(3.9) Pathophysiology of seizure disorders Flashcards
What are seizures a result of?
Disordered, synchronous, and rhythmic firing of a population of brain neurons (which is synchronized hyperexcitability)
What can focal onset seizure also be classified as?
- Aware and impaired awareness
- Motor and non-motor onset
What can focal onset seizure progress to?
Focal to bilateral tonic-clonic
What can generalized onset seizure also be classified as?
- Motor: tonic clonic and other motor
- Non-motor: absence seizures
What can unknown onset seizure also be classified as?
- Motor: tonic clonic and other motor
- Non-motor
- Unclassified
What is the first step of pathway for propagation of focal seizures?
Seizure activity spreads from a focus in one part of the brain (red area of neocortex) - this is a focal seizure
What happens next in the pathway for propagation of focal seizures?
Focal seizures frequently progress to secondary generalized seizures via projections to the thalamus (focal to bilateral seizure)
What happens in the pathway for propagation of primary generalized seizures?
- 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
What are the electroencephalogram (EEG) patterns of focal and generalized seizures?
Both seizures yield different EEG patterns
What does the EEG from a focal seizure look like?
Focal sharp waves from a focal seizure in the electrodes over the right temporal area
What does the EEG from a generalized (tonic-clonic) seizure look like?
Shows involvement of both hemispheres of the brain
What characterizes an AWARE type of focal seizures?
- No loss of consciousness
- Subjective experiences (auras) also occur like abdominal discomfort, sense of fear
What characterizes impaired awareness of focal seizures?
- Aura is common
- Postictal state due to impaired awareness
What is a postictal state?
After a seizure, a pt will not recover a normal level of consciousness immediately
Postictal state may last for seconds to hours depending on:
- Area of the brain affected
- Length of seizure
- Use of anti-epileptic drugs (AEDs)
- Age
What are sxs of postictal state?
- Confusion
- Disorientation
- Anterograde amnesia
What can absence type of generalized seizure be?
Typical or atypical
What characterizes absence types of generalized seizure?
- In typical, no convulsions, aura, or postictal period
- In atypical, slower onset than typical
What characterizes the first phase of the generalized tonic-clonic (grand mal) seizure?
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
What characterizes the second phase of the generalized tonic-clonic (grand mal) seizure?
Called the clonic phase:
- Begins as relaxation periods become more prolonged
- Involves violent jerking of body that lasts 1-2 min
What do focal to bilateral tonic clonic seizures start out as and there can be what?
Start out as a focal seizure and there can be a brief aura
What is the therapeutic goal of seizures?
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
When can drug therapy be withdrawn in seizure pts?
Drug therapy can be gradually withdrawn in pts who have been clinically-free of seizures for 2-5 yrs
What is paroxysmal depolarizing shift (PDS)?
A large depolarization that triggers a burst of action potentials
How does depolarization in PDS happen?
Involves the 1) activation of AMPA and NMDA channels by glutamate and 2) voltage gated Ca channels, leading to influx of cation
What follows depolarization in PDS and what does it involve?
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
What is the depolarization in PDS normally dampened w?
Normally dampened by feed-forward and feedback inhibition - involving GABAergic neurons
What is disrupted in PDS?
Disrupted excitation/inhibitory balance
What can cause withdrawal from anti-epileptic drugs (AEDs)?
Esp sudden discontinuation
What drugs aggravate or increase the risk of seizures?
- Alcohol
- Theophylline
- CNS stimulants
- Bupropion
- OCs
- Withdrawal from depressants
- Clozapine
What is the mechanism of clozapine that increases the risk of seizures?
Clozapine is converted to norclozapine via CYP1A2 and norclozapine is responsible for increasing seizure risk
