Seizures

Question 1

Epilepsy definition

Answer 1

Disorder characterized by periodic occurrence of spontaneous, unprovoked seizures

Question 2

Surround inhibition

Answer 2

Strongly firing neurons silence connected neurons via inhibitory interneurons

Question 3

3 steps of seizure

Answer 3

Initiation
Propagation
Termination

Question 4

Seizure initiation

Answer 4

High frequency bursts of APs and hyper synchronization of a group of neurons
Results in burst of action potentials driven by calcium influx through NMDA receptors

Question 5

Seizure propagation

Answer 5

Increased extracellular potassium reduces hyperpolarization
Accumulation of calcium in presynaptic terminals increases neurotransmitter release
Activation of NMDA receptors causes more calcium influx and neuron activation
High enough activation can overcome surround inhibition and hyperpolarization

Question 6

Seizure resolution and aftermath

Answer 6

Generally spontaneous, likely depletion of ionic gradients, neurotransmitters, and ATP plus activation of inhibitory circuits
Status epilepticus: long lasting seizure or burst of multiple seizures, potentially lethal
Postictal period: after resolution, characterized by drowsiness, confusion, depression/anxiety, sometimes psychosis

Question 7

Seizure classes

Answer 7

Focal
Generalized
Non-convulsive (absence)

Question 8

Focal seizures

Answer 8

Localized brain region
May become generalized
Simple: retains consciousness
Complex: loses consciousness

Question 9

Jacksonian March

Answer 9

Muscle jerking that spreads from a specific point to nearby muscle groups, associated with focal seizures

Question 10

Automatisms

Answer 10

Unusual, unconsciously created activities or movements associated with focal seizures

Question 11

Generalized seizures

Answer 11

Typically no warning, always loss of consciousness

Question 12

Tonic-clonic seizures

Answer 12

Generalized, involve sustained general muscle contractions followed by alternating contraction and relaxation

Question 13

Myoclonic seizures

Answer 13

Generalized, involve brief shock-like contraction of muscles that may be general or localized

Question 14

Absence seizures

Answer 14

Abrupt loss of consciousness without loss of muscle strength or large movements, may be followed by postictal disorientation

Question 15

Atonic seizures

Answer 15

Sudden loss of muscle strength, usually retaining consciousness

Question 16

Anti seizure drug mechanisms

Answer 16

Either enhancing GABA signaling or reducing glutamate signaling
Block ionic movement and/or neurotransmitter release
Inhibit or activate the postsynaptic membrane

Question 17

Benzodiazepines

Answer 17

Positive allosteric modulator of GABAa receptors, no effect without GABA
Increase frequency of receptor opening, potency of GABA

Question 18

Barbiturates

Answer 18

Positive allosteric modulator of GABAa receptor, agonist at high concentrations
Increase duration of receptor opening, efficacy of GABA
More overdose risk

Question 19

Vigabatrin

Answer 19

Inhibits GABA-T enzyme (responsible for GABA degradation)

Question 20

Tiagabine

Answer 20

Inhibits GAT-1 (GABA reuptake transporter)

Question 21

Carbamazepine

Answer 21

Voltage gated sodium channel inhibitor
Rate dependent effect

Question 22

Gabapentin

Answer 22

Minimal activity at GABA receptor
Voltage gated calcium channel inhibitor, binds alpha2delta subunit and disrupts it

Question 23

Perampanel

Answer 23

Non competitive AMPA (glutamate) receptor antagonist
Serious psychiatric and behavioral side effects

Question 24

Anti seizure drug pharmacokinetics

Answer 24

Good bioavailability, cross blood brain barrier, low extraction ratio
High potential for drug-drug interactions, serious side effects