Lecture 20: Neurophysiology of Epilepsy Flashcards
What is an epileptic seizure?
Abnormal, excessive electrical discharge from neurones
- Often associated with loss of consciousness but not always.
- Recurrent seizures
- Can be considered as imbalance between excitation and inhibition
- Brain dysfunction
- Syndrome (now disease) with many possible causes; Structural, genetic, metabolic, functional
What are the classifications of Epilepsy;
Focal: Specific to a part of the brain.
- > Manifestation depends on which part of the brain
- > Aware or impaired
- > Can spread over both hemispheres i.e focal to bilateral
Generalised: Networks involving extensive regions of both hemispheres from the outset
-> Manifestations vary greatly
Write some notes on EEG and Epilepsy:
- 30-70% of patients with proven epilepsy have altered EEG
- Sleep improves sensitivity
- EEG important in identifying the seizure type and hence the correct seizure syndrome for an individual patient.
Define:
- Tonic
- Clonic
- Tonic / Clonic
- Myoclonic
- Atonic seizures
- Myoclonic-astatic seizure
- Absence seizures
- Atypical absence seizures
- Tonic = Stiff
- Clonic = Jerky
- Tonic / Clonic = Stiff->Jerky
- Myoclonic = Single jerk
- Atonic seizures = Loss of muscle tone
- Myoclonic-astatic seizure = Jerk, loose tone and fall
- Absence seizures = absent for ~20 seconds
- Atypical absence seizures = More prolonged than absent
Write some notes on focal seizures:
- Consciousness may be preserved
- Focal aware seizure (Simple partial)
- > Motor
- > Visual
- > Somatosensory
- > Auditory
- > Psychic (aura)
Depends on local
- Consciousness may be impaired
- Focal impaired awareness seizure (Complex partial)
- > Patient is unresponsive with subsequent amnesia
Write some notes on eliptogenesis, how it spreads etc
- Seizures occur as a result of abnormal synchronous activation of large numbers of hyperexcitable neurons which are connected in networks.
- Can be propogated via normal and abnormal paths
- Spread through synapses and non synpatic i.e gap junctions
- Everyone has circuitry that could generate seizures
NOT WELL UNDERSTOOD
What could generate epileptic seizure?
Not a single process
- Overproduction or deletion of synapses
- Neurogenesis or neural death
- Axonal sprouting
- Imbalance of neurotransmitters
- Alteration of ion channels
- Inflammation
- mTOR pathway
- Role of kindling
NEED TO DEVELOP ANTIEPILPTOGENIC DRUGS
Can epileptic seizures be caused structural if so how?
Yes, Structural lesions;
- Tumours
- Gliosis
- > Strokes i.e ischeamic or haemorrhagic
- > Vascular malformations
- > Abscesses
- Malformations of cortical development
- Encephalitis
What was found when network changes were investigated?
Following insult they found that network changes increased the chance of eliptogenesis but did not gurantee it. Further studies being done to investigate what differentiates between the rats that did and didnt have epileptic fits.
Write some notes on how inflammation can lead to eliptogenesis:
- Microglial cells can create a pro and anti-inflammatory environment following trauma (Early phase)
- Astrocytes which are activated in late phase inflammation contribute to this inflammatory profile. (potentially)
- This can lead to the development of post traumatic epilepsy
Describe the role of antibodies and epilespy:
Antibody induced epilepsy syndromes are frequently being found.
- Anti-voltage gated K channels
- Anti-NMDA receptor
- Anti-GABA
etc etc etc all forming differing seizures
Whats the role of mTOR and epilepsy?
Overactive mTOR pathway because of mutations results in enhance neuronal growth and synapse complexity but generates epileptic seizures
Write some notes on ion channels:
- Voltage vs ligand gated
- Excitatory vs inhibitory
- Differing locations around synapses
- Substantially plastic
- Alteres synaptic efficiency
i. e NMDA receptors important in long term potentiation, memory etc
Describe how ion channels are involved in eliptogeneis:
Mutations in ion channels are involved in epilptogeneis i.e
- Mutations in voltage gated K channels = Benign familial neonatal epilepsy
- Mutations in Na channels i.e dravet syndrome -> Loss of Na channels prevent K channels from properly repolarising between APs (closer to threshold, more chance firing etc)
Describe the relationship between absent seizures and Ca channels:
- Absent seizures due to abnormal activation of T type Ca channels in the thalamus
- Hyperpolarisation of thalamic relay neurones produces synchronous depolarisation of the cortex via excitatory neurones
Describe how glutamate excess is epileptogenic:
- Low Mg2+ unblocks NMDA receptors and Glutamate can causes excess activation
How can GABA result in seizures?
Blockade of GABA receptors by drugs antagonists, can result in seizures
What are some examples of mutations in genes encoding ligand gated ion channels:
- Autosomal dominant nocturnal frontal lobe epilepsy (ACh receptor mutation)
- Generalised epilepsy with febrile seizures plus (mutation of GABAa recep)
- Anglemans syndrome (GABAa mutation)
What are some drugs to treat seizures?
Na channel blockers (presynaptic)
-> prevent sustained repetitive firing from extended depolarisation
Enhancement of GABA transmission
Action on Ca channels
Blocking Glutamate transmission
What are the effects of seizures:
- Kindling (Repetitive exposure to (initially) sub threshold electrical stimulation eventually produces spontaneous seizures) (Theory that seizures beget seizures)
- Anatomical rearrangement of local circuits (Excitatory neurons branch collaterals)
- With neuronal death, there is sprouting of unlesioned axons occurs to fill in dendritic regions
Describe the impact of seizures on the dentate gyrus of the hippocampus:
- Mossy fibres of granule cells in dentate gyrus innervate pyramidal cells of CA3 region
- When granule cells die, surviving neurons develop collaterals that form new connections
- Form recurrent excitatory connections -> Alter normal balance between feedback inhibition and excitation
