Epilepsy and Seizure Disorders - PowerPoint Presentation

Slide1

Epilepsy and Seizure Disorders

PYSC 4080

By: Misha NiliSlide2

Contents

Definitions

History

Seizure Stages

Classification

Mechanisms of Action

Neurotransmission

Genetics

Neuroanatomy

Neurodevelopment

TreatmentsSlide3

Cuttlefish

https://www.youtube.com/watch?v=l1T4ZgkCuiMSlide4

Action Potentials & Epilepsy

https://www.youtube.com/watch?v=MtJyHp_AZL8Slide5

Definitions

Seizure:

A sudden episode of abnormal electrical activity in the brain characterized by

excessive excitation

and

synchronization

of neurons. Slide6

In other words...Slide7

Definitions

Epilepsy:

A chronic neurological syndrome characterized by at least two recurrent seizures that occur without evident cause.

Important to note:

Seizures that occur with apparent cause are not labelled as epilepsy

Seizures are the manifestations/symptoms of epilepsySlide8

Historical Overview

Described in historical texts as a spiritual condition

In Babylonian texts – described as possession by evil or angered spirits, treated with an exorcism

Greek mythology – the Sacred Disease

Associated with moon spirits

Important figures like Hercules and Julius Caesar described to be afflictedSlide9

Historical Overview

Hippocrates first to associate it as a treatable problem with the brain

Termed the word ‘grand mal’ or the Great DiseaseSlide10

Epidemiology

Prevalence:

Affects 0.6% of Canadians

About 15,500 new cases every year

1% of people worldwide =60 000 000!

Age of onset:

Often occurs in childhood, but can develop at any point in life

30% of new cases begin in early childhood and adolescence

High prevalence in those aged 65+Slide11

Epidemiology –Age of OnsetSlide12

Causes – A mystery to neuropsychology!Slide13

Causes

Head trauma

Brain malformations

Lack of oxygen during birth

Maternal drug use 

Brain tumors

Congenital conditions (Down's syndrome, Autism spectrum)

Genetic factors

Drug use/substance abuse

Kidney and liver defects

Stroke

Alzheimer's diseaseSlide14

Stages of a seizure

Typically, there are 3 stages:

Preictal

/

prodromal

Ictal

postictalSlide15

Preictal/prodromal

stage

Auras

Perceived smells, sights, tastes

Forced thinking

Physical sensations – nausea, headaches, dizziness

Unusual feelings

Can happen minutes, hours, or even days before a seizure

Can serve as warning sign

EEG readings show general decreased brain activitySlide16

Ictal Stage

The seizure itself – what others observe

Can be convulsive or non-convulsive

May include a temporary loss of consciousnessSlide17

Post-ictal stage

Body relaxes, after-effects

Loss of consciousness may persist

May also include:

Numbness

Headaches

Fatigue

Confusion

Partial paralysis

Biting of the tongue

Loss of bladder and bowel controlSlide18

EEG

Common way to study and diagnose epilepsy

Records electrical activity of cortical neurons by measuring voltage fluctuations caused by ionic currentsSlide19

EEG – Non-epileptic patientSlide20

EEG – Patient undergoing a seizureSlide21

Classification by seizure typeSlide22

Focal vs. Generalised – Stadium Analogy

Chattering

Chanting

CheeringSlide23

Sweeping Lady exampleSlide24

Classification by seizure type

Epileptic syndromes are classified not by underlying causes by the types of seizures that occur. There are 3 main categories:

Partial/focal seizures

Generalised seizures

Unclassified seizuresSlide25

Partial/focal seizures

Seizure activity starts in one area of the brain

Can go unnoticed, symptoms confused with other events

Very common, 60% of epileptic patients are afflicted with this

Can spread and become a

secondarily generalised seizure

Two categories:

Simple partial seizure

Complex partial seizureSlide26

Simple Partial Seizure

No loss of consciousness - often a warning before more severe seizures

Typically last a minute

Symptoms include:

Sensory: numbness, tingling in one region

Motor: jerking of limbs, facial muscles

Autonomic: increased heart rate, blushing, nausea

Psychic: Hallucinations, déjà vu, anxiety/panicSlide27

Complex Partial Seizure

Vary greatly due to start region of the brain and spread

Altered consciousness and awareness

Unresponsive, can last up to 3 minutes

Symptoms include:

Incomprehensive mumbling

Walking around

Fidgeting

No memory of episodeSlide28

Generalized Seizures

Consciousness lost at the beginning of episode (only affects some types)

Seizure activity in the entire brain

Many different types:

Generalised tonic

clonic

(grand mal)

Absence (petit mal, non-convulsive)

Myoclonic

Tonic (drop attacks)

Atonic

(drop attacks)Slide29

Tonic Clonic/Grand mal Seizures

Most recognizable form

Sudden loss of consciousness and sudden stiffness of body (tonic)

Followed by jerking of the muscles (

clonic

)

Breathing suspended or impaired

Biting of tongue, loss of bladder control

Typically lasts under 2 minutes, followed by confusion, soreness and sleepSlide30

Absence/petit mal seizures

Sudden impairment of consciousness, an interruption of ongoing activities

Blank stare, slowed sentence, pause in movement

Unresponsive

Lasts a few seconds to half a minute

No post-seizure period of disorientationSlide31

Myoclonic Seizures

Myo

-muscle

Clonic

- jerk

Jerking of a group of muscles, shock-like

No loss of consciousness

Myoclonic

jerks different from seizuresSlide32

Clonic Seizures

Repetitive and rhythmic jerking of muscle groups

No loss of consciousness

Can go straight back to activities after seizureSlide33

Tonic Seizures

Sudden stiffening of body and limbs

Person will fall if standing

Most often occur during sleep

No loss of consciousness, last less than a minuteSlide34

Atonic seizures

Sudden loss of muscle tone- go completely limp

Will fall if standing

In children, only head will drop

Typically lasts less than 30 seconds

No loss of

consciounessSlide35

Classification by syndromes

Classified based on common features, onset time, and EEG findings

Less severe:

Benign

rolandic

epilepsy

Childhood absence epilepsy

Juvenile

myoclonic

epilepsy

More severe, episodes may cause diffuse brain dysfunction and are resistant to treatment:

Lennox-

Gastaut

syndrome

West SyndromeSlide36

Impact of Epilepsy

Effects different for partial and generalised seizures

Generalised – affect various functions simultaneously

Partial seizures – vary with which part of the brain the are initiated in

Hippocampus – memory

Broca’s

area,

Wernicke’s

area - language

Outgoing and incoming words

Frontal lobe – executive functions, planningSlide37

Mechanisms of Action

Causes are more often unknown!

Something that triggers:

Increased capacity for excitation

Decreased capacity for inhibitionSlide38

Mechanisms of Action

Initiation of a seizure:

1) high-frequency bursts of action potentials

2)

hypersynchronization

of a neuronal populationSlide39

At the single neuron level - Action PotentialsSlide40

At the single neuron level - Action Potentials

During excitation:

Inward Na

+

, Ca2

+

currents

During inhibition:

Inward CI

-

, outward K

+

currentsSlide41

Mechanisms of Action

Bursts of action potentials become a

paroxymal

depolarizing shift

Has a plateau-like depolarization

Rapid repolarization,

hyperpolarization

follows

Initiated by a Ca2+ depolarization, which leads to the opening of Na+ channels

Hyperpolarization

modulated by K+ channels and

Cl

- influx (mediated by GABA)Slide42

Mechanisms of Action

Kindling hypothesis of

epileptogenesis

“Seizures beget seizures”

Study with animal models – evoked repeated seizures with low-intensity stimuli in the hippocampus

Symptoms intensified – freezing to convulsionsSlide43

Mechanisms of Action

Seizure propagates, recruits surrounding neurons via local connections

Partial seizures spread into the other hemisphere via the corpus

callosum

Increase in extracellular K+ and accumulation of Ca2+ in

presynaptic

terminals also causes recruitment of more neurons

Type, number and distribution of voltage- and

ligand

-gated channels

Channels determine the direction, degree, and rate of changes that allow for the generation of APsSlide44

Mechanisms of Action

Not understood how seizures end, typically under 2 minutesSlide45

Neurotransmission -Glutamate

Major excitatory amino acid neurotransmitter

Receptors found on both principal and inhibitory

interneurons

Ionotropic

Metabotropic

Slide46

Neurotransmission - Glutamate

Ionotropic

receptors

Three subtypes – AMPA,

kainate

, NMDA

All allow for fast transmission by allowing ion influx upon activation by glutamate

Specifically inflow of Na+, outflow of K+

NMDA becomes permeable to Ca2+ during depolarizationSlide47

Neurotransmission - Glutamate

Interesting study involving rats:

Agonists of

ionotropic

receptors

Induce seizure activity

Antagonists of

ionotropic

receptors

Suppresses

seizure activitySlide48

Neurotransmission - Glutamate

Metabotropic

receptors

Slow transmission - G-protein coupled

signalling

pathwaysSlide49

Neurotransmission - GABA

Major inhibitory neurotransmitter

Two receptor types:

GABA A

Post-synaptic

Permeable to

Cl

- ions, which induces

hyperpolarization

, thus inhibiting APs

Study found that agonists, like barbiturates and benzodiazepines, can suppress seizure activitySlide50

Neurotransmission - GABA

Second receptor type:

GABA B

Pre-synaptic, therefore, modulate synaptic release

Associated K+ channels

K+ currents lead to

hyperpolarization

and the inhibition of APs

Agonists like

baclofen

suppress seizuresSlide51

Factors Affect Excitability

Biochemical modification

Phosphorylation

of glutamate receptors like NMDA may lead to increased permeability to Ca2+, thus greater excitability

Modulating gene expression, as by RNA editing

Change the ion specificity of glutamate receptors Slide52

General Factors Affect Excitability

Changes in circuitry

Sprouting of excitatory neurons

Loss of inhibitory neurons

Loss of excitatory neurons that “activate” inhibitory neurons

Shortening of axons leads to more effective coupling of synaptic contacts

Changes in gap junction synaptic functionSlide53

Genetics

Mutations in expression of voltage-gated and ion channels

Na+ channels:

SCN1A

,

SCN1B

,

SCN2A1

Cl

- channels:

CLCN2A

GABA receptors:

GABRG2

(GABA-receptor gamma-2 subunit)

GABRA1

(GABA-receptor alpha-1 subunit)Slide54

Genetics

Twin studies

Study with 199 twins

Concordance

rates were 4 times higher in MZ twins than DZ twins

20%

of affected twin pairs had an epileptic first-degree relative

Concordance

high for generalized epilepsies

compared

to partial/focal epilepsiesSlide55

Neuroanatomy-Hippocampus

Focus of epileptic seizures

Hippocampal

sclerosis – seen with temporal lobe epilepsy

Not known whether epilepsy is caused by

hippocampal

abnormalities or whether the hippocampus is damaged by the effects of repetitive seizuresSlide56

Neuroanatomy-Hippocampus

Why the hippocampus?

Considered one of the most excitable parts of the brain

Limbic system

One of the very few brain regions that is capable of constant generation of new neuronsSlide57

Neuroanatomy-Thalamus

Childhood absence epilepsy

GABAergic

neurons of the thalamic reticular nucleus in the

thalamocortical

loop involved in producing bilateral spike and wave discharge loop, characteristic of this form of epilepsySlide58

Neuroanatomy - Thalamus

Increased activity of GABA A receptor – therefore excessively pruned

Decreased inhibition

Increased expression of Ca2+ channels in the regionSlide59

Neurodevelopment

Defects in cell proliferation in the germinal zone

Impaired neuronal migration and differentiation can lead to malformation of important cortical areas

Some conditions include focal cortical dysplasia,

lissencephaly

,

heterotopia

, and

polymicrogyriaSlide60

Neurodevelopment

Delayed or inadequate integration of inhibitory neurons in neuronal circuits

GABAergic

neurons do not migrate

sufficiently

to cortical centres, leading to imbalance of excitatory/inhibitory conditions

Defects in pruning and remodeling during early critical periods can trigger

hyperexcitabilitySlide61

Pilocarpine Model of Temporal Lobe Epilepsy

Pilocarpine –

muscarinic

agonist

Rats repeated injected with this

Represents human epileptic condition for complex partial seizures

Induces 3 states:

Acute period that builds up to limbic status

epilepticus

Latent period – normalization of behaviour

Chronic period with spontaneous recurrent seizuresSlide62

Treatment - Surgical

Temporal lobe resection or

lesionectomy

Remove seizure focus area

Multiple

Subpial

Transection

Concerns only gray matter

Hemispherectomy

Corpus

CallosotomySlide63

Treatment - Medications

Anti-epileptic and anti-

convulsant

drugs

Vary according to age and syndrome type

70% of patients are able to control seizures with medications

Phenytoin

,

carbamazepine

and

valproateSlide64

Treatment - Neuropsychological

Mind-over-body

Medical and surgical treatments can only treat epilepsies with known causesSlide65

Treatment - Neuropsychological

Aura treatments

Certain behaviours to offset aura

Ex. olfactory auras and jasmine oil

Eventually could use imagination of smell to halt seizures!

Ex. Visualization of fishingSlide66

Treatment - Neuropsychological

Biofeedback

Countermeasures treatment

Fights the onset of seizures

Ex. Relaxation of muscles and de-stressing exercises

Ex. Heightening of arousal levelsSlide67

Treatment - Neuropsychological

EEG Biofeedback

Seizures must be evoked!

“Feed back” EEG information in an easily understandable form

Ex. musical tones, spaceship racing games for children

Train patients to recognize and control mind states

Basically operant conditioning for the brain

Rewarded for altering the brain states towards the desired directionSlide68

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