45 - Cellular Basis of Epilepsy Flashcards
Lifetime prevalence of epileptic seizure globally
9%
Groups in which epilepsy is more common
Under-developed countries, lower socioeconomic groups
Standardised mortality rate of epileptics versus general population
~3x (risk is higher in those with more poorly-controlled epilepsy)
What is an epileptic seizure?
A transient occurrence of clinical signs and/or symptoms due to excessive and hyper-synchronous activity of populations of neurons in the brain.
Broad type of neuronal firing in epilepsy
Discrete group of neurons begin firing synchronously, innervate another group of neurons which then also begin firing synchronously. These innervate first set of neurons, and this forms a loop of oscillatory firing.
Secondary seizure
Where synchronised firing from the initial epileptic focus spreads to other regions.
What is epilepsy?
A group of neurological diseases with enduring alterations in the brain resulting in abnormally increased predisposition to seizures.
Having a single seizure does not equal epilepsy.
Proportion of epileptics who have a genetic basis
~30% (also called idiopathic or primary)
Things that can cause structural/metabolic epilepsy
Brain tumour, encephalitis (symptomatic or secondary epilepsy)
Name for epilepsy of unknown aetiology
Cryptogenic (EG meso-temporal sclerosis - a type of hippocampal sclerosis)
What is a seizure to epilepsy?
A symptom
ILAE classifications of seizures
1
2
3
1) Focal/partial
2) Generalised
3) Unclassifiable
Focal/partial seizures
Arise in a limited number of cortical neuron within one hemisphere.
Can spread to involve the whole brain.
Generalised seizures
Appear to arise simultaneously in both hemispheres
much more likely to be a genetic basis
ILAE classifications of epilepsies
1
2
3
1) Genetic (idiopathic)
2) Structural/metabolic (symptomatic)
3) Unknown
Genetic (idiopathic) epilepsy 1 2 3 4
Underlying brain is structurally and functionally normal.
–Usually onset during childhood/teenage and may remit.
–Usually respond well to medication.
–Likely have a genetic basis - ion channels
Structural/metabolic epilepsy
1
2
3
Seizures result from some identifiable structural/functional brain abnormality.
–Uncommonly remit, and often incompletely controlled with medication.
- Can sometimes be treated with surgery
Complex partial seizures
Arise in temporal limbic areas.
Lead to altered conscious state.
Current broad concept of what leads to epilepsy
1
2
3
• Disturbance in the balance between inhibition and excitation of cortical neurones and neuronal networks.
– either increases or decreases in neuronal inhibition or excitation.
• Result in neuronal networks that fire in an uncontrolled, hypersynchronous, self sustained manner.
• May result from a wide variety of causes:
– Genetic, congenital/developmental, traumatic, infectious,
metabolic, drugs etc.
Brain mechanics that can be altered, leading to epilepsy 1 2 3 4
•Alterations in neuronal network components
– Loss of inhibitory neurons
– Gain of excitatory neurons
(neurogenesis)
– Aberrant sprouting (after a brain injury, axons can get disconnected, and this can go wrong)
- Alterations in intrinsic neuronal cellular excitability
- Alterations synaptic transmission
- Alterations in the extra-neuronal environment (EG astrocytes not taking up glutamate properly)
Location of the hippocampus
Medial temporal lobe
Most-sensitive structure to inducing seizure activity
Hippocampus
Epileptic remodelling in the hippocampus
1
2
3
Fewer neurons in the dentate gyrus.
Hypertrophy of glial cells.
Increased connections to other hippocampal areas
4 main subregions of hippocampus
CA1, CA2, CA3, dentate gyrus
