SEMINAR ON

Epilepsy

(Once Sacred Disease)World Epilepsy Day

(26th March)

Introduction & Epidemiology

History

In past, believed that disorders was also caused by presence of demons in a person & if person breathed On or touched another the demon would spread to another person unless that person split immediately.

Epilepsy has existed for thousands of years but only in past hundreds years or so has it begun to Understood.

•The first person actually credited with the electrical theory was John Hughlings Jackson in 1873.

•  It was held that epilepsy was the result of erratic electrical discharges throughout the entire body

In the 1930’s the 1st method for testing the electrical hypothesis for epilepsy was discovered by HANS BERGER when he invented the EEG

HANS BERGER , German Neurologist

1873 - 1943

Manifestation of seizures by uncontrolled body movements…..

WHAT IS EPILEPSY..?? Epilepsy is a condition in which a person has recurrent SEIZURES with disturbance of consciousness, with or without characteristic body movements (CONVULSIONS)

So…WHAT IS SEIZURE? Paroxysmal event due to abnormal, excessive, hypersynchronous discharge from aggregate of CNS neurons.

CONVULSIONS..

EPIDEMIOLOGY

•Incidence of epilepsy is around 0.3-0.5% in different Population of world.

•The prevalence of epilepsy has been estimated at 5-10 person per 1000.

EPILEPSY IN WORLD

Epilepsy is one of the commonest neurological disorder …

Injury or Death can result from poorly treated or Untreated Epilepsy…

Epilepsy Incidence Rates by Age*

10

100

1000

0 10 20 30 40 50 60 70 80

All Epilepsy Types

Age (years)

Inci

denc

e pe

r 10

0,00

0

*Data from Rochester, MN (1975-84)Hauser WA et al. Epilepsia. 1991;32:429-445.

MORTALITY OF EPILEPSY

Patient with Epilepsy Have risk of death is roughly 2 or 3 times Greater than normal people without epilepsy

Significant number of patient die because of Accident , Status Epilepticus and a syndrome Known as SUDEP ( Sudden Unexpected Death in Epileptic Patient )

•Exact cause of Epilepsy is not Known..

•According to Some researches ……

Epilepsy occurs due to Iron Channels Mutation Congenital Imbalance of Neurotransmitter Etc…..

PATHOPHYSIOLOGY

SeizureReduced GABA

Receptor functionNMDA Receptor

Activation

GABA receptor mediates inhibition responsible for normal termination of a seizure

NMDA (Glutamate) receptor activation required for propagation of seizure activity

ETIOLOGY

CNS– Head trauma

• Seizure in 1 week of injury not predictive of epilepsy– Stroke– Vascular malformations– Mass (tumor/abscess)– Meningitis/encephalitis– Congenital malformations/ cortical dysplasias– Idiopathic

SYSTEMIC– Hypo/hyperglycemia– Hypo/hypernatremia– Hypocalcemia– Uremia– Hepatic encephalopathy– Hypoxia– Hyperthermia– Drug overdose or withdrawal

ANTI MICROBIALS & ANTIVIRAL :- Acyclovir , Isoniazid

ANESTHETICS & ANALGESIC :- meperidine , Tramadol , Local Anesthetic

PSYCOTROPIC :- Lithium , Antipsychotic , Antidepressent

ANTI MALERIAL :- Chloroquine , Mefloquine

DRUG OF ABUSE :- Amphetamine , Cocaine , Phencyclidine

DUE TO SOME DRUGs…

•Maximal Electroshock Seizures

•Pentylenetetrazol (PTZ) Clonic Seizures

•Chronic Focal Seizures

•Kindled Seizures

EXPERIMENTAL MODELS

Classification of SEIZURES

CLASSIFICATION OF SEIZURES

The International League Against Epilepsy (ILAE) published a modified version of the International classification of epileptic seizures in 1981

Based on clinical features & electroencephalic findings rather than underlying etiology or cellular substrate.

Classification of Seizures

Focal (partial)

Simple partial

Complexpartial

Partial seizures

evolving to secondary

generalized

Generalized

Absence

Myoclonic

Clonic

Tonic

Tonic-Clonic

Atonic

Unclassified epileptic

Neonatal

Infantile

Seizures

– Electrical discharges in a relatively small group of dysfunctional neurones in one cerebral hemisphere

– Structural abnormalities– Aura may reflect site of

origin– + / - LOC

Generalized

– Diffuse abnormal electrical discharges from both hemispheres

– Symmetrically involved– Cellular, biochemical or

structural abnormalities– No warning– Always LOC

Partial

What is AURA..??? When the effects of a partial seizure appear as a ‘warning sign’ before a larger seizure, they are known as an Aura.

Partial Seizures evolving to Secondarily Generalized Seizures

Simple partial (Relatively w/o impaired consciousness)

Partial Seizures (Focal Onset)

Complex partial (impaired consciousness)

Simple Partial (Relatively w/o impaired Consciousness) Motor symptoms (focal motor seizure)

Involves motor strip Manifested by abnormal movement of an extremity Jacksonian march- spread to involve contiguous regions Todd’s paralysis- post ictal transient hemibody weakness Epilepsia partialis continua-rare instance, seizures continue for hours &

days

Somatosensory symptoms Autonomic symptoms Psychic symptoms

Complex partial (impaired consciousness)

Typically frontal or temporal lobe onset

Often stereotyped for the individual patient

Average duration 1-3 minutes

Frequently seen in adult onset epilepsy

Automatisms: coordinated involuntary movements.

Simple Partial Seizures to Generalised Seizures Complex Partial Seizures to Generalised Seizures Simple Partial Seizures to Complex Partial Seizures to

Generalised Seizures

Partial Seizures evolving to Secondarily Generalized Seizures

Absence Myoclonic Clonic Tonic Tonic-clonic Atonic

Generalized seizures

Sudden onset Interruption of ongoing activities Blank stare Brief upward rotation of eyes Duration: a few seconds to 1/2 minute Evaporates as rapidly as it started Usually begin in childhood(Ages 4-8) or early adolescence

Absence Seizure(Petit Mal Epilepsy)

Tonic PhaseSudden sharp tonic

contraction of muscles throughout the body

respiratory muscle: stridor / moan /ictal cry

Respiratory inhibition cyanosis

Tongue bitingUrinary incontinence

Clonic PhaseSuperimposition of periods of

muscle relaxation on the tonic muscle contraction

Small gusts of grunting respiration

Frothing of salivaDeep respirationRemains unconsciousGoes into deep sleepAwakens feeling sore,

headaches

10-20 s

Tonic-clonic seizures(Grand mal/Epileptic fit)

•Myoclonus•Regularly repeating at a rate of 2-3 per sec

•Loss of muscle tone•Patient may fall to ground•Drop attacks

•Extremely brief (<0.1 sec) Muscle contraction•Jerky muscle movements

Clonic seizures

Atonic seizures

Myoclonic seizures

Non-epileptic seizures

May be manifestation of conversion disorder, factitious disorder or malingering

Features that may distinguish from epileptic seizures• Pre-attack preparation, absence of post-ictal confusion• “Disorganized” movements, pelvic thrusting, thrashing• Bilateral convulsions without loss of consciousness• Violent or goal-directed behavior, obscene language

Video EEG may help to diagnose

Pseudoseizures

They are disorder in which epilepsy is a predominant feature & there is sufficient evidence (clinical, EEG,radiological or genetic observations) to suggest a common underlying mechanism

Juvenile Myoclonic Epilepsy Lennox-Gastaut Syndrome Mesial Temporal Lobe Epilepsy Syndrome

Epilepsy Syndromes

Epidemiology by Seizure Types

Reproduced with permission from Hauser WA. Epilepsia. 1992;33(suppl 4):S10.

Complex Partial (36%)

Unclassified (3%)Myoclonic (3%)

Absence (6%)Partial Unknown

(7%)

Other Generalized (8%)

Simple Partial (14%)

Generalized TC (23%)

Diagnosis & Investigations

Epilepsy Differential Diagnosis

The following should be considered in the differential diagnosis of epilepsy:

Syncope attacks (when pt. is standing; results from global reduction of cerebral blood flow; prodromal pallor, nausea, sweating; jerks!)

Cardiac arrythmias (e.g. Adams-Stokes attacks). Prolonged arrest of cardiac rate will progressively lead to loss of consciousness – jerks!

Migraine. (Basilar migraine may lead to loss of consciousness!)

Hypoglycemia – seizures or intermittent behavioral disturbances may occur.

Narcolepsy – inappropriate sudden sleep episodes

Panic attacks PSEUDOSEIZURES – psychosomatic and

personality disorders

I. LABORATORY ANALYSIS :

Haematological: CBP( complete Blood Picture)

Biochemical: Calcium, glucose

Radiological: CT head

Microbiological: Lumbar Puncture(Always used with justification)

Investigations

II. Confirmation of epilepsy:◦ Dynamic investigations : result changes with attacks

E.g. EEG◦ Static investigations : result same between and during attacks

E.g. Brain scan

Cont……..

Electroencephalography (EEG)

WHAT IS EEG……????? A record of the electrical activity of large numbers of neurons in the brain, recorded with electrodes applied to the surface of the scalp.

• EEG indicated whenever epilepsy suspected

• Uses of EEG in epilepsy– Diagnostic: support diagnosis, classify seizure, localize

focus, quantify– Prognostic: adjust anti-epileptic treatment

Electroencephalography (EEG)

• Note:– Normal in 10-20% of epileptic patients– Background slowed by:

• diffuse cerebral process, postictal state

– Artifact from:• Eye rolling, tremor, other movement, electrodes

• Interpreted in the light of proximity to seizure

Normal EEG

EEG in Grand Mal Epilepsy

Pharmacotherapeutics

Classification:Barbiturate

Phenobarbitone

Deoxybarbiturate:

Primidone

Hydantoin

Phenytoin

Fosphenytoin

Iminostilbene

Carbamazepine

Oxcarbazepine

Succinimide Ethosuximide

Aliphatic Carboxylic Acid

Valproic Acid

Divalproex

Benzodiazepines

Diazepam

Lorazepam

Clobazam

Clonazepam

Phenyltriazine

Lamotrigne

Cyclic GABA

Analogues

Gabapentine

Pregabalin

Cont…

Phenytoin

Mechanism of Action:-At Therapeutic Dose:• Prolonging The Inactivation State of Voltage Sensitive Neuronal Na+ChannalAt High Dose:• ↓Ca++ Influx• Inhibition of Glutamate • Facilitation of GABA Response

Use:•GTCS and partial seizures.•Digitalis induce Arrhythmia

Dose:•100mg BD•In Children 5-8mg/kg/day

Therapeutic Plasma Conc. Is 10-20 µg/ml

•Gingival hyperplasia

•Hirsutism

•Hypersensitivity

•Megaloblastic Anemia

•Foetal Hydantoin Syndrome

•Osteomalacia

•Lymphedenopathy

ADRs …..(Phenytoin)

Other:•Ataxia•Vertigo•Hyperglycemia•Diplopia•Epigastric Pain•Nausea•Vomiting•Thrombophlebitis

Carbamazepine

Mechanism of Action:-•Prolongation of Na+ Channel Inactivation

Use:-•DOC for Partial Seizures & GTCS•DOC for Trigeminal Neuralgia

Dose:-200-400mg TDSIn Children 15-30mg/kg/day

Therapeutic Plasma Conc. Is 5-10 µg/ml

•Dizziness•Headache•Ataxia•Vertigo•Diplopia•Photosensitivity•Leucopenia•Aplastic Anemia•Hepatotoxicity•In Elderly Water Retention and Hyponetramia

ADRs….(Carbamazepine)

Valproic acid(Sodium Valproate)

Mechanism of Action:-•Prolongation of Na+ channel inactivation •Inhibition of T type Ca+2 current•Increased activity of GABA •Decrease release of Glutamate

Broad Spectrum Anti Seizure Drug

Uses:-•DOC in Absence, Myoclonic, Atonic Seizure•Alternative Drug in GTCS, Partial Seizure

Dose:-•200mg TDS•In Children 15-30mg/kg/day

Therapeutic Plasma Conc. Is 40-100 µg/ml

In Pregnancy:-•Neural Tube Defects•Spina Bifida

In Young Girls:-•Polycystic ovarian Disease•Menstrual Irregularity

ADRs………(Valproic Acid)

•Anorexia•Vomiting•Loose motion•Weight gain•Curling of Hair•Hypersensitivity Reaction

•First line Drug in emergency

Diazepam

Use:-•In Children Febrile Convulsion( Rectal instillation of Diazepam)

Dose:-•0.2-0.5 mg/kg slow i.v. inj.

•Thrombophlebitis•Fall in BP•Respiratory depression

ADRs…

ADR:-•Local Thrombophlebitis

Lorazepam

Dose:-•0.1 mg/kg inj. i.v.

Use:-•During Emergency & Status Epilepticus

Newer DRUGS•Topiramate

•Zonisamide

•Levetiracetam

•Vigabatrin

•Tiagabine

•Lacosamide

Treatment & General Management

Seizure Treatment

• Acute Management– 90% of seizures stop without treatment in under 5

minutes– Can give lorazepam or diazepam for seizures >5min– Monitor ABCDs, avoid injury and aspiration– Treat underlying medical conditions

• Long Term Management– Decide if therapy needed

• Seizures due to secondary causes (metabolic d/o, EtOH withdrawal, immediately following head trauma/stroke) may not need longterm Rx.

• Single generalized tonic-clonic seizure recurs in about 50%– Anti-epileptic medications

• Try single therapy• Add second medication if: Seizures not controlled with single

drug and maximal levels/side effects are achieved• Treat the seizures, not drug levels

Cont…

TREATMENT OF EPILEPSY…

At personal level…….•Identity card

•No. of nears & dears

•Visiting card of Dr

•Drugs in pocket advanced for 15 days

•Maintain seizure diary ( onset, duration etc)

General management

•Adequate sleep

•Avoid fasting

•Avoid working near moving machines

•Avoid swimming

•Avoid driving

Instruction for nears n dears…

•Ensure airway protection/ position to prevent aspiration

•Do not place anything in the mouth except when to suction

•DO NOT try to force suction/airway through clenched teeth

•When the patient stops convulsing, place patient in lateral decubitus

•Assess safety of patient

•Ensure lights in room are on

•Remove any object within reach of patient that could cause injury

•Loosen clothing

•Side rails should be up if patient is in bed

•Do not try to “hold the patient down

•Control the Seizures

•Same Drugs Should be Continued

•Valproate + Folic acid

•Phenytoin + Vit K

•Regular Ultrasound(USG) & other Assessments

EPILEPSY IN PREGNANCY…

•Planning to become Pregnant – minimum drugs

•NEWER Drugs-less Teratogenicity

DOC:-Among older drugs-Carbamazepine Lamotrigine-Preferred Drug Topiraamate-also used C/I Typical Absence Seizure

Status Epilepticus

Definition:-• Continuous seizure lasting greater

than 30 minutes

• Two or more sequential seizures without recovery of full consciousness lasting >30 minutes

Status Epilepticus

• Lorazepam 4 mg (0.1 mg/kg children) IV push at rate of 2 mg/min (can be given IM)

• Diazepam 10 mg (0.2-0.3 mg/kg) IV push at rate of 2 mg/min

• Fosphenytoin 150 mg/min (20 mg/kg) IV up to(can be given IM) Phenytoin sod.20 mg/kg IV no faster than 50 mg/minConsider Phenobarbitone sod. 50-100 mg (20 mg/kg) IV

• If Seizure continues: Intubation required

• General Anesthesia – Titrate to burst Suppression (Continuous EEG monitoring required)

– Pentobarbital (5 mg/kg load, 0.5-3 mg/kg/hr maint.)– Propofol (1-2 mg/kg load over 5 min, 2-10 mg/kg/hr maint.)– Midazolam(0.2 mg/kg slow IV bolus, 0.05-0.5 mg/kg/hr maint.)

PATIENT EDUCATION

•3 Years medication

•Do Not change brand of drugs

QUIZ TIME…

1. 22nd February2. 21st March3. 18th April4. 26th March

World Epilepsy day…?

4. 26th March

Full Form of HPLC..?

High Performance Liquid Chromatography

Who discovered 1st method for testing electrical hypothesis of epilepsy?

1. John Hughlings Jackson2. Robert Koch3. Hans Berger4. None of above

3. HANS BERGER

1. Absence seizures2. Clonic seizures3. Tonic-clonic seizures4. Atonic seizures

Blank stare Is seen in Which type of seizures?

1. Absence seizure.

1. Shock2. Hypoglycemia3. Pseudoseizures4. Narcolepsy

Which of the following is not included in differential diagnosis of Epilepsy?

1. Shock

Full Form of EEG…?

Electroencephalography

1. Phenytoin2. Sodium Valproate3. Carbamazepine4. Fosphenytoin

Which of the following is a broad spectrum anti-epileptic Drug?

2. Sodium Valproate

1. Lorazepam2. Diazepam3. Phenytoin4. Fosphenytoin

Which One of the following drugs is not used in status Epilepticus?

3. Phenytoin

1. Clonazepam2. Diazepam3. Lorazepam4. Clobazam

Which of the following anti-epileptic drug is given By Intra-rectal route?

2. Diazepam

1. 6 months2. 1 year3. 3 years4. 18 months

Duration of Medication in Epilepsy..?

3. 3 years