Epilepsy

1. EPILEPSY
INTRODUCTION:
 Epilepsy is a condition characterized by Recurrent episodes of seizures.
 Seizures result from Episodic electrical discharges in cerebral neurons associated
with prolonged depolarization during which sustained, high-frequency repetitive
firing occurs, followed by prolonged hyperpolarization.
 Goal of the Drug is to Restore Normal Patterns of Electrical activity.
DEFINITIONS:
 EPILEPSY: Epilepsy is a chronic disorder that causes unprovoked, recurrent
seizures. A seizure is a sudden rush of electrical activity in the brain. There are two
main types of seizures.
(OR)
Epilepsy include a chronic condition of recurrent or repeated seizures. A seizure is a
transient, paroxysmal, pathophysiological disturbance of cerebral function caused by
a spontaneous excessive discharge of cortical neurons.
 SEIZURE: A seizure is when there's an abnormal surge of electrical activity in the
brain, due to complex chemical changes in nerve cells (this is technically known as
electrochemistry, or when chemical reactions can produce an electrical current).
(OR)
A seizure may be abnormal movements or an arrest of movement, a disorder of
sensation or perception or a disturbance of behaviour or an impairment of
consciousness. Almost any required or genetic pathological process involving the
brain may cause epilepsy. The symptoms of epilepsy include falling down, shaking of
hands, legs and bodies, biting the teeth, foaming in the mouth etc.
 EPILEPTIC SEIZURE: An epileptic seizure is a transient occurrence of signs
and/or symptoms due to abnormal excessive or synchronous neuronal activity in the
brain. Epilepsy is a disease characterized by an enduring predisposition to generate
epileptic seizures and by the neurobiological, cognitive, psychological, and social
consequences of this condition.

2. EPEDIOMOLOGY:
 Epilepsy is a common disorder which affects 50 million people worldwide. As the
disorder is not curable there is a very high prevalence or existing population with this
disorder. Every year several hundreds of thousands join this pool of patients as new
cases.
 It is a compilation of the most recent epidemiological studies, focusing first on
studies from France and then on those from Europe and, where relevant, the rest of
the world.
 With a conservative estimate of 1% as prevalence of epilepsy, there are more than 12
million persons with epilepsy (PWE) in India, which contributes to nearly one-sixth
of the global burden.
AETIOLOGY:
Although there are many causes of seizures, some are more common than
others.
-Head injuries & toxins: heredity sound, head injuries, brain lesions, biochemical
disturbances also are likely to produce convulsions.
-Emotional stress
-Drug-induced
-Psychosocial causes: They are eccentricity, poverty of emotions, hypersensitivity and
rigidity.
-Specific Structural Causes Associated with Epilepsy
 Hypothalamic hamartoma
 Aicardi syndrome
 Focal cortical dysplasia
 Cavernous and other vascular malformations
 Dysembryoplastic neuroepitumors tumors (DNETS), gangliogliomas, and low-grade
tumors

3.  Mesial temporal sclerosis (MTS)
 Multiple Sclerosis
 Traumatic brain injury (TBI)
 Perinatal brain injury
 Vascular injury
 Hemimegaloencephaly
 Schizencephaly
 Periventricular nodular heterotopia (PVNH)
 Polymicrogyria (PMG)
Genetic causes of epilepsy
 CDKL5
 PCDH19
 Ring chromosome 20
-Metabolic causes of Epilepsy
 Glut 1 (Glucose Transport) Deficiency Syndrome (SLC2A1)
 Vitamin dependent
 Pyridoxine
 P5P
 Folinic acid
 Creatine transporter
 Mitochondrial
 Storage disorders
-Infectious causes of Epilepsy
 Neurocysticercosis
 Cerebral malaria
 TORCH infections (toxoplasmosis, other agents, rubella/German measles,
cytomegalovirus, and herpes simplex)- typically acquired during pregnancy and
present in very early life with seizures, growth and developmental delay, small head
size, cataracts or visual problems, rash and enlargement of the liver
 Bacterial meningitis- may cause seizures during the initial presentation however,
seizures often do not persist after it is successfully treated
 Viral encephalitis

4.  Tuberculosis
 Human immunodeficiency virus (HIV)
NORMAL CNS FUNCTION:
There is a balance exists between the inhibitory (γ-aminobutyric acid (GABA)) and
the excitatory (glutamate) neurotransmission
Excitatory neurotransmitters increase the likelihood of postsynaptic neurone
depolarization and generation of an action potential Inhibitory neurotransmitters reduce the
likelihood of postsynaptic neurone depolarization and generation of an action potential.
An imbalance between glutamate and gamma-aminobutyric acid neurotransmitter systems
can lead to hyperexcitability but catecholaminergic neurotransmitter systems and opioid
peptides were shown to play a role in epileptogenesis as well.

5. PATHOPHYSIOLOGY:
A seizure occurs when a portion of the brain becomes overly excited or when nerves
in the brain begin to fire together in an abnormal fashion. Seizure activity can arise in areas of
the brain that are malformed from birth defects or genetic disorders or disrupted from
infection, injuries, tumors, strokes, or inadequate oxygenation.
The seizures result from an abrupt imbalance between the forces that excite
and inhibit the nerve cells such that the excitatory forces take precedence. This electrical
signal then spreads to the surrounding normal brain cells, which begin to fire in concert with
the abnormal cells.
o Decreased inhibitory system + increased excitation  genesis of seizures
o Abnormalities in Ion Channel (Na+, K+, Ca+2) may cause seizures.
SYMPTOMS:
Symptoms vary from person to person. Some people may have simple staring
spells, while others have violent shaking and loss of alertness. The type of seizure depends on
due to etiological factors
Inhibitory neurotransmitter
when GABA receptors blocked
rhythmic & repetitive
hypersynchronous dicharge
of neurons
seizures
excitatory neurotransmitter
Glutamate
bind to
NMDA
Receptor &
opens
calcium
channels
seizures

6. the part of the brain affected and cause of epilepsy Behavioural changes, aura or visual
hallucinations before a seizure attack.
Symptoms of Epilepsy:
 Wild, monotonous bodily movements.
 Blackouts, disorientation and periods of unresponsiveness.
 Sudden fear.
 Tongue biting.
 Speech arrest.
 Loss of consciousness.
 Loss of bladder and rectum control.
 Aspiration Pneumonia.
 Headache, muscular pains and temporary weakness post seizure.
 Difficulty learning.
 Poor self-esteem, depression and suicidal thoughts.
CLASSIFICATION OF SEIZURES:
Seizures are broadly characterised as partial seizures (caused by a focal lesion)
and generalized seizure (caused by diffuse brain dysfunction). The psychiatric manifestations
of epilepsy are divided into those associated with seizures itself and those occurring between
seizures (interictally).

7. Generalized seizures
A. Generalized Tonic- Clonic seizures
 Major Epilepsy
 Commonest
 Last for 1-2 mins
 Unconsciousness & Tonic Spasm followed by clonic jerking & depression of all
CNS function
B. Absence Seizures
 Minor Epilepsy
 Last for 1/2 min
 Momentary Loss of consciousness & patient freezes and stares in one direction.
 Little / no bilateral jerking.

8. i. TYPICAL: Consist of impairment of consciousness without loss of muscles tone and
posture. Often manifest as inattention, an empty stare or interruption of speech or
motion. Attacks are often triggered by hyperventilation.
ii. ABSENCE SEIZURE ATYPICAL: Characterized by combination of impairment of
consciousness and motor or autonomic changes. *May have tonic (stiffness) or clonic
(jerking) spells or may have automatism (involuntary behaviour). *The EEG doesn’t
have 3/sec spike and wave pattern.
C. Atonic Seizures
 Akinetic Epilepsy
 Unconsciousness with relaxation of all muscles.
I) Brief Atonic Seizure: Leads to sudden fall or droop attack. Usually last for one or
two seconds.
II) Long Atonic Seizure: Sudden loss of consciousness. Fall to floor and remain
completely flaccid for one or several minutes.
D. Myoclonic Seizure
 Shock like momentary contraction of a single muscle.
E. Infantile spasms
 In infants
 Most typical epilepsy
 Muscle spasm
 Progressive Mental Deterioration
2. Partial Seizures
A. Simple Partial Seizure
 Cortical focal Epilepsy
 Lasts for 1/2 to 1 min
 No loss of consciousness
 Convulsions are confined to a particular area of cortex
B. Complex Partial Seizure
 Temporal lobe epilepsy
 Attacks of Bizarre & confused behaviours
 Emotional changes
 Purposeless movements

9.  Lasts for 1-2 min
 Aura (feeling & Seizures) often precedes
C. Simple Partial / Complex Partial Seizure Secondarily Generalized
 Partial Seizure occurs first and evolves into Generalized Tonic-clonic with loss
of consciousness
STATUS EPILEPTICUS: A condition when consciousness does not return between
seizures for more than 30 min. This state may be life-threatening with the development of
pyrexia, deepening coma and circulatory collapse.
FEBRILE SEIZURE: A febrile seizure is a convulsion in a child that's caused by a fever. The
fever is often from an infection. Febrile seizures occur in young, healthy children who have
normal development and haven't had any neurological symptoms before.
Infantile spasms Infantile spasms (also called epileptic spasms) are a type of seizure.
A seizure is a burst of uncontrolled electrical activity between brain cells that causes

10. temporary abnormalities in muscle tone or movements, behaviours, sensations and/or states
of awareness. Not all seizures are alike.
DIAGNOSTIC TESTS IN SEIZURE DISORDERS :
Haematological tests
• Serum
• Glucose – Hypoglycaemia.
• E & U – Electrolyte imbalances, increased blood urea nitrogen.
• Increased blood alcohol/ ammonia levels.
• Urine
• To detect medication toxicity.
• To detect Organic & Amino – aciduria.

11. Skull x-ray:
• Evidence of fractures.
• Evidences of space occupying lesions (shift in calcified pineal gland, bony erosions,
separated sutures, calcifications).
EEG:
• Tonic-clonic: high, fast voltage spiked in all leads.
• Absence: 3/s, rounded, spiked wave complexes in all leads.
• Infantile spasms: Hypsarrhythmia’s.
• Complex partial: square-topped, 4-6/s spike wave complexes over involved lobe.
CT/ MRI:
• show Structural changes
• Indicated in Focal seizures.
• Neonatal or Early Infancy onset.
• Status Epilepticus
• Focal Slowing/ paroxysmal EEG Activity.
• Echoencephalography
• Midline shifts in brain structures
• Cerebral Angiography
• Vascular abnormalities; subdural hematoma
Syncopes
• Global amnesia
• Cardiogenic (arrhythmia, ischemia, aortic stenosis)
• Breath-holding attacks • Benign paroxysmal vertigo
• Migraine
• Panic attack
• Psychogenic or Pseudo epileptic attacks
• Narcolepsy
• Cataplexy
• Sleep apnoea
MANAGEMENT:
Non pharmacological therapy:
During fits outside the hospital, the following are important:
• Place patient on the LEFT LATERAL position.
• If febrile, tepid sponge and expose to cold air.
• Loosen tight clothing around the neck.

12. • Put a soft mouth gag in between the jaws to prevent biting of the tongue.
HOME REMEDIES
• Exposure of limbs to naked flame: Risk of burns and tetanus
• Using spoon/ sticks as mouth gag: Oral ulcers, tooth dislocation, risk of aspiration
• Instillation of pepper into the eyes: Conjunctivitis, keratitis, risk of blindness
• Incisions and scarifications: Risk of tetanus
• Use of Cow’s urine concoction (alligator pepper, garlic, tobacco leaves): Risk of
hypoglycaemia
• Alcohol administration: Risk of hypoglycaemia
PHARMACOLOGICAL THERAPY:
CLASSIFICATION OF ANTI EPILEPTIC DRUGS:
Anti-epileptic drugs are classified as:
Mechanism of Action
These drugs act via various mechanisms –
 Decreased axonal conduction by preventing Na+ influx through fast Na+
channels – Carbamazepine, Phenytoin
 Increased inhibitory tone by facilitation of GABA mediated hyperpolarization-
Barbiturates, BZDs
 Decreased excitatory effects of glutamic acid – Lamotrigine, Topiramate (blocks
AMPA Receptors), Felbamate (blocks NMDA Receptors)
 Decreased Presynaptic Ca2
+ influx through type-T channels in thalamic neurons
– Valproic acid & Ethosuximide.

13. SCHEMATIC REPRESENTATION
CLASS OF DRUG ALONG WITH THEIR MECHANISM OF ACTION

14. ANTI-EPILEPTIC DRUGS:
1. Phenytoin
Mechanism –
Blocks axonal voltage gated Na+ channels → Prevents seizure propagation
Uses –
 GTCS
 Partial Seizures
 Status Epilepticus
 Trigeminal Neuralgia (Non-Epileptic Use)
Side Effects –
 CNS Depression
 Hirsutism
 Osteomalacia
 Gingival Hyperplasia
 Megaloblastic Anaemia
 Hypersensitivity/ Allergy
Contraindications –
 Myoclonic Seizure
 Absence Seizures
2. Carbamazepine
Mechanism –
Blocks axonal voltage gated Na+ channels → Prevents seizure propagation.
Uses –
 GTCS

15.  Partial Seizures [DOC]
 Trigeminal Neuralgia [DOC]
 Mania & Bipolar Disorder
 Diabetes Insipidus
Side effects –
 CNS Depression
 Osteomalacia
 Megaloblastic Anaemia
 Aplastic Anaemia
 Exfoliative Dermatitis.
 Increased ADH Secretion (Dilutional hyponatremia)
 Cleft Lip & Palate
 Spina bifida (if given to pregnant mother)
 Hepatotoxic
 Allergy (Steven Jenson’s Syndrome/ Toxic Epidermal Necrolysis)
Contraindications –
 Myoclonic seizures
 Atonic Seizure
 Absence Seizures
3. Valproic Acid
Enzyme inhibitor
Mechanism –
 Blocks axonal voltage gated Na+ channels → Prevents seizure propagation.
 But also, inhibition of GABA Transaminase (increases GABA levels)
 Blockade of T-Type Ca2+ channels
 Decreases Glutamate levels
Uses –
 GTCS
 Absence Seizures
 Myoclonic Seizure
 Dravet Syndrome
 Tardin Dyskinesia
 Mania & Bipolar Disorder
 Migraine Prophylaxes
 Status Epilepticus (Used IV)
Side Effects –
(MNEMONIC – VALPROATE)
V = Vomiting, Nausea (most common)
A = Alopecia, curling of hairs
L = Liver toxicity
P = Pancreatitis
R = Rashes
O = Obesity
A = increased Ammonia
T = Teratogenic (causes Neural Tube Defects), Thrombocytopenia
E = Enzyme inhibitor

16. 4. Ethosuximide
Mechanism –
Blockade of T-type Ca2
+ channels in Thalamic neurons
Uses
 Absence Seizures
 Ethosuximide is drug of choice in children(<2yrs)
Other Ant seizure Drugs
1. Lamotrigine
 Blocks Na+ channels & Glutamate Receptors
 Also, T type CCB
 Used in Various Seizures
 Side effects – Stevens – Johnson Syndrome (Rashes)
 These are safer in pregnancy [NOT TERATOGENIC]
2. Levetiracetam :
 Mechanism – SV2A inhibitor
 Used in focal Onset & Generalized Tonic-clonic seizures.
 Safe in pregnancy
3. Topiramate
 Block Na+ channels and glutamate Receptors (AMPA blocker)
 Enhances GABA Activity.
 Also, mild carbonic Anhydrase inhibitor
Uses –
 In focal seizures in adults & children > 2 years.
 Migraine prophylaxis
 Decreasing craving in Alcoholics
 Obesity
4. Felbamate
 Blocks Na+ channels and glutamate receptors (NMDA blocker)
 Used in Partial Seizure
 Side effects is Aplastic Anaemia.
5. Gabapentin
 Affect Ca 2
+ channels.
Uses –
 Seizure states
 Neuropathic Pain
 Post herpetic neuralgia
Side effect – Sedation
6. Zonisamide
 Na+ channel blocker, T type Ca2+ Channel blocker
 Also, Carbonic Anhydrase inhibitor
 Used in Seizure states
 Side effect is Renal Stone formation

17. 7. Locasamide
 Na+ channel blocker
 CRMP2 Protein inhibitor
8. Vigabatrin
 Inhibits Transaminase
 Used in treatment of infantile spasms with Tuberous Sclerosis
 Side effect is leads to Visual impairment
9. Ezogabine
 K+ channel opener
 Used to treat Partial Seizure
10. Barbiturates & Benzodiazepams
They block the GABA receptor
Example –
 Clonazepam – Absence Seizures
 Lorazepam – Status Epilepticus
 Carbamazepine – Partial Seizure etc.

18. SURGICAL THERAPY:
 LOBECTOMY: A lobectomy or lobe resection is a surgical procedure in which a
lobe of the brain is surgically removed. The most common form of paediatric
epilepsy surgery is temporal lobectomy. Some studies have shown that up to 80
percent of children become seizure free after this procedure.
 LESIONECTOMY: Lesionectomy is a type of brain surgery used to treat people
with epilepsy. The goal of lesionectomy surgery is to remove the seizure focus while
preserving vital functions such as speech, sensation, movement, and memory.
REFERENCES:
 Clinical pharmacy & therapeutics - Roger & walker, Churchill Livingstone
publication.
 Pharmacotherapy: A pathophysiologic approach – Joseph T. Dipiro et.al.Appleton &
Lange.
 https://medical-junction.com/anti-epileptic-drugs/
 Goodman & Gilman’s The Pharmacological Basis of Therapeutics.
…. THE END ….