Seizure and Epilepsy

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Seizure and Epilepsy
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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.

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• 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
• electroencephalography.
• 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.

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What is Epilepsy?

• Epilepsy is a general term used for a group of
  disorders that cause disturbances in electrical
  signaling in the brain.
• 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.

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Classification of Seizures and Epilepsy
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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
  pathophysiology.

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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
  inheritance patterns.
• In the more mundane situation,epilepsy often
  develops after a discreate cortical injury such
  as penetrating head wound.

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Epilepsy Development
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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 epilepsy.
• Electrical mapping of seizure foci by EEG and
  MRI.
• The ketogenic diet is an option for some
  childerns.

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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(gt14 Hz) and occur
  when a person is thinking actively.
• Delta waves are very slow (lt4 Hz) and occur when
  a person is sleeping and
• Theta (4-7)for emotional stress.

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Electroencephalogram
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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 neurons.
• Electrical recording of brain activity (single or
  group of neuron) can be made by intracellular or
  extracellular electrode.
• EEG represents a set of field potentials as
  recorded by multiple electrodes on the surface of
  scalp.

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Electric current flow for EPSP of pyramidal
neuron in cerebral cortex
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The Polarity of of The Surface EEG Depends The
location of Synaptic Activity in Cortex
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Seizure Focus

• 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 partial seizures.

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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.

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Intracellular and Extracellular Recording.
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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 neurons.
• 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.

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Recording from Neurons in Brain Slice
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The Spread of Seizure Activity

• The spread of seizure activity involves normal
  cortical circuitry.
• 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.

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Interplay Between Exitation and Inhibition in the
Neuronal Circuit
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The Pathways for Propagation for Partial and
Pri-Generalized Seizure

• A- Partial seizure spread
• 1-via intrahemispheric
• commissural fibers.
• 2-homotopic contralateral
• cortex.
• 3-subcortical centers.
• -Secondary Generalization
• partial seizure activity spread
• From sub-cortical centers to
• Thalamus.
• B-Primary generalized seizure
• diffuse interconnections between
• Thalmus and cortex

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Generalzed Seizures

• Generalized seizures evolve from thalamocortical
  circuits.
• Generalized seizures and the associated
  epilepsies are heterogeneous in term of their
  manifestations and ethiologies.
• 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 distinguishing features.

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Seizures and Brain

• Prolonged seizure for 30 or more minutes can
  cause brain damage.
• 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.

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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 neuronal death.
• The pattern of brain injury is particularly
  striking in hippocampus ,with the loss of
  pyramidal neurons in the CA1 and CA3 regions.
• The cellular and molecular mechanisms of
  excitotoxicity are still not fully understood.

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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 a partial seizure.