Epilepsy- Definition, cause, Types of Epilepsy, Pathophysiology, Diagnosis, Treatment options along with Mechanism of action

1. Prepared by:
HIMIKA RATHI
EPILEPSY

2. What is EPILEPSY?
Epilepsy is a chronic CNS disorder characterized by brief episodes of
Seizure is a sudden time limited involuntary alteration of behavior
with or without loss of consciousness accompanied by an
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3. Pathophysiology of EPLILEPSY
• Each individual neuron is linked with hundreds of other neuron via
synapses.
• Neurons discharge electrical current and neurotransmitters are
released at synaptic levels and permits inter-communication.
• There are two types of Neurotransmitters:
1. Inhibitory Neurotransmitters: GABA (Gamma amino butyric acid)
acts on ion channels and increases chloride outflow and decreases
chances of action potential.
2. Excitatory Neurotransmitters: Glutamate and Aspartate allows
sodium and calcium influx which paves way for action potential
formation.

4. • Seizures occur due to the imbalance between the inhibitory and
excitatory Neurotransmitters.
• A normal neuron discharges repetitively at low baseline frequencies.
If neurons are damaged, injured/ suffer a chemical/ metabolic insult,
the changes in discharge pattern develops.
• During epilepsy, regular low frequency discharges are replaced by
bursts of high frequency discharges followed by periods of inactivity.
• A single Neuron discharging in an abnormal manner is usually not
clinically significant. But when a whole population of neurons
discharge synchronously in an abnormal manner, epileptic seizure
occurs.

5. Causes of EPLILEPSY
• In 28% cases, cause can be determined, in rest 72% cases, cause is
idiopathic.
• Determined causes:
1) Inherited genetic
2) Acquired: Trauma, Metabolic infections, Tumour, Neuro surgery,
Drugs, etc.
of inhibitory neurotransmitter such as the
4) Increase excitatory neurotransmitter.

6. 5) Concentration of is reversed.
6) Abnormality in the potassium conductance.
7) Defect in the voltage sensitive channel
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7. Drugs that Induces Seizures
• Alcohols: ethanol, ethylene glycol, methanol, propylene glycol
• Anesthetics: bupivacaine, cocaine, lidocaine, procaine, proparacaine,
enflurane, etomidate, isoflurane, ketamine.
• Antibiotics: cephalosporins,ciprofloxacin, gentamicin, cilastatin,
isoniazid
• Anticholinergics: atropine, benztropine mesylate, diphenhydramine
• Antidepressants: amitriptyline, amoxapine, clomipramine,
desipramine,doxepin
• Antihistamines: astemizole, brompheniramine, chlorpheniramine,
diphenhydramine, doxylamine

8. • Antineoplastics: bleomycin, busulphan, carmustine, chlorambucil,
cisplatin,cytarabine,mechlorethamine
• Antiparasitics: chloroquine, oxamniquine, pyrimethamine
• Antivirals: acyclovir, amantadine
• Asphyxiants: acetylene, butane, carbon dioxide, ethane
• Cardiovascular Agents: aprindine, digoxin, lidocaine, lorcainide.
• Drugs Of Abuse: amphetamines, cocaine, lysergic acid diethylamide
(LSD), marijuana, methamphetamine ("ice"), phencyclidine (PCP)
• Drug Withdrawal: anticonvulsants,barbiturates, benzodiazepines

9. Diagnosis
• Neurological examination/ Neuropsychological Tests
• Medical history
• Genetic Testing
• Electroencephalogram (EEG)
• CT Scan/ MRI Scan
• fMRI
• Positron Emission Tomography (PET Scan)
• SPECT (Single Photon Emission Computerized Tomography)
• SISCOM (Subtraction Ictal SPECT categorized to MRI)

10. Types of
epilepsy
Generalized
seizures
Tonic – clonic
seizure (Gran
mal seizure)
Absence
seizure
(petit mal
seizure)
Atonic
seizure
Myoclonic
seizure
Localized (partial
or focal)
Simple partial
seizure
(jacksoninan)
Complex partial
(psychomotor)
seizure
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11. Types of EPLILEPSY
• Generalized seizures
1.Tonic-clonic seizures(Major epilepsy,
Grand mal)
• Lasts 1-2 min
• Usual sequences is aura-cry-
unconsciousness-tonic of all
body muscles-clonic followed by
prolong sleep
• Stiffening of arms and legs followed by
rhythmic jerking.

12. Types of EPLILEPSY
2. Absence siezures (Minor epilepsy, Petit
mal)
• Lasts about 1-2 min
• Momentary loss of consciousness
• Little jerking
• Often subside prior to puberty.

13. Types of EPLILEPSY
3. Atonic seizures (Akinetic epilepsy)
• Unconsciousness with relaxation of all
muscles
• Due to excessive
• Patient may fall , after 10 seconds to a
minute, they recover and regain
consciousness and can stand and walk
again.

14. Types of EPLILEPSY
4. Myoclonic seizures
of
muscles of limb or the whole body
• Juvenile myoclonic epilepsy (JME) is
the most common form of this
condition.

15. Types of Epilepsy
• Simple partial seizure(Cortical focal epilepsy)
oLasts 1/ 1-2 min
oConvulsion are of muscles or localized sensory
disturbance depending on the area of cortex involved in seizure
oWithout loss of consciousness
oComplex partial seizure(Temporal lobe epilepsy, Psychomotor
epilepsy)
oAttack of bizarre and and purposeless movement
oEmotional changes lasting 1-2 min along with impairment of
consciousness.
oThe seizure focus is located in the temporal lobe.
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16. TYPES OF TREATMENT
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• Medication
• Surgery
• Non-pharmacologic treatment
1. Ketogenic diet
2. Vagus nerve stimulation (VNS)
3. Lifestyle modifications

17. CLASSIFICATION
1. Barbiturate: Phenobarbitone
2. Deoxybarbiturate: Primidone
3. Hydantoin: Phenytoin, Fosphenytoin
4. Iminostilbene: Carbamazepine, Oxcarbazepine
5. Succinimide: Ethosuximide
6. Aliphatic carboxylic acid: Valproic acid (sodium valproate)
7. Benzodiazepines: Clonazepam, Diazepam, Lorazepam,
Clobazam
8. Phenyltriazine: Lamotrigine
9. Cyclic GABA analogue: Gabapentin
10. Newer drugs: Vigabatrin, Topiramate, Tiagabine, Zonisamide,
Levetiracetam
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18. CLASSIFICATION
• Group 1- Blockade of voltage-dependent Na+ or Ca channels
(generalised and partial seizures)
• Group 2- Enhance inhibitory events mediated by GABA (absence,
generalised, partial seizures)
• Group 3- Blocks T-type calcium channels (absence seizures).
• Group X- Reduce events mediated by excitatory amino acid glutamate

19. Sodium
Channel
Calcium
Channel
GABAERGIC
Phenytoin
Carbamazepine
Oxcarbazepine
Zonisamide
Lamotrignine
Ethosuximide Benzodiazepines
Barbiturates
Tiagabine
Vigabatrine
Gaba pentin
Glutamate CA inhibitor Other
Felbamate
Topiramate
Acetazolamide Levetiracetam
Progesterone

20. Group 1- Blockade of voltage-dependent Na+ or Ca
channels (generalised and partial seizures)
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21. Carbamazepine
Clinical uses:
• Primary generalized tonic clonic seizures.
• Partial seizures with or without secondarily generalization.
• Bipolar disorders.
• Chronic pain syndromes: Trigeminal neuralgia.
Pharmacokinetics:
• Initial half-life is 20- 40 hrs but decreases to 20-40 hr on chronic
medication.
• Active metabolite: 10-11 epoxy carbamazepine.

22. Carbamazepine
Dose:
• Available only in oral form.
• Effective in children, in whom a dosage of 15-25 mg/kg/d is appropriate.
• In adults, daily doses of 1 g or even 2 g are tolerated.
Neurotoxic side effects :
• Blurred or double vision
• Lethargy, headache.
• Worsening of myoclonic, Atonic & absence seizures.

23. Carbamazepine
Systemic side effects :
• Nausea, vomiting, diarrhea
• Hyponatremia & fluid retention.
• Rash, pruritus
Rare side effects :
• Blood dyscrasias: Agranulocytosis, aplastic anemia.
• Dermatitis/rash
• Stevens-Johnson syndrome.
• Serum sickness, pancreatitis
• Hepatic failure

24. Phenytoin
Clinical uses :
• Partial & generalized tonic clonic seizures.
• 2nd line agent for patients with mixed seizures (myoclonic/tonic-
clonic).
• Status epilepticus.
Neurotoxic Side effects:
• Dose related : Diplopia & Ataxia.
• Peripheral neuropathy.
• Behavior changes.

25. Phenytoin
Systemic side effects :
• Skin rash
• Lymphadenopathy ( abnormally enlarged lymph nodes)
• Gingival hyperplasia
• Pulmonary fibrosis
• Hirsutism
• Teratogenic ( Fetal Hydantoin syndrome includes cleft lip and palate,
congenital heart disease)
• Megaloplastic anemia ( folate deficiency ).
NOTE – phenytoin is also an anti-arrthymetic drug treatment with
phenytoin should not be stopped abruptly.

26. Lamotrigine
Decreases the release of excitatory neurotransmitters
(glutamate/aspartate).
Clinical uses :
• Monotherapy in partial seizures
• Adjunctive therapy in generalized tonic clonic seizure
• Mixed seizures
Side effects :
• Dizziness, headache, Diplopia
• Nausea
• Hypersensitivity skin rash
not to be used in those < 16 years

27. Oxcarbazepine
It is a 10- keto analogue to carbamazepine.
Clinical uses:
• Partial seizures
• Generalized tonic clonic seizures
• Affective disorders
• Trigeminal neuralgia
Side effects :
• CNS : sedation, dizziness, ataxia, diplopia
• Hyponatremia but less less than carbamazepine
• Allergic skin reaction

28. Zonisamide
• Sulfonamide derivatives.
• Blocking of voltage dependent Na & T- type Ca channels.
• Partial & Generalized tonic clonic seizures.
• Useful against infantile spasm and certain types of myoclonias.
Side effects :
• CNS: confusion, ataxia, sedation, poor concentration
• Anorexia & weight loss
• Skin rash
• decreased sweating, hyperthermia
• Renal stones (rare)
C/I : Allergy to sulfonamides.

29. • Group 2- Enhance inhibitory
events mediated by GABA
(absence, generalised, partial
seizures)
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30. Phenobarbital
M.O.A :
• Binds to GABA receptor improving its effect by extending GABA
mediated chloride channel opening.
Clinical uses:
• Partial seizures
• Generalized tonic clonic seizures
• Neonatal seizures
• Status epilepticus
Side effects:
• Sedation, ataxia, nystagmus ( rapid, rhythmic and involuntary eye
movements), vertigo
• Agitation & confusion, at high doses.
• Alteration of sleep cycles

31. Gabapentin
It is an amino acid, an analogue to GABA.
Clinical uses:
• Partial seizures
• Generalized tonic clonic seizures
• Neuropathic pain: post herpetic neuralgia
Side effects:
• CNS: sedation, ataxia, headache, tremor
• GI upset.
• Weight gain.

32. Tiagabine
Inhibition of GABA reuptake into presynaptic neurons.
Clinical uses:
• Adjunctive treatment for partial and generalized seizures
Side effects:
• CNS: sedation, tremor, depression, confusion
• Nausea, abdominal pain
• Not recommended in children under age of 12 years.

33. Vigabatrin
• Irreversible inhibitor of GABA transaminase.
Clinical uses:
• 2nd line treatment in patients with refractory partial seizures
• 1st line treatment in infantile spasm (west’s syndrome)
• May worsen myoclonic jerks and generalized absence and precipitate
status epilepticus
Side effects :
• CNS: sedation, dizziness, headache
• Change in mood, agitation
• Retinal toxicity… irreversible
• Weight gain

34. Clonazepam
Clinical uses
• Myoclonic seizures
• Generalized seizures (mainly absence)
• Status epilepticus
• Infantile spasm
Side effects:
• Sedation, ataxia, irritability.
• Cardiovascular & Respiratory depression .
• Hyper salivation in pediatric .
• Idiosyncratic reaction like blood dyscrasia is rare.

35. Group 3- Blocks T-type calcium channels (absence seizures).
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36. Ethosuximide
• Reduces T- type calcium currents in thalamic neurons
• Effective against absence seizures
• May increase tonic- clonic seizures
Side effects :
• Nausea & Vomiting.
• Sleep disturbances.
• Drowsiness & Hyperactivity.

37. Drugs With Multiple Mechanisms Of
Actions
● Valproate
● Felbamate
● Topiramate

38. Valproate
M.O.A:
• Blocking voltage- dependent sodium channels
• Enhances GABA synthesis
• Inhibits GABA transaminase
• Acts against T- type calcium current
Clinical uses:
• Absence seizures
• Generalized tonic clonic seizures
• Bipolar disorders
• Migraine prophylaxis

39. Valproate
Side effects:
• CNS: Tremor
• Dose related GI symptoms
• Increase appetite & weight gain
• Hair loss
• Hepatotoxicity esp. < 2 years.
• Thrombocytopenia
• Teratogenic, spina bifida ( major birth defect, type of neural tube defect

40. Felbamate
M.O.A:
• Inhibition of voltage – dependent sodium channels
• Potentiate GABA response at GABA receptors
• Inhibition of the excitatory N-methyl-D-aspartate (NMDA)
receptors
Clinical uses:
• Broad spectrum of action
• Effective in some patients with partial seizures
• 3rd line drug in refractory seizures- in lennox gastaut syndrome
Side effects:
• CNS: Insomnia, Diplopia, Ataxia
• Weight loss.

41. Topiramate
M.O.A:
• Blockage voltage – dependent sodium channels
• Enhances activity of GABA at non benzodiazepine
• Site on GABA (A) receptors
• Antagonizes NMDA receptors
• Weakly inhibits carbonic anhydrase enzyme
Clinical uses:
• Adjunctive therapy for partial & generalized seizures
• Adjunctive therapy for Lennox-Gastaut syndrome & infantile spasm

42. Topiramate
Side effects:
• CNS: confusion, ataxia, poor concentration
• Cognitive impairment
• Visual disorders: myopia, glaucoma (rare)
• Weight loss
• Parasthesia & renal stones due to inhibition of carbonic anhydrase
enzyme.
• Teratogenic in animals

43. Drugs With Unknown Mechanism Of
Actions
Levetiracetam:
• Broad spectrum
• Add- on therapy for refractory partial seizures
Side effects:
• CNS: Fatigue, dizziness, agitation, anxiety
• Increases susceptibility to infection, rhinitis or flu like symptoms
• Anemia, leukopenia

44. Pregabalin
Clinical uses:
• Adjunctive therapy for partial seizures
• Peripheral neuropathic pain.
Renally excreted and is not hepatically metabolized
Side effects :
• Dizziness, somnolence and ataxia
• Blurred or double vision
• Weight gain
• Peripheral edema
• May cause euphoria
• New onset myoclonus has been reported

45. ECT
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• Electroconvulsive therapy (ECT), formerly known as electroshock
therapy, and often referred to as shock treatment, is
a psychiatric treatment in which seizures are electrically induced in
patients to provide relief from mental disorders.

46. KETOGENIC DIET
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• Based on finding that starvation, which burns fat for energy has an
antiepileptic effect
• Used primarily to treat severe childhood epilepsy, has been effective in
some adults & adolescents
• High fat, low carbohydrate and protein intake
• Requires strong family commitment

47. VAGUS NERVE STIMULATION
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• Device is implanted to control seizures by delivering
electrical stimulation to the vagus nerve in the neck, which
relays impulses to widespread areas of the brain.
• Used to treat partial seizures when medication does not
work.

48. COMMON CAUSES OF FAILURE OF
ANTIEPILEPTICS
1. Improper diagnosis of the type of seizures
2. Incorrect choice of drug
3. Inadequate or excessive dosage
4. Poor compliance
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49. TREATMENT IN SPECIAL
SITUATIONS
ANTIEPILEPTIC AND PREGNANCY :
• Seizures are very harmful for pregnant women.
• Monotherapy usually better than drugs combination.
• Folic acid is recommended to be given for every pregnant
women with epilepsy.
• Phenytoin, sodium valproate are absolutely contraindicated and
oxcarbamazepine is better than carbamazepine.
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50. EPILEPSY IN ADOLESCENTS AND YOUNG
ADULTS
Important points to remember are:
• Avoiding sleep deprivation,
• alcohol and substance abuse, driving, potentially risky leisure activities
like rock climbing, horse riding, etc.
• Prolonged television (TV) viewing, playing video games and dancing
in dark rooms with flickering/flashing lights (discotheques).
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51. SURGERY IN EPILEPSY
• All patients with medically intractable epilepsy (MIE) should be
evaluated at a center performing epilepsy surgery.
• A patient having MIE with an identifiable lesion on imaging, correlated
with electrophysiology [Electroencephalogram (EEG)] is a potential
candidate for epilepsy surgery. Even if imaging is negative, patients
still can be surgical candidates on further investigation.
• Epilepsy surgery should be done only in specialized centers.
• Surgery has a high chance of achieving seizure freedom (in 60– 70% of
cases) and a reduction in seizure frequency in the remaining 30–40%
cases.
• When indicated it should be considered as early as feasible rather than
an option of last resort.
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52. SURGERY IN EPILEPSY
• Epilepsy surgery may be resective or nonresective.
• Resective surgery includes lesionectomy (resection of the lesion and
the surrounding epileptogenic area), amygdalohippocampectomy with
or without temporal lobe resection, multilobar resection and
hemispherectomy.
• Nonresective surgery includes multiple subpial transections corpus
colostomy and vagus nerve stimulation (VNS).
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53. Summary

54. Pathophysiology
Decrease in INT/Increase in ENT/Abnormalities in Ion channel
Rhythmic and repetitive hyper synchronous discharge of neuron
Seizures
Repetitive Seizures
Epilepsy

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