Epilepsy (NBIO) Flashcards
What is a Seizure?
A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronus neuronal activity in the brain
What is epilepsy?
- A pathological and enduring tendency to have recurrent seizures
- AND
- By the neuro-biologic, cognitive, psychological and social consequences of this condition
What is a seizure? (2)
And
What do all seizures share?
Abnormal neuronal firing in particular brain network
* Seizure is a symptom which:
1. May be experienced
2. May alter consciousness
3. May have external signs
4. Often have EEG signature
What is a seizure? (3)
And
How do seizures differ?
- Brain network involved
- Signs and symptoms
- Causes
- Drug therapy
- Prognosis
What are the 2 main types of seizures?
- Generalised seizures
* Starts simultaneously in both hemispheres - Focal seizures
* Seizure starts in a focus and then spreads
What are Generalised seizures?
- Originating at some point within and rapidly engaging, bilaterally distributed networks
- Typical Absence
- Myoclonic
- Tonic-clonic
What is an Absence seizure?
- Mainly childhood in onset
- Freq brief attacks (1-30s)
- Sudden loss and return of consciousness
- No aura and no post-ictal state
- Some invol movts
What are Myoclonus seizures?
- Sudden, brief, shock-like muscle contractions
- Usally bilateral are jerks
- Precipitated by sleep deprivation and alcohol
What are Tonic-clonic seizures?
- Sudden onset, gasp, fall
- Tonic phase with cyanosis
- Clonic phase
- Post-ictal phase
- Tongue bitten and incontinence
- Noisy breathing
- Headache and muscle pain after
What are Atonic seizures?
- A rare type, affects more people with neurologic handicaps
- Complete collapse for a few seconds
What are Focal seizures?
- Originating within networks limited to one hemisphere
- They propagate–> symp evolve
Old Vs New terminology
- Simple partial = Focal with awareness
- Complex partial = Focal without awareness
What are temporal seizures?
Warning (Aura)
* Epigastric rising sensation
* Olfactory and gustatory
* Deja vu
Loss of awareness
* Arrest reaction and blank stare
* Oral automatisms (lip-smacking)
* Manual automatisms
How do we study seizures experimentally?
- Hippocampul slices exposed to stimuli provoking acute seizures
- Animals with CNS injury causing seizures
- Rodent genetic models
What are the Pros/cons to hippocampul slices?
- Pros
* Realistic epileptic discharges creeated
* V.Det neurophysiology and Neuropahrma
* More humane
2.Cons
* Reduced model, not all connections present
* Model of acute seizures not recurrent
* Typically non-physiological triggers needed
What have acute slice models taught us?
- Mechanism dependant on model used
* Yound rodents
* GABA function
* etc - Epiletiform discharges due to combo of effects:
* Neuronal busting
* Synaptic
* Glia
* Non-synaptic
Epileptic neuron vs Epileptic network?
- Both bursting neurons and tightly connected neurons in a network are needed to cause a seizure
What are the stages of a seizure?
- Initiation
- Synchronisation
- Termination
Explain the Initiation phase of a seizure
- A micro seizure occurs, which is a small area of excessive activity surrounded by an area of inhibition
- When this inhibition breaks down, the micro-seizures coalesce to form the seizure itslef
- An imbalance of excitation vs inhibition
Explain the Synchronisation phase of a seizure
- The middle phase of a seizure
- This phase synchronises effects of other axons to other brain regionsto become epileptic
- How a seizure propagates
Explain the Termination phase of a seizure
- Synaptic inhibiton occurs
- A depolarisation block
- SYnaptic depletion
- IC acidification
- Hyperpolarisation due to K channels
What are in vivo models for acute seizures?
- Standard method of drug discovery
- Give drugs to rodents to see if it prev a seizure when induced
- Issue is dont test on epileptic brain, test on brain they induce seizure on
What is Epileptogenesis?
The process following an injury that leads to the first of a series of spontaneous and recurring seizures whether clinically obvious or not
- Injury –> Latent period –> Recurring seizures
What is ‘Kindling’?
- Giving tiny electrical stimulus to hippocampus, repeat every day
- Causes seizures in rats and then will continue to have them without electrical shock
What changes occur during kindling?
- Early on (before seizures) inhibition is increased
- ‘Over-Kindling’ leads to cell loss and abnormal neuronal sprouting anf spontaneous seizures
- Memory and spatial deficits can occur
What are the 3 major changes in epileptogenesis models?
- Structural:
E.g. Neurogenesis, axonal sprouting) - Molecular:
E.g. Neuronal channels and receptors - Functional:
E.g. Gap junctions
What are the causes of epilepsy?
Genetically based (mono+poly genic)
Structural: e.g. malformations of dev
Acquired
* Trauma
* Stroke
* Infection
* Tumour
How is epilepsy treated?
- Correct diagnosis
- Matching drug treatment to syndrome
- Genral lefe dvice
- Identifying any surgical candidates
What do anti-epileptic drugs target?
Key regulators of neuronal excitability
- Ion channels
- Neuro-Transmitter receptors
Why are Na channels a target?
- Sodium channels are a target – drugs bind better during the activated channel state
- Prolong the inactivated state of the channel – block increases with repetitive use
- Reduces burst firing – the onset of the block is slow, allowing some bursts to occur
- The main action may be to stop the spread of seizure
What are non-pharma treatments?
- Resection of epileptic focus
- Vagal nerve stimulation
- Ketogenic diet
