Epilepsy: Diagnostics, Medications, Myths and Facts

1. Abdul Waheed
M.Pharm-Pharmacology
Department of Pharmacology
Amity University Noida

2. Epileptic seizure
 Epilepsy is a chronic brain disorder
 characterized by tendency to recurrent seizures or fits.
 The seizures can leads to loss of consciousness, disturbance of
movement, muscle spasms, autonomic and mental functions.
 At least 12 millions people in India and 65 millions of people
worldwide are affected.
 Epilepsy affects all the ages, races, sex, education, economic
status and social classes across all geohraphical boundaries

3.  As per WHO epilepsy is one of the most common serious brain
disorders that affects not only the individual, but also has impect
on family and the society in general.
 Mechanism of epilepsy is believe to be imbalance in
neurotransmitter release i.e. abnormally increase the level of
excitatory neurotransmitter glutamate while decrease in inhibitory
neurotransmitter GABA.
 Several types of epilepsy have now been linked to defective
genes for ion channels that control the flow of ions and regulate
neuron signalling.
 During the seizure, neurons may fire 500 times faster than normal
neuron.

4. Types of seizures
Generalised seizures
 Tonic - clonic
 Tonic
 Clonic
 Atonic
 Absence
 Myoclonus
Focal (partial) seizures
 Simplex partial
 Complex partial
 Partial onset with secondary
generalisation

5. Generalised tonic-clonic seizure
(grand mal)
 The most common seizure
 Major epilepsy
 Last for 1-2 min
 symptoms:
 Cry, loss of consciousness, fall
 Tonic phase- generalised muscle contraction, apnoea
 Clonic phase- rhythmic contraction of muscles, tongue
bite, foaming, enuresis
 Terminal sleep and gradual regaining of consciousness
(transient confusion)

6. Absence
 Cognitive dysfunction with a sudden onset
 lasting ½ min.
 Minor epilepsy
 Stare, expressionless face; arrest of ongoing activity;
generally no motor phenomena
 Loss of consciousness
 EEG shows characteristics 3 cycles per second spike
and wave pattern.
 Occurs in genetic (idiopathic) epilepsies, mostly in
children

7. Myoclonic seizure
 Sudden, quick, arrhythmic muscle contraction
 No loss of consciousness
 EEG: generalised polyspike and wave activity
 Occurs in genetic (idiopathic) epilepsies
 Not only an epileptic phenomenon- it can be the sign
of diffuse encephalopathies

8. Atonic seizures
 Akinetic epilepsy
 Unconsciousness
 Relaxation of all muscles due to excessive inhibitory
discharge
 Patient may fall

9. Simplex partial seizures
 Cortical focal epilepsy
 Last ½ - 1 min.
 No loss of consciousness
 Symptoms depend on area of brain involved:
 Motor
 Sensory
 Autonomic
 Psychosensory

10. Complex partial seizures
 Temporal lob epilepsy
 Origin is most often in the temporal lobe
 A common seizure type in adulthood
 Loss of consciousness: stare, ‘going blank’
 Last 1-2 min.
 Automatisms:
 oral automatisms
 fiddling with the hands
 Confused behaviour and purposeless movements

11. Experimental models
 Maximal electroshock method
50 mA for 0.2 second
 Pentylenetetrazol (PTZ) clonic seizure
70mg/kg
 Chronic focal seizure
Application of alumina cream on the motor cortex of
monkey
 Kindled seizure
90mk/kg

12. AEDs
Old
 Primidon
 Phenobarbital
 Phenytoin
 Clobazam
 Clonazepam
 Ethosuximid
 Valproate
 Carbamazepine
New
 Lamotrigine
 Oxcarbazepine
 Topiramate
 Gabapentin
 Felbamate
 Vigabatrin
 Levatiracetam
 Zonisamide
 Tiagabin

13. Mechanism of action of AEDs
Inhibition of voltage gated Na, Ca
channels
Na: phenytoin, carbamazepine,
oxcarbazepine, lamotrigine,
topiramate, felbamate, zonisamide
Ca: ethosuximid, valproate?
lamotrigine, topiramate, zonisamide
Potentiaton of GABA mediated
inhibition
phenobarbital, benzodiazepins,
vigabatrin, tiagabine, topiramate,
valproate, gabapentin, felbamate
Decrease of glutamate mediated
excitation
felbamate, topiramate

14. Side effects of AEDs
 Allergy
 Central nervous system side effects (dose dependent)
 drowsiness, headache
 dizziness, dysequilibrium
 cognitive dysfunction (memory)
 Idiosynchratic reactions / chronic side effects
 bone marrow suppression
 hepatic failure
 rash
 weight gain, weight loss
 tremor
 polycystic ovary syndrome
 visual field defect

15. Diagnostic tools
 Primary diagnosis of epilepsy includes eye–witness and family
history.
 Electroencephalograph (ECG) is the cornerstone for diagnosis
of epilepsy and measures the brain wave activity.
 Neuroimaging like computed tomography (CT) scan, magnetic
resonance imaging (MRI) and positron emission tomography
(PET) techniques are used to diagnose abnormalities in
structure and function of brain.
 Video recording is also useful for the monitoring of epileptic
events.

16. Myths and Facts
 Myth: Epilepsy is because of possession by evil sprit and hence
sorcery is the treatment.
Fact: Neurological disorder, drugs to treat
 Myth: Epilepsy is mental illness
Fact: No, it’s a brain disorder
 Myth: People with epilepsy are below normal in their intelligence
Fact: epilepsy does not affect intelligence or memory.
 Myth: Marriage cure epilepsy
Fact: off course not! Medicines do.
 Myth: Seizure can be stopped by giving a key in the hand or
making a person to smell onion or shoe
Fact: False, the attack stops on its own and not due to the above
factors.

17. References
 KD Tripathi, Essential of medical pharmacology, jaypee
publication, 6th edition, p.no. 401.
 Schmidt D, Schachter S.C.Drug treatment of epilepsy in adults.
BMJ. 2014 Feb 28;348:g254.
 Aristea S. Galanopoulou, Merab Kokaia, Jeffrey A. Loeb, Astrid
Nehlig, Asla Pitkänen, Michael A. Rogawski, Kevin J.
Staley, Vicky H. Whittemore, and F. Edward Dudek. Epilepsy
Therapy Development: Technical and Methodological Issues in
Studies with Animal Model. Epilepsia. Aug 2013; 54(0 4): 13–23.