put halorhodopsin in the brain, which enables entry of Cl-.
define epilepsia partialis continua
Patient experiences recurrent motor epileptic seizures that are focal (hands and face)
what causes epilepsa partialis continua
acute brain lesions
what drugs are used to treat epilepsy partialis continua
no many drugs work.
light activation of the light-activated chloride-pump, halorhodopsin, transfected into pyramidal cells in the focus
Used lentiviral vectors to transfect predominantly pyramidal neurones with halorhodopsin
