2. Contents
1. Introduction
2. Definition of Epilepsy and seizures
3. Epidemiology
4. Aetiology
5. Classification
6. Neurobiology of seizures
7. Diagnosis
8. Management/Treatment
9. Economic importance and social
implications.
10. Overview of my project work
3. INTRODUCTION
Etymology: From Greek word epilepsia=“seize” or
“possess”
Believed to a demonic possession
Countered by Hippocrates, 400BC; and Galen, 2nd
Century AD
Associated with the indigent?
Communicable?
4. Definition of epilepsy and seizures
Epilepsy is a disorder of the brain
characterized by an enduring predisposition to
generate epileptic seizures (ILAE and IBE)
Seizures are episodes of abnormal high
frequency electrical discharges of a group of
neurons in the brain.
5. Some causes of seizures
Seizures may be caused by:
Hypoxia
Hypoglycemia
Stroke
Brain tumours
Head trauma
Withdrawal from alcohol
6. Epidemiology
2nd most common neurological disorder(next
to stroke)
0.5-1%(Rang et al, 2007) of world population.
USA=1-2%
7. Aetiology
idiopathic
Environmental perturbation e.g. intrauterine or
neonatal complications.
Traumatic/Symptomatic: due to lesions in the foci.
Cryptogenic
Precipitating factors;
Primary reading epilepsy
Catamenial epilepsy
Photosensitive epilepsy
Emotional stress, hyperventilation etc.
8. Classification
1. Partial(focal) seizures: one
hemisphere only. No loss of
consciousness
2. Generalized seizures: both
hemispheres. Loss of memory. Involves
the whole brain including reticular
system.
9. Partial seizures
a. Simple partial seizures-memory fully is retain
b. Complex partial seizures-altered
consciousness, repetitive behaviour
(automatism)
c. Jacksonian epilepsy-progress along anatomic
lines as discharge spread across the cortex
Partial seizures may evolve into generalized
seizure termed secondarily generalized
seizures.
10. Generalized seizures
1. Primarily generalized tonic-clonic seizures
or grand mal (Yoruba=warapa;
Ogoni(Gokana)=goi)
Brief tonic phase followed by clonic
phase
Last 3-5mins
Confusion, drowsiness after recovery.
11. Generalized seizures
2.Absence seizure or petit mal
Common in children
No falling, short loss of consciousness
Lasts 10-15secs
child concentration is affected
12. Generalized seizures
3.Status epilepticus
A medical emergency
More than 30minutes of continuous
seizure
Recurrent episodes of tonic-clonic
seizures
No full recovery of consciousness
between sequential episodes
13. Classification of Epileptic Seizures
2 major classes (ILAE 1981):
• Partial-onset seizures
– begin in a focal area of the cerebral
cortex
• Generalized-onset seizures
– have an onset recorded
simultaneously in both cerebral
hemispheres.
14. Neurobiology of epilepsy
Neuronal mechanism is poorly understood
Evidence suggest excessive excitatory
neurotransmission mediated by glutamate in
the brain.
• Glutamate=major excitatory neurotransmitter
• Binds to NMDA receptors===> Ca influx; NO
release===>excitation
16. Diagnosis
Seizure must be recurrent with at least 24hrs
interval
Differential diagnosis is made by the use of
electroencephalogram (EEG)
17. Management/treatment
First aid:
Keep patient away from source of injury
Support respiration if suffocating
Allow foams to drip out freely
Take to a doctor
Accurate diagnosis of the type of seizure and
then a rational use of drugs.
18. Management and treatment
• Pharmacological
• Non-pharmacological
Pharmacological: Drugs based on 3 principles
1. Inhibition of excitatory glutamate
neurotransmission
2. Inhibition of Na and Ca
influx==>suppression of repetitive
depolarization
3. Augmentation of GABA inhibitory
neurotransmission
19. Classification of AEDs
• Sodium channel blockers
• Calcium current inhibitors
• Gamma-amino butyric acid (GABA) enhancers
• Glutamate blockers
• Drugs with unknown mechanism of action
20. Sodium Channel Blockers
Sodium Channel Blockers
They prevent the return
of Na channels to the
active state by stabilizing
them in the inactive state.
:. prevent repetitive firing
of the axons
21. Calcium
Channel
Blockers
• The influx of calcium ions produces a partial
depolarization of the membrane which causes an
action potential to be generated in the cell.
• CCBs inhibit T-calcium channels
22. GABA Enhancers
The GABA system
can be enhanced by
• Binding directly to
GABA-A receptors
• Blocking
presynaptic GABA
uptake
• Inhibiting GABA
metabolism by
GABA transaminase
• Increasing GABA
synthesis.
24. The role of astrocytes
Non neuronal cells in the brain
Maintain homeostasis
Found to be morphologically and functionally
altered in different epileptiforms
Target of new drugs
25. Drugs of choice for epilepsy types
Partial and secondarily generalized seizures
1. Carbamazepine………..100-200mg 1-2x(up to 0.8-
1.2g)daily
2. Sodium valproate……..200mg b.i.d (up to 1-2g)
Phenytoin………………….3-4mg/kg b.i.d( up to 200-
400mg)
Lamotrigine………………..200-400mg daily in divided
doses
Gabapentine………………0.9-1.2g daily in divided
doses
Topiramate…………………200-400mg daily in divided
doses
26. Drugs of choice for epilepsy types
Generalized tonic-clonic seizure
1. Sodium valproate…..200mg b.i.d(up to 1-2g)
2. Lamotrigine……………200-400mg in divided doses
Clonazepam…………….2-6mg daily in divided doses
Topiramate……………..200-400mg in divided doses
Carbamazepine……….100-200mg 1-2x (up to0.8-
1.2mg) daily
Phenytoin……………….3-4mg/kg b.i.d(max.200-
400mg)
27. Drugs of choice for epilepsy types
Absence seizure
1. Ethosuximide ………..1-1.5g in divided doses of
500mg
2. Sodium valproate….200mg b.i.d(up to 1-2g)
Clonazepam…………….2-6mg daily in divided
doses
Lamotrigine…………….200-400mg daily in divided
doses
28. Drugs of choice for epilepsy types
Atypical seizures, tonic, myclonic, atonic etc.
1. Sodium valproate…1-2g
2. Clonazepam………..2-6mg daily in divided doses
3. Lamotrigine………..200-400mg
4. Phenytoin…………..200-400mg
5. Ethosuximide……..1-1.5g daily in divided doses
6. Phenobarbital…….60-90mg nocte
29. Drugs of choice for epilepsy types
Status epilepticus
1. Lorazepam……..1mg i.v. repeat over 10mins
2. Clonazepam……1mg i.v. over 30mins
3. Diazepam……….10-20mg i.v. over 2-4mins
Phenytoin……….15-18mg/kg i.v. @ 50mg/min
Phenobarbital….10-20mg/kg i.v. @100mg/min
30. General guide to AED therapy
Start with monotherapy .
Give the most minimal dose possible.
Drug withdrawal should be gradual.
Treatment should span over 2years.
For pregnant women, lowest dose of
monotherapy should be given.
Epileptic fits are self limiting-do not panic.
Epileptics should not operate machines.
31. Non-pharmacological management
Use of ketogenic diet.
Vagus nerve stimulation.
Surgery.
Lifestyle modification/Relaxation.
Alternative therapy: Yoga, Ayurveda,
Acupuncture, etc.
32. Botanicals
• Valerian (European traditional botanical),
• Passiflora incarnata (native North and South
American botanical),
• Kava kava (Pacific native botanical),
• Piper nigrum (traditional Chinese medicine),
and
• Withania somnifera (Ayurvedic medicine)
33. Economic and social implication
Loss of jobs==>poverty.
Career termination==>withdrawal,depression.
Loss of lives==>loss of human resources.
Stigmatization==>feelings of dejection.
34. Overview of my research work
TITLE: The neuropharmacological effects of the
essential oil of Curcuma longa in mice.
The Plant Curcuma longa (Syn Tumeric)
Family; Zingiberaceae
vernacular: ata le funfun---Yoruba
sila kavanda----Gokana(Bodo)
other spp C. domestica, C. xanthorrhiza, C.
zedoaria, C. wenyujin, etc.
37. Ethnomedicinal uses of C.spp.
liver ailments, skin diseases and wound
healing, jaundice, gastric ulcer, joint
inflammation, diabetics, cold and flu
symptoms, biliary disorders, anorexia, cough,
hepatic disorders, rheumatism, and sinusitis
(Jain et al, 1991).
Gonorrhea, peptic ulcers, appetite stimulant,
carminative, astringent and anti-diarrheal
agent, aromatic stomachic and diuretic
38. Ethnosocial uses
• Spice in ‘pepper soup’
• Major component of curry (spice)
• Spice in local drinks called ‘Kunnu’
• Tumeric tea
• Larvicidal
• Insect repellant
39. The scope of my work
Plant collection and identification
Hydrodistillation of the rhizomes to obtain EO
Density determination and formulation of the EO
Acute toxicity studies(LD50 ), (Lorke, 1983) i.p., p.o.
Parameters studied/models
• Novelty induced Behaviours (NIB)-
Rearing/Locomotor
• Anxiolytic test (EPM)
• Anticonvulsant assessment (PTZ/Strychnine)
• Antidepressant activities (Forced Swimming Test)
40. PRELIMINARY RESULTS
1. Density of the essential oil
2. Acute Toxicity/LD50
3. NIB
• Rearing
• Locomotion
4. Anxiolytic
5. Anticonvulsant:-Pro-convulsant
6. Antidepressant
41. RESULTS
• Density: 0.98g/ml
• Acute Toxicity/LD50
P.O.: 693mg/kg
I.P.: 490mg/kg
• Anticonvulsant: Pro-convulsant (≥400 mg/kg)
• Other results are being analysed
42. Discussion/conclusion
• The essentail oil (EO) demonstrated significant
CNS activities-CNS stimulant
• The EO is moderately toxic
• Preliminary results indicate that the EO
possesses anxiolytic, antidepressant and pro-
convulsant effects in mice
• The plant may be further evaluated for other
neuropharmacological activities
• These results may serve as lead-finding for
novel drug discovery
43. References
• Bennet, P. N. and Brown, M.J. Clinical pharmacology 9th edition, Churchhill
Livingstone 2003. Pp. 414-421.
• Bruton, L.L., Lazo, S.J., Parker, L.K. Goodman and Gilman’s the Pharmacological
basis of therapeutics, 11th edition. McGraw-Hill Companies 2007.
• EMDEX, The complete drug formulary for Nigeria’s health professionals,
2008/09 edition. Pp 34-42.
• Katzung, B.G. Basic and clinical pharmacology 10th edition.
• Losi, G., Cammarota, M. and Carmignoto, G. The role of astrologia in
epileptic brain, Frontiers in Pharmacology, 2012.
• Rang, H.P., Dale, M.M., Ritter J.M., Flower, R.J. Rang and Dale’s
pharmacology, 6th edition, Elsevier Inc 2007. Pp 575-587.
• Roth, J.L. Status epilepticus, Medscape 2011.
• Saxena VS, Nadkarni VV. Nonpharmacological treatment of epilepsy. Ann
Indian Acad Neurol 2011; 14:148-152.