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Neurobiology of Adult Brain Disorders > Epilepsy > Flashcards

Epilepsy Flashcards

1
Q

Define seizure

A

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

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2
Q

Define epilepsy

A

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

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3
Q

Define eplieptogenesis

A

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

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4
Q

What are the two main types of seizures?

A

partial, generalized

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5
Q

What are the two types of partial seizures?

A

simple partial, complex partial

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6
Q

What are the types of generalized seizures?

A

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

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7
Q

define partial seizure

A

seizures arising from a focal area of the brain

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8
Q

define generalized seizure

A

seizures which involve the entire brain

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9
Q

define a simple partial seizure

A

focal seizures without the loss of consciousness

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10
Q

define a complex partial seizure

A

focal seizures with the loss of consciousness

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11
Q

What are the two types of epilepsies?

A

idiopathic and symptomatic

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12
Q

Define an idiopathic epilepsy

A

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

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13
Q

Define symptomatic epilepsy

A

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

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14
Q

What are some of the in vivo models of epilepsy?

A

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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15
Q

What are some in vitro models of epileptiform activity?

A

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

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16
Q

Define temporal lobe epilepsy

A

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

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17
Q

What is the most common form of epilepsy?

A

TLE - temporal lobe epilepsy

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18
Q

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

A

feedback
feed-forward inhibition

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19
Q

What are four possible causes of hyperexcitability

A

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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20
Q

What are the major neurotransmitters in the brain?

A

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

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21
Q

__ is the brain’s major excitatory neurotransmitter

A

glutamate

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22
Q

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

A

ionotropic - fast synaptic transmission
metabotropic - slow synaptic transmission

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23
Q

What are the three subtypes of ionotropic glutamate receptors?

A

AMPA, kainate, NMDA
glutamate-gated cation channels

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24
Q

What are the most common types of metabotropic glutamate receptors?

A

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

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25
Q

Metabotropic glutamate receptors modulate __ __

A

synaptic activity

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26
Q

What are some modulates of glutamate receptors?

A

glycine, polyamine sites, Zinc, redox site

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27
Q

What is the major inhibitory neurotransmitter in the CNS?

A

GABA

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28
Q

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

A

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

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29
Q

What are two cellular mechanisms of seizure generation?

A

excitation - too much
inhibition - too little

30
Q

Describe the excitation cellular mechanism of seizure generation

A

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

31
Q

Describe the inhibition cellular mechanism of seizure generation

A

ionic - inward cl, outward K currents
neurotransmitter - GABA

32
Q

What neuronal factors modify neuronal excitability?

A

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

33
Q

What are possible inherited types of epilepsy?

A

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

34
Q

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

A

true

35
Q

What are methods of acquired epilepsy?

A

auto-immune
changes in channel expression after seizure

36
Q

What synaptic factors modify neuronal excitability?

A

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

37
Q

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

A

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

38
Q

What are four mechanisms for generating hyperexcitable networks?

A

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

39
Q

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

A

cortical electrical activity; scalp

40
Q

What is the advantage and disadvantage of an EEG?

A

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

41
Q

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

A

EEG

42
Q

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

A

extracellular
excitatory post-synaptic potential
apical dendrite
pyramidal cell

43
Q

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

A

similarly
pyramidal cells
cortex
5
scalp electrode

44
Q

What are four clinical applications of an EEG?

A

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

45
Q

Describe seizure initiation of focal seizure generation

A

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

46
Q

Describe propagation of focal seizure generation

A

activation of nearby neurons
loss of surrounding inhibition

47
Q

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

A

paroxysmal depolarizing shift
intererictal epileptiform spike

48
Q

What are causes of acquired epilepsy?

A

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

49
Q

What are the three stages of development of acquired epilepsy?

A

acute
latent
chronic

50
Q

Describe the development of acquired epilepsy

A

insult to CNS
epileptogenesis
epilepsy

51
Q

Define the kindling model of delayed epileptogenesis

A

repeated subconvulsive stimuli resulting in electrical afterdischarges

52
Q

Describe the kindling model of delayed epileptogenesis

A

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

53
Q

Describe the hippocampus implication of epileptogenesis

A

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)

54
Q

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

A

mossy fiber sprouting
ectopic granule cell migration
hilar basal dendrite sprouting

55
Q

T/F: hippocampal circuit changes with hippocampal sclerosis

A

true

56
Q

What does neuronal ‘birthdating’ with BrdU reveal?

A

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

57
Q

T/F: new neurons generated during epileptogenesis integrate normally

A

false, integrate abnormally

58
Q

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

A

ectopic
temporal lobe epilepsy
granule cell layer

59
Q

Ectopic cells contribute to __ __ __

A

mossy fiber sproutin

60
Q

T/F: Ectopic cells have normal physiology

A

false, abnormal physiology

61
Q

Basal dendrites receive __ __ __

A

excitatory MF input

62
Q

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

A

juvenile, immature, and newborn
aberrant
mature; normal

63
Q

Abnormally interconnected __ __ impair the __ __

A

granule cells
dentate gate

64
Q

What is hypothesized to impair the dentate gate?

A

formation of recurrent excitatory connections in the epileptic dentate gyrus

65
Q

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

A

mossy fibers axons
aberrant
hippocampal

66
Q

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

A

hilar basal dendrites
hilus
hippocampal

67
Q

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

A

hilus, abnormal

68
Q

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 __ __ __

A

attractor; final common pathway

69
Q

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

A

genetic; acquired
single channels
reorganization; whole

70
Q

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

A

hippocampus

71
Q

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

A

hippocampal-derived

72
Q
A

Neurobiology of Adult Brain Disorders (10 decks)

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