42 - Cerebral Cortex and Epilepsy Flashcards
Grand Mal Seizure
Generalized Compulsive Seizure
Paleocortex
Hippocampus & Olfactory Regions
3 Layers
Neocortex
6 Layers
Majority of the cortex
Layers
Organize inputs of cortical neurons
Organize the outputs
Excitatory Neurons
Spiny
Glutamatergic
Inhibitory Neurons
Smooth or Sparesly Spiny
GABAergic (Glycinergic rare in neocortex)
Biophysical properties differ from excitatory cells
Pyramidal Neurons
Main excitatory neurons
Polarized (Apical dendrite extending to pial surface)
Large - Layers 3 & 5
Small - Layers 2, 3, 4 & 6
Long-range axons projecting to other cortical regions
Spiny Stellate Cells
Excitatory interneurons
Small
Multipolar
Layer 4
Axons usually project only to local cortical region
Basket Cells
Inhibitory interneurons
Layers 3 & 4
Chandelier Cells
Inhibitory interneurons
Layer 3
Synapse on axon initial segment of pyramidal cells
Double Bouquet Cells
Inhibitory Interneurons
Layers 2, 3 & 4
Three molecular markers that account for nearly all neocortical inhibitory cells
PV
SST
5HT3aR
Alpha Rhythm
The first wave observed
Most dominant rhythm in humans
Beta Rhythm
Higher frequencies
Signify alert, working, thinking
Theta Rhythm
Drowzy
Relaxed
Delta Rhythm
Sleeping
Factors influencing whether or not you can MEASURE cortical potentials with an EEG
Voltage of cortical discharge
Area of cortex involved in synchronous activity
Degree of synchrony
Complications in measuring an EEG
Complex geometry of brain & head
Emphasis on radially-orientated pyramidal neurons
Many cytoarchitectural differences reflected in cortical layering
Conductivity varies in different directions
Not all cells behave in the same manner
Normal
Excitation and inhibition balance each other out
Seizure
Excitation outweighs inhibition
Cellular changes contributing to seizure
Membrane properties Synaptic strength Connectivity Glia (ionic homeostasis, NT uptake) Metaboloic changes Cell death Trauma, infection, dysplasia, infarcts
Epilepsy
Not a single disorder, but a group
All contain seizures
Definition: >1 unprovoked seizure (3% of US population)
Some acquired
Some idiopathic
Genetic factors sometimes but not always
Seizure semiology is highly variable
Extent/duration vary
Different brain areas involved in different manifestations
Seizures are intermittent
Brain immaturity modifies clinical and EEG expressions of seizures
Seizure
Paroxysmal change in behavior due to abnormal electrical brain activity
10% of the US population
Interictal EEG abnormalities
Marker of seizure susceptibility
Generalized onset seizures
Tonic-clonic (convulsive)
Absence (non-convulsive)
Myoclonic (muscle jerks, +/- loss of consciousness)
Focal (partial) seizures
Simple partial seizures (no loss of consciousness)
Complex partial seizures (consciousness altered or lost)
Focal seizures with secondary generalization
Focal epilepsy - Idiopathic
Benign focal epilepsy of childhood
Central midtemporal spikes (rolandic)
Occipital spikes
Focal epilepsy - Symptomatic
Epilepsia partialis continua (Rasmussen’s Syndrome)
Temoral lobe epilepsy
AD frontal lobe epilepsy
Generalized onset seizures - Idiopathic
Childhood absence epilepsy
Juvenile myoclonic epilepsy
Other generalized idiopathic epilepsies
Generalized onset seizures - Symptomatic
West syndrome (infantile spasms)
Lennox-Gastaut syndrome
Landau Kleffner syndrome
Interictal
Phenomenon happening between seizures
Spikes and hsarp waves (epileptiform discharges)
Focal vs. generalized
Sometimes multifocal
Ictal
Seizures event, itself
Cellular basis of EEG epileptiform discharges
Paroxysmal Depolarizing Shift (PDS)
Interictal PDS
AMPA and NMDA excite
GABA inhibits
Excitatory signals are encased in an “inhibitory surround”
When this breaks down, we have an ictal event.
Cortical Circuit
Excitatory input coupled to tandem inhibitory input.
There is also autoinhibition coupled to the nerve’s output
All this helps to refine the signal
Cellular Events during a seizure
Tonic Phase:
AMPA and NMDA are ON ON ON ON ON ON ONNNNN
GABA is on.
Clonic Phase:
AMPA and GABA alternate which one is dominant
Leads to rhythmic bursts
Untreated Recurrent Seizures
Hippocampal Sclerosis:
Granule Cell Layer ragged and deformed
Pyramidal cells missing
Hippocampal Sclerosis
Profound loss of CA1 and CA3 pyramidal cells
Profound loss of neurons in the dentate hilus
Relative survival of CA2 pyramidal cells and dentate granule cells
Untreated Recurrent Seizures - Cellular Effects
Cell death, initially selective
Synaptic reorganization
Structural remodeling
Neurogenesis (?!)
Changes in intrinsic protective or trophic mechanisms
Effects on future seizure susceptibility
Interference with normal neuronal development
Untreated Recurrent Seizures - Outcomes
Developmental delays (infancy & early childhood) Failure to acquire interpersonal and vocational skills (adolescence and young adulthood) Specific cognitive dysfunction Memory deficits (temporal lobe epilepsy) Language deficits (Landau-Kleffner syndrome) Other cognitive defects (CSWS) Psychiatric disturbances, especially depression Higher mortality rate
Absence Seizure
3Hz spike wave running through entire brain
Often misdiagnosed for ADD
Kid just zones out for a sec
3 Key Elements of Thalamocortical Circuitry that contribute to an Absence Seizure
Reciprocal connectivity
Specific synaptic mechanisms
Intrinsic burst-firing capability in key neurons
Thalamocortical Neurons
Relay neurons in the thalamus
Intertwined with reticular neurons
Low threshold Ca2+ channels
Burst when inhibited strongly
Reticular Neurons
Inhibitory regulators of thalamocortical neurons
STRONG
Epilepsy
IT IS A CHANNELOPATHY
Too much sodium influx
OR
Not enough potassium efflux
Twins
Um not always paired with epilepsy
Maybe environment
Maybe de novo mutations
