Pathophysiology of Seizures and Epilepsy

Excitable cells have a resting

membrane potential

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

fast sodium channels

When fast sodium channels open, the neuron has?

action potential

Potassium plays a major role in __ and __

repolarization, hyperpolarization

What depolarizes the cell to threshold?

chemical transmission

What hyperpolarizes the cell?

chemical transmission

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

don't, fire

Types of chemical transmission

excitatory and inhibitory

Excitatory Chemical transmission: makes the postsynaptic neuron more likely to

generate an AP close to threshold, cell depolarizes

Excitatory Chemical transmission: Ion channel/receptor complex selective for

sodium or calcium

Excitatory Chemical transmission: Principal neurotransmitter

glutamate

Inhibitory Chemical transmission: Makes the postsynaptic neuron less likely to

generate an AP, farther away from threshold; cell hyperpolarizes

Inhibitory Chemical transmission: Ion channel/receptor complex selective for

potassium or chloride

Inhibitory Chemical transmission: Principal neurotransmitter

GABA

Excitatory Chemical transmission:

EPSP

Inhibitory Chemical transmission:

IPSP

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

no

Is a single or IPSP sufficient to hyperpolarize the cell?

no

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

temporal, summation

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

two, presynaptic, NT

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

inhibitory, algebraically, PSP

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

Sources of neuronal EXCITATION: at the whole brain level

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

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

channels permeable to sodium or calcium

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

receptors for the excitatory NT glutamate

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

activation of nicotinic receptors by acetylcholine

Sources of neuronal INHIBITION: at whole brain level

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

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

channels permeable to potassium or chloride

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

receptors for the inhibitory neurotransmitter, GABA

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

disruption, excitation

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

much, little

Brain electrical activity: AWAKE the activity is

widely distributed

Brain electrical activity: ASLEEP the activity is

more synchronized

Brain electrical activity: AWAKE synchronous activity in the brain

not in large areas

Brain electrical activity: ASLEEP neurons firing

greater numbers but in fewer places

Brain electrical activity: ASLEEP synchronous activity

not in large areas of the brain

Is having a seizure the same thing as having epilepsy?

no

Seizure vs epilepsy

event vs neurological disease

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

epilepsy =

continued occurrence of seizures, particularly with no discernible cause

Risk Factors for Developing Epilepsy

veterans, brain tumor, stroke, dementia

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

unknown

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

gene mutation

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

refractory, neurodevelopmental

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

SCN1A, sodium

Dravet Syndrome: inheritance

usually de novo not inherited

Dravet Syndrome: Most common mutation type is a

truncating mutation, protein is too short

Dravet Syndrome: Leading hypothesis

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

Dravet Syndrome: first seizures occurs

first year of life

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

neurodevelopmental delay

Dravet Syndrome: Vast majority of patients have lifelong

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

Dravet syndrome: motor dysfunction

ataxia, tremor, dysarthria, spasticity

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

synaptic, cortex

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

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

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

inappropriate, excessive

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

excitation, inhibition, balance

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

epilepticus, brain

Seizure =

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

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

Transient

usually, unless person is in status epilepticus

Paroxysmal

sudden

What forms an epileptogenic focus?

A group of neurons are abnormally hyperactive and hypersynchronous

What is an epileptogenic focus?

the area of the brain from which the seizure originates

Epileptogenic focus functions

autonomously, causing excessive paroxysmal electrical discharges

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

neighboring, distant

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

control, behavior, function

What is described as an electrical storm in the brain?

seizures

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

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

Seizure threshold =

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

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

lower

Prodrome =

a difficult to describe feeling that a seizure may occur

Aura =

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

Is aura part of the seizure?

yes

Is prodrome part of the seizure?

no

Ictal phase =

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

Post-ictal phase =

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

Epilepsy syndromes =

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

Automatisms =

purposeless, repetitive motor activity seen during some types of seizures

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

focal, awareness

Clinical Manifestations of Seizures: changes in

motor control, sensation, behavior, consciousness, autonomic function

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

region

Seizures common comorbidities

Psychiatric, cognitive, social

Seizures Classified by:

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

Type of onset

focal or generalized

level of awareness

aware or impaired

first prominent s/sx

motor or nonmotor

Three broad types

Focal Onset, Generalized Onset and Unkown Onset seizures

Focal onset seizures: Activity begins in

one hemisphere of the brain

Focal onset seizures: can be

localized or widely distributed

Focal onset seizures: most common site

temporal lobe

Focal onset seizures: can become

bilateral

Generalized onset seizures. Activity begins

bilaterally, both hemispheres

Generalized onset seizures: Considered more

severe than focal onset seizures

Aware seizure =

knowledge of self and environment during the seizure

Aware and impaired classification is not used for

generalized onset seizures or unknown onset seizures

Motor involves the

musculature in any form

Motor can be either

an increase or a decrease in muscle contraction

Absence seizures =

type of generalized onset, nonmotor seizure