SEI URE

TJIARN[MD]

PATHOPHYSIOLOGY

PATHOPHYSIOLOGY OF SEIZURE

EXCESSIVELY SYCHRONOUS
AND SUSTAINED DISCHARGE OF A GROUP OF NEURONS
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

RAPID AND CONTINUOUS FIRING

OF ACTION POTENTIALS FROM A SMALL GROUP OF ABNORMAL , DEPOLARIZED, NEURONS
Fischer, J. (1998). Drug Therapy of Epilepsy. University of Illinois, Chicago.

PATHOPHYSIOLOGY OF SEIZURE

MANIFESTATIONS VARY,
DEPENDING ON THE EPILEPTIC SEIZURE FOCI
Berne, R. M., Levy, M. N., Koeppen, B. M., & Stanton, B. A. (2004). Physiology. (5th ed.). United States of America, Elsevier.

RECRUITMENT OF ADJACENT NEURONS (NEURONS WITH WHICH THEY FORM CONNECTIONS WITH)

PATHOPHYSIOLOGY OF SEIZURE

PERSISTENT INCREASE IN
NEURONAL ACTIVITY
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

PEDIATRICS IN REVIEW October 1, 1998 vol. 19 no. 10 342-351 doi:

10.1542/pir.19-10-342

PATHOPHYSIOLOGY OF SEIZURE
ASSOCIATION WITH TRAUMA, OXYGEN
DEPRIVATION, TUMORS, INFECTION, METABOLIC DERANGEMENTS

None found in half of epileptic patients

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE
DISORDERS OF NEURONAL MIGRATION
LINKED WITH GENETIC OR INTRAUTERINE CAUSES Agyria or Pachygyria Neuronal Heterotopia
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE
DISORDERS OF NEURONAL MIGRATION
LINKED WITH GENETIC OR INTRAUTERINE CAUSES = Epileptogenic Foci (Diffuse Hyperexcitability)
(Chevassus au Louis et al., 1999)

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

Imaging features of tuberous sclerosis. Axial T2 -weighted MRI (left) and contrast-enhanced axial T1 -weighted MRI (right). The image on the left shows multiple focal areas of broadened gyri, blurring of the gray-white junction and increased signal in the subcortical white matter typical of cortical tubers. The image on the right shows multiple subependymal nodules (arrows) consistent with subependymal hamartoma and a large enhancing lesion at the right foramen of Monro consistent with a giant cell astrocytoma. MRI, magnetic resonance imaging

PATHOPHYSIOLOGY OF SEIZURE

KINDLING PHENOMENON
REPETITIVE SUBCONVULSIVE STIMULATION
ROLE IN EPILEPTIC EPISODES POST BRAIN INJURIES
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

KINDLING PHENOMENON

* CONCEPT: SPARK > FLAME > BONFIRE

* STIMULUS INDUCED SYNCHRONOUS ADs

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

NEUROCHEMICAL
MECHANISMS
GABA HYPOTHESIS = reduced GABAergic inhibition results to epileptic episodes (vv.)
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

GABA HYPOTHESIS

Decreased GABA release Desensitized receptors

http://www.medscape.org/viewarticle/570744_3

GABA HYPOTHESIS
* EVIDENCE OF DECREASING AMPLITUDE OF INHIBITORY POST SYNAPTIC POTENTIALS (IPSPs) WITH REPETITIVE ACTIVATION OF CORTICAL UNITS
Decreased GABA release Desensitized receptors
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

GABA HYPOTHESIS
* INHIBITORY EFFECTS OF GUANIDO COMPOUNDS AND PENICILLIN (etc.) ON GABAergic TRANSMISSION
*** uremic complications = ANTAGONIST

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

NEUROCHEMICAL
MECHANISMS
GLUTAMATE = activation of ionotropic and metabotropic postsynaptic glutamate receptors is proconvulsant
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

GLUTAMATE
* INCREASED SENSITIVITY OF NMDA receptors
* ENHANCED ENTRY OF Ca2+ INTO NEURONS
*** uremic complications = AGONISt

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

GLUTAMATE

http://www.medscape.org/viewarticle/570744_3

GLUTAMATE

http://www.medscape.org/viewarticle/570744_3

PATHOPHYSIOLOGY OF SEIZURE

NEUROCHEMICAL
MECHANISMS
CATECHOLAMINES
Dopamine vs Norepinephrine in epileptic rats and patients
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

ROLE OF SUBSTANTIA NIGRA

MARKED INCREASE IN METABOLIC ACTIVITY = COMMON FEATURE AMONG GENERALIZED TYPES OF Sz

PATHOPHYSIOLOGY OF SEIZURE

ICTOGENESIS
EXCITABILITY, A KEY FEATURE
- CAUSE: ALTERED MEMBRANE PROPERTY - SUBOPTIMAL REGULATION OF ENVIRONMENT, ECF IONS - ENHANCEMENT OF EXCITABILITY

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

ICTOGENESIS

EXCITABILITY FROM INDIVIDUAL NEURONS EXCITABILITY FROM NEURONAL MICROENVIRONMENT EPILEPTIC CELL PROLIFERATION

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
MECHANISMS THAT CAUSE SIGNAL AMPLIFICATION, SYNCHRONICITY, AND SPREAD OF ACTIVITY
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
ALTERATIONS IN IONIC MICROENVIRONMENT INCREASED POTASSIUM = EXCITABILITY; DECREASED EXTRACELLULAR CALCIUM
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
DECREASED SIZE OF EXTRACELLULAR SPACE PROMOTING EHAPTIC INTERACTIONS

Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
EHAPTIC INTERACTIONS * CURRENTS FROM EXCITED NEURONS CAUSE ADJACENT NEURONS TO SHARE THE EXCITEMENT
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
FAILURE OF ION TRANSPORT Na-K pump : regulatory role in neuronal excitability Cl-K co-transport : Cl Concentration; GABA
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
PRESYNAPTIC TERMINAL BURSTING
Amount of NT release = depolarization Synchronization due to abnormal Action Potential bursts at axonal arborizations of thalamocortical relay cells
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

INTERICTAL-ICTAL TRANSITION
SYNAPTIC MECHANISM: DECREASED EFFECTIVENESS OF INHIBITORY SYNAPTIC MECHANISMS / FACILITATION OF EXCITATORY MECHANISMS
Engelborghs, S., D Hooge, R., & De Deyn, P. P. (2000). Pathophysiology of epilepsy. University of Antwerp. Antwerp, Belgium

PATHOPHYSIOLOGY OF SEIZURE

MANIFESTATIONS VARY,
DEPENDING ON THE EPILEPTIC SEIZURE FOCI
Berne, R. M., Levy, M. N., Koeppen, B. M., & Stanton, B. A. (2004). Physiology. (5th ed.). United States of America, Elsevier.

PATHOPHYSIOLOGY OF SEIZURE

Berne, R. M., Levy, M. N., Koeppen, B. M., & Stanton, B. A. (2004). Physiology. (5th ed.). United States of America, Elsevier.