BasicMech-epilepsy introduce-from NCBI

8/14/2019 BasicMech-epilepsy introduce-from NCBI

1/30

B-SlideB-Slide 11

Basic Mechanisms Basic Mechanisms

Underlying SeizuresUnderlying Seizuresand Epilepsyand Epilepsy

American Epilepsy Society


2/30

B-SlideB-Slide 2 2

Basic Mechanisms Underlying Basic Mechanisms Underlying Seizures and Epilepsy Seizures and Epilepsy

Seizure: the clinical manifestation of anabnormal and excessive excitation andsynchronization of a population of corticalneuronsEpilepsy: a tendency toward recurrentseizures unprovoked by any systemic or acute neurologic insults

Epileptogenesis: sequence of events thatconverts a normal neuronal network into ahyperexcitable network


3/30

B-SlideB-Slide 33


Feedback andfeed-forwardinhibition, illustratedvia cartoon andschematic of simplifiedhippocampal circuit

Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed.Babb TL, Brown WJ. Pathological Findings in Epilepsy. In: Engel J. Jr. Ed.Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.Surgical Treatment of the Epilepsies. New York: Raven Press 1987: 511-540.


4/30

B-SlideB-Slide 44



5/30

B-SlideB-Slide 5 5

EpilepsyGlutamate EpilepsyGlutamate

The brains major excitatory neurotransmitter

Two groups of glutamate receptors Ionotropicfast synaptic transmission

NMDA, AMPA, kainate Gated Ca ++ and Gated Na+ channels

Metabotropicslow synaptic transmission Quisqualate Regulation of second messengers (cAMP and

Inositol) Modulation of synaptic activity

Modulation of glutamate receptors Glycine, polyamine sites, Zinc, redox site


6/30

B-SlideB-Slide 6 6

EpilepsyGlutamate EpilepsyGlutamate

Diagram of thevarious glutamatereceptor subtypesand locations

From Takumi et al, 1998


7/30

B-SlideB-Slide 7 7

EpilepsyGABA EpilepsyGABA

Major inhibitory neurotransmitter in theCNS

Two types of receptors GABA Apost-synaptic, specific recognition

sites, linked to CI - channel

GABA B presynaptic autoreceptors, mediatedby K + currents


8/30

B-SlideB-Slide 8 8

EpilepsyGABA EpilepsyGABA

Diagram of the GABA A receptor

From Olsen and Sapp, 1995

GABA siteGABA site

Barbiturate siteBarbiturate site

BenzodiazepineBenzodiazepinesitesite

Steroid siteSteroid site

Picrotoxin sitePicrotoxin site


9/30

B-SlideB-Slide 99

Cellular Mechanisms of Cellular Mechanisms of Seizure Generation Seizure Generation

Excitation (too much) Ionicinward Na +, Ca ++ currents

Neurotransmitterglutamate, aspartate

Inhibition (too little)

Ionicinward CI -, outward K + currents NeurotransmitterGABA


10/30

B-SlideB-Slide 10 10

Neuronal (Intrinsic) Factors Neuronal (Intrinsic) Factors Modifying Neuronal Excitability Modifying Neuronal Excitability

Ion channel type, number, and distribution

Biochemical modification of receptors

Activation of second-messenger systems

Modulation of gene expression(e.g., for receptor proteins)


11/30

B-SlideB-Slide 1111

Extra-Neuronal (Extrinsic) Factors Extra-Neuronal (Extrinsic) Factors Modifying Neuronal Excitability Modifying Neuronal Excitability

Changes in extracellular ion concentration

Remodeling of synapse location or configuration by afferent input

Modulation of transmitter metabolism or uptake by glial cells


12/30


Mechanisms of GeneratingHyperexcitable Networks

Excitatory axonal sprouting

Loss of inhibitory neurons

Loss of excitatory neurons drivinginhibitory neurons


13/30

B-SlideB-Slide 1313

Electroencephalogram (EEG) Electroencephalogram (EEG)

Graphical depiction of cortical electrical

activity, usually recorded from the scalp.

Advantage of high temporal resolution but poor

spatial resolution of cortical disorders.

EEG is the most important neurophysiologicalstudy for the diagnosis, prognosis, and treatment

of epilepsy.


14/30

B-SlideB-Slide 1414

10/20 System of EEG Electrode10/20 System of EEG Electrode Placement Placement


15/30


Physiological Basis of the EEG Physiological Basis of the EEG

Extracellular dipole generatedby excitatory post-synapticpotential at apical dendrite of

pyramidal cell


16/30


Physiological Basis of the EEG Physiological Basis of the EEG (cont.)(cont.)

Electrical fieldgenerated by similarlyoriented pyramidalcells in cortex (layer 5) and detected byscalp electrode


17/30


Electroencephalogram (EEG) Electroencephalogram (EEG)

Clinical applications

Seizures/epilepsy

Sleep

Altered consciousness

Focal and diffuse disturbances incerebral functioning


18/30


EEG Frequencies EEG Frequencies

Alpha: 8 to 13 Hz

Beta: > 13 Hz

Theta: 4 to under 8 Hz

Delta:


19/30

B-SlideB-Slide 1919

EEG Frequencies EEG Frequencies

EEG FrequenciesA) Fast activity

B) Mixed activity

C) Mixed activityD) Alpha activity (8 to 13 Hz)E) Theta activity (4 to under 8 Hz)F) Mixed delta and theta activityG) Predominant delta activity

(13 Hz)

Niedermeyer E, Ed. The Epilepsies: Diagnosis and Management.

Urban and Schwarzenberg, Baltimore, 1990


20/30


Normal Adult EEG

Normal alpha rhythm


21/30

B-SlideB-Slide 2121

EEG Abnormalities EEG Abnormalities

Background activity abnormalities Slowing not consistent with behavioral state

May be focal, lateralized, or generalized

Significant asymmetryTransient abnormalities / Discharges Spikes Sharp waves

Spike and slow wave complexes May be focal, lateralized, or generalized


22/30


Sharp Waves Sharp Waves

An example of aleft temporallobe sharp wave(arrow)


23/30

B-SlideB-Slide 2323

The Interictal Spike and The Interictal Spike and Paroxysmal Depolarization Shift Paroxysmal Depolarization Shift

Intracellular andextracellular eventsof the paroxysmaldepolarizing shiftunderlying theinterictalepileptiform spikedetected by surfaceEEG

Ayala et al., 1973


24/30

B-SlideB-Slide 2424

Generalize Spike Wave DischargeGeneralize Spike Wave Discharge


25/30


EEG: Absence Seizure EEG: Absence Seizure


26/30


Possible Mechanism of Possible Mechanism of Delayed Epileptogenesis Delayed Epileptogenesis

Kindling model: repeated subconvulsivestimuli resulting in electrical

afterdischarges Eventually lead to stimulation-induced clinical

seizures

In some cases, lead to spontaneous seizures(epilepsy)

Applicability to human epilepsy uncertain


27/30


Cortical Development Cortical Development

Neural tube

Cerebral vesicles

Germinal matrix

Neuronal migration and differentiation

Pruning of neurons and neuronalconnections

Myelination


28/30


Behavioral Cycling and EEG Behavioral Cycling and EEG Changes During Development Changes During Development

EGA = embrionic gestational ageEGA = embrionic gestational ageKellway P and Crawley JW. A primer of Electroencephalography of Infants,Kellway P and Crawley JW. A primer of Electroencephalography of Infants,Section I and II: Methodology and Criteria of Normality. Baylor University CollegeSection I and II: Methodology and Criteria of Normality. Baylor University Collegeof Medicine, Houston, Texas 1964.of Medicine, Houston, Texas 1964.


29/30

B-SlideB-Slide 2929

EEG Change During Development EEG Change During Development EEG Evolution and Early Cortical Development

Estimated GestationalAge, in Weeks

EEG Evolution

8 First appearance of EEG signal acrosscortex


30/30


EEG Change During Development EEG Change During Development (cont.)(cont.)

EEG Evolution and Early Cortical Development

Estimated GestationalAge, in Weeks

EEG Evolution

40 Predictable cycles of active and quietsleep

44 - 46 First appearance of sleep spindles duringquiet sleep

4 Months Post-Term Sleep onset quiet sleep and emergence of

mature sleep architecture

Kellway P and Crawley JW. A primer of Electroencephalography of Infants,Kellway P and Crawley JW. A primer of Electroencephalography of Infants,Section I and II: Methodology and Criteria of Normality. Baylor University CollegeSection I and II: Methodology and Criteria of Normality. Baylor University Collegeof Medicine, Houston, Texas 1964.of Medicine, Houston, Texas 1964.

BasicMech-epilepsy introduce-from NCBI

Documents

Transcript of BasicMech-epilepsy introduce-from NCBI