Pathophysiology of Seizures and Epilepsy

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Excitable cells have a resting

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1

Excitable cells have a resting

membrane potential

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2

When a neuron depolarizes to a threshold voltage, what channels open?

fast sodium channels

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3

When fast sodium channels open, the neuron has?

action potential

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4

Potassium plays a major role in __ and __

repolarization, hyperpolarization

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5

What depolarizes the cell to threshold?

chemical transmission

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What hyperpolarizes the cell?

chemical transmission

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7

In a healthy brain, there is a balance between excitation and inhibition, so that groups of neurons __ repeatedly and synchronously "__" inappropriately

don't, fire

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Types of chemical transmission

excitatory and inhibitory

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Excitatory Chemical transmission: makes the postsynaptic neuron more likely to

generate an AP close to threshold, cell depolarizes

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Excitatory Chemical transmission: Ion channel/receptor complex selective for

sodium or calcium

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Excitatory Chemical transmission: Principal neurotransmitter

glutamate

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Inhibitory Chemical transmission: Makes the postsynaptic neuron less likely to

generate an AP, farther away from threshold; cell hyperpolarizes

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Inhibitory Chemical transmission: Ion channel/receptor complex selective for

potassium or chloride

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14

Inhibitory Chemical transmission: Principal neurotransmitter

GABA

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15

Excitatory Chemical transmission:

EPSP

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16

Inhibitory Chemical transmission:

IPSP

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17

Is a single EPSP sufficient to bring the cell to threshold and generate an action potential?

no

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18

Is a single or IPSP sufficient to hyperpolarize the cell?

no

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19

In both IPSP and EPSP, __ or spatial __, or both must occur

temporal, summation

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20

Spatial summation occurs when __ or more __ neurons release __ onto one postsynaptic cell at the same time

two, presynaptic, NT

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21

The various excitatory and __ postsynaptic potentials add __ to determine the overall postsynaptic potential (__) reaching the axon hillock

inhibitory, algebraically, PSP

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22

Temporal summation occurs when __ presynaptic neuron fires in rapid __ such that a previous PSP has not fully dissipated before the next PSP is __ to it

one, succession, added

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23

Sources of neuronal EXCITATION: at the whole brain level

abrupt source of sensory input - loud noise, flashing light, the startle response

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Sources of neuronal EXCITATION: at the cellular level (Opening of)

channels permeable to sodium or calcium

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25

Sources of neuronal EXCITATION: at the cellular level (activation of)

receptors for the excitatory NT glutamate

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Sources of neuronal EXCITATION: at the cellular level (other sources)

activation of nicotinic receptors by acetylcholine

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Sources of neuronal INHIBITION: at whole brain level

Sleep, particularly slow-wave sleep, is a time of decreased responsiveness to excitatory stimuli

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Sources of neuronal INHIBITION: At the cellular level (opening of)

channels permeable to potassium or chloride

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29

Sources of neuronal INHIBITION: At the cellular level (activation of)

receptors for the inhibitory neurotransmitter, GABA

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30

At its most basic level, a seizure represents a __ in the balance between neuronal __ and inhibition

disruption, excitation

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A seizure could result from the brain having too __ excitation or too __ inhibition

much, little

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32

Brain electrical activity: AWAKE the activity is

widely distributed

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33

Brain electrical activity: ASLEEP the activity is

more synchronized

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34

Brain electrical activity: AWAKE synchronous activity in the brain

not in large areas

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35

Brain electrical activity: ASLEEP neurons firing

greater numbers but in fewer places

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36

Brain electrical activity: ASLEEP synchronous activity

not in large areas of the brain

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37

Is having a seizure the same thing as having epilepsy?

no

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38

Seizure vs epilepsy

event vs neurological disease

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39

A single seizure - or multiple seizures arising from and temporally associated a precipitating event, such as head trauma, does not mean

a person has epilepsy

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40

epilepsy =

continued occurrence of seizures, particularly with no discernible cause

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41

Risk Factors for Developing Epilepsy

veterans, brain tumor, stroke, dementia

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42

Epilepsy foundation states that about 50% of people who have epilepsy have a cause that is ___

unknown

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43

Dravet Syndrome: An example of epilepsy caused by a __ __

gene mutation

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44

Dravet Syndrome: Early-onset epilepsy syndrome characterized by __ epilepsy and __ problems beginning in infancy

refractory, neurodevelopmental

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Dravet Syndrome: Mutation of the __ gene which codes for the alpha subunit of a __ channel in the brain

SCN1A, sodium

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Dravet Syndrome: inheritance

usually de novo not inherited

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Dravet Syndrome: Most common mutation type is a

truncating mutation, protein is too short

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48

Dravet Syndrome: Leading hypothesis

affects neurons that release GABA. An inability to fire off an AP; too little inhibition

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Dravet Syndrome: first seizures occurs

first year of life

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Dravet Syndrome: as seizures continue, the child will show signs of

neurodevelopmental delay

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Dravet Syndrome: Vast majority of patients have lifelong

persistent and refractory seizures as well as moderate to severe cognitive impairment

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Dravet syndrome: motor dysfunction

ataxia, tremor, dysarthria, spasticity

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53

Neurons are organized in complex networks - many circuits involve __ links between the thalamus and the __

synaptic, cortex

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54

Within a network, a wave of excitation is often followed by a wave of __, due to the presence of inhibitory neurons using the NT __

inhibition, GABA

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If sufficient numbers of neurons fire together, are then inhibited, then fire again, the resulting __ depolarization and __ can be detected as large waves on the __

synchronized, hyperpolarization, EEG

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56

During a seizure, the synchronized activity is __ (abnormal) and __

inappropriate, excessive

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57

During a seizure, Groups of neurons are hyperexcitable, either by too much __ or too little __; __ between the two states is lost

excitation, inhibition, balance

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Worst case scenario - severe, treatment-refractory, status __ which causes __ death

epilepticus, brain

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Seizure =

single occurrence of signs and/or symptoms due to abnormal excessive and synchronous neuronal activity in the brain

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Seizure results when a sudden

imbalance occurs between the excitatory and inhibitory forces within a network of neurons in favor of a sudden-onset net excitation

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Transient

usually, unless person is in status epilepticus

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Paroxysmal

sudden

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What forms an epileptogenic focus?

A group of neurons are abnormally hyperactive and hypersynchronous

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What is an epileptogenic focus?

the area of the brain from which the seizure originates

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Epileptogenic focus functions

autonomously, causing excessive paroxysmal electrical discharges

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66

Electrical activity can spread to __ groups of neurons and in some cases, to __ neurons

neighboring, distant

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Seizures result in disturbances of motor __, sensation, __, consciousness, autonomic __

control, behavior, function

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What is described as an electrical storm in the brain?

seizures

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A person is considered to have epilepsy if they meet ANY of the following conditions

At least two unprovoked seizures occurring more than 24 hours apart. OR One unprovoked seizure and a high probability of further seizures. OR diagnosis of epilepsy syndrome

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Epilepsy is considered to be resolved for individuals who had an age-__ epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for the last __ years, with no seizure medicines for the last __ years

dependent, 10, 5

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71

Seizure threshold =

the level of stimulation (balance of excitation and inhibition) which will cause a seizure

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People with epilepsy have a __-than-normal seizure threshold

lower

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73

Prodrome =

a difficult to describe feeling that a seizure may occur

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74

Aura =

at the beginning the patient may experience a particular sensory, autonomic or psychic symptom that is characteristic of seizures

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Is aura part of the seizure?

yes

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Is prodrome part of the seizure?

no

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Ictal phase =

period of time from the first S/Sx to the end of the seizure activity

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Post-ictal phase =

Recovery period after the seizure; time between the end of an epileptic seizure and return to baseline

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Epilepsy syndromes =

clustering of findings of seizures with other clinical phenomena define specific epilepsies

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80

Automatisms =

purposeless, repetitive motor activity seen during some types of seizures

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81

Automatisms are typically seen in __ seizures with impaired __ and motor onset

focal, awareness

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Clinical Manifestations of Seizures: changes in

motor control, sensation, behavior, consciousness, autonomic function

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Focal seizure symptoms depend on which __ of the brain is affected

region

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Seizures common comorbidities

Psychiatric, cognitive, social

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Seizures Classified by:

type of onset, level of awareness, first prominent S/sx

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86

Type of onset

focal or generalized

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level of awareness

aware or impaired

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first prominent s/sx

motor or nonmotor

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89

Three broad types

Focal Onset, Generalized Onset and Unkown Onset seizures

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90

Focal onset seizures: Activity begins in

one hemisphere of the brain

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Focal onset seizures: can be

localized or widely distributed

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Focal onset seizures: most common site

temporal lobe

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Focal onset seizures: can become

bilateral

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94

Generalized onset seizures. Activity begins

bilaterally, both hemispheres

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95

Generalized onset seizures: Considered more

severe than focal onset seizures

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96

Aware seizure =

knowledge of self and environment during the seizure

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97

Aware and impaired classification is not used for

generalized onset seizures or unknown onset seizures

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98

Motor involves the

musculature in any form

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Motor can be either

an increase or a decrease in muscle contraction

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Absence seizures =

type of generalized onset, nonmotor seizure

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