Seizure and Epilepsy
History of Seizure & Epilepsy
• In 1860 ,The modern neurobiological analysis of
epilepsy was made by Jackson.
• He realized that seizures need not involve loss of
conciousness but could be associated with focal
symptoms such as jerking of an arms etc.
• This observation was the first formal recognition
of what we call partial seizure.
He also observed the progression of focal
neurological symptoms to convulsions with The
loss of conciousness so called jacksonian march.
• In 1886 ,Victor Horsley developed the first surgical
treatment for epilepsy.
• In 1912 medical innovations by A.Haupmann ie the first
use of Phenobarbital as an anticonvulsant ,
• In 1929 Hans Berger Developed the
• In 1937 the discovery of phenytoin(Dilntin) by Houston
Merritt and Tracey Putnam.
• In 1950 ,the modern surgical treatment by the work of
wilder Penfield and Herbert Jasper.
What is Epilepsy?
• Epilepsy is a general term used for a group of disorders
that cause disturbances in electrical signaling in the
• Like computer, the brain is a highly complex electrical
system, powered by roughly 80 pulses of energy per
second. These pulses move back and forth between
nerve cells to produce thoughts, feelings, and memories
• An epileptic seizure occurs when these energy pulses
come much more rapidly-as many as 500 per second for
a short time-due to an electrical abnormality in the brain.
Classification of Seizures and Epilepsy
Impartance of Classiffication
• Not all seizures are the same thats why Classification is
impartant for pathogenesis & treatment .
• Numerous factors that affect the type and severity of
seizures are ignored in the seizure classification,ie
Etiology of seizure,the age, and family history.
• Thus a classiffication of the epilepsies continues to
evolve ,principally based on clinical observation rather
than a precise cellular ,molecular, or
genetic understanding of the underlying
Development of the Epileptic Condition
• Factors leading to development of epileptic
condition are an unsolved mystery.
• But still in some forms of epilepsy ,many genes
are involved and thus genetic epilepsy syndromes
in humans have complex rather then mendelian
• In the more mundane situation,epilepsy often
develops after a discreate cortical injury such as
penetrating head wound.
Treatment of Epilepsy
• The same treatment does not work for every
patient because the type and severity of
epilepsy varies from patient to patient
• Surgical removal of the temporal lobe in
certain patients with partial seizures of
hippocampal origin could reduce or cure
• Electrical mapping of seizure foci by EEG and
• The ketogenic diet is an option for some
Two Methods of Investigating the Brain
• 1. EEG 2. MRI
• An EEG (electroencephalogram) is a record of the
electrical activity of the brain (brain waves).
• Alpha waves are fast waves (8-13 Hz) and occur when a
person is relaxed and quiet.
• Beta waves are very fast waves(>14 Hz) and occur when a
person is thinking actively.
• Delta waves are very slow (<4 Hz) and occur when a
person is sleeping and
• Theta (4-7)for emotional stress.
Electroencephalogram and collective
behavior of cortical neurons
• Neurons are exitable cells,thus it assume that
seizure result either directly or indirectly from a
change in the excitability of single or group of
• Electrical recording of brain activity (single or group of
neuron) can be made by intracellular or extracellular
• EEG represents a set of field potentials as recorded
by multiple electrodes on the surface of scalp.
Electric current flow for EPSP of pyramidal
neuron in cerebral cortex
The Polarity of of The Surface EEG Depends
The location of Synaptic Activity in Cortex
• Partial seizures originate with in small group of neurons
known as a seizure focus.
• Despite the range of seizure type that can be
distinguished by their clinical features,
The generation of seizure activity can be understood by
considering two characteristic electrographic patterns,
*the partial seizure and
*the generalized seizure.
• Most of our knowledge about the pathophysiology of
seizures is derived from the studies of animal model of
Neurons and Seizure Focus
• Neurons in a seizure focus have characteristic activity
ie at how electical activity in a single neuron or group of
neurons leads to the generation of seizure.
• Each neuron within a seizure focus has a stereotypic
and synchronized response called the paroxysmal
depolarizing shift (PDS).
• The PDS consists of a sudden, large,long-lasting
depolarization ,which triggers a train of action
potentials at the peak of the PDS.
Intracellular and Extracellular Recording.
Mammalian Brain Slice Preparation
• The development of in vitro tissue slice preparations has
also been particularly valuable in the study of seizure.
• The tissue slice technique has revolutionized the study
of the electrophysiological properties of mammalian
• Recording from the brain slices has been used to
investigate various aspects of the function of
mammalian neurons,including ,
*The response of neurons to different neurotransmitters
and neuromodulators ,
and properties of the single channels.
Recording from Neurons in Brain Slice
The Spread of Seizure Activity
• The spread of seizure activity involves normal cortical
• Thus thalmocortical,subcortical,and transcallosal
pathways can all become involved in seizure spread.
• Once both hemispheres become involved the seizure
has become secondarily generalized.
At this point the patient loses consciousness.
• Seizure spread occure in rapidly in few seconds,but can
also evolve over many times.
Interplay Between Exitation and Inhibition
in the Neuronal Circuit
The Pathways for Propagation for Partial and
A- Partial seizure spread:
partial seizure activity spread
From sub-cortical centers to
B-Primary generalized seizure:
diffuse interconnections between
Thalmus and cortex
• Generalized seizures evolve from thalamocortical
• Generalized seizures and the associated epilepsies are
heterogeneous in term of their manifestations and
• Primary generalized seizure is difficult to distinguish
from secondry generalized seizure,
• however the cellular mechanisms and the absence of
primary generalized seizure in childhood are the
Seizures and Brain
• Prolonged seizure for 30 or more minutes can cause
• Brain tissue can compensate for the metabolic stress
of a partial seizure or the transient decrease on
oxygen delivery during a single generalized tonic-
clonic seizure and reduction of ATP and
Phosphocreatine but fail during prolonged seizures.
• Repeated generalized seizure without return to full
conciousness between seizures is called,
status epileptics ,ie non convulsive seizure.
Excitotoxicity and Brain Damage
• Brain damage from repeated seizure can
occure independently of cardiopulmonary
or systemic metabolic changes,suggesting
that local factors in the brain can result in
• The pattern of brain injury is particularly
striking in hippocampus ,with the loss of
pyramidal neurons in the CA1 and CA3
• The cellular and molecular mechanisms of
excitotoxicity are still not fully understood.
An overall View
• Seizures are one of the most dramatic examples of the
collective electrical behavior of the mammalian brain.
• The distinctive clinical pattern of partial seizure and
generalized seizures can be due to different patterns of
cortical neurons activity and progression by loss of
GABA-ergic sorround inhibition.
• The EEG can be used to identify certain electrical activity
patterns associated with seizures.
• As EEG is limited approaches ,several much more
powerful approaches are available to locate the focus of