seizure and epilepsy mechanisms

1. Pathogenesis of seizures
Dr. Mohammed Mahdy

2. • Seizures are transient events that include
symptoms and/or signs of abnormal excessive
hypersynchronous activity in the brain
• definition of epilepsy requires at least two
unprovoked seizures more than 24 hours
apart. 2005

3. • 2014, Epilepsy was defined as a disease of the
brain defined by any of the following
conditions:
• (1) at least two unprovoked (or reflex)
seizures occurring >24 hours apart, or
• (2) one unprovoked (or reflex) seizure and a
probability of further seizures similar to the
general recurrence risk (at least 60%) after
two unprovoked seizures, occurring over the
next 10 years, or
• (3) diagnosis of an epilepsy syndrome.

5. Pathophysiology
•persistent increase of
neuronal excitability.

6. Epileptogenesis
interictal-
ictal
transition
Ictogenesis

7. Ictogenesis
Excitability

8. Excitability
• Individual neurons,
• Neuronal environment or
• Population of neurons

9. EXCITABILITY ARISING FROM
INDIVIDUAL NEURONS

10. Functional and perhaps structural
changes occur in the postsynaptic
membrane
Altering the character of receptor
protein - conductance channels
Favoring development of paroxysmal
depolarizing shift (PDS) and enhanced
excitability

11. Functional and perhaps structural
changes occur in the postsynaptic
membrane
Altering the character of receptor
protein - conductance channels
Favoring development of paroxysmal
depolarizing shift (PDS) and enhanced
excitability

12. Functional and perhaps structural
changes occur in the postsynaptic
membrane
Altering the character of receptor
protein - conductance channels
Favoring development of paroxysmal
depolarizing shift (PDS) and enhanced
excitability

16. Ca++
• Latent Ca++ channels are used, that the efficacy
of Ca++ channels is increased
• or that the number of Ca++ channels is
chronically elevated

18. K+
K+

19. K+

20. K+

23. EXCITABILITY ARISING FROM
NEURONAL MICROENVIRONMENT
• Both functional and structural alterations
occur in epileptic foci (both neurons and glia)
Change
in
concentrations of cations
and anions
Metabolic alterations
neurotransmitter levels

25. GLIA ????
clear neurotransmitters from the
extracellular space
Buffer extracellular K+
correcting the increased
extracellular K+

26. GLIA ????
• In seizure focus:
• proliferation of glia, different morphology
and physiology than normal
• Affect K+ Buffering capacity of glia

27. EPILEPTIC CELL POPULATION
decrease of
inhibitory
influences
facilitation
of
excitability

28. Ex. TLE
Mossy
fiber
sprouting
increased
excitability
Reduce
dentate
granule cells
inhibitory
effect
Increased
excitability
seizure

29. Mechanisms of interictal-ictal
transition
synaptic
• Depression of GABA-ergic
inhibition
• NMDA receptor activation ;
voltage-dependent EPSPs
• Frequency potentiation of
EPSPs
• Actions of modulators
Non synaptic
• Alterations in ionic
microenvironment
• Decreases in size of
extracellular space
• Failure of ion transport :
Na+-K+ pump or Cl--K+ co-
transport
• Presynaptic terminal
bursting
• Ephaptic interactions

30. Non synaptic
• Alterations in ionic microenvironment ; e.g.
increased extracellular K+, decreased
extracellular Ca++
• Failure of ion transport : Na+-K+ pump or Cl--
K+ co-transport

32. Presynaptic terminal bursting

33. Ephaptic interaction
Decreased extracellular space

35. KINDLING

37. Definitions
• Epileptogenesis: sequence of events that converts a
normal neuronal network into a hyperexcitable
network
• Epileptogenesis: is the process by which a brain
network that was previously normal is functionally
altered toward increased seizure susceptibility, thus
proba togenerate
(Dudek and Staley
havinganenhancedprobability spontaneous
recurrentseizuresS(R)sS
2012;Goldstein and Coulter2013.)

38. Epileptogenesis