Seizure Discord Flashcards
What are seizures?
sudden and excessive excitation and synchronization of a population of cortical neurons in the brain that cause a variety of clinical manifestation
epilepsy
- a disease of spontaneous recurrent seizures
- random firing of cells (abnormal neurons undergo prolonged depolarizations with rapid firing
- abnormal synchronization
- altered neuronal microenviornment - imbalance btwn exictatory and inhibitory signals
epoleptogeneisis
sequence of events that converts a normal neuronal network into an epileptic network
what is the prevalence of epilepsy?
- prevalence of 1-3% in lifetime
- third most common neurological disorder (localized- focal or partial; spread to cause a secondary generalized seizure; affect all cortical neurons)
- highest frequency of ID in children under 5 and adults over 65
Whats an EEG?
- graphical depiction of cortical electrical activity – recorded from the scalp
- advantage of high temporal resolution but poor spatial resolution of coritcal disorders
- EEG- important neurophysiological study for diagnosis, prognosis, and treatment of epilepsy
What are EEG abnormalities?
Background activity:
* slowing not consitent with behavioral state
* significant asymmetry
Transients abnormalities/discharges:
* spikes
* sharp waves
* spike and slow wave complexes
* may be focal, lateralized, or generalized
What causes epilepsy?
- largely >60% idiopathic (unknown)
- children: congenital malformations, perinatal injuries or hypoxia, developmental neruologic disorders, metabolic defects, injury, and infection, hormonal imbalance
- young adults: head trauma, brain tumors, infection, and arteriovenous malformations
- elderly: cerebrovascular disease, CNS degenerative disease, and brain tumor
- genetic- increased risk by 2-3x with first degree relative connection
Whats the general model for seizure triggers?
- imbalance of exictatory (glutamate) and inhibitory (GABA) signals
siezure triggers: - EPSPs
- Na+ influx
- Ca++ currents
- paroxysmal depolarization
control: - IPSPs
- K+ Efflux
- Cl- influx
- pumps
- low pH
What are the mechanisms of generating hyper-excitable networks?
- excitatory axonal “sprouting”
- loss of inhibitory neurons
- loss of excitatory neurons “driving” inhibitory neurons
what are extrinsic factors modifying neuronal exictability?
- changes in extracellular ion concentrations
- remodeling of synapse location or configuration by afferent input
- modulation of transmitter metabolism or uptake by glial cells
What are the two types of GABA recpetors?
- GABAA: post synaptic, specific recognition sites, ligand-gated Cl- channel
- GABAB: presynaptic GPCRs, simulate opening of K+ currents causing hyperpolarizatoin
what can decrease synthesis of GABA?
changes in astrocytes
What can cause convulsions in experimental animals?
glutamate and selective agonsits of NMDA-, kainite- & AMPA- receptors
What receptors are enhanced in patients with temporal lobe epilespy?
NMDA receptors
Increase in what is observed druing seizures?
Increased glutamate, a major excitatory neurotransmitter, release
What are the two groups of glutamate receptors?
Ionotropic- fast synaptic transmission
* NMDA, AMPA, kainite
* Ligand gated Na+/K+ and Ca++ channels
Metabotropic- slow synaptic transmission
* regulation of second messengers- GPCRs (cAMP and inositol)
* Modulation of synaptic activity
What are modulators of glutamate receptors?
- Glycine
- polyamine sites
- zinc
- redox site
What happens when an epileptogenic focus is in a state of partial depolarization?
- high frequent bursts of action potentials
- hypersynchonization of a neuronal population
- membranes of these cells have increased ionic permeability– susceptible to activation by stimuli
What does a general model of siezures look like?
- population of pathologically excitable neurons
- increase in excitatory glutamtergic activity through recurrent connections- spread discharge
- reduction in activity of normally inhib GABA projections
What is evidential of the pathophysiology of seizures?
- Decreased binding of GABA and benzos
- decreased Cl- currents in response to GABA
- decreased glutamate decarboxylase activity– synthesizes GABA
- interfere with GABA causes seizures
- increased sensitivity to excitatiry amino acid transmission
- progressive increase in glutamate release during kindling
- increased glutamate and aspratate
- upregulation of NMDA receptors in kindled rats
What can happen in the brain if cortical excitations go unchecked?
- spreads to the adjacent cortex and contralateral cortex (interhemispheric pathways) and to anatomically and functionally related pathways in subcortical nuclei
- clinical manifestations of seizures begin– signs depned on where in the brain seizure originates
What are the 4 classifications of epilepsy?
- focal
- generalized
- generalized and focal
- unknown
What are the two types of focal seizures?
- Focal with retained awareness
- focal impaired awareness
What does a focal seizure mean?
local onset that can be determined
