PAT H O P H Y S I O LO G

Y OF
SEIZURES/EPILEP
SY

SKENARIO 4 | BLOK 16

PATHOPHYSIOLOGY
IN F LA MAT I ON

Experimental evidence demonstrates that seizures induce high

levels of inflammatory mediators in brain regions involved in
the generation and propagation of epileptic activity
Prototypic inflammatory cytokines such as interleukin(IL)-1b,
IL-6 and TNF-a are upregulated in activated microglia and
astrocytes, and then trigger a cascade of downstream
inflammatory events that also involves neurons and
endothelial cells of the blood-brain barrier

Vezzani, A. 2014. Epilepsy and Inflammation in the brain: overview and pathophysiology. American Epilepsy Society. 14(1): 3-7

SKENARIO 4 | BLOK 16 | EPILEPSI

11/3/16

Neurons
Ion channels
Glutamate/GABA
receptors

Astrocytes
Glutamate
release

CNS

Neurons/Glia

Glia/Neurons

Inflammation
(cytokines, danger
signals, complement,
COX, chemokines, cell
adhesion molecules

Periphery

Inflammatio
n

Epileps
y

Excitabili
ty

Neurogenesis,
Sprouting,
Angiogenesis,
Astrocytic
dysfunction

Infection,
Trauma, Stroke,
Febrile seizures

Initial
Injury

Seizure
s

Leukocytes

Infection,
autoimmunity

BBB
breakdown
(albumin, IgG)

Astrocytes

Ionic imbalance,
Glutamate
uptake

Vezzani, A. 2014. Epilepsy and Inflammation in the brain: overview and pathophysiology. American Epilepsy Society. 14(1): 3-7
SKENARIO 4 | BLOK 16 | EPILEPSI

11/3/16

IL-1b

Glutamate
receptors
Inhibit the
astrocytic reuptake
of glutamate
GABAmediated Cl
fluxes

NMDA receptormediated Ca2+

influx

Glial release
via TNF-a

Promoting
excitotoxicity
Extracellular
Glutamate
levels

Reducing
inhibitory
transmission

Dysregulation of inhibitory GABAA neurotransmission with imbalance of excitatory and

inhibitory mechanisms

Vezzani, A. 2014. Epilepsy and Inflammation in the brain: overview and pathophysiology. American Epilepsy Society. 14(1): 3-7
McCance, KL. Huether, SE. 2014. Pathophysiology: The Biologic Basis for Disease in Adults and Children. Elsevier: Canada. 730p
SKENARIO 4 | BLOK 16 | EPILEPSI

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PATHOPHYSIOLOGY

IO N -C H A N N E L DY SF U N C T IO N

Chang, BS. Lowenstein, DH. 2003. Epilepsy: Mechanism of Disease. N Engl J Med; 349:1257-66
SKENARIO 4 | BLOK 16 | EPILEPSI

11/3/16

PATHOPHYSIOLOGY

IO N -C H A N N E L DY SF U N C T IO N

A. Shows normal neuronal-ion-channel function and the action

potential
B. Mutations in SCN1B which encodes a voltage-gated sodiumchannel subunit allow passage of an increased sodium current
greater depolarization
C. Mutations in KCNQ2 and KCNQ3, which both encode
potassium channels, decrease the potassium outflow
increase neuronal firing frequency

Chang, BS. Lowenstein, DH. 2003. Epilepsy: Mechanism of Disease. N Engl J Med; 349:1257-66
SKENARIO 4 | BLOK 16 | EPILEPSI

11/3/16

CLINICAL
M A N F I S E S TAT I O N S
OF
SEIZURES/EPILEPSY

SKENARIO 4 | BLOK 16

TONIC-CLONIC SEIZURES
C LI N IC A L MA N IF E ST

Duration of Seizures(by minutes)

5 minutes

Convulsi
on
Starts with
no warning

Prodrom
e
Focal
seizures
Sudden loss
of
consciousne
ss

Brief
flexion
of
Motor
signs
trunk
Opening of mouth
and
Upward deviation
of eyes

Protracted
extension
Tonic Phase
First in the back
and neck, then the
arm and legs
Piercing cry
Spasm of
respiratory
muscles
Pupils dilated
Bladder may
empty

Clonic
Phase
Mild
generalized
tremor
Violent flexor
spasms that come
in rhythmic salvos
and agitate
The face becomes
violaceous and
contorted
Rapid pulse, BP,
pupils dilated,
salivation and
sweating
Apneu

Ropper, AH. Samuels, MA. Klein, JP. 2014. Principles of Neurology. McGraw-Hill:
Ebook. 318-54p
SKENARIO 4 | BLOK 16 | EPILEPSI

Terminal
All movements
Phase1
have ended
Motionless
Limb in deep
coma
Breathing may be
quite
Eyes and mouth
begin to functions
Not remember

More than 30 min

Status Epilepticus

Prolonged seizures,
more than 30
minutes

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