(3.9) Pathophysiology of seizure disorders

Question 1

What are seizures a result of?

Answer 1

Disordered, synchronous, and rhythmic firing of a population of brain neurons (which is synchronized hyperexcitability)

Question 2

What can focal onset seizure also be classified as?

Answer 2

• Aware and impaired awareness
• Motor and non-motor onset

Question 3

What can focal onset seizure progress to?

Answer 3

Focal to bilateral tonic-clonic

Question 4

What can generalized onset seizure also be classified as?

Answer 4

• Motor: tonic clonic and other motor
• Non-motor: absence seizures

Question 5

What can unknown onset seizure also be classified as?

Answer 5

• Motor: tonic clonic and other motor
• Non-motor
• Unclassified

Question 6

What is the first step of pathway for propagation of focal seizures?

Answer 6

Seizure activity spreads from a focus in one part of the brain (red area of neocortex) - this is a focal seizure

Question 7

What happens next in the pathway for propagation of focal seizures?

Answer 7

Focal seizures frequently progress to secondary generalized seizures via projections to the thalamus (focal to bilateral seizure)

Question 8

What happens in the pathway for propagation of primary generalized seizures?

Answer 8

• Primary generalized seizures propagate via diffuse interconnections between the thalamus and cortex (no discrete focus)
• The earliest clinical signs show involvement of both brain hemispheres

Question 9

What are the electroencephalogram (EEG) patterns of focal and generalized seizures?

Answer 9

Both seizures yield different EEG patterns

Question 10

What does the EEG from a focal seizure look like?

Answer 10

Focal sharp waves from a focal seizure in the electrodes over the right temporal area

Question 11

What does the EEG from a generalized (tonic-clonic) seizure look like?

Answer 11

Shows involvement of both hemispheres of the brain

Question 12

What characterizes an AWARE type of focal seizures?

Answer 12

• No loss of consciousness
• Subjective experiences (auras) also occur like abdominal discomfort, sense of fear

Question 13

What characterizes impaired awareness of focal seizures?

Answer 13

• Aura is common
• Postictal state due to impaired awareness

Question 14

What is a postictal state?

Answer 14

After a seizure, a pt will not recover a normal level of consciousness immediately

Question 15

Postictal state may last for seconds to hours depending on:

Answer 15

• Area of the brain affected
• Length of seizure
• Use of anti-epileptic drugs (AEDs)
• Age

Question 16

What are sxs of postictal state?

Answer 16

• Confusion
• Disorientation
• Anterograde amnesia

Question 17

What can absence type of generalized seizure be?

Answer 17

Typical or atypical

Question 18

What characterizes absence types of generalized seizure?

Answer 18

• In typical, no convulsions, aura, or postictal period
• In atypical, slower onset than typical

Question 19

What characterizes the first phase of the generalized tonic-clonic (grand mal) seizure?

Answer 19

Called the tonic phase:
- Begins abruptly, often w diaphragm contraction (no aura)
- Tonic rigidity in all extremities (lasts 15-30 secs)
- Tonus is interrupted by a tremor that corresponds to relaxation

Question 20

What characterizes the second phase of the generalized tonic-clonic (grand mal) seizure?

Answer 20

Called the clonic phase:
- Begins as relaxation periods become more prolonged
- Involves violent jerking of body that lasts 1-2 min

Question 21

What do focal to bilateral tonic clonic seizures start out as and there can be what?

Answer 21

Start out as a focal seizure and there can be a brief aura

Question 22

What is the therapeutic goal of seizures?

Answer 22

To bring seizures under control within 60 minutes to minimize neurologic and CV complications, including:
- Abnormal glucose utilization
- Compromised CNS blood flow
- Lactic acid accumulation
- CV collapse
- Long term impact on cognitive fx
- Worsening of seizure disorder

Question 23

When can drug therapy be withdrawn in seizure pts?

Answer 23

Drug therapy can be gradually withdrawn in pts who have been clinically-free of seizures for 2-5 yrs

Question 24

What is paroxysmal depolarizing shift (PDS)?

Answer 24

A large depolarization that triggers a burst of action potentials

Question 25

How does depolarization in PDS happen?

Answer 25

Involves the 1) activation of AMPA and NMDA channels by glutamate and 2) voltage gated Ca channels, leading to influx of cation

Question 26

What follows depolarization in PDS and what does it involve?

Answer 26

Followed by hyperpolarization involving the activation of GABA receptors (influx of Cl ions) and voltage and calcium dependent K channels, leading to an efflux of K

Question 27

What is the depolarization in PDS normally dampened w?

Answer 27

Normally dampened by feed-forward and feedback inhibition - involving GABAergic neurons

Question 28

What is disrupted in PDS?

Answer 28

Disrupted excitation/inhibitory balance

Question 29

What can cause withdrawal from anti-epileptic drugs (AEDs)?

Answer 29

Esp sudden discontinuation

Question 30

What drugs aggravate or increase the risk of seizures?

Answer 30

• Alcohol
• Theophylline
• CNS stimulants
• Bupropion
• OCs
• Withdrawal from depressants
• Clozapine

Question 31

What is the mechanism of clozapine that increases the risk of seizures?

Answer 31

Clozapine is converted to norclozapine via CYP1A2 and norclozapine is responsible for increasing seizure risk