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Prevalence 7.6 per 1000 persons

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BACKGROUND
• Epilepsy is one of the most common
neurologic diseases in children.

• 1 in 150 children is diagnosed with epilepsy

during the first 10 years of life, with the
highest incidence rate observed during infancy.
Aadberg, et al. Pediatrics May 2017, 139 (5) e20163908

• No available data on lifelong and active cases

of epilepsy in the Philippines

Moalong KMC, et. al. Epilepsy Behav. 2021

Feb;115:107491.

BACKGROUND
Estimated prevalence is 9 per 1000 persons-years
~ 990,000 Filipinos are living with epilepsy

Large epilepsy treatment gap

Reasons:
• Limited number of physician’s confident in
diagnosis and treatment
• Limited access of medications – most
pronounced in geographically isolated and
financially disadvantaged areas
Moalong KMC, et. al. Epilepsy Behav. 2021
Feb;115:107491.

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LEARNING OBJECTIVES
• Discuss the definition of seizures vs. epilepsy
• What is the pathophysiology of seizures
• Classification of Seizure types (video presentation)
• Classification of the Epilepsies
• Discuss special conditions – febrile seizures; neonatal seizures
• Discuss Status Epilepticus
• Management of Seizures, Epilepsy and Status Epilepticus

What is a seizure?

• transient and reversible alteration of behavior caused by a

paroxysmal, abnormal and excessive (hypersynchronous)
neuronal discharge
• an event of cerebral origin
• sudden and transitory abnormal phenomena (motor, sensory,
autonomic, or behavioral)
• transient dysfunction of one part or all of the brain

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EPILEPSY

• a disease of the brain characterized by an enduring predisposition to

develop seizures.

• Practical (or Operational) Definition:

1. At least two (2) unprovoked (or reflex) seizures occurring >24 h
apart.

2. One unprovoked (or reflex)seizure and with risk factors for

increased seizure risk recurrence (~60%) occurring over the next 10
years.

3. Diagnosis of an epilepsy syndrome.

Fisher, RS, et. Al. Epilepsia. 2014 Apr;55(4):475-82.

Risk of epilepsy after 2 seizures

• After two unprovoked seizures, the risk

of a 3rd by 60 months is 73% (59-87%,
95% confidence intervals.

• Adoption of 60% as the lower end of

the confidence interval for the
recurrence risk is epilepsy.
Hauser et al. Risk of recurrent
seizures after two
unprovoked seizures. NEJM
1998;338:429.

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Epilepsy is RESOLVED

• individuals who had an age-dependent epilepsy

syndrome but are now past the applicable age

• those who have remained seizure-free for the last 10

years, with no seizure medicines for the last 5 years

SEIZURE vs. EPILEPSY

Seizure Disorder ≠ Epilepsy

• A seizure is the symptom of • Sz Disorder is VAGUE

the disease. • May include other
• Epilepsy is the disease associated conditions such as
with spontaneously recurring febrile seizures, acute
seizures symptomatic seizures.
• DO NOT USE as
DIAGNOSIS

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Basic Pathophysiology of Seizures and Epilepsy

• 3 physiologic requirements for seizures to
occur:
1. population of pathologically
excitable neurons
(HYPEREXCITABILITY)

2. increase in excitatory
(glutaminergic) activity through
recurrent connections in order to
spread the discharge

3. reduction in the activity of the

normally inhibitory GABAergic
projections
(HYPERSYNCHRONY)

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Basic Pathophysiology of Seizures and Epilepsy

EXCITATORY TRANSMISSION
• Glutamate – main excitatory neurotransmitter
• 2 post- synaptic receptors
• non-NMDA (kainate and amino-3-
hydroxy-5-methyl-isoxasole propionic
acid or AMPA)
• “fast” excitatory postsynaptic
potential (EPSP)

• NMDA (N-methyl-D-aspartate)
• Requires glycine; receptor has a Mg
ion blocking pore opening
• Has prolonged sustained EPSP

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Basic Pathophysiology of Seizures and Epilepsy

INHIBITORY TRANSMISSION
• gamma-amino-butyric acid (GABA)
• Main inhibitory neurotransmitter

• Influx of Ca++ →depolarization → release

GABA into the synaptic cleft → binds to its
receptors (GABAA) → chloride ions (Cl−)
enter the neuron.
• Cl− influx increases the negative
charge inside the postsynaptic neuron
→ hyperpolarization.
• The resultant change in membrane
potential is called an inhibitory
postsynaptic potential (IPSP)

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Common Etiology of Seizures in children

EPILEPSY

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CONDITIONS ALSO PRESENTING WITH

SEIZURES
▪ Febrile seizures in children age 0.5 – 6 years old

▪ Acute Symptomatic Seizures

▪ Drug (Alcohol Withdrawal, Adverse Drug Reactions)
▪ Metabolic (Na+, Ca+2, Mg+2, glucose, O2, renal, HPN)
▪ Post-traumatic seizures
▪ Seizures within first week of infection or stroke

▪ Convulsive syncope

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APPROACH TO DIAGNOSIS

Seizure Type Epilepsy Epilepsy

Classification Syndrome

• Are the • Where on • What is the • Do the

events the brain cause? seizures
seizures? did the and other
seizures patient
start? factors fit a
clinical
pattern?

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New Definition and Classification

• 2014: Fisher – Practical Definition of Epilepsy

• 2017: Fisher - Operational classification of seizure types

• 2017: Scheffer – ILAE Classification of the epilepsies

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Seizure Confirmation
‘‘constellation of symptoms’’

Onset
CLINICAL Presence or absence
HISTORY of awareness

1st Prominent
feature
Stereotyped pattern with
recurring features and
evolution
Glauser, TA. Continuum (Minneap Minn). 2013;19(3 Epilepsy):656-681.

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2017 ILAE SEIZURE TYPE CLASSIFICATION

(Basic Version)

GENERALIZED
FOCAL ONSET UNKNOWN ONSET
ONSET

IMPAIRED MOTOR
AWARE MOTOR
AWARENESS Tonic-Clonic
Tonic-Clonic
Other
Other
MOTOR ONSET
NON-MOTOR ONSET NON-MOTOR
NON-MOTOR
(Absences)
FOCAL TO BILATERAL TONIC-
CLONIC
UNCLASSIFIED *

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Basic Pathophysiology of Seizures and Epilepsy

FOCAL SEIZURES

Focal to bilateral
FOCAL tonic clonic sz

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Basic Pathophysiology of Seizures and Epilepsy

Generalized Seizures

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Complex Simple
Partial Partial
OLD TERMS
TO AVOID
Secondarily
Localization-
generalized
related
tonic-clonic

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FOCAL ONSET GENERALIZED ONSET UNKNOWN ONSET

AWARE IMPAIRED
AWARENESS MOTOR MOTOR
Tonic-Clonic Tonic-Clonic
MOTOR ONSET Clonic Epileptic spasms
Automatisms Tonic
Atonic Myoclonic NON-MOTOR
Clonic Myoclonic-atonic Behavior arrest
Epileptic spasms Atonic
Hyperkinetic Epileptic spasms
Myoclonic
Tonic NON-MOTOR (Absences)
NON-MOTOR ONSET Typical
Autonomic Atypical
Behavioral arrest Myoclonic absences UNCLASSIFIED *
Emotional Eyelid myoclonia
Sensory
2017 ILAE SEIZURE TYPE CLASSIFICATION
FOCAL TO BILATERAL TONIC-CLONIC (Expanded Version)

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Epilepsy Diagnosis
• Precipitating factors
• Age, position, activity,
intercurrent illness,
medications
• Predisposing factors
• Past medical history
CLINICAL • recent illness or
HISTORY neurological
symptoms
• Family history
• Febrile Seizures
• Epilepsy
• Developmental
Problems
Glauser, TA. Continuum (Minneap Minn). 2013;19(3 Epilepsy):656-681.

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SEIZURE TYPE * ETIOLOGY

FOCAL GENERALIZED UNKNOWN
STRUCTURAL

GENETIC

INFECTIOUS
FOCAL &
FOCAL GENERALIZED UNKNOWN
GENERALIZED
METABOLIC

IMMUNE

EPILEPSY SYNDROME UNKNOWN

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DEFINITION OF TERMS

CLONIC Regularly repetitive jerking of similar muscle groups

Sustained muscle contraction lasting for few

TONIC seconds to minutes

TONIC-CLONIC Sequence of tonic followed by clonic phase

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• FEATURES:

• IMPAIRED AWARENESS

• PROMINENT FEATURE: HEAD JERKING

• Head jerking and left shoulder jerking
• Left eye clonic movements

• SEIZURE TYPE:
• FOCAL IMPAIRED AWARENESS (MOTOR)
SEIZURE (BASIC)
• FOCAL CLONIC SEIZURE (EXPANDED)

https://www.youtube.com/watch?v=NoDnk_o4c9Q

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FEATURES:
• Sudden generalized
stiffening
• Followed by bilateral
clonic arm movements

SEIZURE TYPE:
• Generalized tonic clonic
seizure

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FEATURES:
• Blank staring
• Bimanual automatism
• Head version to right
• Bilateral tonic flexion of
arms & legs
• Bilateral clonic movements

SEIZURE TYPE:
• FOCAL TO BILATERAL TONIC
CLONIC SEIZURE

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DEFINITION OF TERMS

Sudden, brief (<100 msec) involuntary single or multiple

MYOCLONIC
contraction(s) of muscles(s); less sustained than clonus.

ATONIC Sudden loss of muscle tone (1-2 secs)

Generalized seizure; myoclonic jerk followed by an

MYOCLONIC-ATONIC atonic motor component.

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FEATURES:
• Repeated irregular brief
jerks of both arms; appears
unsustained

SEIZURE TYPE:
• Generalized Motor Seizure
(BASIC)
• Generalized Myoclonic
Seizure

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FEATURES:
• Repeated sudden head
drops
• Able to answer the guardian
during the cluster of
seizures

SEIZURE TYPE:
• Focal motor seizure (BASIC)
• Focal Atonic seizure
(Expanded)

https://www.youtube.com/watch?v=9obFVWW47NE&t=3s

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DEFINITION OF TERMS

ABSENCE (Typical) A sudden onset, interruption of ongoing activities, a

blank stare, possibly a brief upward
deviation of the eyes. Usually with rapid recovery.

Arrest (pause) of activities, freezing, immobilization;

BEHAVIOR ARREST often associated in focal seizures

MAIN CLUE – presence or absence of rapid recovery after seizure.

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FEATURES:

• Sudden unresponsiveness
• Oral automatisms
• Eyes deviated upwards

SEIZURE TYPE:
• Generalized nonmotor
seizure (BASIC)
• Typical Absence Seizure
(expanded)

https://www.youtube.com/watch?v=H3iLQi6wt94

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FEATURES:
• Appears unresponsive
• Unilateral hand
automatism
• With post-ictal symptoms
(nausea)

SEIZURE TYPE:
• FOCAL IMPAIRED
AWARENESS NON-MOTOR
SEIZURE (Behavioral
Arrest)

https://www.youtube.com/watch?v=t0uYV5LW2pU

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DEFINITION OF TERMS

sudden flexion, extension, or mixed extension–flexion

of predominantly proximal and truncal muscles that is
Epileptic spasms
usually more sustained than a myoclonic movement
but not as sustained as a tonic seizure.

Focal forms may occur→ Grimacing, head nodding, or

subtle eye movements.

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FEATURES:
• Repeated sudden
truncal flexion with
arm extension

SEIZURE TYPE:
• Epileptic spasms

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COMMON DESCRIPTORS OF BEHAVIORS DURING AND

AFTER SEIZURES

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SEIZURE TYPE * ETIOLOGY

FOCAL GENERALIZED UNKNOWN
STRUCTURAL

GENETIC

INFECTIOUS
FOCAL &
FOCAL GENERALIZED UNKNOWN
GENERALIZED
METABOLIC

IMMUNE

EPILEPSY SYNDROME UNKNOWN

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2017 ILAE Epilepsy Classification

LEVEL 1 – According to seizure type

LEVEL 2 – Epilepsy according to seizure type

• Focal epilepsy, generalized epilepsy

Level 3 – Epilepsy Syndrome

• Childhood absence epilepsy, West Syndrome, LGS

Level 4 – Epilepsy with etiology

• SCN1A mutation in Dravet Syndrome; Tuberous Sclerosis Complex; KCNQ2
encephalopathy

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Seizure Type Identification

• RELEVANCE:
• Basis of Epilepsy diagnosis or Epilepsy Syndrome
Diagnosis.

• One of the main factors to determine which anti-seizure

medication to start.

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CRITERIA FOR SYNDROME CLASSIFICATION

• seizure type
• age at onset
• precipitating factors
• natural history
• Cause
• anatomic localization of seizure onset
• ictal and interictal EEG abnormalities

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Childhood Absence Epilepsy

• “pyknolepsy”
• age of onset : 5 - 15 yrs.
• peak: 6-7 yrs.
• absence seizures/daily; several times a day
• Typical EEG : 3 per second spike and wave complex
• activated by hyperventilation

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CHILDHOOD ABSENCE EPILEPSY

• Pyknolepsy; petit mal epilepsy

CRITERIA FEATURES

Age of Onset 4-10 years of age (peak: 5-7 years)

Sex Predilection
Etiology
Seizure Types
Ictal and Interictal Findings
Natural history/ Outcome
More common in FEMALES
Genetic
Typical Absence Sz (4-20 seconds)
NORMAL awake background
Interictal:
Ictal: generalized high amplitude 3Hz spike (double spike) wave
discharges with a gradual regular slowdown from the initial to
terminal phase of the discharge
Provoked by hyperventilation
Normal development & neurologic state

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CHILDHOOD ABSENCE EPILEPSY

• Treatment
• First line: Ethosuxamide, Valproate, Lamotrigine (mono or in
polytherapy)
• LTG
• Control absences 50-60%; but may worsen myoclonic jerks
• 2nd line: Clonazepam, Clobazam, Acetazolamide

• Phenytoin and Phenobarbital – ineffective

• AVOID: Carbamazepine, Oxcarbazepine, Vigabatrin, Gabapentin,

Tiagabin

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JUVENILE MYOCLONIC EPILEPSY

• Janz Syndrome; Impulsive Petit mal of Janz
CRITERIA FEATURES

Age of Onset 8-26 yrs; peak onset 1st seizure – 12-18yrs; occurs earlier in girls

Sex Distribution M=F **

Etiology Genetic – GABRA1 (CACNB4), EFHC1, ICK – heterogenous

Seizure Types Myoclonic jerks w/o noticeable change in awareness

• Usually occurs in awakening; triggered by sleep deprivation
Tonic clonic seizures – 80-95% (clonic-tonic-clonic)
Typical Absence – 10-18%

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JUVENILE MYOCLONIC EPILEPSY

CRITERIA FEATURES
Ictal and Interictal INTERICTAL:
Findings • NORMAL EEG background
• bursts of 4- to 6-Hz irregular polyspike activity (more in sleep)

ICTAL:
• Bilateral, synchronous polyspike-wave (PSW) discharge
(preceeding the MJ)
• PSW can have 5-20 spikes (12-16Hz) increasing in
amplitude, maximal over the frontal leads
• Slow wave (3-4Hz) can precede or follow the PSW
• Photosensitivity – 30%
Natural history Most frequent IGE; not associated with neurologic or mental
deterioration
Outcome High risk of recurrence; potentially lifelong treatment

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JUVENILE MYOCLONIC EPILEPSY

• Treatment
• LIFESTYLE – regulate sleep-wake cycle
• AVOID: Carbamazepine – aggravate the MJ; Oxcarbazepine
• Lamotrigine – controversial; may worsen MJ; induce
absence status or increase GTCS

• 1st LINE: Valproic Acid, Phenobarbital

• 2nd LINE: Levetiracetam, Topiramate, Zonisamide
• Other options: Lacosamide**, Perampanel*

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Rolandic Epilepsy (Self-limited Epilepsy with

Centro-Temporal Spikes)
CRITERIA FEATURES
Age of Onset 1-14 years (peak: 7-10yrs)
Sex Predilection 1.5 Male preponderance
Etiology Genetically determined; AD trait;
Ch loci 15q14; 16p12-11.2; 11p13 (ELP4 gene)
Seizure Types Infrequent, single focal aware seizures:
1. Unilateral facial sensorimotor symptoms (30%) - Hemifacial
sensorimotor seizures
2. Oropharyngeal manifestations (53%)
3. Speech arrest (40%)
4. Hypersalivation (30%)
- May progress to focal impaired awareness seizures (42%)
- May progress to hemiconvulsions or GTCs
- duration: 1-3 mins; often occurs SLEEP (near sleep onset or near
awakening)
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Rolandic Epilepsy
CRITERIA FEATURES
Ictal and Interictal Interictal centro-temporal spikes (C3,C4 – high central); (C5,C6 – low
Findings central) supra-sylvian; often bilateral; activated by drowsiness &
nREM sleep;

Natural history/ Outcome 2.5x more likely to have speech sound disorder
5.8x – more likely to have dyslexia
- May develop mild reversible, cognitive and behavioral
abnormalities
- Maybe worse onset before 8 yrs

- Excellent prognosis; remission 2-4 years from onset and before 16

years

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Rolandic Epilepsy

• Treatment:
• May not need AED Tx if seizures are infrequent or if
seizures occurred near natural age of remission

• 1st line: CBZ or VPA

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Developmental and/or Epileptic

encephalopathies

Epileptic activity itself contributes to severe

cognitive and behavioral impairment above and
beyond that expected from the underlying
pathology and that these can worsen over time

Berg et al 2010

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DEVELOPMENTAL AND/OR EPILEPTIC ENCEPHALOPATHY

• For many encephalopathies, there is a developmental

component independent of the epileptic encephalopathy
• Developmental delay may precede seizure onset
• Co-morbidities
eg. cerebral palsy, autism spectrum disorder, intellectual
disability
• Outcome poor even though seizures stop
eg. KCNQ2, STXBP1 encephalopathies

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DEVELOPMENTAL AND/OR EPILEPTIC ENCEPHALOPATHY

• Developmental encephalopathy
• May begin in utero
• Post birth
• Epileptic encephalopathy
• Can occur at any age
• May have remediable component – right vs wrong AED
• Move towards GENE encephalopathy
• eg. CDKL5 encephalopathy, SCN2A encephalopathy
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West Syndrome

• Infantile Spasms/ Epileptic

Spasms

• Age of onset: 3-9 mos.

• Early onset
• Genetic, metabolic or
congenital malformations
• later onset
• Focal cortical dysplasia

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West Syndrome

• Seizure Type
• Epileptic spasms
• Occur in clusters (awakening or transition from slow NREM
to REM)
• Lasts for 1-2 sec;
• Maybe followed by a sustained tonic contraction →
“spasm-tonic seizure”
• Can be asymmetric or asynchronous

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West Syndrome

• EEG
• ICTAL:
• Hypsarrhythmia
• Diffuse, very high voltage slow activity associated with
diffuse or multifocal spikes in wakefulness
• SLEEP: diffuse irregular spike wave discharges (1-3
seconds) alternating with theta/beta activity
(paroxysmal alternating pattern); random voltage
attenuation

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West Syndrome

• Etiology
• Genetic – 25%
• CDKL5, ARX, STXBP1, etc.

• Underlying etiology is suspected if with developmental delay prior

to spasms
• Pachygyria, lissencephaly, cortical dysplasia, holoprosencephaly

• Vascular accidents/ strokes – HIE

• Antenatal CNS infections – CMV, toxoplasmosis, etc.

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West Syndrome
• Treatment
• Most are refractory to treatment
• ACTH – 12 IU/kg x 2 wks or 40 IU/kg x 2 wks → 75% effective
• Prednisone (2 mg/kg/day) x 2 weeks
• Prednisolone – 40-60mkday x 2 weeks →67% responder
• Vigabatrin (100-150 mg/kg/day) → IS due to Tuberous sclerosis
• ADR- retinal toxicity
• Valproate + clonazepam – 25-30% effective; but relapse are is high
• Levetiracetam
• Zonisamide

• Ketogenic diet

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West Syndrome

• Prognosis
• Generally poor
• Prognosis depends on etiology
• Unknown etiology → poor outcome and recurrent seizures
• Predictors of worse outcome;
• Younger age of onset
• Other seizures prior to IS
• Refractory IS

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OTHER RELEVANT CONDITIONS

PRESENTING WITH SEIZURES

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NEONATAL SEIZURES

• Seizures are the most

common neurological
emergency in the
neonatal period
• Occurrence ~ 1–5 per
1000 live births

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NEONATAL SEIZURE TYPES

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CLASSIFICATION OF NEONATAL SEIZURES

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F S • Event occurring between 3 mos to 5 years

• Peak → 18 mos
E E
• (+) febrile illness in the absence of CNS infection
B I or other defined cause
• Temperature > 38.5 C
R Z
I U • Normal neurologic outcome

L R • Brief generalized tonic-clonic seizures

E E • Differential Dx: Rigors, febrile delirium, febrile

myoclonus, syncope
(1980) Consensus statement. Febrile seizures: long-term management of children
with fever-associated seizures. Pediatrics 66: 1009- 1012.

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FEBRILE SEIZURES

• Risk for epilepsy is small (1-3%)

• seizure risk is increased when:
• seizure lasts more than 15 minutes (febrile Status epilepticus)
• more than 1 seizure in 24 hours (complex FS)
• focal features (complex FS)
• abnormal neurologic development/ neuro exam
• In the absence of specific clinical indications, there is no
further need for diagnostic tests
• Mainstay of treatment is fever control

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FEBRILE SEIZURES
FEBRILE STATUS
SIMPLE COMPLEX
EPILEPTICUS
• Generalized • Focal • Duration > 30 mins
• Brief • Prolonged > 10-15 • Focal features
• Single episode mins
• Recurrence within 24 • Present in 5% of pts with
• Risk for epilepsy – hrs during febrile FS
2% illness
• Todd’s paralysis –
0.4%
• Risk for epilepsy – 4-
12%

(Annegers, et al. 1987; Nelson & Ellenberg, 1978; Berg & Shinnar, 1996)

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FEBRILE SEIZURE RISK FACTORS

Risk Factor Predicting a 1st Predicting recurrence Predicting epilepsy after
Febrile seizure after 1st FS 1st FS

FHx of FS in 1st degree relative + + -

Developmental delay or neurologic + - +
problem
Complex FS - +
Onset < 18 months + -
Temperature at 1st seizure + -
Duration of Illness before seizure + -
Attendance at day care + ? -
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FEBRILE SEIZURE RISK FACTORS

Risk Factors Predicting a 1st Predicting Predicting
Febrile seizure recurrence after epilepsy after
1st FS 1st FS
FHx of FS in 1st degree relative + + -
Developmental delay or neurologic problem + - +
Complex FS - +
Onset < 18 months + -
Low Temperature at 1st seizure + -
Duration of Illness before seizure + -
Attendance at day care + ? -
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KEY POINTS IN EVALUATION IN FS

• Routine blood exam and neuroimaging – NOT RECOMMENDED

• Lumbar Puncture
• < 18 months (CNSP-PPS Guidelines, 1997)
• < 12 months (AAP guidelines, 2011)
• Routine EEG
• Not justified → does not predict recurrence
• “hypnagogic spike-wave” → appears by 3-4 years of age
• Complex FS → 40% abnormal EEG (Johsi,et. al. 2005)

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KEY POINTS IN MANAGEMENT OF FS

• Immediate management
• Rectal diazepam – 0.5 mg/kg (Knudsen, 1979)
• Nasal/buccal midazolam – 0.2-0.5 mg/kg (Appleton,
1995)
• Rectal lorazepam – 0.1 mg/kg

• Check for source of infection

• Lumbar tap ??

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KEY POINTS IN MANAGEMENT OF FS

• No study has demonstrated any form of treatment alters the risk for
epilepsy.

• Prevention of FS recurrence
• Phenobarbital – 4-5 mg/kg/day; may be effective
• Ineffective in preventing recurrence
• S/E: behavioral changes, ↓ IQ ~ 4 pts (Farwell, 1996)
• Valproic Acid
• S/E: hepatoxicity (Dreifuss, et. al. 1987)

• Antipyretics →NO EFFECT

• Cold sponge bath → NO EFFECT (Newman, 1988)
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STATUS EPILEPTICUS

• Seizures so frequent or so prolonged as to create a fixed and lasting

condition. (Mortality : 20- 30%)

• A continuous, generalized tonic-clonic seizure lasting more than 30

minutes or absence of lucid intervals in between seizures

• Most seizures last for 3 to 5 minutes and occasionally up to 10

minutes. If seizure persists more than 10 minutes, therapeutic
intervention must be initiated

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STATUS EPILEPTICUS

• a condition resulting either from the failure of the mechanisms

responsible for seizure termination or from the initiation of
mechanisms, which lead to abnormally, prolonged seizures (after
time point, t1).

• It is a condition, which can have long-term consequences (after

time point t2), including neuronal death, neuronal injury, and
alteration of neuronal networks, depending on the type and
duration of seizures.

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STATUS EPILEPTICUS

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Super
refractory
SE

Foreman. 2012.

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Shovron S. J Neurol Neurosurg

Psychiatry 2001;70 (suppl II):ii22–
ii27
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STATUS EPILEPTICUS

(VanHaerents, Continuum (Minneap Minn)

2019;25(2, Epilepsy):454–476.)

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Trinka (2015). Epilepsia, 56(10):1515–1523,

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SUDDEN DEATH IN EPILEPSY (SUDEP)

• most common epilepsy-related cause of mortality

• ~ 17% of deaths in patients with epilepsy
• Proposed Mechanisms:
• Cardiogenic Model
• Seizure induced cardiac arrhythmia
• Cardiocerebral channelopathies
• Mutations in SCN1A, SNC8A, ATP1A3, and KCNQ1

• Mixed respiratory/cardiogenic models

• seizure-induced dysautonomia
• High adenosine during seizure → cardiorespiratory collapse →
depression in the brainstem → dysautonomia

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SUDEP RISK FACTORS

• polytherapy with more than three ASMs
• male gender
• young age at epilepsy onset
• developmental delay
• poor AED compliance
• nocturnal seizures
• poorly controlled tonic-clonic seizures (especially if > 3 per yr)
• high frequency of seizures (especially if > 50 per yr)
• having epilepsy for > 30 yr in adults

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Evaluation After 1st Seizure

• History
• Seizure type
• Onset; level of awareness; seizure triggers; home videos
(helpful)
• Physical Examination
• Anthropometrics – HC
• Physical findings – facial features; skin lesions;
ophthalomologic exam
• Neurologic exam – focal deficits; muscle tone; sensory
testing; limb asymmetry

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ELECTROENCEPHALOGRAPHY (EEG)

• should be performed in all cases of a

first unprovoked nonfebrile seizure to
help predict the risk of seizure
recurrence
• A normal EEG does not exclude epilepsy
• Not all abnormal EEGs mean epilepsy

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NEUROIMAGING PROCEDURES

•Indications:
•Focal seizures
•postictal focal deficits
•patient's status is not returning to baseline;
•trauma preceding the seizure
•patients with a high-risk medical history
•CT Scan vs. MRI
• CT scan – trauma (bleed); mass; increased ICP
• MRI with contrast – Preferred imaging (non-
emergency)

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MAJOR ISSUES IN EPILEPSY

MANAGEMENT
SEIZURE CONTROL

• Etiology
• Comorbidities
• IQ
• Personality disorder
Anti-Seizure Meds (ASM) • Cognitive problems Improved
Ketogenic Diet • Emotional Factors Quality of Life
• Socioeconomic Factors
Epilepsy Surgery • Ability to deal with complex
VNS ASM regimen
• blood tests
Other alternative Tx • drug assays

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Management of Epilepsy

• WHEN TO INITIATE ANTI-SEIZURE MEDICATION?

• Diagnosis of epilepsy has been established.
• After 1st unprovoked seizure

Generalized
• EEG with GSW discharges
• FHx - sibling with epilepsy
Focal
• Particular abnormalities on brain MRI
• Abnormal neurological examination
• Nocturnal seizure
• Todd’s phenomenon after the seizure

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CHOOSING THE RIGHT ASM

EFFICACY SAFETY
• Seizure type • Effect on cognition
• Epilepsy syndrome • Effect on behavior
• Etiology • Psychiatric effects
• Age • Teratogenicity
• Major congenital
CONVENIENCE malformations
• Ease of administration • Drug interactions
• Drug preparation • Hepatotoxicity
• Availability

Adverse Drug
Good seizure
Effects
control
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ANTI-SEIZURE MEDICATIONS

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Summary of Evidence and Recommendations

Epilepsy Treatment Guidelines (ILAE, 2013)
Seizure type Class I Class Class III Level of efficacy and effectiveness evidence
or epilepsy II (in alphabetical order)
syndrome
Focal 1 0 19 Level A: OXC
seizures: Level B: None
Children Level C: CBZ, PB, PHT, TPM, VPA, VGB
Level D: CLB, CZP, LTG, ZNS
Generalized 0 0 14 Level A: None
Tonic-Clonic: Level B: None
Level C: CBZ, PB, PHT, TPM, VPA
Children Level D: OXC
Absence 1 0 7 Level A: ESM, VPA
seizures Level B: None
Level C: LTG
Level D: None

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Recommendations for ASM in Primary Care

Philippine League Against Epilepsy (PLAE) mhGAP Task Force on Epilepsy (Aug 2018)

Seizure type Children and Adolescents Girls and Women of

(<18 years old) Childbearing Potential
(12 yrs and older)
Focal Seizures, w/ or w/o 1st Line: Carbamazepine Levetiracetam or
evolution to Lamotrigine
Bilateral tonic-clonic seizures 2nd line: Phenobarbital or
Valproic acid
Generalized onset seizures 1st line: Valproic Acid Levetiracetam or
Lamotrigine
2nd Line: Phenobarbital or
Levetiracetam
Unknown Onset 1st Line: Valproic Acid Levetiracetam or
Lamotrigine
2nd line: Phenobarbital or
Levetiracetam

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Advantages and Disadvantages of ASM

Antiseizure Medication Advantages Disadvantages
Carbamazepine Unsurpassed efficacy for Drug interaction,
focal seizures hypersensitivity reactions,
sedation, do not use for GGE

Oxcarbazepine Works in focal seizures, Hyponatremia, does not work

possibly better tolerated in in GGE, drug interaction
children than CBZ

Valproic Acid Unsurpassed efficacy in Less efficacious than CBZ for

IGE, works in focal epilepsy focal seizure, high
teratogenicity among AEDs,
drug interaction, liver failure

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Advantages and Disadvantages of ASM

Antiseizure Medication Advantages Disadvantages
Levetiracetam Low risk of drug interaction; Psychiatric side effects, only
low risk of hypersensitivity add-on use in myoclonic
reactions seizures
Lamotrigine Mood stabilizer, works in Drug interaction;
focal seizures and absence hypersensitivity reactions,
seizures slow titration
Phenobarbital Works in focal seizures and Less well tolerated than
in myoclonic seizures CBZ for focal seizures, drug
interaction, hypersensitivity
reactions, sedation, do not
use for absence seizures

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GRADUAL DISCONTINUANCE OF ASM

CRITERIA:

1. Seizure - free 2 to 5 years on ASM/s (mean 3-5 years)

2. Single type of focal seizure or single type of
generalized seizures
3. Normal neurologic examination / normal I.Q.
4. Normal neuroimaging
5. EEG normalized with treatment

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SUMMARY OF MANAGEMENT

HIGH RISK OF SEIZURE RECURRENCE

DIAGNOSE (EPILEPSY)

CLASSIFY FOCAL GENERALIZED UNKNOWN

?
CARBAMAZEPINE
VALPROIC ACID/VALPROATE
OXCARBAZEPINE
TREATMENT LEVETIRACETAM LEVETIRACETAM
LAMOTRIGINE
LAMOTRIGINE

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S TAT U S E P I L E P T I C U S
MANAGEMENT GOALS
• STOP the SEIZURE
• prompt administration of appropriately selected anti-
seizure medications
• WHAT is the CAUSE
• identification and management of any seizure
precipitant(s)
• MINIMIZE COMPLICATIONS
• identification and management of associated systemic
complications.

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1 st L i n e A S M f o r S E
• Benzodiazepines
• GABA-A receptor agonist
• increased chloride conductance and neuronal hyperpolarization
Drug Initial Dose Administration rates Adverse events Considerations
and alternative dosing
recommendations

0.15-0.3 mg/kg IV up to Up to 5 mg/min (IVP) Hypotension Rapid redistribution (short

Diazepam Peds: 2–5 years, 0.5 mg/kg Respiratory depression duration), active metabolite,
10 mg/ dose, may IV contains propylene glycol
(PR); 6–11 years, 0.3
repeat in 5 min
mg/kg (PR); greater than
12 years, 0.2 mg/kg (PR)

0.2 mg/kg IM/IV up to Peds: 10 mg IM (>40 kg); Respiratory depression Active metabolite, renal
Midazolam Hypotension elimination, rapid redistribution
maximum of 10 mg 5 mg IM (13–40 kg); (short duration)
0.2 mg/kg (intranasal);
0.5 mg/kg (buccal)

0.1 mg/kg IV up to Up to 2 mg/min (IVP) Hypotension Dilute 1:1 with saline

Lorazepam* 4 mg per dose, may Respiratory depression IV contains propylene glycol
repeat in 5–10 min

Brophy GM, et al, Neurocrit Care. 2012

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2 nd l i n e A S M O p t i o n s
Drug Initial Dose Adverse events

Phenobarbital 15-20 mg/kg IV, may give Hypotension

an additional Respiratory depression
5–10 mg/kg

Phenytoin** 20 mg/kg IV, may give Arrhythmias

an additional Hypotension
Purple glove syndrome
5–10 mg/kg

Valproate Sodium 20–40 mg/kg IV, may Hyperammonemia

give an additional Pancreatitis
20 mg/kg Thrombocytopenia

Levetiracetam 1,000–3,000 mg IV
Peds: 20–60 mg/kg IV
Brophy, et al. Neurocrit Care (2012) 17:3–23.
(40-60mg/kg/day)**
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REFERENCES
• Moalong KMC, Espiritu AI, Fernandez MLL, Jamora RDG. Treatment gaps and challenges in epilepsy care in the Philippines.
Epilepsy Behav. 2021 Feb;115:107491. doi: 10.1016/j.yebeh.2020.107491. Epub 2020 Dec 13. PMID: 33323340.
• Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC,
Lee BI, Mathern GW, Moshé SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical
definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. Epub 2014 Apr 14. PMID: 24730690.
• Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy:
Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522-530. doi:10.1111/epi.13670
• Fisher RS, Cross JH, D'Souza C, et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia.
2017;58(4):531-542. doi:10.1111/epi.13671
• Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for
Classification and Terminology. Epilepsia. 2017;58(4):512-521. doi:10.1111/epi.13709
• Tatum, W. (2018). The First Seizure: Is It Epilepsy? In D. Schmidt, W. Tatum, & S. Schachter (Authors), Common Pitfalls in
Epilepsy: Case-Based Learning (pp. 49-65). Cambridge: Cambridge University Press. doi:10.1017/9780511845796.005.
• Schmidt, D. (2018). Which Drug is Best? In D. Schmidt, W. Tatum, & S. Schachter (Authors), Common Pitfalls in Epilepsy: Case-
Based Learning (pp. 108-139). Cambridge: Cambridge University Press. doi:10.1017/9780511845796.008
• Bauer D, Quigg M. Optimizing Management of Medically Responsive Epilepsy. Continuum (Minneap Minn). 2019;25(2):343-361.
doi:10.1212/CON.0000000000000709.

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“In the end we retain from our studies only that

which we practically apply.”
– Johann Wolfgang Von Goethe

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GOOD AFTERNOON

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