Epilepsy Flashcards
(24 cards)
Epilepsy
Condition where patients have unprovoked and repeated epileptic seizures (ES)
ES: Abnormal electrical discharge from neurons in the cerebral cortex
Partial seizure/ Focal seizure
- Neurons in a restricted part of the brain discharge in simultaneously in a abnormally hypersynchronised manner
- Seizures may start off as partial and secondarily generalize
Generalised seizure
Involves all of the neurons in the brain.
Typically involved with a loss of conciousness.
Pathophysiology of seizures
Caused by the inbalance of excitatory and inhibitory NTC.
What is excitatory and inhibitory neurotransmission dependent on
Ion channels: Voltage and ligand gated.
Where are NTC dependent ion channels located
Along axons and synapses.
regional differences in amounts of different receptors
Plasticity of ion channels
Excitatory N. transmission
GLutamate is major NTC
3 types of glutamate receptor
Different subtypes, high and low affinity.
NMDA receptors
Activated by NMDA, leading to opening of ion channels for Na+, K+, Ca2+ resulting in further depolarisation and release of NTC chemicals into synapse
NMDA receptors coagonist for glycine.
Slower activation compared to non NMDA receptors
Hyperpolarisation leads to Mg2+ binding and blocking channel, Mg2+ expelled upon partial depolarization.
Non NMDA receptors:
Activated by kainic acid and AMPA.
Permeable to Na and K , impermeable to Ca2_
Rapidly activated and inactivated
Describe the events at the synapse starting from partial depolarisation to release of NTC into the synapse for excitatory synapse.
As Kainic acid or AMPA binds to non NMDA receptors, Na and K ion channels open, allowing its influx, causing partial depolarisation.
P.D causes Mg2+ to be expelled from the NMDA receptors allowing NMDA to bind, leading to inc Na, K , Ca2+ permeability.
Ca2+ stimulates fusion of vesicles containing NTC with the specialised regions of the presynaptic membrane.
Role of metabotropic receptors
GPCR, role in development, unclear in seizures but likely important role in prevention
Inhibitory transmission
GABA receptors are linked to Cl- channels, binding of 2 GABA molecules causes Cl- influx leading to hyperpolarisation,
Allosteric binding sites which modulates Cl- channels
Drugs which induce seizures
Picrotoxin: Non competitive antagonist
Bicuculine: Competitive antagonist
Penicillin: Enters and blocks GABA channels
Domoic acid and kainate: Glutamate receptor agonist
Strychine: blocks glycine receptors
4-amino pyridine: blocks K currents
Seizure treating medications
Na+ channel blockers: Phenytoin, Carbamazapine
Enhanced GABA transmission: Vigabatrin, tiagabine, benzodiazapine, phenobarbitone
Reduced glutamate transmission: Topirimate, felbamate
How do Na+ channel blockers work
Stabalise Na current in the inacitve form leading to delayed recovery, to prevent sustained firing due to extended depolarization
Frequency dependent changes in synaptic efficacy
Repeated subclinical electrical stimuli progresses to spontaneous reccurent sz due to changes in ion channels
Excit synapses potentiate with repeated firing
Inhib syn decrease in efficacy with repeat
Local receptor change
NMDA receptors change following neuronal injury, can be perpetuated by seizures:
Seziures may alter gene expression and mRNA levels, produce glial changes, neuronal sprouting and neuronal death
- Produce alterations in synaptic circuitry and receptor expression
Hallmark of partial seizure
interrictal spike on EEG, simultaneous activation of neurons in a abnorm hypeersynchronised manner
Neurons undergo a large depolarizing shift superimposed on a burst of action potentials. Reccurent excitatory circuits lead to excessive synchronisation
How do seizuress spread
Recurrent circuitry and receptor dependent plasticity of excitatory and inhibitory synapses, altered NMDA, AMPA components
- maybe altered glutamate uptake
and K+ buffering by glia
Generalised seizure with major motor manifestationstypes
Tonic- Sustained Bilateral contraction of axial and limb muscles
Clonic- regular repeated Bilateral contraction of axial and limb muscles
Tonic-clonic: sustained followed by clonic motor movments
Myoclonic: sudden, brief jerks of axial and limb muscles
Epileptic: Brief tonic contraction of bilat axial and limb muscle with inital myoclonic component. Occurs 2-10 sec in clusters
Generalised seizures with no/ minor motor manifestations
Absent seizure: abrupt onset and end, brief, eeg shows generalised spike and slow wave discharge 3-4 HZ
Atypical absnece - Longer duration, more gradual onset and offset
Atonic- Loss of muscle tone, slump of head or trunk
Astatic- Where seizure type (clonic ,tonic, myoclonic) is unknown
Partial seizure
Preserved consciousness
Aura= evolution into different type of seizure
Symptoms dependent on part of brain invovled in discharge
E.g parithesiae- Somato senosry cortex/ parietal
buzzing/ ringing- temporal
bright/ dark spots= occipital
psychic- dejavu
abdominal- vague discomfort/ unpleasant sensation
olfactory gustatory = smell or taste unpleasant
focal motor seizure: : Lateral deviation of eyes, deviation of head and trunk (may or may not invovle loss of consciousness)
Complex partial seizure:
Loss of consciousness, patient has amneisa for episode
Mutations in ion channels
K+ = BFNE (benign familial ...) Na+= begning familial neontal epilepsy, myoclonic, generalised + febrile seizure Ca2+ = Absent seizures
