Lecture 21

Question 1

What are seizures associated with

Answer 1

1) Change in mental state
2) Tonic or clonic movements
tonic–>musculature contractions
clonic–>jerking/repetitive movements
3) Abnormal electrical activity in the brain

Question 2

What are convulsions

Answer 2

Type of seizure, always accompanied by involuntary jerking movements
Can be seen in epileptic attacks

Question 3

Requirement for classification of epilepsy

Answer 3

Seizures must be recurrent and spontaneous (Epileptogenesis)
Epilepsy is common in early and late life (infants–>febrile seizures from fever)

Question 4

What causes seizures

Answer 4

Abnormal brain activity

Question 5

Diagnosis of epilepsy

Answer 5

1) EEG to pick up abnormal electrical activity (synchronous activity with large amplitude) in the cerebral cortex
2) Anatomical MRI to detect visible brain damage, sometimes found in epileptic brains
3) PET scan, to identify regions of brain with abnormal glucose metabolism, synonymous with abnormal neuronal activity

Question 6

2 types of seizures

Answer 6

1) Focal onset/partial onset
seizures focused on 1 brain hemisphere, patients are conscious
Focal aware, focal impaired awareness
2) Generalized onset
Seizures occur in both hemispheres, throughout the cortex and more, patients are unconscious
Generalized tonic-clonic, generalized absence seizures

Question 7

What does Focal aware seizures involve

Answer 7

Either sensory and/or motor systems
Somatosensory (contralateral tingling of limb, face, or side of body), visual (flashes of light, scotomas, unilateral or bilateral blurring), auditory (ringing, hissing), autonomic (sweating, flushing, epigastric sensations), contraversive (head and eyes turned to opposite sides), focal motor (tonic-clonic movements of upper or lower limb)

Question 8

Focal impaired awareness seizures

Answer 8

1) Affect temporal lobe, most common type of epilepsy
2) Preceded by an aura (intense deja vu, gut feeling, or sensory hallucination)
3) Simple automatisms (involuntary repetitive movements)
4) Psychomotor attacks (may walk and talk (appear conscious) but won’t remember

Question 9

Characteristic of a Generalized tonic-clonic seizure (grand mal)

Answer 9

Immediate and complete loss of consciousness, loss of balance, and impairment of breathing (leading to hypoxia and acidosis)

Question 10

3 main phases of generalized tonic-clonic seizures

Answer 10

1) Tonic phase: lasts 30 seconds, muscles of arms, legs, and trunk will stiffen
2) Clonic phase: lasts 1-3 minutes, muscles of arms, legs, and face will rapidly and intensely extend and flex, jerky movements
3) Post-ictal phase: post seizure phase, muscles are sore, regain consciousness, tired, nausea, confusion

Question 11

Characteristic of a Generalized absence seizure (petit mal)

Answer 11

1) EEG reading presents a recognizable 3Hz pattern
2) Common in children
3) Lose consciousness–>zone out (cessation of talking, staring into space, fluttering eyelids) lasting 10 seconds

Question 12

Normal EEG

Answer 12

Larger amplitude at occipital cortex–>alpha rhythm
Present in a conscious, awake person at rest

Question 13

Neuron activity in Generalized TONIC-clonic seizures (grand mal)

Answer 13

Tonic phase–>sustained depolarization of neurons, rapid and continuous firing of action potentials

Question 14

Neuron activity in Generalized tonic-CLONIC seizures (grand mal)

Answer 14

Clonic phase–>pacemaker activity in neurons, multiple action potentials being fired with each depolarization event

Question 15

Neuron activity in Generalized absence seizures (petit mal)

Answer 15

Slow pacemaker activity of neurons, depolarization results in multiple action potentials firing hence a SPIKE on 3Hz spike-and-wave EEG pattern

Question 16

Epilepsy side effects

Answer 16

Head injury, anoxia, stroke, tumors, infections, genetic defects, etc
Some epilepsies are inherited (high concordance for epilepsy between monozygotic twins)

Question 17

What directly causes Epilepsy

Answer 17

Altered Ion channels (voltage gated Na+ and K+ channels)
Can be inherited mutations and acquired damage to ion channels
BUT NO CURE, nor a drug that is anti-epileptic just anticonvulsant

Question 18

What is Epileptogensis

Answer 18

The underlying pathological process occurring in the brain that results in the development of spontaneous recurrent seizure activity
No drug can prevent/stop this process, hence chronic treatment

Question 19

Targets for anti-seizure drugs

Answer 19

Voltage gated ion channel activity, glutamate inhibition, GABA potentiation

Question 20

Action of many anti-seizure drugs

Answer 20

Mimic or potentiate the GABA inhibitory pathways or inhibit the glutamate excitatory pathways

Question 21

3 ways to affect GABA system

Answer 21

1) Stimulation of GABA postsynaptic receptors
2) Inhibition of GABA transaminase
3) Inhibition of the GABA transporter

Question 22

Effect of Stimulating GABA postsynaptically with agonist

Answer 22

Agonist: benzodiazepines, and phenobarbital (barbiturate(
Increases inhibition of postsynaptic neuronal firing, including excitatory neurons

Question 23

Effect of Inhibiting GABA transaminase

Answer 23

Inhibit metabolism of GABA–>more GABA in synapse–>Increase GABA postsynaptic action

Question 24

Effect of Inhibition of GABA transporter

Answer 24

Prevents reuptake of GABA by glial cells and neurons–>increases amount of GABA at synapse–>Increases GABA postsynaptic action

Question 25

What is a Use-dependent block

Answer 25

Blocking the most active sodium channels and stabilizing their inactivated state

Question 26

Which drugs result in a use-dependent block

Answer 26

Carbamazepine, phenytoin, and valproate

Question 27

Voltage gated Na+ channels at Rest

Answer 27

Closed, preventing entry of Na+ into the cell

Question 28

Voltage gated Na+ channels when Open

Answer 28

Open due to depolarization, now allow entry of Na+ into the cell

Question 29

Voltage gated Na+ channels during refractory period (right after open)

Answer 29

Channels inactive due to conformational change, preventing entry of Na+

Question 30

Mechanism of Carbamazepine, phenytoin, and valproate on Voltage gated Na+ channels

Answer 30

Enter open ion channels
Preferentially block the most active channels (usually from neurons with abnormal activity, seizures)
1) Block Na+ influx
2) Stabilizing channel’s inactivated state
3) Increasing length of refractory period

Question 31

Which seizures are carbamazepine, phenytoin, and valproate used for

Answer 31

Focal + generalized tonic clonic seizures—>carbamazepine, phenytoin, and valproate
Absence seizures–>valproate