2. Definitions:-
It is a Chronic medical condition characterized by
two or more unprovoked seizures.
It is not a disease, it is a syndrome
What is the difference between seizure & epilepsy ?
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3. Seizure:
The clinical manifestations (signs and symptoms) of
excessive and hyper synchronous, usually self
limited, activity of neurons in the cerebral cortex.
Epilepsy:
Epilepsy is a broad term for a variety of brain disorders
characterized by seizures, or convulsions. Epilepsy can
result from a direct injury to the brain at birth or from a
metabolic disturbance in the brain at any time later in life.
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4. Seizures
A seizure is a transient alteration of behavior due
to abnormal synchronous electrical activity in the
brain
A seizure can be defined as abnormal, uncontrolled electrical
activity in brain cells. Nerve cells transmit signals from the
brain in two ways by
1. altering the concentrations of salts (sodium, potassium
calcium,) within the cell
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5. 2.Releasing chemicals called neurotransmitters
(gamma aminobutyric acid).
The change in salt concentration conducts the impulse
from one end of the nerve cell to the other.
Epilepsy
Epilepsy is a chronic neurological condition
characterized by recurrent seizures that are caused
by abnormal cerebral nerve cell activity.
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7. Treatment:
Up to 80% of parts can expect partial or complete
control of seizures with appropriate treatment.
Antiepileptic drugs suppress but do not cure
seizures
Antiepileptic are indicated when there is two or
more seizures occurred in short interval
An initial therapeutic aim is to use only one drug
monotherapy)
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8. TREATMENT OF SEIZURES
Seizure disorder Drugs
Tonic-clonic(Grand mal) Carbamazepine or
Drug of Choice Valproate or
Phenytoin or
Phenobarbital or
Topiramte
Alternatives: Lamotrigine (as adjunct or alone)
Gabapentin (as adjunct)
Partial (simple or complex) Carbamazepine or Lamotrigine
Drug of choice orTopiramte or Phenytoin or
Valproate
Alternatives: Phenobarbital
Gabapentin (as adjunct )
Zonisamide
9. Treatment cont,d
Absence ( petit mal) Valproate or
Drug of choice Ethosuximide
Alternatives: Clonazepam
Lamotrigine
Myoclonic, Atonic Valproate
Drug of choice
Alternatives: Clonazepam
Febrile Seizures Diazepam, rectal
Diazepam ,i.v
Valproate
10. Mechanism of Action
Reducing electrical excitability of cell
membranes, possibly through inhibition of sodium
channel.
Enhancing GABA-mediated synaptic inhibition. This
may be achieved by an enhanced pre- or post- synaptic
action of GABA, by inhibiting GABA-transaminase, or
by drugs with direct GABA-agonist properties.
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11. Mechanism of Action
A few drugs appear to act by a third mechanism,
namely inhibition of T-type calcium channels.
Newer drugs act by other mechanism, yet to be
elucidated.
Drugs that block excitatory amino acid
receptors are effective in animal models, but
not yet developed for clinical use.
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13. IN VITRO METHODS
1. Hippocampal slices
2. Electrical recording from isolated brain cells
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14. IN VIVO METHODS
1. ELECTRICALLY INDUCED SEIZURE
2. CHEMICALLY INDUCED CONVULSION
3. SEIZURES INDUCED BY FOCAL LESIONS
4. OTHERS
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15. HIPPOCAMPAL SLICES
Procedure and Evaluation:-
Choose Rodent decapitated & hippocampus is dissected
0.5mm
Preincubate for 2 hr thickness slices
Slices are
at 28c warm saline are made
transferred in
with 95%O2 &5%
Perspex chamber
CO2
Intracellular recording from
pyramidal neuron in the slice Drug are added in Record the shock
are done by passing saline medium induce neurons
micropipettes under firing
microscope
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16. ADVANTAGES
mechanical stable
Useful model for studying the neurophysiologic
mechanisms of convulsant and antiepileptic drugs
For screening of antiepileptic drugs
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17. ELECTRICAL RECORDING FROM
ISOLATED BRAIN CELLS
Procedure :-
Put in bath Patch pipettes
Taken isolated neuron are filled with
containing
salts at 7.3 pH same solution
recording of capacitative currents Drug are added
is done ,at room temp.(21-24c) in bath solution
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18. Evaluation
Effect of drug on capacitative component of current Ic
is seen
Ic = Cdv/dt
Where C = specific membrane capacitance
dv/dt rate of change of membrane potential
Using this technique find out the sensitivity of
calcium and potassium channels to neurotransmitters
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19. IN VIVO METHOD
Electrically induced seizures
These are three types
1. Threshold model
2. Maximal electroshock seizures (MES)test
3 . Focal electrical stimulation such as kindling
Corneal electroshock kindling
Kindling by stimulation of the other brain areas
Chemically induced kindling
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20. Threshold model
Procedure and evaluation:-
Male mice of 18-30g Corneal or ear electrode are
in group of 8-10 are used to provide constant
taken current at frequency of 50-
60/sec for 0.2 sec
Threshold is
Elevation of determined as a voltage
threshold by test drug inducing hind limb
is taken as measure of extension in 50% mice
efficacy
Advantage:
This test determine the ability of drug to alter the seizure threshold for tonic
limb extension
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21. Maximal electroshock seizure (MES)TEST
Electrical
Electrode are moistened with
stimulation is
saline solution before
applied by corneal
application
or ear electrode
current Stimulation for
Measures various phages: phage of
mice 50mA&for rat 150mA
tonic limb flexion for 1.5sec. followed
and 250 voltage for mice &
by tonic limb extension for 10 sec.
750 for rat
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22. Evaluation
Suppression of tonic hind limb extension is
taken as measure of efficacy in this test and
anticonvulsant potency is determined by
calculation of ED5o for suppression of tonic
hind limb extension
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23. KINDLED RAT SEIZURE MODEL(epilepsy induces epilepsy)
PROCEDURE:-
Female sprague- Electrode is implanted
Dawely rats of 270- in right amygdala for
400g are taken electrical stimulation
Daily electrical stimulus of
400 – 500 µ A are applied
During the daily electrically
in following 5 stages ….. stimulation of amygdala, seizures
develop which ,as classified by
Racine
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24. Class - 1 Immobility , eye closure
Class- 2 Facial clonus and head nodding
Class- 3 Facial clonus and head nodding & fore limb
clonus
Class- 4 Rearing, often accompanied by bilateral fore limb
clonus
Class-5 Rearing with loss of balance and falling
accompanied and generalized clonic
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25. Evaluation :-
Four different measure of drug efficacy are measured for kindling:-
Seizure latency
Seizure severity
Seizure duration
After discharge duration
Merits:-
The efficacy of drug against the process of epileptogenesis as well as
against the fully kindled state can be measured
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26. Chemical induced convulsions
1. Chemoconvulsionsants inducing generalized seizures after
systemic administration :-
e.g.pentylenetetrazol, picrotoxin, isonizid,pencillin, strychine,p
ilocarpine,NMDA,DDT,methioninen ,sulfoxime bicculine
2. Chemoconvulsant inducing focal seizure after central
administration :- e.g.pencillin.,quinolinic acid, ptz
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27. METHODS OF CHEMICALLY INDUCED
CONVULSIONS:-
• Pentylentetrazol(PTZ) test:-
Procedure:-
8-10 mice are taken and 1% solution of PTZ are administered i.v. infusion
Seizure are developed in following manner
1. jerks(first twitch)
2. Generalized clonic seizure with loss of lightening reflexes
3. Maximal tonic clonic seizure
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28. SEIZURES INDUCED BY FOCAL LSIONS
CORTICALLY IMPLANTED MODEL
ALUMINIUM HYDROXIDE GEL MODEL
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30. CONCLUSION
Characteristics for ideal model:-
Development of spontaneously occurring seizure
Type of seizure similar to that seen in human epilepsy
EEG correlates of epileptic like activity
Age dependency in the onset of epilepsy
At present there is no models that satisfy all above criteria
only genetic model come close to above criteria.
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