Epilepsy

Question 1

Epilepsy

Answer 1

Condition where patients have unprovoked and repeated epileptic seizures (ES)
ES: Abnormal electrical discharge from neurons in the cerebral cortex

Question 2

Partial seizure/ Focal seizure

Answer 2

• 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

Question 3

Generalised seizure

Answer 3

Involves all of the neurons in the brain.

Typically involved with a loss of conciousness.

Question 4

Pathophysiology of seizures

Answer 4

Caused by the inbalance of excitatory and inhibitory NTC.

Question 5

What is excitatory and inhibitory neurotransmission dependent on

Answer 5

Ion channels: Voltage and ligand gated.

Question 6

Where are NTC dependent ion channels located

Answer 6

Along axons and synapses.

regional differences in amounts of different receptors
Plasticity of ion channels

Question 7

Excitatory N. transmission

Answer 7

GLutamate is major NTC
3 types of glutamate receptor
Different subtypes, high and low affinity.

Question 8

NMDA receptors

Answer 8

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.

Question 9

Non NMDA receptors:

Answer 9

Activated by kainic acid and AMPA.
Permeable to Na and K , impermeable to Ca2_
Rapidly activated and inactivated

Question 10

Describe the events at the synapse starting from partial depolarisation to release of NTC into the synapse for excitatory synapse.

Answer 10

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.

Question 11

Role of metabotropic receptors

Answer 11

GPCR, role in development, unclear in seizures but likely important role in prevention

Question 12

Inhibitory transmission

Answer 12

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

Question 13

Drugs which induce seizures

Answer 13

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

Question 14

Seizure treating medications

Answer 14

Na+ channel blockers: Phenytoin, Carbamazapine

Enhanced GABA transmission: Vigabatrin, tiagabine, benzodiazapine, phenobarbitone

Reduced glutamate transmission: Topirimate, felbamate

Question 15

How do Na+ channel blockers work

Answer 15

Stabalise Na current in the inacitve form leading to delayed recovery, to prevent sustained firing due to extended depolarization

Question 16

Frequency dependent changes in synaptic efficacy

Answer 16

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

Question 17

Local receptor change

Answer 17

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

Question 18

Hallmark of partial seizure

Answer 18

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

Question 19

How do seizuress spread

Answer 19

Recurrent circuitry and receptor dependent plasticity of excitatory and inhibitory synapses, altered NMDA, AMPA components
- maybe altered glutamate uptake
and K+ buffering by glia

Question 20

Generalised seizure with major motor manifestationstypes

Answer 20

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

Question 21

Generalised seizures with no/ minor motor manifestations

Answer 21

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

Question 22

Partial seizure

Answer 22

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)

Question 23

Complex partial seizure:

Answer 23

Loss of consciousness, patient has amneisa for episode

Question 24

Mutations in ion channels

Answer 24

K+ = BFNE (benign familial ...)
Na+= begning familial neontal epilepsy, myoclonic, generalised + febrile seizure
Ca2+ = Absent seizures