Transcript epilepsy-1233773401615061-1 - EPILEPSY Association Of Sri Lanka

Recent Advancements in
Epilepsy
Dr. Helal Uddin Ahmed
Assistant Registrar
National Institute of Mental Health
[email protected]
Introduction
Definition: The occurrence of transient
paroxysms of excessive or uncontrolled
discharges of neurons, which may be caused
by a number of different etiologies, leading
to epileptic seizures.
Synonyms: Seizure Disorder
Historical Background
Epilepsy derived from a Greek
term: Epilambanei -to posses, to
take hold of, to grab or to seize.
Vedic period of 4500-1500BC :
Ancient Indian Medicine refined and
developed the basic concept of
epilepsy
Charaka Samhita- The Ayurvedic
literature 400 BC: Describe
epilepsy as ‘Apasmara’ means loss
of consciousness.
Historical Background contd
Hippocrates 400 BC: ‘This is not
a sacred disease rather disorder of
brain’ . He
described some
physical treatment of epilepsy and
stated it is an incurable chronic
illness.
Ibn Sina 370 AH:
describe epilepsy as a
brain disease.
Historical Background contd
Europe and USA 1857: Bromide was used as
first anti-epileptic drugs.
1873 H. Jackson: Neurologist of Londondescribed
relationship
of
electrochemical
discharge of brain and seizure.
1920 H. Berger: German Psychiatrist developed
EEG to measure brainwaves and its application in
the field of epilepsy.
Historical Background contd
1909: Formation International league against epilepsy
(ILAE).
1912: Use Phenobarbitone as AED.
1938: Use Phenytoin as AED.
1950-1970: Developed many AED.
1981: ILAE classified epilepsy.
1997: ILAE, IBE and WHO jointly established Global
campaign against epilepsy.
Epilepsy synonyms in South East Asia
India: Apasamra, Mirgee,Lata, Laran
Srilanka: Apasamra
Indonesia: Ayan
Thailand: Rake Lom Ba Mu, Role Lom Chak
Bangladesh: Khichuni, Mrigee, Batash (bad
wind)
Epidemiology of Epilepsy
Epilepsy knows no geographical, racial or social
boundaries. About 50 million people in World have
Epilepsy.
It occurs in men and women and can begin at any age, but
is most frequently diagnosed in infancy, childhood,
adolescence and old age.
Prevalence:
Developed countries- 0.5% (0.4% - 1%)
Developing countries- five times higher
Incidence:
After infancy annual incidence- 20-70/100000 in
developed countries.
Developing countries- Incidence is double. (100/100000)
The life time risk of
having a single seizure:
About 5%.
Prevalence in South East Asian Countries
Bangladesh:
population.)
0.1%
(in
adult
India: 0.9% in Bangalore, 0.5% in
Mumbai, 0.4% in Delhi and 0.3% in
Kolkata.
Sri Lanka: 0.9% (In Kandy District)
Pakistan: 0.99%
Nepal: 0.73%
Thailand: 0.72%
Myanmar: 0.1%
Classification of Seizures
ILAE Classification (1981)
I. Partial (Focal)seizures
A. Simple partial seizures
B. Complex Partial
Seizures
C. Partial Seizures
evolving to secondary
generalized seizures
(tonic-clonic, tonic or
clonic)
II. Generalized seizures
(Convulsive and non-convulsive)
A. Absence seizures
i) Typical
ii) Atypical
B. Myoclonic seizures
C. Clonic seizures
D. Tonic seizures
E. Tonic-Clonic seizures
F. Atonic seizures
(Combinations may occur: myoclonic
and atonic or myoclonic and tonic)
III. Unclassified epileptic
seizures
Causes of Epilepsy
In 28% cases cause can be
determined. Rests (72%) are
Idiopathic.
Determined causes:
Inherited genetic
 Acquired : trauma,
Neuro surgery,
Inflammatory, Metabolic,
Infections, Tumor, Toxic
disorders, drugs, etc.
 Congenital: inborn error of
metabolism.
Withdrawal of drugs
Alcohol,Benzodiazepine,
Barbiturates, Other AntiEpileptics
Drugs That Induce Seizures
Antibiotics: Penicillin, INH, Cycloserin, Ciprofloxacin,
Metronidazole.
Anti Diabetic: Insulin,Phenformin.
Hormonal: Prednisolone, OCP, Oxytocin
Cardiac: Lidocaine,Procaine, Disopiramide
Anesthetics: Methohexital, Ketamin, Halothane,Propofol
Antimalarial: Chroloquine, Mefloquine, Proguanil.
Anti Spastic: Baclofen
Stimulant: Aminophylline, Doxapram, Theophyline.
Radiographic
contrast:
Meglumine
derivatives,
Metrizamide.
Drugs That Induce Seizures
Antidepressant: TCA- (Amitriptaline, Imipramine,
Clomipramine), Dosulepin, Buproprion. Venlafaxine,
Duloxitine,Reboxetine
Antipsychotics: Chlorpromazine, Zotepine,
Loxapine,Depot Anti-psychotics,Clozapine
Mood Stabilizer: Lithium
Psycho stimulant: Amphetamine
Safe Psychiatric medication in Epilepsy
Antidepressant: Moclobemide, SSRI (with cautious)
Antipsychotics: Haloperidol, Trifluphenazine, Sulpiride
Pathophysiology of Epilepsy
In normal brain inhibitory circuits limits synchronous
discharge. GABA is particularly play this role.
When GABA receptors blocked Rhythmic and
repetitive hypersynchronus discharge of neurons 
seizures
Excitatory NT  Ach , Aspartate and Glutamate also
involved to develop seizures
Intracellular recording shows burst of rapid action
potential firing with reduction of transmembrane
potential.
 inhibitory system +  excitation   genesis of
seizures
Abnormalities in Ion Channel
(Na+, K+, Ca-) may cause seizures.
(Prolongation of depolarization state)
Pathophysiology of Epilepsy
Repeated subthreshhold of a neuron
generates an action potentials 
seizures
It has been suggested that chronic
epileptic discharges may lead to
secondary epileptogenesis.
Short, uncomplicated seizures cause
no
permanent/
progressive
neorological dysfunctions in human
brain
BUT
uncontrolled generalized tonic-clonic
seizures or status epilepticus is
associated with high neurological
morbidity and permanent brain
damage ( due to hypo perfusion,
hypoxia, acidosis and other metabolic
disturbance).
contd
Clinical Presentations
(Partial Seizures)
Simple Partial Seizures:
Consciousness is fully preserved
 Motor disturbance may involve any body part
 Tingling , numbness, electrical shock like feelings
 Flashing light and colours,Simple hallucinations
 Changes in skin color, Blood pressure, Heart rate,
Pupil size, Piloerection.
 Psychic manifestation: Dysphasic- when cortical
speech area affected, Dysmnestic- disturbance of
memory,
Cognitive symptoms- dreamy state,
Affective
symptoms- fear, depression, anger,
irritability, elation,
erotic thoughts, Illusion of size,
structured hallucination.
Clinical Presentations
Definition:
Clinical Presentations
(Partial Seizures)
Clinical Presentations
(Partial Seizures)
Complex Partial Seizures
(Psychomotor Seizures/Temporal lobe Epelepsy)
 Always involved impairment of consciousness.
 Majority originate in Temporal lobe (60%); but
also originate
another lobe –
particularly
Frontal(30%).
 May start as simple partial seizures then progress.
 Aura may be present-short live (few seconds)
 Automatism: Oro-Alimentary, Mimicry, Gestural,
Ambulatory, Verbal, Responsive and Violent.
Duration: < 3 minutes.
Clinical Presentations
(Complex Partial Seizures)
Definition:
Clinical Presentations
(Generalized Seizures)
Generalized Tonic-clonic (grand mal)
Convulsive seizures
No Aura but have prodormal phase- general malaise
Tonic phase: stiff, crying out, tongue bite,
apnea,cyanosed,
increase heart rate and blood
pressure, fall, labored
breathing, salivation.
Clonic phase: intermittent clonic movements of muscles,
followed by brief relaxations, involved four limbs.
Incontinence at the end of clonic phase.
Duration: few minutes
Post ictal period: drowsiness, confusion, headache, deep
sleep
Generalized Tonic-clonic (grand mal)
Definition:
Clinical Presentations
(Generalized Seizures)
Typical Absence Seizures (Petit mal):
 Occur almost exclusively in
childhood or early adolescent.
Sudden loss of consciousness and
cease all
motor activities.
Suddenly appears blank and stares,
fluttering
of the eyelids,
swallowing, flopping of the head.
Attacks last only a few seconds (<10
sec)
and
often pass unrecognized. About
100-200
attacks may occur/day.
Characteristic EEG : 3 per sec
generalized spike and wave
Attacks precipitate by fatigue,
drowsiness,
relaxation , photic
stimulation or hyperventilation.
Clinical Presentations
Typical Absence Seizures (Petit mal)
Clinical Presentations
Myoclonic seizures
Abrupt , very brief, involuntery flexion movements.
Involve whole body or part of the body
Occur most commonly at morning, shortly after walking.
May occur in healthy people (physiological)
Atonic Seizures
Brief loss of muscle tone.
Heavy fall , with or without loss of consciousness.
Versive seizures
A frontal epileptic foci may involve the frontal eye field.
Force deviation of the eyes and turning head to the opposite
side.
Status Epilepticus
Series of recurrent Tonic-Clonic seizures occurs without
regaining consciousness over 30 min.
Waist Syndrome: Infantile spasm, hypsarrhythmic patterns of
EEG, severe encepalopathy with mental retardation.
Clinical Presentations
Infantile Spasm: Sudden brief seizures, typically tonic flexor
spasm of waist, extremities and neck. 20% mortality, who
survive 75% have mental retardation, 50% have life long
seizures.
Juvenile myoclonic epilepsy: Inherited condition.Under
recognized syndrome with myoclonic jerks, tonic-clonic or
clonic- tonic-clonic seizures or absence seizures. EEG shows
spike and wave pattern of 3.5-6 Hz.
Lennox-Gastaut syndrome: Devastating disorder in children.
Mixed types of seizures and mental retardation. Usually
cognitive deficit present. EEG shows slow (<2.5 Hz ) spike
and wave patterns.
Catamenial epilepsy: Epileptic women experienced that their
seizures worsen during menstruation; due to the imbalance
between the proconvulsant estrogen and anticonvulsant
progestogen.
Diagnosis of Epilepsy
Thorough History taking :
From patients
From reliable valid informants
From observer (who observed seizures)
Physical Examination:
Specially neurological system
Higher Psychic function
Laboratory Investigation:
S. Electrolytes, S. Prolactin, Blood sugar, CBC, TFT,
LFT, RFT, CSF study
Imaging:
EEG, Video EEG telemetry, CT Scan of Brain, MRI of
Brain, MRS, PET, SPECT.
Polysomnography
Differential Diagnosis
Condition mimicking
Seizures:
1. Pseudoseizure
2. Syncope
3. Some sleep
disorders
4. Hypoperfusion in
brain
5. Cardiac Arrhythmia
6. Emotional Outburst
7. Dissociative fugue
8. Drop Attacks
9. Migraine
10. Hypoglycaemia
True Seizure Vs Pseudoseizure
Features & Lab findings
True Seizure
Pseudoseizure
Resemble known seizure types Yes
No
Tongue bite
Yes
No
Duration
Short
Long
Post-Ictal Phenomena
Present
Absent
Injury
Yes
No
Occurs during sleep
Yes
No
Can be precipitated by
suggestion
No
Yes
EEG during attack
Abnormal
No Change
EEG after attack
Slowing
pattern
No Change
Serum prolactin (after attack)
Raised
No change
Anti Epileptic drug usage
Suppress
seizures
No Change
(may worsen)
Management of Epilepsy
Medical treatment:
Immediate care of seizures
Move persons away from danger
Recovery position (semi prone)
Ensure clear airway
Do not insert anything into mouth
Urgent medical attention- (patent airway, O2 ,
anticonvulsant, investigate cause)
Should not be left alone after recovery
Consider about regular AED
Surgical treatment:
Indicated when seizures shown to be intractable to medical treatment.
Removal of epileptic focus (eg:mesial temporal sclerosis)
Anterior Temporal Lobectomy
Corpus callostomy
Subpial transection
Vagus Nerve stimulation
Ketogenic diet
Guidelines for Anticonvulsant Therapy
Start with one first line drugs
Start with low dose: Gradually increase to effective dose
or until side effects.
Check compliance
If first drug fails due to side effects or continue seizures,
start second line drugs whilst gradually withdrawing
first.
Try Three AED singly before using combinations
Beware about drug interactions
Do not use more than two drugs in combination at any
one time
If above fails consider occult structural or metabolic
lesion and whether seizures are truly epileptic.
Choice of Anti Epileptic Drugs
Epilepsy Type
Partial and /or
Secondary GTCS
First-Line
Second-Line
Third-Line
Carbamazepine
Lamotrigine
Oxcarbazepine
Topiramate
S. Valporate(in
children)
S. Valporate
Tiagabine
Gabapentin
Clobazum
Phynytoin
Phenobarbital
Vigabatrin
Acetazolamide
Primary GTCS
S. Valporate
Lamotrigine
Topiramate
Carbamazepine
Phynytoin
Gabapentin
Phenobarbital
Tiagabine
Acetazolamide
Absence
S. Valporate
Lamotrigine
Ethosuximide
Clonazepum
Acetazolamide
Myoclonic
S. Valporate
Clonazepum
Piracetam
Lamotrigine
Phenobarbital
AED: Indications and Dosage
AED
Seizure type
Dose
Doses Therapeutic
range
per day
range
(mg/day)
(μmol/L)
250-2000
2-3
30-50
Carbamazepine
Partial,Secondary GTCS,
Sodium
Valporate
Primary & Secondary GTCS,
Absence, Myoclonus
400-2500
1-2
NA
Phenytoin
Partial, Secondary GTCS
150-350
1
40-80
Lamotrigine
Lorazepum
Clonazepum
25-500
4 i.v.
1-8
1-2
-2-4
NA
NA
NA
Ethosuximide
Partial, secondary GTCS
Status Epilepticus
Partial (adjunctive),
Myoclonus
Childhood Abssence
500-1500
2
200-700
Topiramate
Partial, secondary GTCS
200-600
1-2
NA
Phenobarbital
Partial, secondary GTCS
60-100
1
50-150
AED

Side Effects 
Neurological
AED: Side Effects
Sodium
Valporate
Carbamazepine
Phenobarbital
Topiramate
Phenytoin
Ataxia,
Nystagmus,
Diplopia,
Tremor
Ataxia,
Nystagmus,
Diplopia
Ataxia,
Nystagmus,
Diplopia
Neuropathy
Ataxia
Ataxia,
Nystagmus,
Diplopia,
Tremor,
Dystonia,
Asterixis
Neuropathy
Cognitive &
behavioral
Drowsiness
Drowsiness
Drowsiness
Drowsiness
Dermatological
Rashes,
Alopecia
Rashes, SJS,
Rashes
Confusion
Drowsiness
----
Hematological
Blood
dyscrasias
Megalobastic Anaemia,
Osteomalacia
----
Blood
dyscrasias
Osteomalacia
Endocrine
Hepatology &
Kidney
Pancreatitis
Liver
damage
Blood
Dyscrasias,
Thrombo-cytopenia
-------
-------
---Nephro-lithiasis
---Liver damage
Others
Nausea,
Weight Gain
Hyponatremia
Foliate deficiency,
Depression (adults),
Excitement (Children),
SLE
SLE
Facial
Dysmorphism
Foliate
deficiency
Drug Interactions
Other AEDs,
Antimalarials
Other AEDs,
OCP,
Antimalarials,
Corticosteroids
Other AEDs,
CCB,OCP,
Digoxin,
Antidepressant,
Antimalarials
Nausea,
depression,
Taste
alteration,
Weight loss
Other AEDs,
OCP
Rashes,
Hirsutism,
Gum
Hypertrophy,
Other AEDs,
OCP, Anti
Arrythmic,
Antimalarials,
Corticosteroids
Thyroxine
Withdrawal of AED
After complete control of seizures for 2-4 years,
withdrawal of Anti Epileptic drugs may be
considered. But in case of special professional group
(car driver, machine man etc) withdraw the AED after
keen follow-up.
AED should be tapered during the stopping of
medications.
Slow reduction by increments over at least 6 months.
If the patient is taking two AEDs one drug should be
slowly withdrawn before the second is tapered.
Prognosis
Generalized seizures are more readily controlled than partial
seizures.
Childhood onset epilepsy (particularly classical absence
seizures) carries the best prognosis for successful drug
withdrawal.
The presence of a structural lesion makes complete control of
epilepsy less likely.
Epilepsy outcome: After 20 years
50% seizure-free, without drugs, for last 5 years
20% seizure-free, continue to take medication, for last 5 years
30% seizures continue in spite of adequate dose of AEDs.
Refractory epilepsy: When seizure control is not achieved
with the first two appropriate and well tolerated AED
schedules taken as mono therapy or in combination.
Psychiatric comorbidities in Epilepsy
Mood variation: Nearly 1 in 3 patients of epilepsy report
significant concern about their mood.
Depression: Upto 55% prevalent in patients with epilepsy.
Suicide rate: In depressed patients with epilepsy is 5 times
higher than that in the general population and 25 times higher
in patients with complex partial seizures of temporal lobe
origin.
Anxiety : Upto 50% prevalent in patients with epilepsy.
Psychosis: Incidence of Psychosis 3.3% in patients with
idiopathic generalized epilepsy, 14% in Temporal lobe epilepsy.
In the concern of severity; Psychosis occurs in 0.6-0.7%
patients with epilepsy in community and 19-27% of epilepsy
patients who require hospitalization.
Recent Research and Achievements
Drug treatments: Sodium valporate or Lamotrigin is chosen as
first line treatments for Absence seizures and partial seizures.
[BMJ vol 318 ]
SANAD (Standard and New Anti-epileptic Drugs) study : Valporate
is significantly better than Topiramate and Lamotrigine in
treatment of idiopathic generalized seizures.[Lancet vol 369 March
2007]
Surgery: In developing countries, in patients with Mesial TLE
are feasible by a knowledgeable team consisting epileptologist,
neurosurgeon, and technicians with using MRI and EEG. [Epilepsia
49(3):381-5.2008]
In Benign Rolandic Epilepsy: Children with BRE demonstrated
specific recognition impairments due to cortical auditory
dysfunction. [Epilepsia, 49(6):1018-1026.2008]
Recent Research and Achievements
Seizure after Stroke: Overall incidence of seizures within
24 hours after stroke was 3.1%. Higher incidence seen in
hemorrhagic stroke (8.4%). Seizures after stroke had higher
mortality at 30 days after stroke.[Epilepsia 49(6):974-981.2008]
Akershus Study: Seizure free epilepsy patients on AED
monotherapy improve neuropsychological performance after
withdrawn the AED but a relative risk of seizures relapse
2.46, compared to those continuing medications. [Epilepsia
49(3):455-463.2008]
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Famous Persons with Epilepsy
Aristotle
Socrates
Julius Caesar
Fyodor Dostoyevsky
Lord Byron
Vincent Van Gogh
Alfred Nobel
Vlaldimir Illyich Lenin
Naepoleon Bonaparte
Tony Greig
Acknowledgements
Professor AH Mohammad Firoz
Director-cum-Professor, NIMH
Professor Dr. Md. Enayet Karim
Professor, NIMH
All Respected Teachers of NIMH
All Doctors of NIMH
&
Dr. Imtiaz Ahmed, Sanofi Aventis
Mr. Subrata Kumar Saha, Sanofi Aventis.
THANK YOU