Epileptic Seizure , Epilepsy and

Status Epilepticus
Objective :
1. Know the definition of Seizure & Epilepsy
2. Describe the classification of seizures
3. Describe the etiologies of Epilepsy & Status
Epilepticus
4 Describe the management of Epilepsy
5 Describe Anti Epileptic Drugs / AEDs including
mechanism of action and side effect
6. Describe the definition of Status Epilepticus & its
management
• Compulsory reference:
Ropper AH, Samuels MA. Epilepsy and other
seizure disorder. In: Adam and Victor’s
Principles of Neurology, 9th ed. USA: McGraw-
Hill; 2009p.304-330.
A. Summary Seizure & Epilepsy
( 5th semester )
An Epileptic Seizure : a “transient “ occurrence
of sign and or symptoms ( = clinical
manifestation ) due to abnormal excessive and
synchronous neural activity in the brain
• Most Seizure / Epileptic seizure, self limiting,
stop within seconds to 2-5 minutes
• An epileptic seizure may be the result of an
acute precipitant ( acute symptomatic =
provoked ) or occur in the absence of precipitant
factor ( unprovoked )
Provoked or unprovoked Epileptic
Seizure
• Epilepsy is a condition characterized by
recurring epileptic seizures, usually sponta-
neous / unprovoked due to a chronic
underlying process in the brain
• Generally , Epilepsy is a condition in which an
individual tends to experience recurrent
unprovoked seizures ; the risk to develop
recurrence on person with a single
unprovoked seizure : 40 - 50 %
• People with Epilepsy ( pwe ) during their
treatment , may get acute symptomatic
seizure cause by trigger factor ( trigger factor
for pwe = etiology of ASS of non pwe )
• A single seizure is not diagnosed as epilepsy.
Two or more initial seizures occure within a
24 hours period are considered as a single
seizures.
• But, …
• A first seizure / a single seizure often the first
identifiable sign of epilepsy in some cases
A single seizure with evidence cortical lesion :
• Neurological abnormality and
• Chronic abnormality in neuro-imaging or
• Epileptiform abnormality on EEG

• Could serve as the basis for diagnosis of

Epilepsy ( Guberman & Bruni J )
Reflex Epilepsy
• Seizure / Epileptic seizure provoked consistently
by a specific environmental stimulus, not
spontaneous
• Not applied by internal influences :
menstruation, fatigue, stress, nor specific
precipitans to pwe (patient with epilepsy)e.g.
sleep deprivation
• Patients may also experience spontaneous sei-
zure !
Epileptic seizure continued

Clinical presentation of Epileptic Seizure:

sudden episodic (= transient ) disturbances of
consciousness, mental function, motor
activity, sensory activity and or autonomic
activity
Simplified : Convulsion & non convulsion
• Acute provoke seizure / acute symptomatic
seizure
seizure occur in context of an acute brain
insult or acute systemic disorder such as head
trauma, stroke, an intracranial infection or
toxic / metabolic insults

The term ‘ Acute ‘ :

*Forsgren L,Hesdorffer D(2009) : occuring during the first
week after the insult

*Guberman A,Bruni J(1999): occurring less than 1-2weeks

after the brain or metabolic disturbance.
Type of Epileptic Seizure :
• Partial ( = Focal,localized ) Seizure
paroxysmal dysfunction of neuro-glial-vascular
network at one hemisfer or specific area of one
hemisfer of brain
Clinical : the seizure associated with the function
of specific area at localized lesion
* Simple : no alteration of consciousness
*Complex : altered consciousness or complete lack
of contact with the environment
• Generalized Seizure
paroxysmal dysfunction of neuro-glial-vas-
cular network at more diffuse area of the
whole brain
Clinical :
Primary : bilaterally synchronous onset
Secondary : partial seizure progress to
secondarily generalized seizure
Epileptic seizures are fundamental elements
of epilepsy
Epilepsy has to be differentiated from epilep-
tic seizure !
Case synopsis :
• Anne 45 y-o, during 24 hours :
- Clinical manifestation:
* new onset seizure
* Recurrent seizures
* Focal onset evolving to generalized seizures

- Brain imaging in emergency condition : CT Scan

without contrast: left focal abnormality: poorly
circumscribed hypointens, hemorrhage and edema

- Diagnosis ………………..? Epileptic seizures or Epilepsy ?

B.EPILEPSI and STATUS
EPILEPTICUS
 HOW
? ?
Epileptic seizure → → Epilepsy
 C.Epileptogenesis

• a transformation process of a non epileptic

neuronal network became a seizure
generating network because of chronically
hyper-excitable condition via a complex
process.
• There is latent interval between the initial
epileptic event and the chronic epileptic
phase.
• Scheme 1
Initiating insult : head injury, cns infection, stroke, brain injury
caused by other etiology

Functional / structural
changes

Seizure

Rapid effect long-term effect

- Acute symptomatic seizure - late/remote symptomatic seizure
- Remote symptomatic epilepsy
• Schema 2

intiating insult remotesymptomatic

Latent period :
Weeks, months, years
Case synopsis :
• Anne 45 y-o, during 24 hours :
- Clinical manifestation:
* new onset seizure
* Recurrent seizures
* Focal onset evolving to generalized seizures

- Brain imaging in emergency condition : CT Scan

without contrast: left focal abnormality: poorly
circumscribed hypointens, hemorrhage and edema
- New onset seizure = Rapid effect

- Diagnosis : Acute Symptomatic Seizures caused by

brain hemorrhage
• Continued

Her new MRI with contrast showed

Mass : Glioma, the doctor could make D/ Epilepsy

* initiating insult , acute structural lesion of the

brain → rapid onset : acute symptomatic seizures
→ latent period → unprovoked seizures , chronic
structural brain lesion → Epilepsy
 D .How to DIAGNOSE EPILEPSY
• The diagnosis is a process consist of three
steps :
1. Differentiate episodic attacks / paroxysmal
events : ask the patient and witness (es ) to
describe in detail, step by step → to
establish a correct diagnose seizures and
Epilepsy
2. Classification of type of seizure
3. To establih the Etiology
 Classification of Epileptic Seizure
• According to classification of the international
leaque against epilepsy (ILAE)
• is based on:
– Clinical manifestation & Electroencephalogram
(EEG)
Epileptic seizure (simplified) 1981
I. Partial / local seizures
II. Generalized seizures
III. Unclassified epileptic seizures
NOTE :
• Diagnosis of epileptic seizure type not always
easy.
The type of epileptic seizure is importance to
decide selection of AEDs / Anti Epileptic Drugs
 Etiology Epilepsy

• Often multifactoral; genetic and acquired

• Any type of lesion affecting the cerebral
cortex can cause seizures. The role of
subcortical and brainstem can be more
recognized ( Berg AT,Millichap JJ,2013 )
• Etiology is very much age dependent
• Age related : Newborn , Infants / young
children, Older children / adolescents,
Adults, Elderly
• Adults : trauma , tumors, cerebrovascular,
inherited metabolic, drugs
• Elderly : cerebrovascular, drugs, tumors,
degeneratif
• Epilepsy can be classified etiologically * as:
Remote symptomatic due to known or
identifiable acquired brain lesion
Cryptogenic, is unknown; could be due to an
acquired brain lesion after an insult, which has
not yet been identified
Idiophatic , which etiology is unknown,
presumed to be genetic
* Epilepsia 1989;30 ( 4 ) : 389 - 399
• The genetic factor:
the mode of inheritance is very complex;
almost of all the genes identified which
contribute to susceptibility to epilepsy are
genes that code for ion channels.
Only a few of idiopathic seizure is a simplified
(Mendelian) pattern of inheritance
• Gene expression influenced by environmental
factors and often age dependent
• Gene expression influenced by environmental
factors and often age dependent

• Genetic factor in Certain epilepsies or seizure

syndrome have strong environment or aqui-
red component e.g. post trauma Epilepsy &
Febrile Convulsion ( Guberman A,Bruni J,1999)
Etiology continued
• Genetic
• Part of monogenic genetic defects that cause brain
abnormalities have epilepsy : abnormalities of ion
channels or neurotransmitter receptors.
• Chromosomal abnormalities have epilepsy / increased
risk of epilepsy eg. Trisomy 21 ( Down Syndrome),
Alzheimer in older people
• Mitochondrial DNA disorders
• Specified inherited metabolic disordres ,↑incidence of
seizure : hypoparathyroidism, Wilson disease
• Hereditary neurocutaneous disorders: Tuberous
sclerosis, Sturge-Weber syndrome
Genetic continued…
• Overall risk of unprovoked seizures in
offspring of a parent with epilepsy is
approximately 6% ( twice high in maternal
than paternal ) ; risk ↑↑ to 9-12% in
idiopathic E.
Etiology continued

Acquired Etiology
Remote symptomatic epilepsy ( term and concept 1981 )
• epilepsy that occurs in association with antecedent
condition that has been demonstrated to increase
the risk of developing epilepsy
• epilepsy due to known or identifiable acquired
brain lesion
Acquired continued

Acquired Brain lesion

• Hippocampal sclerosis
• History of prenatal & peri-natal injury : toxemia,
eclampsia, forceps delivery, peri-natal hemorrhage
and ischemic-hypoxic encephalopathy
• Post-traumatic / head trauma
• Cerebral tumor
• Central nervous system infection / inflammation /
immunology
• Cerebral-vascular disease
• Degenerative diseases and dementia
Cranium tumor
Tuberculoma
• The best thought of ETIOLOGY

in any given individual, the etiology are

interaction among *genetically determined
seizure thresholds, *underlying predisposing:
structural pathologies or metabolic
disturbance and *acute precipitating
factors.
 CLINICAL DIAGNOSE
• The important thing: detail & systematical
interview
• Medical history including neurological history,
family history, previous psychiatric problem
• video recording ( if available )
• careful general and neurological examination.,
attention to vital sign, cutaneous/ subcutaneous
lesion, heart rhythm , focal neurologic signs, optic
fundi and development assessment in children.
• Seizure type based on the description of
attack from patient and eye witness
• If possible 4 stages of attack: prodrome, aura,
ictus and post ictal state
• Abnormality of skin: tuberous sclerosis
/adenoma sebaseum, neurofibromatosis/café
au lait patches, port wine naevus
• Sometimes need other supportive diagnostic
procedures
Differential Diagnose

There are other episodic attack not caused by prima-

rily abnormal brain activity : Non Epileptic Seizure

– Psychogenic: psychogenic non-epileptic seizure

(PNES) : pseudo-seizure / hysterical reaction,
panic attack.

– Nonpsychogenic nonepileptic seizure (NPNES) an

attack caused by disturbance of circulation or
cardiogenic eg.: Transient ischemic attack,
syncope, drop attack
• DD/ of episodic attack / paroxysmal event of:
* Alteration of consciousness, motoric /
sensoric disturbance caused by cerebral
abnormality of non epileptic lesion ( NENP)
or Psychogenic Non Epileptic (PNE)
DD/ ……
* Only lost or alteration of awareness / cons-
ciousness
DD/ ……
* Only motor or sensory phenomena attack
DD/ ……
* Drop attack
DD/ ……
Table1. The Attack Characteristics of Epileptic Seizures
versus Psychogenic Seizures
Characteristic Epileptic seizure Psychogenic seizure
* Duration Brief (seconds to minutes) Minutes to hours
* Presence of other Variable Frequently
* Diurnal Pattern Day or Night Usually day, never during
sleep
* Physical Injury May occur Rare
* Motor activity Stereotypic Avoidance behavior, forced
eye closure, irregular
extremity movements, side
to side head movement
*Post-ictal confusion, Common Uncommon
headache, sleep
Table2. The Attack Characteristics of Epileptic Seizures
versus Syncope

Features Syncope Seizure

* Occurrence Awake, mostly upright Awake or a sleep
* Premonition sweating, Common Rare
light-headedness
* Onset Less abrupt Abrupt
* Post-ictal recovery Rapid Slow
* Post-ictal confusion Uncommon Common
* EEG Usually normal May be abnormal
Triggering factors in reflex epilepsies
• Visual
Photic stimulation, patterns, television, video games, eye
clossure, eye fluttering, color
• Auditory
Music (piece, note), specific voice , specific sound
• Somato-sensory
Tap or touch, hot water immersion, tooth brushing
• Mental (thinking)
Calculation, problem solving (e.g., chess, math problems),
card games, drawing
• Motor
Movement (kinesiogenic), swallowing, eye movements
(convergence)
• Other (combination) : reading, Eating, Exercise, being
startled
•
•
•
 Supportive Diagnostic Procedure

1. Blood examination:
Complete peripheral blood incl. erytrocyte
sedimentation rate, sodium, potassium,
calcium, magnesium and blood glucose,
renal and hepatic function & thyroid
function
 2 Neuro imaging

• Indications : all pts w.epilepsy ( pwe ) should have

initial CT or MRI, except typical syndrome of primary
generalized epilepsy or typical benign rolandic
epilepsy
• The sensitivity in detecting abnormality in epilepsy
is related to : pathologies underlying epilepsy, ima-
ging techniques and experience of the interpre-
ting physician.
• Emergency indication:
– First time seizure & new focal neurological deficit
– Seizure w.persistent or worsening mental alter
ation / consciousness
– Partial seizure
– Seizure w fever
– Seizure w recent head trauma
– Seizure w persistent headache
– Seizure w history of cancer
– Seizure w history of anticoagulan
– Seizure w suspected or history of HIV/AIDS
– Status epilepticus
1. MRI is the procedure of choice, should be
done if CT scan is negative or many
abnormalities which missed on CT
The disadvantages: requiring patient lie
longer, some times need sedation or
anestesia for children or confused pts ,
contraindicated for those who have
pacemaker or other metal implant, more
expensive and not always readily available
at hospital in Indonesia
1. Neuroimaging continue

2. CT Scan now readily available at many hospitals in

Indonesia ,preferable done with contrast &
coronal cut
Insensitive to lesions at the base of the brain,
orbitofrontal, mesio-temporal and small cortical
lesions.
Twelve-30% of cases with a negative CT show
relevancy abnormalities on MRI
NOTE
Structural lesions at neuroimaging is
considered as etiology of Epilepsy only when
it correlates with the site of seizure origin
which suitable w. clinical manifestation and
determined by EEG
3.Electrophysiology : Electroencephalogram
/EEG
• To ensure an episodic event is epileptic
seizure or not
• To classify the type of seizure
• To localized the focus of seizure
• To enchance the decision to stop AEDs
International 10-20 system of electrode placement for routine scalp
electroencephalography
Generalized
Partial
Electro Encephalo Gram / EEG

• sampling brain activities during 20-30 minutes or

longer

• The result: in the limit of normal or abnormal

• EEG in the limit of normal found in 10-20% of pwe

• One - 2% people without seizure / epilepsy :

epileptiform activity (+)

• Epilepsy cannot be diagnosed from EEG alone

Note:
• A single seizure with evidence of neurological
abnormality or abnormality in neuroimaging or
• A single seizure accompanied by epileptiform
abnormality on EEG
→ Could serve as the basis for diagnosis of
epilepsy ( Guberman A,Bruni J,1999)
• An epileptiform abnormality on EEG, chance of
seizure recurrence are high → treatment may be
made even after first-time seizure (Maganti RK,Rutecki
P,2013 )
 Management 0f Epilepsy
The holistic management of Epilepsy extends far
beyond the usage Oral Anti -Epileptic Drugs /
AEDs. The Multi-disciplinary approach consist of
dedicated medical staff , Neurologist, Psycho
logist, Psychiatrist, Social worker.

Management of acute symptomatic seizure (ASS)

different with epilepsy
Acute symptomatic seizure/ ASS ( of non pwe ) or
Epileptic seizure on PWE
• Stop seizure and prevent seizure recurrent
• Self limiting → Anti convulsion is given only if
prolonged or recurrent
• Investigate the etiology or Precipating factor and
treat !.
( Seizure precipitants :
* in PWE : a factor that preceds the onset of the attack
* in A S S : a factor is considered to be an explanation of
why the seizure happened )
Treatment of Epilepsy
• Accurate diagnosis of epilepsy is essential
• Select which patient should be treated w
AEDs *
• AEDs is longterm treatment *
• Selection of AED is based on type of epileptic
seizure
* ( AEDs should be : minimal side effects , Optimal quality
of life beside complete control of seizures )
AEDs
• Walker, Surges, Fisher (2009)
• The mode of action of AEDS : Multifarious and
often poorly defined; most of them have a
number of putative targets
• Most important : Know the target
• Main target : Blockade/ modulation channel of
Sodium , Calcium channels & GABA receptors and
Enchancement of neurotransmitter GABA
• The other target : Glutamate and Glutamate
receptors, Protein and Cyclic Nucleotide-
Gated channel, Potassium channel, Synaptic
vesicle
AEDs continued

The list of AEDs available in Indonesia and Its

target
• Voltage Gated Sodium Channel
Main Action : Carbamazepin, Lamotrigin,
Oxcarbazepin, Phenytoin
Only at high Concentration : Phenobarbital,
Benzodiazepine
• Calcium Channel : Carbamazepin, Gabapentin,
Lamotrigin, Levetiracetam, oxcarbazepin,
Phenobarbital, Phenytoin, Topiramate, Zonizamide
AEDsContinued…

• GABA and GABA receptors: All benzodiazepine:

Diazepam and midazolam
• Glutamate and Glutamate receptors : Topiramate,
Levetiracetam, Magnesium
• Cyclic Nucleotide-Gated Channels :Gabapentin,
Levetiracetam
• Synaptic Vesicle Protein : Levetiracetam
 Antiepilepsy Drugs/AEDs (1)
• Explain to pts or the family, AEDs not curative
– To control / suppress seizures
– Minimal side effects
– Reach optimal quality of life
• AEDs selection not always easy
– Effectiveness : Seizure type, dose
– Available
– Affordable
– Should be individualized
– Begin w. monotherapy
 AEDs continued
– Require dosage adjustment
– Observation many conditions which influence
efficacy
• Need the pts commitment: compliance
• Different AEDs have different effectiveness
for different type of seizure or specific
epileptic syndromes
Broad spectrum : for > 1 type ( focal / partial and
generalized seizures )
Different AEDs continue…

Broad spectrum : for > 1 type ( focal / partial and generalized

seizures ) : Valproate
Generalized seizures :
• First line : valproate ,lamotrigine carbamazepin,topiramate
• Second line : clobazam, levetirazetam ,topiramate, clonazepam ,
phenobarbital, phenytoin

Partial onset seizures :

• First line :carbamazepin, lamotrigin, levetiracetam,oxcarbazepin,
topiramate
• Second line : clobazam ,clonazepam ,gabapentin ,phenobarbital
phenytoin, pregabalin, zonizamide

Note
• Absence seizure : don’t use Phenobarbital, Phenytoin, Carbamazepin
• Myoclonic seizure : don’t use carbamazepin, phenytoin
 Conditions ↓ Effectiveness of AEDs
• Bad compliance
• Drug interaction
• Alcohol & recreational drugs
• Sleep deprivation
• Physical and psychological stress
AEDs continue…

*Consider no AEDs if:

• Seizure only every few years (few and far
between)
• Once in a year
• Non disabling , brief simple partial seizure
• Benign syndromes
 Table 3. Initial and maintenance daily doses
AED Starting dose in average Maintenance dose in average
(mg/day) (mg/day)
Carbamazepine (CBZ) 100-200 400-1600
2-3 times/day
Clobazam (CLB) 10 mg 10-30
1-2/day
Gabapentin 300-900 900-3600
2-3 times/day
Levetiracetam (Lev) 500-1000 1000-3000
Twice daily
Oxcarbazepine (Oxc) 30 900-1800
Twice daily
Phenobarbital (PB) 30-50 30-200
1-2 time daily
Phenytoin (PHT) 200-300 200-400
1-2 times daily
Topiramate (TPM) 25 100-300
Twice daily
Valproate (VPA) 400-500 500-2500
2-3 times
Zonizamide (ZNS) 50 200-600
1-2 times
AEDs continued..

Adversed effects / side effects

• Commonly dose related
• Often in the period of dose titration/early of
medication
• Patients should be forewarned
• Titration rate should be slow
• Manifestated as mild, stable or dissapear 
severe mental changes
Adversed effects / side effects continued..

• Allergic skin rash

• Other immune mediated reactions hepatitis,
pancreatitis, lymphadenopathi, bone marrow
suppression (leucopenia, thrombocytopenia)
• Hyponatremia
1. AEDs continued

Monitoring of serum AEDs

1. An Non-routine procedure
2. Therapeutic range of an AED is only guidline
3. In ‘Well controlled pts’, level subtherapeutic
/ above usual range, adversed effects (-) 
dose does not change
AEDs continued

Long-term follow-up
1. Many studies : seizure free on AEDs for 2 years or
more before withdrawl → stipulation of 2 years :
arbitrary ( Kwan P & Leung H,2009 )
2. Chronic active : epilepsy in which seizure are still
occuring 5 or more years after the initiation of
therapy
3. To asses the occurrence of intractibility
• Intractability is considered if:
Seizures are * frequent enough or severe enough
to cause significant negative effects on quality of
life, despite treatment with at least two appro-
priate AEDs in adequate doses for a period of
time
Sometimes are considered if *AEDs psychosocial-
ly disabling for pts and intolerable side effects of
AEDs
• Potential causes of medically intractable:
• wrong diagnosis
• inadequate dose
• inattention to lifestyle factors which could
provoke seizures
• underlying progressive brain lesion or metabolic
disorder
• intrinsically intractable epilepsy
 Other treatment in Indonesia
• Epilepsy surgery for
– Epilepsy symptomatic
– Intractable case
• The Goal
– Maximizing seizure control
– Minimizing adverse drug effects
– Reduce psychososial disability
Result of surgical treatment
• Classification seizure outcome by Engel (1993)
modified:
I. Class I
A. Completely seizure free
B. Aura only
II. Class II
A. R are seizures
B. N octurnal seizures only
III. Class III: worthwhile decrease in seizures
IV. Class IV
A. N o significant seizure reduction
B. Seizure worse
• Type and incidence of complication depend on the
type and extend of procedure
 Plenary

Case synopsis
• Anne 45 y-o, new onset seizures and altered
consciousness. Type seizure: stared, head
turned to the right then generalized tonic-
clonic, 1-2 minutes
• Her first seizure occurred when she was
talking. Convulsion stop → Immediately not
recall anything pre & during the attack
• Hystory of illness : no fever, no headache no
seizure previously , but personality changes 2
month before
• Working Diagnosis :

• Type of seizure :
• Status Epilepticus ?
* first attack ; 1 – 2 minutes ; stop still
confused for 10 minutes . She complaint
spontaneously or asking the question ?
* second attack : 60 minutes later,
generalized tonic – clonic 2-3 minutes ;
unresponsive → third attack :…………….
• Inj Phenytoin 18 mg /kg BB iv / infusion; rate 50mg
/min

• 48 hours : no attack and clinically improve. Start :

Carbamazepin 400mg/24 hours.
• Imaging study with MRI shows a large, poorly
circumscribed cortical, left temporal lobe
lesion with areas of hemorrhage and necrosis

↓
Biopsy : malignant Glioma
↓
Chronic Process
• Final Diagnosis ?
Epilepsy or not Epilepsy
 C. Status epilepticus
• Status epilepticus is defined as seizures
occuring continuously or recurrently for
at least 30 minutes without recovery
• Most seizures (normally ), self limiting,
stop within seconds to 2-5 minutes; but
sometimes can take the form of :
prolonged seizures or repetitive seizures
without recovery in between → Status
epilepticus .
Status epilepticus is Neuro- emergency condition

The on going seizures lead to neuronal injury and

potentially at greater risk of systemic complication
an operational definition of status epilepticus
( don’t wait until 30 minutes to treat ! )
• Operational definition of status epilepticus :

5 minutes or more of
(a) generalized continuous seizures or
(b) two or more discrete seizures between
which there is incomplete recovery of
consciousness
↓
stage of Early SE/ Premonitory phase
• There are 2 types of status epilepticus:
convulsive and non-convulsive

• The form of convulsive status epilepticus/ status

convulsivus is continuous or repetitive convulsive
motor activity

• The form of non-convulsive status epilepticus : patient

suddenly showed depressed consciousness/
awarenes, agitation , disorientation or disturbance of
memory / behaviour accompanied by continuous
epileptiform activity in EEG lasting at least 30 minutes
• Epilepsia partialis continua or focal motor
status epilepticus
clinical manifestation vary in a part of body
or one side of the body ; from very subtle with
twitching of the corner of the mouth or one eye to
severe jerking of one side of the body or part of one
side of the body, while the patient still
conscious
 Patophysiology status epilepticus

• The mechanisms by which seizures can progress to

status epilepticus until now under studies. There are
conditions which disrupt self limiting event that
usually lasting only seconds to minutes

• From study in animal and human, there is evidence of

alteration in both inhibitory and excitatory
mechanism and other mechanism influence the
neuro-vascular network activity, like metabolic effects
, changes in calcium homeostatis, acute inflammation
and disruption of the blood brain barrier.
 Continued…
• The most common risk factors generalized
convulsive status epilepticus (GCSE) on adult :
- low AED level in pwe
- previous cns injury e.g. hypoxia/anoxia
stroke, trauma
- alcohol abuse,
- tumor
- infection
- many drugs
• Continued.

• Non-convulsive status epilepticus is reported

as complication of critical illness, e.g. multiple
organ failure, anoxic-ischemic ,encephalopa-
thy, neuro-oncologic cases, certain drugs
toxicity
• Physiology changes in status epilepticus: two
phases:
• Compensation phase: cerebral metabolism is
greatly increased caused by seizure activity, but
sufficient to overcome metabolic demands
and cerebral tissue is protected from hypoxia,
metabolic damage, massive autonomic activity
and cardiovascular changes
 Continue..
• Decompensation phase: neuronal exhaus-
tion. Greatly increased of cerebral metabolic
demands cannot fully overcome  hypoxia ,
altered cerebral and systemic metabolism.
Autonomic changes persist, cardio-respiratory
function progressively fail

• These changes do not necessarily occur in all

cases.
 Management Status Epilepticus
• Stage of EARLY Status Epilepticus

• Refer to Emergency Unit

* Initial treatment: Drug of choice is benzodiazepine ;

Lorazepam prefer than diazepam, but not available in
Indonesia
Diazepam 10mg, can repeated at interval 5 minutes

* Adequate Breathing, free Airway and give oxygen

Community health centre / Hospital setting
• Intravenous line for fluid (adequate Circula-
tion ) and drug administration
• Give attention to body temperature, pulse,
blood pressure, cardiac rhythm.
• Total dose first step: diazepam 30mg.rectally,
10-20mg iv bolus at 2-5 mg/minute, depends
on the situation.
• Find out the cause / precipitating factor : emergency blood
examination : Complete peripheral blood ,glucose,
electrolytes, renal function, liver function, gas analyses,
sometimes level of AED

• Glucose 40% 50 ml IV: not routine only if suspected

hypoglycaemia

• Thiamine inj: compromized nutrition state, alcoholism or if

glucose was given.

• Lowered high temperature.

• High blood pressure do not decrease too soon : correlated
with other clinical sign.
• Find out underlying disease.
• Note : treatment prolonged ASS ₌ stage early SE
Seizure couldn’t stop → Stage of established SE
(if possible consult to neurologist !! )
• Give phenytoin IV 15 mg/kg slowly at rate 50mg/min
maintenance 100mg every 8 hours.
• Alternative drug:phenobarbital IV 10mg/kg slowly at
rate 100mg/min.
• Should be monitored the function of cardiorespi-
ration
• if condition could’t overcome = Stage of refractory SE
→ consult and refer to neurologist in the intensive care
facility
 A protocol for the intravenous antiepileptic
drug treatment of convulsive status epilepticus
(SE).
For general practioner
• Stage of early SE ; if seizures continue after 30 min → stage of
established SE

General practioner with consult to Neurologist Stage of

established SE ( → Emergency Unit )

• Phenytoin IV infusion of 15 mg/kg at a rate of 50 mg/min, or

Fosphenytoin IV infusion of 15mg/kg at a rate of 100mg /min if seizures
continue after 30/60 min .If no respon → stage of refractory SE
Note: Fosphenytoin not always available at many hospital in Indonesia
Fosphenytoin sodium 75mg equivalent to phenytoin sodium 50mg
• Or Phenobarbital IV infusion of 10 mg/kg at a rate100mg/min
• Identify & treat medical complications & treat acidosis
• Investigation : for establishing the etiology
• If seizure continue ( Refractory Status Epilepticus ) → ICU
facilities
Thankyou
• Appendix
Table 3. International Classification of Epileptic
Seizures Source: Epilepsia 1981; 22: 489-501

I. Partial Seizures ( seizures beginning locally )

A. Simple partial seizures ( consciousness not
impaired )
1. With motor symptoms
2. With somato-sensory or special symptoms
3. With autonomic symptoms
4. With psychic symptoms
Table 3. International Classification of Epileptic
Seizures (continued)

B. Complex partial seizures (with impairment of consciousness)

1. Beginning as a simple partial seizure and progressing to
impairment of consciousness
a. with no other features
b. with features as in A. 1-4
c. with automatisms
2. With impairment of consciousness at onset
a. with no other features
b. with features as in A. 1-4
c. with automatisms

C. Partial seizures secondarily generalized

Table 3. International Classification of Epileptic
Seizures (continued)
II. GENERALIZED SEIZURES ( Bilaterally symmetrical and without
focal onset )
A. 1. Absence seizures
2. Atypical absence seizure
B. Myoclonic seizures
C. Clonic seizures
D. Tonic seizures
E. Tonic clonic seizures
F. Atonic seizures

III. UNCLASSIFIED EPILEPTIC SEIZURES (Inadequate or incomplete

data)
• 29th International Epilepsy Congress, Rome, 2011 ILAE
Proposal for revised :

• Classification seizures type : generalized, focal and

unknown.
* Generalized : tonic-clonic , absence, tonic, clonic ,
atonic , myoclonic
* Focal : characterized according to one or more fea-
tures :aura, motor, sensory, autonomic , aware-
ness/ responsiveness ( altered or retained )
→ may evolve to bilateral convulsive seizure
* Unknown : Insufficient evidence to characterized
as focal, generalized or both
• 29th International Epilepsy Congress, Rome,
2011 ILAE Proposal for revised
• New term and concept of Etiology:
- Genetic . Heredity plays very important role;
its mechanism are complex
- Structural & metabolic of the brain
- Unknown : might be genetic, structural or
metabolic
Table4. Drug interaction
Added drug Level of AEDs affected
Pht Cbz Val Pb Clb
1. Pht -  tot  free   or - rarely 
2. Cbz  or     or  -
3. Vpa tot  free   -  -
4. Pb  or    - -
5. Clb rarely  - rarely  - -
6. Diltiazem   - - -
7. Erythromycin -  - - -
8. Cyprofloxacin  - - - -
9. INH    - -
10. Ticlopidine  - - - -
11. Dexamethason  - - - -
12. Rifampicin  - - - -
13. Antacids  - - - -
14. ASA free - - - -
Table5. Drug interaction

Drug affected Anti epileptic added

Phenytoin Carbamazepin Phenobarbital Valproate
1. Benzodiazepine  - 
2. Dexamethason  -  -
3. Digoxin  - - -
4. Doxycycline   - -
5. Furosemide  -  -
6. Haloperidol   - -
7. Oral contraceptive    -
8. Theophyline   - -
9. Tricyclic anti -  - Possibly 
depressants
10. Warfarin    -