Hyper-excitable neurons lead to excessive excitability in surrounding neurons, causing seizures (hyper-synchronization). This occurs due to an imbalance of excitatory vs inhibitory neurotransmitters - glutamate activation and lowered calcium channel thresholds increase neuronal excitation, while reduced GABA inhibition decreases the inhibitory surround. This disruption of the normal depolarization-afterhyperpolarization cycle in neurons results in a continuous firing state and seizure focus.

1. Lena Aloufi
PHYSIOPATHOLOGY OF
EPILEPSY

2. A seizure is the physical findings or changes in behavior that occur after an
episode of abnormal electrical activity in the brain.
• A seizure is the clinical manifestation of epilepsy.
WHAT IS A SEIZURE?

3. Epilepsy is: a tendency toward recurrent seizures
unprovoked by any systemic or acute neurologic
insults.
Epileptogenesis is: sequence of events that
converts a normal neuronal network into a
hyperexcitable network.
DEFFINITIONS

4. • Action potential carry electrical signals down the axon.
• Chemical messenger called neurotransmetters (NT) are released from
synaptic vesicle when the action potential arrives at the synapse.
• The NT cause an new electrical signal in the other neuron.
HOW NEURONS COMMUNICATE ?

6. 1- Excitatory 2- Inhibitory
Aspartate GABA
Glutamate Glycine
CLASSIFICATION OF
NEUROTRANSMETTERS
3- Amines 4- Polypeptides
5- nonsynaptic transmetters

7. There are two phenomenon's in the pathophysiology of a seizure:
• hyper-excitability of a neuron
• hyper synchronization:
That means that a hyper-excitable neuron leads to excessive excitability of
a large group of surrounding neurons.
PATHOPHYSIOLOGY

8. stereotypic synchronized response of each
neuron in a seizure focus it consist of :
• depolarization phase
• after hyperpolarization phase
PATHOPHYSIOLOGY

9. Depolarization phase :
it occur due to glutamate and calcium channel activation
resulting in series of action potentials
After hyperpolarization phase :
it occur due to activation of potassium channels and gaba
receptors resulting in inhibition of action potentials
so when The paroxysmal depolarization shift after
hyperpolarization is disrupted, the inhibitory surround is lost and
the neurons fires continiously resulting in seizure focus

10. The onset of seizures :
• Small group of abnormal neurons undergo: o Prolonged
depolarization o Rapid firing of repeated action
potentials
• The action potential then spreads to adjacent neurons or
neurons with which they are connected into the process.
• A clinical seizure occurs when the electrical discharges
of a large number of cells become abnormally linked
together, creating a storm of electrical activity in the
brain.
• Seizures may then spread to involve adjacent areas of
the brain or through established anatomic pathways to
other distant areas.
Lets Summarize Pathophysiology of
Epilepsy in the following points

11. instability of cell membrane at the cortical
level leads to susceptible cell membrane to
polarization abnormalities (lower threshold)
that any ionic imbalance in the immediate
chemical environment of the neurons will
spontaneously result in:
1- Excessive excitation (Ach,Glutamate)
2- Decreased Inhibition (GABA)
At the molecular level

12. References:
• Harper's Illustrated Biochemistry,
MacGrowHil; 27th edition, 2006.
• Brain’s clinical neurology, Oxford
Medical Publication, 10th edition,
2012.
• Neuroscience. Pur ves et al;
3rdedition 2005.
• Text Book of Medical Physiology,
W.B. Saunders; 10th edition, 2000.
SUMMARY
Hyper-
excitable
state
Decreased
inhibitory
input - GABA
Increased
excitatory
input –
Glutamate
Voltage- gated
ion channels
in favour of
excitation