Epilepsy Flashcards by Brooklyn Conaghan

Define seizure

the clinical manifestation of an abnormal and excessive synchronization of a population of cortical neurons

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Define epilepsy

a tendency toward recurrent seizures unprovoked by any systemic or acute neurologic insults

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Define eplieptogenesis

sequence of events that converts a normal neuronal network into a hyperexcitable network

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What are the two main types of seizures?

partial, generalized

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What are the two types of partial seizures?

simple partial, complex partial

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What are the types of generalized seizures?

absence, myoclonic, clonic, tonic, tonic-clonic, and atonic

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define partial seizure

seizures arising from a focal area of the brain

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define generalized seizure

seizures which involve the entire brain

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define a simple partial seizure

focal seizures without the loss of consciousness

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define a complex partial seizure

focal seizures with the loss of consciousness

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What are the two types of epilepsies?

idiopathic and symptomatic

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Define an idiopathic epilepsy

arises from an unknown cause thought to have a strong genetic basis

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Define symptomatic epilepsy

epilepsy that arises from a known cause which may include, head injury, brain tumor, stroke

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What are some of the in vivo models of epilepsy?

numerous genetic models
acquired focal models (lesions, injury)
chemoconvulsant models of seizures (kainic acid)
chemoconvulsant models of status epilepticus (kainic acid)
electrical stimulation
models of epileptogenesis

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What are some in vitro models of epileptiform activity?

resected tissue from patients with epilepsy
cell culture models
acute slice models
organotypic slices

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Define temporal lobe epilepsy

an epilepsy syndrome with seizure arising from the temporal lobe with a high degree of involvement of the hippocampus

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What is the most common form of epilepsy?

TLE - temporal lobe epilepsy

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Basic mechanism underlying seizures and epilepsy are __ and __ __.

feedback
feed-forward inhibition

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What are four possible causes of hyperexcitability

excitatory post synaptic potentials (EPSPs)
inhibitory post synaptic potentials (IPSPs)
changes in voltage gated ion channels
alteration of local ion concentrations

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What are the major neurotransmitters in the brain?

glutamate, GABA, Acetycholine, dopamine, serotonin, histamine, and other modulators (neuropeptides, hormones)

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__ is the brain’s major excitatory neurotransmitter

glutamate

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What are the two groups of glutamate receptors and how do they differ?

ionotropic - fast synaptic transmission
metabotropic - slow synaptic transmission

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What are the three subtypes of ionotropic glutamate receptors?

AMPA, kainate, NMDA
glutamate-gated cation channels

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What are the most common types of metabotropic glutamate receptors?

g-protein coupled, regulation of secondary messengers (cAMP and phospholipase C)

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Metabotropic glutamate receptors modulate __ __

synaptic activity

What are some modulates of glutamate receptors?

glycine, polyamine sites, Zinc, redox site

What is the major inhibitory neurotransmitter in the CNS?

GABA

What are the two types of GABA receptors? How do they differ?

A: post-synaptic, specific recognition sites, linked to Cl- channel B: presynaptic autoreceptors that reduce transmitter release by decreasing calcium influx, postsynaptic coupled to G-proteins to increase K current

What are two cellular mechanisms of seizure generation?

excitation - too much inhibition - too little

Describe the excitation cellular mechanism of seizure generation

ionic - inward sodium and calcium currents neurotransmitter - glutamate, aspartate

Describe the inhibition cellular mechanism of seizure generation

ionic - inward cl, outward K currents neurotransmitter - GABA

What neuronal factors modify neuronal excitability?

ion channel type, number and distribution post-translational modification of channels (phosphorylation) activation of second-messenger systems that affect channel function (G proteins) modulation of gene expression of ion channels

What are possible inherited types of epilepsy?

voltage-gated ion channel mutations ligand-gated ion channel mutations

T/F: different mutations in the same gene can result in radically different types of seizures and epilepsy

true

What are methods of acquired epilepsy?

auto-immune changes in channel expression after seizure

What synaptic factors modify neuronal excitability?

alterations in expression of transmitter gated ionotropic channels post-translational changes in neurotransmitter channels remodeling of synapse location or configuration changes in gap junction synaptic function

What are some non-synaptic (extrinsic) factors modifying neuronal excitability?

changes in extracellular ion concentration changes in extracellular space modulation of transmitter metabolism or uptake by glial cells

What are four mechanisms for generating hyperexcitable networks?

Excitatory axonal 'sprouting' loss of inhibitory neurons loss of excitatory neurons 'driving' inhibitory neurons change in neuronal firing properties (channelopathies)

EEG's are graphical depictions of __ __ __, usually recording from the __

cortical electrical activity; scalp

What is the advantage and disadvantage of an EEG?

Advantage of high temporal resolution but poor spatial resolution of cortical disorders

What is the most important neurophysiological study for the diagnosis, prognosis, and treatment of epilepsy?

EEG

Describe the physiological basis of the EEG; __ dipole generated by __ __ __ at __ __ of __ __

extracellular excitatory post-synaptic potential apical dendrite pyramidal cell

Describe the physiological basis of the EEG; electrical field generated by __ oriented __ __ in __ (layer _) and detected by __ __

similarly pyramidal cells cortex 5 scalp electrode

What are four clinical applications of an EEG?

seizures/ epilepsy sleep altered consciousness focal and diffuse disturbances in cerebral functioning

Describe seizure initiation of focal seizure generation

burst of action potentials, i.e. paroxysmal depolarizing shift hypersynchronization of neighboring cells

Describe propagation of focal seizure generation

activation of nearby neurons loss of surrounding inhibition

Intracellular and extracellular events of the __ __ __ underlying the __ __ __ detected by surface EEG

paroxysmal depolarizing shift intererictal epileptiform spike

What are causes of acquired epilepsy?

severe head injury cerebral hemorrhage brain tumor CNS infection early life febrile seizures

What are the three stages of development of acquired epilepsy?

acute latent chronic

Describe the development of acquired epilepsy

insult to CNS epileptogenesis epilepsy

Define the kindling model of delayed epileptogenesis

repeated subconvulsive stimuli resulting in electrical afterdischarges

Describe the kindling model of delayed epileptogenesis

eventually lead to stimulation-induced clinical seizures in some cases, lead to spontaneous seizures (epilepsy) applicability to human epilepsy uncertain

Describe the hippocampus implication of epileptogenesis

seizures lead to neuronal injury leads to rewiring of neuronal networks leads to increased excitability leads to enhanced susceptibility to further seizures leads to seizures (cyclic)

Newborn granule cells in rodent epilepsy models contribute to three distinct anatomical alterations in the epileptic brain, name them

mossy fiber sprouting ectopic granule cell migration hilar basal dendrite sprouting

T/F: hippocampal circuit changes with hippocampal sclerosis

true

What does neuronal 'birthdating' with BrdU reveal?

increased generation of new neurons in the hippocampal dentate gyrus during epileptogenesis

T/F: new neurons generated during epileptogenesis integrate normally

false, integrate abnormally

__ granule cells are also seen in human __ __ __ and is associated with __ __ __ dispersion

ectopic temporal lobe epilepsy granule cell layer

Ectopic cells contribute to __ __ __

mossy fiber sproutin

T/F: Ectopic cells have normal physiology

false, abnormal physiology

Basal dendrites receive __ __ __

excitatory MF input

__, __, and __ granule cells underlie __ neuronal integration in rodent TLE models. __ cells are comparatively __

juvenile, immature, and newborn aberrant mature; normal

Abnormally interconnected __ __ impair the __ __

granule cells dentate gate

What is hypothesized to impair the dentate gate?

formation of recurrent excitatory connections in the epileptic dentate gyrus

Newborn granule cells sprout __ __ __ that result in __ integration into __ circuitry

mossy fibers axons aberrant hippocampal

Newborn granule cells sprout __ __ __ that recieve mossy fiber synapses in the __, further altering the __ activity

hilar basal dendrites hilus hippocampal

Newborn granule cells migrate into the __, resulting in __ granule cell layer morphology

hilus, abnormal

Seizures appear to represent an __ state for the brain wherein slight disruptions in normal brain circuitry or physiology arising from many different situations can result in a __ __ __

attractor; final common pathway

Known causes of epilepsy are __ and __ and can range from __ modificationations of __ __ to __ of __ brain regions

genetic; acquired single channels reorganization; whole

Currently, the study of epileptogenesis in the __ of rodents are the most common

hippocampus

__ __ epileptogenesis presents a special case because of the lifelong neurogenesis in this region

hippocampal-derived