EPILEPSY
DR. MANSOUR AL MOALLEM
Definitions :
An epileptic seizure is an abnormal and
excessive focal or generalized discharge of
neurons usually accompanied by an
observable behavioral abnormality.
It is a symptom of the brain hyper-excitability
which may affect otherwise normal individuals
(e.g. with ECT, head trauma).
Epilepsy is a prediposistion to recurrent
epileptic seizure, with various etiologies.
Seizures are paroxysmal discrete events
although they may recur in close
succession without an intervening
return to normal consciousness
producing a state called status
epilepticus . Generalized convulsive
status epilepticus may be life
threatening if not terminated within a
few hours.
Seizures usually spontaneous or
provoked by nonspecific factors
increasing brain excitability such as
sleep deprivation, drug or alcohol
ingestion or withdrawal or
hypoglycemia.
Rare patients have their seizures
provoked consistently by specific
sensory stimuli (e.g. flickering lights,
video games or television, a specific
piece of music, reading, immersion in
hot water, etc.): the reflex epilepsy.
Epidemiology of Epilepsy
• 5% - 7% will have a seizure at
sometime during their life
• 1% - 2% of the population suffers from
epilepsy
• Peak age incidence: newborn, first
decade, elderly
• In only 50% is an etiology identifiable
• 80% respond well to treatment
Is Epilepsy Inherited ?
Genetic factors play only a minor role in
most type of epilepsy. Certain inherited
diseases, which are rare, have epilepsy as
one of their manifestations. Absence
seizures have a tendency to run in
families. In general, a child with an
epileptic parent has about a 5% chance of
developing epilepsy.
Major Causes of Seizures in Different
Age Groups
Etiology
Of seizure
Newborn
Infancy
Perinatal injury
*
*
Metabolic defect
*
*
Childhood
Congenital
Malformation
*
*
Infection
*
*
Adolescenc
e
Genetic epilepsy
*
*
*
Genetic disease
*
*
*
*
*
*
*
Postnatal trauma
Brain tumor
Vascular disease
Young
Adult
Old
Adult
*
*
*
*
Classification of Seizures
International classification of seizures
A) Partial (focal) seizures - with or without
secondary generalization)
1-Simple Partial
a)
b)
c)
d)
motor
sensory
autonomic
psychic
Classification of Seizures (cont)
2-Complex Partial (with or without automatisms)
a) impairment of consciousness at onset
b) simple partial onset followed by
impairment of consciousness
Classification of Seizures (cont)
B) Genleraized seizures
a)
b)
c)
d)
e)
Tonic-clonic (Grand Mal)
Absence (typical Petit Mal or atypical)
Myoclonic
Clonic
Atonic
Simple Partial Seizures (Focal)
• Seizure in which the first clinical and EEG changes
indicates initial activation of a system of neurons
limited to part of one cerebral hemisphere but where
there is no alteration of consciousness.
• Clinical symptoms, is determined by the anatomical
location of the seizure focus. May be: motor signs,
sensory symptoms, autonomic signs and symptoms,
psychic symptoms.
• May evolve to complex partial or secondarily
generalized tonic-clonic seizure.
Complex Partial Seizures
(Psychomotor)
• Impaired consciousness associated with automatic
behaviour
• The phases (in temporolimbic seizure): stare,
stereotyped automatisms, reactive automatisms
• May evolve from simple partial seizure and to a
secondarily generalized tonic-clonic seizure
• Occur in 40% of patients with epilepsy
• Most common seizure type seen in adult
• 50% of patients have onset in childhood
• Drugs control seizure in less than ½ of patients
• Disabling psychosocial disturbances develop in 1/3
Tonic-Clonic Seizure (Grand Mal)
• Abrupt loss of consciousness (may be vague illdescribed warning but no true aura
• Sudden sharp bilaterally symmetrical contraction
muscles, cry, fall, head extension, cyanosis. May be
tongue-biting and incontinence
• Bilaterally symmetrical clonic jerks, may be salivation
and frothing at the mouth
• Deep respiration and relaxation of muscles
• Post-ictal period of depressed consciousness, usually
awakens with muscle stiffness and sometimes
headache
Absence Seizures (Petit Mal)
• Sudden onset brief (usually <10 sec)
interruption of ongoing activities
• Blank stare, usually unresponsive when
spoken to
• May have stereotyped motor
automatisms (mild clonic or tonic),
especially if prolonged
• Abrupt onset and abrupt cessation
• No post-ictal confusion or other
symptoms
Atypical Absence Seizures
• Alteration of consciousness which may not
be complete (some activities may continue
in obtunded child.
• May have loss of tone of face and neck
muscles and/or myoclonic twitching of the
eyelids and mouth.
• Onset and cessation gradual.
Myoclonic Seizures
• Sudden very brief shock-like muscular
contractions.
• May be generalized or confined to the face
and trunk, to one or more extremities, or to
individual muscles or group of muscles.
• May be regularly repetitive or sporadic.
• May occur in other neurological conditions
as well as epilepsy.
Tonic Seizure
• Brief generalized tonic contraction; head
extension, stiffening of all four extremities.
• Tachycardia; apnea, then cyanosis.
• Frequently seen in Lennox-Gastaut
Syndrome, especially during slow wave
sleep.
Clonic Seizures
• Rapidly repetitive bilateral jerking of
extremities and facial muscles and loss
of consciousness.
• May be accompanied by autonomic
changes.
• Post-ictal phase is usually short.
Atnoic Seizures (Drop Attacks)
• Sudden diminution in muscles tone, which
may be fragmentary.
• Extremely brief or no loss of consicouness.
• May occur repetitively in a rythmic,
successive manner.
• Atonic seizure frequently seen in LennoxGastaut Syndrome; drop attacks may occur
in neurological condition other than epilepsy.
Pseudoseizures
• Atypical features (e.g. Partial preservation of
consciousness during convulsion)
• Tendency to occur in company.
• Triggered by emotional upset.
• Urinary incontinence, tongue-biting, injury are
unusual.
• Poor psychosocial history.
• Unresponsive to appropriate AED therapy.
Pseudoseizures (cont)
• 5-20% of outpatient epilepsy population
have pure pseudoseizures.
• 20-30% of uncontrolled epileptic also have
pseudoseizures.
• 20-30% of pseudoseizure patients also
have epilepsy.
• F:M 3-4: 1
• 85% of cases are between 15 and 25
years old.
Differential Diagnosis
•
•
•
•
•
•
•
•
•
Syncope
Psychogenic pseudoseizures
Panic/anxiety/HV attacks
Movement disorders
Sleep disorders (narcolepsy, parasomnias)
Hypoglycemia
TIA΄s
Migraine
Pheochromocytoma
Investigations
• Electroencephalogram EEG
• CT scan brain / MRI brain
Treatment
The Principles :
1-Accurate diagnosis
2-Accurate seizure classification and if possible
syndromic diagnosis
3-Select the most effective drug for seizure type
4-Begin with monotherapy
5-Allow the adequate time to assess the effect of the
drug
6-If the seizure are not controlled, obtain blood levels
7-Change gradually to a second drug if the first drug
Does not control the seizures
Mechanisms of Action of
Anti-epileptic Drugs
Mechanism
Reduction of membrane excitability by
blocking
Voltage-dependent Na channels.
Drugs
Blockage of Calcium-T channels in the
thalamic relay neurons
Ethosuximide
possibly Valproate
Enhancement of GABA inhibitory action
Benzodiazepine
Barbiturates
Figabatrin
Possibly Valproate
Reduction of glutamate excitatory action
Lamotrigine
Unknown
Gabapentin
Phenytoin
Valproate
Lamotrigine
Antiepileptic Drugs of Choice
1st Choice
Monotherapy
Alternative
Monotherapy
Add-on Agent &
Others
VPA
CBZ
PB
PRM
CLB
LTG
VGB
Absence
VPA
ESM
CLB
AZM
LTG
Myoclonic
VPA
NZP
AZM
LTG
Atonic
VPA
NZP
CLB
LTG
Partial
Simple or
Complex
+/-secondary gen..
CBZ
PHT
VPA
PB
PRM
CLB
GBP
LTG / VGB
Seizure Type
Generalized
Tonic-clonic
Legends
AZM= acetazolamide
CZB= clonazepam
LTG= lamotrigine
PHT= phenytoin
VPA= valproic acid
CBZ= carbamazepine
ESM= ethosuximide
NZP= nitrazepam
PRM= primidone
CLB= clobazam
GBP= gabapentin
PB= phenobarbitone
VGB= vigabatrin
Factors associated with an increased
probability of seizure recurrence following
medication withdrawal
•
•
•
•
•
Longstanding, severe epilepsy, initial difficult to control
Structural brain damage and neurological handicap
Partial seizures and mixed seizures
Persistent epileptic findings on EEG
Specific syndromes which are known not remit
e.g. juvenile myoclonic epilepsy
• Adult onset epilepsy
Surgical Treatment of Epilepsy
• Seizure uncontrolled with medical therapy or
intolerable side effects
• Good cognitive function
• Identifiable focus (except for callosotomy)
• Social support system
International Classification of Epilepsies
and Epilepsy Syndromes
1- Localization-related (focal, local, partial)
epilepsies and epileptic syndromes
A. Idiopathic with age-related onset
1. Benign childhood epilepsy with
centrotemporal spikes
2. Childhood epilepsy with occipital
paroxysms
B. Symptomatic
2-Generalized epilepsies and epileptic
syndrome
A- Idiopathic with age-related onset
1. Benign neonatal epilepsy
2. Childhood absence epilepsy (pyknolepsy)
3. Juvenile myoclonic epilepsy (impulsive
petit mal)
4. Juvenile absence epilepsy with generalized
tonic-clonic seizures on awakening
B- Secondary (idiopathic or symptomatic)
1. West syndrome (infantile spasms)
2. Lennox-Gastaut syndrome
C- Symptomatic
1. Nonspecific etiology (early myoclonic
encephalopathy
2. Specific syndromes (epileptic seizures that
may complicate many diseases, e.g.Ramsy
Hunt syndrome, Unverrichs disease
STATUS EPILEPTICUS
What is the defenition?
STATUS EPILEPTICUS
Definition.
Seizure persists for 30 minutes, OR two or
more sequential seizure without full
recovery of the consciousness between
the seizures.
Epidemiology
• 60 per 100,000 individuals per year in the general
population
• Bimodal distribution, high value during the first year of
life and over the age of 60
• Mortality around 22% (pediatric 3%, adult 26% and
elderly 38%)
Determined by:
– age
– seizure duration
– etiology
Etiology.
Majority of patient with SE did not have a history
of epilepsy (38% of children, 40-50% of adult
and 30% of elderly did not a history of
epilepsy).
In adult:
• Low anticonvulsant drug level 34%
• Remote symptomatic
( hemorrhage, tumor) 25%
• CVA 22%
In children:
• Infection
• Fever
• Electrolyte disturbance
Why high morbidity & mortality…
Metabolic Complication Associated
with status epilepticus
• Metabolic & others
– Lactic acidosis
– Hypercapnia
– Hypoglycemia
– Hyperkalemia
– Hyponatremia
– Dehydration
– leukocytosis
Medical complication SE (cont)
• Autonomic
– Hyperpyrexia
– Failure of cerebral autoregulation
– Vomiting
– Incontinence
• Renal
. Prerenal asotemia
– Renal failure from rhabdomyolysis
Medical complication SE (cont)
• Cardiac/Respiratory
– Hypoxia
– Arrhythmia
– High blood pressure
– High output failure
– Pulmonary edema
– Pneumonia
• Cognitive
– Intellectual impairment with memory loss
How you treat…
Management. The goal should always be
immediate diagnosis and termination of
seizures.
• History : From the companion/previous
notes
• Examination:
General / systemic / Neurological
• Investigations:
(1) CBC / deferential
Electrolytes
Blood sugar
Investigations (cont)
(2) EEG
(3) ECG / X-ray / ABG
(4) CT scan brain or MRI brain
Treatment
(1) Monitor vital signs
(2) I.V. line
(3) 02
(4) Anti-epileptic drugs (AED)
The drug should be administered I.V. for
rapid absorption without reacting with
other medications or solutions.
Specific Drug Compounds.
1- Benzodiazepines (BZD)
Diazepam / Lorazepam / Midazolam
• Work by enhancing GABA ergic inhibition
by binding to the BZD-GABA, and
barbiturate receptor complex.
• High lipid solubility, they enter the brain
quickly, but they redistributed to other
areas of the body, reducing their clinical
effect.
Specific drugs compound (cont)
• They have good efficacy (70-80%) to
terminate all type of seizure but with high
rate of relapse due to short half-life.
• Adverse effects respiratory suppression,
hypotention, sedation, and local tissue
irritation.
Diazepam.
Half-life 15 minutes
5-10 mg I.V., it can be repeated
Lorazepam.
Half-life 2-3 hours (less lipid soluble + bind more tight to
GABAergic receptor)
Effect last for 6-12 hrs
4-8 mg I.V.
Midazolam
More lipid soluble than the other two, so shorter half life
with higher relapse.
Good for continue I.V. infusion with titration accordingly.
0.2 mg /kg followed by 0.1- 0.2mg /kg/hr
2- Phenytoin
•
•
•
•
High lipid soluble with long duration
Control 60-80%
Non sedative
Cannot mixed with glucose, it
precipitate out of solution
• Loading dose 18-20 mg/Kg at rate not
exceed 50 mg/min; if no response, it
can be repeated with half the dose.
• Adverse effect : arrhythmia/ hypotention
ESPONSE, Refractory status epilepticus
nsive Care Unit
Consider potential incubation and
mechanical ventilation.
Avoid the use of neuromuscular junction
blockade as it can mask ongoing motor
manifestation. A short acting nondepolarizing agent such as vecuronium is
preferred.
Drugs Therapy Cont..
3- Phenobarbital
Dosage 15-30 mg/Kg
Adverse side effects
-respiratory depression
-hypotention
-sedation
-cardiac depression
4- Midazolam
5- Propofol
Anesthetic agent
Mechanism of action not known
3-5 mg/Kg followed by a continuous
1-18 mg/Kg/hr infusion
Side effect:
lacticacidosis, hypotention and
hypothermia
IF NO RESPONSE
Phenobarbitone or inhalational anesthesia
can be used to achieve burst-suppression
(Require continue EEG monitoring)