Seizure and Epilepsy

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					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
  inheritance patterns.

• In the more mundane situation,epilepsy often
  develops after a discreate cortical injury such as
  penetrating head wound.
Epilepsy Development
            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
                    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.
            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
            Pri-Generalized Seizure
A- Partial seizure spread:
1-via intrahemispheric
 commissural fibers.
2-homotopic contralateral

3-subcortical centers.

-Secondary Generalization:
partial seizure activity spread
From sub-cortical centers to

B-Primary generalized seizure:
diffuse interconnections between
Thalmus and cortex
                 Generalzed Seizures
• 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
  distinguishing features.
               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.
       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
• 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