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Professeur Oreste Battisti
Faculté de Médecine
Université de Liège
Battisti: Convulsions néonatales
1
Summary


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

Seizures in the newborn period constitute a medical
emergency.
Subtle seizures are the commonest type of seizures
occurring in the neonatal period.
Other types include clonic, tonic, and myoclonic seizures.
Myoclonic seizures carry the worst prognosis in terms of
long-term neurodevelopmental outcome.
Hypoxic-ischemic encephalopathy is the most common
cause of neonatal seizures.
Multiple etiologies often co-exist in neonates and hence it is
essential to rule out common causes such as hypoglycemia
,hypocalcemia , meningitis before initiating specific therapy.
A comprehensive approach for management of neonatal
seizures is the best way for management.
Battisti: Convulsions néonatales
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Structure of presentation
Introduction and epidemiology
 Definitions and patterns of convulsions
or neonatal seizures
 Classification: clinical and EEG
 Etiology
 Physiopathology
 Treatment and follow-up

Battisti: Convulsions néonatales
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Epidémiologie



prévalence:80-120 /100,000 naissances
Incidence:1-5/1000
La période néonatale est particulièrement
ciblée
Battisti: Convulsions néonatales
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Causes of Neonatal Seizures and Outcomes
Percent of
Patients Who
Have Normal
Development
Cause
Hypoxic-ischemic encephalopathy
Intraventricular hemorrhage
Subarachnoid hemorrhage
Hypocalcemia
Early-onset
Later-onset
Hypoglycemia
Bacterial meningitis
Developmental malformations
Benign familial neonatal convulsions
Fifth-day fits
50
10
90
50
100
50
50
0
~100
~100
Battisti: Convulsions néonatales
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Prognosis of Neonatal Seizures:
Relation to Neurological Diseases
Neurological Disease
Normal Development
Hypoxic-ischemic encephalopathy
Intraventricular hemorrhage
Primary subarachnoid hemorrhage
Hypocalcemia
Early-onset
Later-onset
Hypoglycemia
Bacterial meningitis
Developmental defect
Battisti: Convulsions néonatales
50%
10%
90%
50%
100%
50%
50%
0%
6
Prognosis in general
Myoclonic seizures carry the worst prognosis in terms of
neuro-developmental outcome and seizure recurrence.
 Focal clonic seizures have the best prognosis.
 Seizures due to Subarachnoid Hemorrhage and late onset
hypocalcemia carry a good prognosis for long term neurodevelopmental outcome while seizures related to
hypoglycemia, cerebral malformations and meningitis
have a high risk for adverse outcome.
 A background abnormality in both term and preterm
neonates indicates a high risk for neurological sequelae.
These changes include burstsuppression pattern, low
voltage invariant pattern and electro-cerebral inactivity

Battisti: Convulsions néonatales
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1. Definition, classification
and patterns of
neonatal:
seizures
convulsions
epilepsy
Battisti: Convulsions néonatales
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The Definition of a Seizure
“paroxysmal discharge of cerebral
neurons sufficient to cause
clinically detectable events that
are apparent either to the subject or
to an observer”
Battisti: Convulsions néonatales
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clinical patterns of seizures
in newborns (Fenichel)
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Apnea with tonic stiffening of body
Focal clonic movements of one limb or both limbs on one
side
Multifocal clonic limb movements
Myoclonic jerking
Paroxysmal laughing
Tonic deviation of the eyes upward or to one side
Tonic stiffening of the body
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Why do neonatal seizures have such
unusual presentations?

Immature CNS cannot sustain a
synchronized, well orchestrated
generalized seizure
Normal Neonatal Motor Activity Commonly
Mistaken for Seizure Activity
AWAKE OR DROWSY
Roving, sometimes dysconjugate eye movements, with
occasional nonsustained nystagmoid
jerks at the extremes of horizontal movement (contrast with
fixed, tonic horizontal deviation of eyes with or without
jerking—characteristic of subtle seizure
Sucking, puckering movements not accompanied by ocular
fixation or deviation
SLEEP
Fragmentary myoclonic jerks—may be multiple
Isolated, generalized myoclonic jerk as infant wakes from sleep
Volpe Neurology of the Newborn..
Battisti: Convulsions néonatales
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Classification of Neonatal Seizures

Clinical

Electroencephalographic
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Classification
I. Clinical Seizure
 Subtle
 Tonic
 Clonic
 Myoclonic
Classification
II. Electroencephalographic seizure

Epileptic

Non-epileptic
Classification of Neonatal
Seizures
ELECTROENCEPHALOGRAPHIC SEIZURE
CLINICAL SEIZURE
COMMON
UNCOMMON
Subtle
+*
Clonic
Focal
+
Multifocal
+
Tonic
Focal
+
Generalized
+
Myoclonic
Focal, multifocal
+
Generalized
+
--------------------------------------------------------------------------------------------------------------*Only specific varieties of subtle seizures are commonly associate with simultaneous
Electroencephalographic seizure activity.
Volpe JJ.Neonatal Seizures:Neurology of the Newborn.4th ed.
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Classification of neonatal seizures
Seizure type
Occurs in
Clinical signs
EEG changes
Subtle
Preterm and Term
Eye deviation (Term)
Blinking, fixed stare (Preterm)
Repetitive mouth & tongue movements Apnea
Pedaling, tonic posturing of limbs
Usually No
Tonic
Primarily preterm
May be focal or generalized
Tonic extension or flexion of limbs (often signals
severe IVH in preterm infants)
Usually No
Clonic
Primarily term
May be focal or multifocal
Clonic limb movements (synchronous or
asynchronous, localized or often with no
anatomic order to progression) Consciousness
may be preserved
Often signals focal cerebral injury.
Yes
Myoclonic
Rare
Focal, multifocal, or generalized Lightning-like jerks
of extremities (upper>lower)
+
Battisti: Convulsions néonatales
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Classification of Neonatal Seizures

Clinical

Electroencephalographic
Battisti: Convulsions néonatales
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Neonatal Seizures

Tonic Seizures
focal or generalized,
may mimic decorticate or decerebrate posturing, primarilyseen in preterms with
intracranial hemorrhage & generally have poor prognosis
Subtle seizures
Consist of chewing motion, excessive salivation and alteration
in respiratory rate including apnea, blinking, nystagmus,
bicycling and pedaling movements, changes in color

Battisti: Convulsions néonatales
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Clonic- focal (repetitive movements localized to a single limb)
or multifocal (random migration of movements from limb to
limb), consciousness may be preserved, primarily seen in
term infants
• Myoclonic- sudden flexor movements (lightning-like
jerks), may be focal, multifocal or generalized, may
occuring singly or in clusters, if due to early myoclonic
encephalopathy it carries a poor prognosis. Brief focal
or generalized jerks of the extremities or body that
tend to involve distal muscle groups
Battisti: Convulsions néonatales
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Clinical Classification

Focal/Multifocal Clonic
 Not
generalized
 Migratory
Focal Tonic
 Generalized Myoclonic

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Neonatal seizures
The most common presentation is focal clonic or multifocal clonic movments. The
rhythmic jerking is well-localized to a limb, may migrate to other limbs, not
necessarily in a contiguous fashion with the infant usually not conscious.
Neonatal seizures do not manifest with generalized clonic activity.
Neonatal seizures may present with focal tonic, so persistently increased tone in a
limb.

Generalized tonic activity, of the whole body, usually is not associated with
seizure activity on EEG, but may be posturing.

Then there are myoclonic seizures; myoclonus being more rapid, more erratic
and non-rhythmic than clonic movements. Focal or multifocal myoclonus is
usually not associated with sz activity, but bilateral synchronous generalized
myoclonic more likely to be seizures with the kids more likely to be sicker, and we
can talk about the difference in mechanism there later as well.

Other than descriptive terminology, there’s this funny classification that’s used,
called “subtle” seizures, because they are.

Some also classify these as “hypomotor” seizures, which may present with
activity arrest, apnea, or eye deviation. The art in diagnosing these as true
seizures, and not just diagnosing every bowel movement as a seizure is in
looking for any associated signs, such as autonomic changes like BP or HR
increase. Autonomic sx may be an isolated finding in preemies, but usually
accompanies sz’s in term. The most common subtle manifestation is tonic
horizontal eye deviation.

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Clinical Classification

Subtile (“Hypomotor”)
 Motor activity arrest
 Apnea
 Eye deviation
 Autonomic changes

Motor automatisms
 Oral-buccal-lingual movements
 Swimming
 Bicycling
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Subtle seizures
More in preterm than in term

Eye deviation (term)

Blinking, fixed stare (preterm)

Repetitive mouth and tongue movements

Apnea

Pedaling and tonic posturing of limbs

“Tonic deviation of the eyes Repetitive fluttering of eyelids
Drooling, sucking, chewing Swimming movements of the
arms Pedaling movements of the legs Paroxysmal
laughing »
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Subtle seizures (ct)

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


Ocular - Tonic horizontal deviation of eyes or sustained
eye opening with ocular fixation or cycled flutering
Oral–facial–lingual movements - Chewing, tonguethrusting, lip-smacking, etc.
Limb movements - Cycling, paddling, boxing-jabs, etc.
Autonomic phenomena - Tachycardia or bradycardia
Apnea may be a rare manifestation of seizures. Apnea
due to seizure activity has an accelerated or a normal
heart rate when evaluated 20 seconds after onset.
Bradycardia is thus not an early manifestation in
convulsive apnea but may occur later due to prolonged
hypoxemia.
Battisti: Convulsions néonatales
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Tonic seizures
Primarily in Preterm

May be focal or generalized

Sustained extension of the upper and
lower limbs (mimics decerebrate posturing)

Sustained flexion of upper with extension of
lower limbs (mimics decorticate posturing)

Signals severe ICH in preterm infants

This type refers to a sustained flexion (mainly in premature) or extension
(mainly in term) of axial or appendicular muscle groups.

Resemble decerebrate (tonic extension of all limbs) or decorticate
posturing (flexion of upper limbs and extension of lower limbs).

Usually there are no EEG changes in generalized tonic seizures.
Battisti: Convulsions néonatales
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Clonic
Primarily in term

Focal or multifocal

Clonic limb movements(synchronous or
asynchronous, localized or often with no anatomic order of progression)

Consciousness may be preserved

Signals focal cerebral injury
They are rhythmic movements of muscle groups.
They have both fast and slow components, occur with a frequency of 1-3 jerks
per second, and are commonly associated with EEG changes.
Multifocal clonic seizures on the 5th day may be related to low zinc levels
in the CSF fluid (benign idiopathic neonatal convulsions).
Battisti: Convulsions néonatales
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Myoclonic
Rare



Focal, multifocal or generalized
Lightning-like jerks of extremities
(upper > lower)
These manifest as single or multiple lightning fast jerks of the
upper or lower limbs and are usually distinguished from
clonic movements because of more rapid speed of
myoclonic jerks, absence of slow return and predilection for
flexor muscle groups. Common changes seen on the EEG
include burst suppression pattern, focal sharp waves and
hypsarrhythmia
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Benign familial neonatal seizures
 Begins on the 2nd – 3rd day of life
 Seizure frequency : 10 – 20 /day
 Patients are normal between seizures
 Seizure stops in 1 – 6 months
Battisti: Convulsions néonatales
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5th day Seizures
5th day of life
○ normal
appearing neonates
mulifocal seizures
○ Present for less than 24 hours
○ Good prognosis
Battisti: Convulsions néonatales
with
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Jitteriness Versus Seizure
CLINICAL FEATURE
JITTERINESS
Abnormality of gaze or eye
movement
Movements exquisitely stimulus
sensitive
Predominant movement
Movements cease with passive
flexion
Autonomic changes
SEIZURE
O
+
+
O
Tremor
+
O
Clonic jerking
O
+
------------------------------------------------------------------------------------------------------------------
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Weird Baby Movements
 Jitteriness
○ Stimulus-sensitive
○ “Tremor”
○ Suppressable
 Benign neonatal sleep myoclonus
 Spinal myoclonus
 Apnea of non-neurologic etiology
○ bradycardia
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Non-epileptic movements
commonly confused with seizures
Jitteriness or tremors
 Normal movements seen more commonly in preterm
infants
- Benign neonatal sleep myoclonus: Occurs during NREM
sleep in preterm infants in the first week of life. Restraint
and benzodiazepines may increase the frequency of jerks,
while on arousal they are usually abolished. EEG will be
normal in this condition.
- Fragmentary myoclonic jerks
- Eye movements: Roving or dys-conjugate eye
movements with occasional non- sustained nystagmoid
jerks.

Battisti: Convulsions néonatales
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Classification of Neonatal Seizures

Clinical

Electroencephalographic
Battisti: Convulsions néonatales
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Electroencephalographic seizure
I. Epileptic

Consistently associated with electrocortical seizure activity on the EEG
 Cannot be provoked by tactile stimulation
 Cannot be suppressed by restraint of
involved limb or repositioning of the infant
 Related to hyper synchronous discharges
of a critical mass of neuron
Electroencephalographic seizures
II. Non-epileptic
 No electro-cortical signature
 Provoked by stimulation
 Suppressed by restraint or repositioning
 Brainstem release phenomena (reflex)
Neonatal Seizures
EEG Classification


Clinical seizure with consistent EEG event
 Clinical seizure occurs in relationship to seizure
activity
 Includes focal clonic, focal tonic and myoclonic
 Responds to antiepileptic drugs
Clinical seizure with inconsistent EEG event
 Clinical seizures with no EEG abnormality
 Seen in all generalized tonic and subtle seizures
 Seen in patients who are comatose, HIE
Battisti: Convulsions néonatales
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Neonatal Seizures
EEG Classification

Electrical seizures with absent clinical
seizures
 Electrical seizures associated with markedly
abnormal background EEG
 Seen in comatose patients
Battisti: Convulsions néonatales
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Epileptic vs Non-epileptic
Neonatal Phenomena
Clinical
Characteristics
Epileptic
Non-epileptic
Increases with
Sensory
stimulation
Rare
Common
Suppresses with
restraint
-
+
Autonomic
Accompaniments
+
Battisti: Convulsions néonatales
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Does absence of EEG seizure activity
indicate that a clinical seizure is nonepileptic?

Certain clinical seizures in the human
newborn originate from electrical seizures
in deep cerebral structures (limbic regions),
or in diencephalic, or brain stem structures
and thereby are either not detected by
surface-recorded EEG or inconsistently
propagated to the surface
Neonatal Seizures
EEG Classification

Clinical seizure with consistent EEG event
 Clinical seizure occurs in relationship to seizure
activity
 Includes focal clonic, focal tonic and myoclonic
 Responds to antiepileptic drugs

Clinical seizure with inconsistent EEG event
 Clinical seizures with no EEG abnormality
 Seen in all generalized tonic and subtle seizures
 Seen in patients who are comatose, HIE
Battisti: Convulsions néonatales
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EEG tracing
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Battisti: Convulsions néonatales
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Exercices on movies
Battisti: Convulsions néonatales
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In addiction
Battisti: Convulsions néonatales
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Focal crisis
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3. Etiology
of
neonatal convulsions
or seizures
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Etiology

It is critical to recognize neonatal seizures,
to determine their etiology, and to treat
them for three major reasons:
1. Seizures are usually related to significant
illness, sometimes requiring specific
therapy
Battisti: Convulsions néonatales
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Etiology
2.Neonatal seizures may interfere with
important supportive measures, such as
alimentation and assisted respirations for
associated disorders.
3.Experimental data give some reason for
concern that under certain circumstances
the seizure per se may be a cause of brain
injury.
Battisti: Convulsions néonatales
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Major Etiologies of Neonatal Seizures in
Relation to Time of
Seizure Onset and Relative Frequency
TIME OF ONSET*
FREQUENCY†
0-3 DAYS
TERM
Hypoxic-ischemic
encephalopathy
Intracranial
hemorrhage‡
Intracranial infection
Developmental
defects
Hypoglycemia
Hypocalcaemia
Other metabolic
Epileptic syndromes
>3DAYS
+
RELATIVE
PREMATURE
FULL
+++
+++
+
+
++
+
+
+
+
+
++
++
++
++
+
+
+
+
+
+
+
+
+
+
+
Battisti: Convulsions néonatales
+
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Comparison of prominent etiologic diagnoses of
seizures in the newborn period. (Data modified from
Mizrahi and Kellaway, 1987; Rose and Lombroso,
1970)
Malformation
Hypoglycemia
Hypocalcemia
Meningitis
Stroke
1970
1987
Trauma
Hemorrhage
Hypoxia-ischemia
0
10
20
30
40
50
Incidence (%)
Fanaroff A, Martin R.Neonatal seizures. In:Neonatal and Perinatal Medicine, Diseases of the Fetus and Infant,6 th ed.
Battisti: Convulsions néonatales
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Etiology

Pregnancy history is important
 Search for history that supports TORCH
infections
 History of fetal distress, preeclampsia or
maternal infections
Battisti: Convulsions néonatales
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Major Causes of Neonatal Seizures In Relation to Time of Seizure Onset and
Relative Frequency
TIME OF ONSET*
FREQUENCY
Cause
Full Term
0-3 Days
Hypoxic-Ischemic encephalopathy
Intracranial hemorrhage
Intracranial infection
Developmental defects
Hypoglycemia
Hypocalcemia
Other metabolic
Epileptic syndromes
+
+
+
+
+
+
+
+
Battisti: Convulsions néonatales
RELATIVE
>3 Days
+
+
+
+
+
Premature
+++
++
++
++
+
+
+++
+
++
++
+
+
+
53
Neonatal Seizures
Etiologic diagnosis
Hypoxic –ischemic encephalopathy
 Metabolic
 Infections
 Trauma
 Structural abnormalities
 Hemorrhagic and embolic strokes
 Maternal disturbances

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Differential diagnosis of neonatal seizures
by peak time of onset






















24 hours
Bacterial meningitis and sepsis Direct drug effect
Hypoxic-ischemic encephalopathy Intrauterine infection
Intraventricular hemorrhage at term Laceration of tentorium or falx Pyridoxine dependency
Subarachnoid hemorrhage
24 to 72 hours
Bacterial meningitis and sepsis
Cerebral contusion with subdural hemorrhage
Cerebral dysgenesis
Cerebral infarction
Drug withdrawal
Glycine encephalopathy
Glycogen synthase deficiency
Hypoparathyroidism–hypocalcemia
Idiopathic cerebral venous thrombosis
Incontinentia pigmenti
Intracerebral hemorrhage
Intraventricular hemorrhage in premature newborns
Pyridoxine dependency
Subarachnoid hemorrhage
Tuberous sclerosis
Urea cycle disturbances
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Causes of neonatal seizures
Ages 1 – 4 days
HIE
 Drug withdrawal
 Dug toxicity

 Lidocaine, penicillin
Intraventricular hemorrhage
 Acute metabolic disorder

 Hypocalcemia
 Hypoglycemia
 Inborn errors of metabolism
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Causes of neonatal seizures
Ages 4 – 14 days


Infection
Metabolic disorders
 Hypocalcemia
 Diet
 Hypoglycemia
 Inherited disorder of
metabolism such as
galactosemia,fructosemia
 Hyperinsulinemic
hypoglycemia
 Becwith syndrome
 Anterior pituitary
hypoplasia



Drug withdrawal
Benign neonatal
convulsion
Kernicterus,
hyperbilirubenemia
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Causes of neonatal seizures
Ages 2 – 8 weeks



Infection
Head injury

Malformations of
cortical development
 Subdural henatoma
 Lissencephaly
Inherited disorder of
metabolism
 Focal cortical dysplasia
 Aminoacidurias
 Tuberous sclerosis
 Sturge weber syndrome
 Urea cycle defects
 Organic acidurias
 Neonatal ALD
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Neonatal Seizures
Etiologic diagnosis



Blood
 Glucose, calcium, magnesium, electrolytes,
BUN
 In hypomagnesemia  MgSO4 0.2 ml/kg
Lumbar puncture
 Indicated in all neonates with seizures unless
related to a metabolic disorder
Inborn errors of metabolism
 Inherited as autosomal recessive or X-linked
recessive
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Neonatal Seizures
Etiologic diagnosis

Inborn errors of metabolism
 Serum ammonia  urea cycle abnormalities
 Acidosis + anion gap + hyperammonemia
urine organic acids should be determined

Unintentional
anesthetic
injection
of
local
 Supportive measures
 Promotion of urine output with IV fluids
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Idiopathic Syndromes of Clinical
Seizures in the Newborn
Epileptic Syndromes
Benign familial Neonatal Seizures
Benign idiopathic neonatal seizures (fifth-day fits)
Early myoclonic encephalopathy
Early infantile epileptic encephalopathy (Ohtahara
syndrome)
Malignant migrating partial seizures
Nonepileptic Syndromes
Benign neonatal sleep myoclonus
Hyperekplexia
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Neonatal Seizures
(Epileptic Syndromes)

Benign familial neonatal seizures
 Begins on the 2nd – 3rd day of life
 Seizure frequency : 10 – 20 /day
 Patients are normal between seizures
 Seizure stops in 1 – 6 months
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Neonatal Seizures
Fifth-day fits –
○ 5th day of life
○ normal
appearing neonates
mulifocal seizures
○ Present for less than 24 hours
○ Good prognosis
Battisti: Convulsions néonatales
with
63
Neonatal Seizures
Etiologic diagnosis

Pyridoxine dependency
 resistant to conventional AED’s
 Inherited as autosomal recessive
 Tx: Pyridoxine 100 – 200 mg IV
 May not have a dramatic effect with IV
pyridoxine thus maintain on oral pyridoxine
10 -20 mg/day x 6 weeks
 Lifelong supplementation : 10 mg/day
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Neonatal Seizures
Etiologic diagnosis

Drug withdrawal seizures
 Barbiturates, benzodiazepenes, heroin and
methadone
 Jittery, irritable, lethargic, may show
myoclonus or frank seizures
 Serum or urine analysis may identify the
responsible agent
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Causes of Neonatal Seizures

Within first 24 hours of life
 Hypoxic ischemic encephalopathy
 Meningitis/sepsis
 Subdural/Subarachnoid/Interventricular




hemorrhage
Intrauterine infection
Trauma
Pyridoxine dependency
Drug effect/withdrawal
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Causes….

24-72 hours
 Meningitis/sepsis
 In premature infants: IVH
 In full-term infants: infarction,
venous thrombosis
 Cerebral dysgenesis
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Causes….
72 hours to 1 week
 Above causes
 Inborn errors of metabolism
 Hypocalcemia
 Familial neonatal seizures
 1 week to 4 weeks
 Above causes
 HSV

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Causes of neonatal seizures
Ages 1 – 4 days
 HIE
 Drug
withdrawal
 Dug toxicity
 Lidocaine, penicillin
 Intraventricular
hemorrhage
 Acute metabolic disorder
 Hypocalcemia
 Hypoglycemia
 Inborn errors of metabolism
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Other Syndromes
Benign idiopathic neonatal convulsions
(BINC or Fifth-day fits)
 Benign familial neonatal convulsions
(BFNC)
 Early myoclonic encephalopathy (EME)
 Early infantile epileptic encephalopathy
(EIEE)
 Glucose transporter type I

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Inborn Errors of Metabolism Associated With
Neonatal Seizures
Conditions That Have a Specific Treatment
Pyridoxine (B6) dependency
Folinic acid-responsive seizures
Glucose transporter defect
Creatine deficiency
Other Conditions
Nonketotic hyperglycinemia
Sulfite oxidase deficiency
Molybdenum cofactor deficiency (combined deficiency)
Carbohydrate-deficient glycoprotein disorder
Lactic acid disorders
Mitochondrial disorders
Maple syrup urine disease
Isovaleric acidemia (sweaty feet, cheesy odor)
Battisti: Convulsions néonatales
71
The patho physiology of
neonatal convulsions
or seizures
Battisti: Convulsions néonatales
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Why are seizure patterns in neonates more
fragmentary than in older children?

The cellular organization of the mature and
immature brain is different. The neonatal brain has
incomplete glial proliferation, w/ continuing
migration of neurons, establishing complex axonal
& dendritic contacts and myelin deposition.
The electrical discharges therefore spread incompletely
and may remain localized to one hemisphere. The
electrical discharges are slow to diffuse and bilateral
synchronous discharges are rare.
Battisti: Convulsions néonatales
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Perinatal Anatomical and Physiological
Features of Importance in Determining
Neonatal Seizure Phenomena
ANATOMICAL
 Neurite outgrowth—dendritic and axonal ramifications—
in process
 Synaptogenesis not complete
 Deficient myelination in cortical efferent systems
Volpe JJ.Neonatal Seizures :Neurology of the Newborn.
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Perinatal Anatomical and Physiological
Features of Importance in Determining
Neonatal Seizure Phenomena
PHYSIOLOGICAL

In limbic and neocortical regions,excitatory synapses develop
before inhibitory synapses ( N-methyl-D-aspartate receptor
activity, gamma-aminobutyric acid excitatory)

Immature hippocampal and cortical neurons more susceptible to
seizure activity than mature neurons

Deficient development of substantia nigra system for inhibition of
seizures

Impaired propagation of electrical seizures, and synchronous
discharges recorded from surface electroencephalogram may
not correlate with behavioral seizure phenomena
Volpe JJ.Neonatal Seizures.In:Neurology of the Newborn.4th ed.
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Probable Mechanisms of Some Neonatal
Seizures
PROBABLE MECHANISM
DISORDER
Failure of Na + -K + pump secondary to
 adenosine triphosphate
Excess of excitatory neurotransmitter
(eg.glutamic acid—excessive excitation)
Hypoxemia, ischemia,
and hypoglycemia
Hypoxemia, ischemia
and hypoglycemia
Pyridoxine dependency
Deficit of inhibitory neurotransmitter
(i.e., relative excess of excitatory
neurotransmitter)
Membrane alteration—  Na +
Hypocalcemia and
Permeability
hypomagnesemia
______________________________________________________________
Volpe JJ.Neonatal Seizures:Neurology of the Newborn. ed.
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Particularity of a Seizure
in a Neonate








Glutamate receptors predominate, and in addition, GABA, which later in life acts
as an inhibitory neurotransmitter, actually acts at at least one receptor in an
excitatory fashion.
some true seizures do not demonstrate a paroxysmal discharge on EEG.
Axons, dendrites, synapses are still in the process of forming and organizing, so
may not be capable of propagating widely enough for electrodes to see. .
The electrical activity is originating from deeper brain regions, such as the
midbrain.
in a few studies looking at human infants with subtle events and EEG correlation,
sometimes the events were associated with discharges and sometimes not
within the same child;
in those infants, the clinical onset was more likely to begin seconds before
discharge seen, suggesting that perhaps the discharges were originating from
deep and travelling up to the cortex.
Another possibility for not seeing discharges on EEG is that the event really is
not a seizure, but could be a brain stem release
brain stem and spinal motor patterns released from inhibition that normally is
imposed by a healthy forebrain and cortex.
Battisti: Convulsions néonatales
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Particularity of a Seizure
in a Neonate

Excitatory activity predominates: No
paroxysmal discharge on EEG?
 True seizure
○ The cortex is undeveloped
○ Deeper origin
 “Brainstem release phenomena”
Battisti: Convulsions néonatales
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Causes of neonatal seizures
Ages 4 – 14 days


Infection
Metabolic disorders
 Hypocalcemia
 Diet
 Hypoglycemia
 Inherited disorder of
metabolism such as
galactosemia,fructosemi
a
 Hyperinsulinemic
hypoglycemia
 Becwith syndrome
 Anterior pituitary
hypoplasia
Drug withdrawal
 Benign neonatal
convulsion
 Kernicterus,
hyperbilirubenemia

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Causes of neonatal seizures
Ages 2 – 8 weeks



Infection
Head injury

Malformations of
cortical development
 Subdural henatoma
 Lissencephaly
Inherited disorder of
metabolism
 Focal cortical
 Aminoacidurias
 Urea cycle defects
dysplasia
 Tuberous sclerosis
 Sturge weber
syndrome
 Organic acidurias
 Neonatal ALD
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Causes of neonatal seizures






-
-
50-65% of all seizures < Hypoxic-ischemic encephalopathy (HIE)
Intracranial hemorrhage
Metabolic causes Common metabolic causes of seizures include
hypoglycemia, hypocalcemia, hypomagnesemia. Rare causes include
pyridoxine deficiency and inborn errors of metabolism (IEM).
Infections
Developmental defects Cerebral dysgenesis and neuronal migration disorders
are rare causes of seizures in the neonatal period.
Miscellaneous
Polycythemia
maternal narcotic withdrawal
drug toxicity (e.g. theophylline, doxapram)
local anesthetic injection into scalp (Accidental injection of local anesthetic into
scalp may be suspected in the presence of unilateral fixed and dilated pupils)
phacomatosis (e.g. tuberous sclerosis, incontinentia pigmentii).
Multifocal clonic seizures on the 5th day may be related to low zinc levels in the
CSF fluid (benign idiopathic neonatal convulsions).
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Les entités cliniques et électrophysiologiques
des paroxysmes du nouveau-né









Syndrome post-hypoxique ou post-asphyxique : « pointes-ondes en bouffées,
entrecoupées par des activités normales » ;
Etat de mal convulsif focal (  occlusive vascular disorder ) : « pointes lentes
rythmiques unilatérales » ;
Etat de mal généralisé : « pointes-ondes en bouffées » ;
Convulsions néonatales bénignes ( à j 4-5 ) : « théta pointu alternant », avec
(myo)clonies ;
Convulsions néonatales bénignes familiales précoces : souvent j 2-3, mais
parfois plus tard, avec prédominance chez le garçon ( anamnèse ! ) : « pas de
tracé spécifique » ;
Encéphalopathie myoclonique précoce : « pointes-ondes en bouffées, jamais
synschrones sur les deux hémisphères, séparées par des tracés plats =
suppression bursts » : penser à une maladie métabolique ( surtout une
hyperglycinémie ou une acidémie-D-glycérique ) ou annonce d’une
encéphalopathie épileptique infantile précoce comme une hypsarythmie.
Convulsions généralisées relatées à un dysfonctionnement de la vitamine B6 (
dosage de l’acide pipécolique sanguin ) [ R/ 100 mg IV pyridoxine ] ;
ou de l’acide folinique ( dosage acide pipécolique, AA sanguins , HVA et 5 HIAA
dans les urines ; [ R/ 100 mg vit B6 et 2.5 mg acide folique ];
anomalie du transporteur 1 du glucose vers le SNC ( GLUT1 deficiency ) :
anomalie à distance des repas.
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AG ou APC
Faits marquants
24-27 semaines
Ondes
polymorphes, discontinues, amples
Possibilités de courtes périodes (1-2 min) d’activités continues
Eveil/sommeil indissociable

28-32 semaines
Bouffées
theta (donc tracé discontinu)
NB 28-29 semaines : ces bouffées sont synchrones (dans les 2
hémisphères)
Après 30 semaines, il y a des bouffées delta
Eveil / sommeil indissociables
32 – 36 semaines
Disparition
des bouffées theta
multifocales
Eveil / sommeil dissociables
Pointes
> 36 semaines
Eveil
/ sommeil structuré
: bas voltage, diffus
REM :ondes lentes avec épisodes d’ondes rapides, activité continue
NREM : activité discontinue
Eveil
> 44 semaines
Tracé
continu en sommeil calme
> 46 semaines
Fuseau
> 48 semaines
Activité
4 à 5 mois
Bouffées
6 à 8 mois
Rythme
de sommeil dans les régions centrales
rythmique occipitale qui disparaît à l’ouverture des yeux
d’ondes pointes frontales ( encoches )
theta pendant l’endormissement
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83
The evaluation
neonatal convulsions
or seizures
Battisti: Convulsions néonatales
84
Maladies métaboliques et pH










Une acidose métabolique avec cétonurie et avec acidose lactique : penser à une maladie
mitochondriale ;
Une acidose métabolique avec cétonurie et sans acidose lactique : penser à une acidurie
organique ;
Une acidose métabolique avec cétonurie, avec ou sans acidose lactique : penser à une
leucinose ;
Une acidose métabolique sans cétonurie, avec acidose lactique et avec hypoglycémie :
penser à une glycogénose ou défaut de la gluconéogenèse ou défaut d’oxydation des
acides gras ;
Une acidose métabolique avec cétonurie, sans hypoglycémie et sans acidose lactique :
penser à un défaut de la chaîne respiratoire ;
Une acidose métabolique avec cétonurie sans acidose lactique et sans hypoglycémie :
penser aussi à une acidurie organique et à une acidurie pyroglutamique ;
Pas d’acidose métabolique sans acétonurie avec hyperammoniémie et hypoglycémie :
penser à un défaut d’oxydation des acides gras, à un défaut en glutamate
déshydrogénase ;
Pas d’acidose métabolique sans acétonurie avec hyperammoniémie et sans
hypoglycémie : penser à un défaut du cycle de l’urée.
Pas d’acidose métabolique sans acétonurie sans hyperammoniémie et sans
hypoglycémie : penser à hyprglycinémie ( sans cétose ), ou un déficit en sulfite oxydase.
Pas d’acidose métabolique avec acétonurie :penser à une leucinose.
Battisti: Convulsions néonatales
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Mandatory investigations
-
-
blood sugar
Hematocrit
bilirubin (if jaundice is present clinically)
serum electrolytes (Na, Ca, Mg)
arterial blood gas, anion gap
cerebrospinal fluid (CSF) examination: CSF examination should
be done in all cases as seizures may be the first sign of
meningitis. It should not be omitted even if another etiology
such as hypoglycemia is present, because meningitis can often
coexist. CSF study may be withheld temporarily if severe
cardio-respiratory compromise is present or in cases with
severe birth asphyxia (documented poor cord pH, seizure onset
within 12-24 hrs). An arterial blood gas (ABG) may have to be
performed if IEM is strongly suspected.
cranial ultrasound (US)
electroencephalography (EEG).
Battisti: Convulsions néonatales
86
Specific investigations

-
-



-
-
Imaging
Neurosonography
CT scan should be done in all infants where an etiology is not available after the first line of
investigations. It can be diagnostic in sub-arachnoid hemorrhage and developmental
malformations.
MRI scan is indicated only if investigations do not reveal any etiology and seizures are
resistant to usual anti-epileptic therapy. It can be diagnostic in cerebral dysgenesis,
lissencephaly and other neuronal migration disorders.
Screen for congenital infections A TORCH screen and VDRL should be considered in the
presence of hepato-splenomegaly, thrombocytopenia, growth retardation, small for
gestational age and presence of chorioretinitis.
Metabolic screen A metabolic screen includes blood and urine ketones, urine reducing
substances, blood ammonia, anion gap, urine and plasma aminoacidogram, serum and CSF
lactate/ pyruvate ratio
Electro-encephalogram (EEG) EEG
Ictal EEG may be useful for the diagnosis of suspected seizures and also for diagnosis of
seizures in muscle-relaxed infants. It should be done as soon as the neonate is stable
enough to be transported for EEG, preferably within first week.
EEG should be performed for at least 1 hour
Inter-ictal EEG is useful for long-term prognosis of neonates with seizures.
A background abnormality in both term and preterm neonates indicates a high risk for
neurological sequelae. These changes include burstsuppression pattern, low voltage invariant
pattern and electro-cerebral inactivity
Battisti: Convulsions néonatales
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Evaluation of Neonatal Seizures
Serum lytes (gluc, Ca, Mg, Na)
 CSF
 Head ultrasound
 EEG (B6?)

Tox screen
 CT or MRI of brain
 ?metabolic w/u, congenital infection w/u

Battisti: Convulsions néonatales
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Grading IVH
Battisti: Convulsions néonatales
89
1. Where is the hemorrhage?
2. Name the Anatomy
3. Grade the Hemorrhage
Grade II Hemorrhage
Extension into lateral ventricle without dilation
Normal Anatomy
Germinal Matrix
Extension into
Lateral Ventricle
(no dilation)
Battisti: Convulsions néonatales
Choroid Plexus
90
Electroencephalographic seizure
I. Epileptic

Consistently associated with electrocortical seizure activity on the EEG
 Cannot be provoked by tactile stimulation
 Cannot be suppressed by restraint of
involved limb or repositioning of the infant
 Related to hyper synchronous discharges
of a critical mass of neuron
Battisti: Convulsions néonatales
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Electroencephalographic seizures
II. Non-epileptic
 No electro-cortical signature
 Provoked by stimulation
 Suppressed by restraint or repositioning
 Brainstem release phenomena (reflex)
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Does absence of EEG seizure activity
indicate that a clinical seizure is nonepileptic?

Certain clinical seizures in the human
newborn originate from electrical seizures
in deep cerebral structures (limbic regions),
or in diencephalic, or brain stem structures
and thereby are either not detected by
surface-recorded EEG or inconsistently
propagated to the surface
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Surface EEG-Silent Seizure
Can “ surface EEG-silent ” seizure in the
newborn result to brain injury?
 Can this be eliminated by conventional
anticonvulsant therapy?
 Further investigation needed

Battisti: Convulsions néonatales
94
Laboratory Studies to Evaluate
Neonatal Seizures
Indicated
Complete blood count, differential, platelet count;
urinalysis
Blood glucose (Dextrostix), BUN, Ca, P, Mg,
electrolytes
Blood oxygen and acid-base analysis
Blood, CSF and other bacterial cultures
CSF analysis
EEG
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Laboratory Studies to Evaluate
Neonatal Seizures
Clinical Suspicion of Specific Disease
Serum immunoglobulins, TORCH antibody titers, and
viral cultures
Blood and urine metabolic studies (bilirubin,ammonia,
lactate, FECl³, reducing substance.)
Blood and urine toxic screen
Blood and urine amino and organic acid screen
CT or ultrasound scan
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Metabolic Evaluation for Refractory
Neonatal Seizures
Consider individually by case specifics
Serum
Glucose
Electrolytes (sodium, potassium, chloride, carbon dioxide), blood urea nitrogen, chromium,
calcium, phosphorus, magnesium
Uric acid
Creative kinase
Serum ammonia
Lactic and pyruvic acids
Biotinidase
Amino acids
Serum carnitine, acylcarnitines
Serum transferrin
Copper and ceruloplasmin
Cholesterol
Fatty acids (short-chain, medium-chain, long-chain)
Pipecolic acid
NeoReviews vol.5 no.6 June 2004
Battisti: Convulsions néonatales
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Metabolic Evaluation for Refractory
Neonatal Seizures
Urine







Organic acids
Acylglycines
Uric acid
Sulfites
Xanthine, hypoxanthine
Guanidinoacetate
Pipecolic acid
Cerebrospinal Fluid





Cell count, glucose,protein
Lactic and pyruvic acids
Amino acids
Organic acids
Neurotransmitters
Other Studies



Skin biopsy
Muscle biopsy
Magnetic resonance imaging with magnetic resonance spectroscopy (especially for
creatine)
NeoReviews vol.5 no.6 June 2004
Battisti: Convulsions néonatales
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The treatment of
neonatal convulsions
or seizures
Battisti: Convulsions néonatales
99
Treatment

Identify the underlying cause:
hypoglycemia - D10 solution
hypocalcemia - Calcium gluconate
hypomagnesemia- Magnesium sulfate
pyridoxine deficiency- Pyridoxine
meningitis- initiation of antibiotics
Battisti: Convulsions néonatales
100
Treatment

To minimize brain damage
 Some controversy when to start
anticonvulsants
 If seizure is prolonged (longer than 3
minutes), frequent or associated
with cardiorespiratory disturbance
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101
Acute therapy of neonatal seizures


If with hypoglycemia- Glucose 10%: 2ml/k IV
If no hypoglycemia- Phenobarbital:20mg/k IV
loading dose
If necessary : additional phenobarbital:
5 mg/kg IV to a max of 20 mg/kg
(consider omission of this additional
Phenobarbital
if with baby is asphyxiated)
Phenytoin: 20 mg/kg, IV (1 mg/kg/min)
Lorazepam:0.05-0.10 mg/kg, IV
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Treatment of neonatal
convulsions
Within 5 minutes:
baby in thermoneutral environment and ensure airway, breathing and
circulation. O2 should be started, IV access should be secured, and
blood should be collected for sugar and other investigations. A brief
relevant history should be obtained and quick clinical examination
should be performed. All this should not require more than 2-5 minutes.
If hypoglycemia or if there is no facility to test blood sugar immediately,
2 ml/kg of 10% dextrose should be given as a bolus injection followed
by a continuous infusion of 6-8 mg/kg/min.
 If hypoglycemia has been treated or excluded as a cause of
convulsions, the neonate should receive 2ml/kg of 10% calcium
gluconate IV over 10 minutes under strict cardiac monitoring. If ionized
calcium levels are suggestive of hypocalcemia, the newborn should
receive calcium gluconate at 8 ml/kg/d for 3 days. If seizures continue
despite correction of hypocalcemia, 0.25 ml/kg of 50% magnesium
sulfate should be given intramuscularly (IM).
Anti-epileptic drug therapy (AED)
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103
Acute Therapy of Neonatal Seizures
With Hypoglycemia -Glucose, 10% solution: 2 mL/kg, IV
No Hypoglycemia
Phenobarbital: 20 mg/kg, IV (1-2 mg/kg/min)
If necessary:
Additional phenobarbital: 5 mg/kg IV to a max. of 40 mg/kg
(consider omission of this additional phenobarbital
if infant is severely “asphyxiated”)
Phenytoin*: 20 mg/kg, IV (0.5-1.0 mg/kg/min)
(Lorazepam: 0.05-0.10 mg/kg, IV) if available
Midazolam: 0.2 mg/kg, IV;then,0.1-0.4 mg/kg/hr, IV
Battisti: Convulsions néonatales
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Acute Therapy of Neonatal Seizures
Other (as Indicated)
Calcium gluconate, 5% solution: 4 mL/kg, IV
Magnesium sulfate, 50% solution: 0.2 mL/kg, IM
Pyridoxine: 50-100 mg, IV; repeat to maximum of 500 mg if
needed
Pyridoxal-5-phosphate,30 mg/kg/day, PO
Folinic Acid, 4 mg/kg/day, PO
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Drug Therapy For Neonatal Seizures
Standard Therapy
AED
Initial Dose
Maintenance Dose
Phenobarbital 20mg/kg
3 to 4 mg/kg per day
Phenytoin
20 mg/kg
3 to 4 mg/kg per day
Fosphenytoin 20 mg/kg phenytoin 3 to 4 mg/kg per day
equivalents
Lorazepam²
0.05 to 0.1 mg/kg
Every 8 to 12 hours
Diazepam²´
0.25 mg/kg
Every 6 to 8 hours
Route
lV, lM, PO
lV, POª
lV, lM
lV
lV
AED= andtiepileptic drug; lV= intravenous; lM= intramuscular; PO= oral
ªOral phenytoin is not well absorbed.
²Benzodiazepines typically not used for maintenance therapy.
³Lorazepam preferred over diazepam.
Battisti: Convulsions néonatales
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Battisti: Convulsions néonatales
107
Pharmacological properties of
Phenobarbital

Enters the CSF/brain rapidly with high efficiency
 The blood level is largely predictable from the
dose administered
 It can be given IM or IV(more preferred)
 Maintenance therapy accomplished easily with
oral therapy
 Protein binding lower in newborn—free levels of
drug are higher
 Entrance to the brain increased by local acidosis
associated with seizures
Battisti: Convulsions néonatales
108
Anti-epileptic drug therapy (AED)
Equipment for resuscitation and assisted ventilation should be available at
the bedside of all neonates given multiple doses
Phenobarbitone
-
-
It is the drug of choice in neonatal seizures.
The dose is 20 mg/kg/IV slowly over 20 minutes (not faster than 1 mg/kg/min). If seizures persist after
completion of this loading dose, repeat dose of phenobarbitone 10 mg/kg may be used every 20-30 minutes till a
total dose of 40 mg/kg has been given.
The maintenance dose is 3-5 mg/kg/day in 1-2 divided doses, started 12 hours afterthe loading dose.
Recommendation for use of prophylactic phenobarbitone still awaits further studies.
Phenytoin and Fosphenytoin
-
-
Phenytoin is indicated if the maximal dose of phenobarbitone (40 mg/kg) fails to resolve seizures or earlier, if
adverse effects like respiratory depression, hypotension or bradycardia ensue with phenobarbitone.
The dose is 20 mg/kg IV at a rate of not more than 1 mg/kg/min under cardiac monitoring. Phenytoin should be
diluted in normal saline as it is incompatible with dextrose solution. A repeat dose of 10 mg/kg may be tried in
refractory seizures. The maintenance dose is 3-5 mg/kg/d (maximum of 8 mg/kg/d) in 2-4 divided doses. Oral
suspension has very erratic absorption from gut in neonates, so it should be avoided. Thus only IV route is
preferred in neonates and it should preferably be discontinued before discharge.
Fosphenytoin, the prodrug of phenytoin, does not cause the same degree of hypotension or cardiac
abnormalities, has high water solubility (therefore can be given IM), and is less likely to lead to soft-tissue injury
compared with phenytoin. It is dosed in phenytoin equivalents (1.5 mg/kg of fosphenytoin is equivalent to 1
mg/kg of phenytoin).
Benzodiazepines
Lorazepam is preferred over diazepam as it has a longer duration of action and results in less adverse effects (sedation and cardiovascular
effects). Midazolam is faster acting than lorazepam and may be administered as an infusion.

Diazepam: 0.25 mg/kg IV bolus (0.5 mg/kg rectal); may be repeated 1-2 times.

Lorazepam: 0.05 mg/kg IV bolus over 2-5 minutes; may be repeated

Midazolam: 0.15 mg/kg IV bolus followed by infusion of 0.1 to 0.4 mg/kg/hour.

Clonazepam: 0.1–0.2 mg/kg IV bolus followed by infusion 10-30 ìg/kg/hr.
Battisti: Convulsions néonatales
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Antiepileptic drugs for refractory seizures
The expected response to anticonvulsants is 40% to the initial 20- mg/kg loading dose of
phenobarbitone, 70% to a total of 40 mg/kg of PB, 85% to a 20- mg/kg LD of PHT, and
95% to 100% to 0.05 to 0.10 mg/kg lorazepam4. In exceptional circumstances when the
seizures are refractory to these first-line drugs, the following second-line drugs might
be tried.

Lidocaine: Start with 4mg/kg/hr IV on first day, reduce by 1mg/kg/hr on each
subsequent day or load with 2mg/kg IV and maintain on 6 mg/kg/hr. Adverse effects
include arrythmias, hypotension and seizures. It should not be administered with
phenytoin.

Paraldehyde: It may be used in seizures refractory to the first line drugs. A dose of 0.10.2 ml/kg/dose may be given IM or 0.3 ml/kg/dose mixed with coconut oil in 3:1 may be
used by per rectal route. Additional doses may be used after 30 minutes and q 4-6
hourly. Adverse effects include pulmonary hemorrhage, pulmonary edema,
hypotension, and liver injury.

Pyridoxine: Therapeutic trial of pyridoxine is reserved as a last resort. IV
administration is the preferred method; however, suitable IV preparations are not
available at present in India. Hence intramuscular (IM) route may have to be used
instead (1 ml of neurobion has 50-mg pyridoxine and 1 ml each may be administered in
either the gluteal region or anterolateral aspect of thigh).

Sodium valproate: It can be used for maintenance therapy in neonates. Per rectal route
may be used in acute condition. IV preparation is now available. Dose is 20-25 mg/kg/d
followed by 5-10 mg/kg every 12 hours.

Vigabatrin: It has been used in neonates for refractory seizures, primarily for infantile
spasms. The dose is 50 mg/kg/day.

Topiramate: It shows promise in neonatal seizures because of its potential
neuroprotective but has also secondary effects
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Alternative Antiepileptic Drugs (AED)
for Neonatal Seizures
Intravenous AEDs
High-dose phenobarbital: >30 mg/kg
Pentobarbital: 10 mg/kg, then 1 mg/kg per hour
Thiopental: 10 mg/kg, then 2 to 4 mg/kg per hour
Midazolam: 0.2 mg/kg, then 0.1 to 0.4 mg/kg per hour
Clonazepam: 0.1 mg/kg
Lidocaine: 2 mg/kg, then 6 mg/kg per hour
Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses
Paraldehyde: 200 mg/kg, then 16 mg/kg per hour
Chlormethiazole: Initial infusion rate of 0.08 mg/kg per minute
Dexamethasone: 0.6 to 2.8 mg/kg
Pyridoxine (B6): 50 to 100 mg, then 100 mg every 10 minutes
(up to 500mg)
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Alternative AEDs for Neonatal
Seizures
Oral AEDs
Primidone: 15 to 25 mg/kg per day in 3 doses
Clonazepam: 0.1 mg/kg in 2 to 3 doses
Carbamazepine: 10 mg/kg, then 15 to 20 mg/kg per day in 2 doses
Oxcarbamazepine: no data on neonates, young infants
Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses
Vigabatrin: 50 mg/kg per day in 2 doses, up to 200 mg/kg per day
Lamotrigine: 12.5 mg in 2 doses
Topiramate: 3 mg/kg per day
Zonisamide: 2.5 mg/kg per day
Levetiracetam: 10 mg/kg per day in 2 doses
Folinic acid: 2.5 mg BID, up to 4 mg/kg per day
NeoReviews vol.5 no.6 June 2004
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Maintenance Therapy of Neonatal Seizures
Glucose: < 8 mg/kg/, IV
Phenobarbital: 3-4 mg/kg/24 hr, IV, IM, or PO
Phenytoin (as fosphenytoin): 3-4 mg/kg/24 hr, IV
Calcium gluconate: 500 mg/kg/24 hr, PO
Magnesium sulfate (50%): 0.2 mL/kg/24 hr, IM
Volpe, Neurology of the Newborn, 5th
ed. 2008
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Treatment of Electroclinical Seizures

Phenobarbital 20 mg/kg
 10 mg/kg boluses until 40-50 microgm/ml
Phenytoin 20 mg/kg
 Lorazepam 0.1 mg/kg
 Pyridoxine 50-100 mg IV with EEG

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Maintenance
anti-epileptic therapy
Monotherapy is the most appropriate
strategy to control seizures. Attempts
should be made to stop all anti-epileptic
drugs and wean the baby to only
phenobarbitone at 3-5 mg/kg/day.
 If seizures are uncontrolled or if clinical
toxicity appears, a second AED may be
added. The choice may vary from
phenytoin, carbamezepine, and valproic
acid.

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Why should the infant with epileptic
seizures be treated with AED
Potential adverse effects of seizure on:
 Ventilatory function
 Circulation
 Cerebral Metabolism
 Brain Development
disturbance in cerebral blood flow
energy metabolism
homeostasis of excitotoxic amino acids
neurogenesis and synaptic reorganization
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Determinants of Duration of
anticonvulsant therapy for neonatal
seizures

Neonatal neurological examination

Cause of neonatal seizure

Electroencephalogram
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Duration of anticonvulsant therapyGuidelines
Neonatal period
 If neonatal neurological examination
becomes normal discontinue therapy
 If neonatal neurological examination is
persistently abnormal,consider etiology and
obtain EEG
 In most such cases- Continue
phenobarbital
- Discontinue phenytoin
- Reevaluate in 1 month
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Duration of anticonvulsant therapyGuidelines
One month after discharge
 If neurological examination has become
normal, discontinue phenobarbital
 If neurological examination is persistently
abnormal,obtain EEG
 If no seizure activity on EEG, discontinue
phenobarbital
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When to discontinue AED
This is highly individualized
Volpe:
try to discontinue all medication at discharge if clinical
examination is normal, irrespective of etiology and EEG. If
neurological examination is persistently abnormal at discharge,
AED is continued and the baby is reassessed at 1 month.
If the baby is normal on examination and seizure free at 1
month, phenobarbitone is discontinued over 2 weeks. If
neurological assessment is not normal, an EEG is obtained. If
EEG is not overtly paroxysmal, AED are tapered and stopped. If
EEG is overtly abnormal, the infant is reassessed in the same
manner at 3 months and then 3 monthly till 1 year of age.
Ellison
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Score de Patricia Ellison:
Stopper le traitement si ∑ < 5 « à terme » ou < 6 à 3 mois du terme
Poids de naissance :
< 1500g
> 1500 g
2
1
type de paroxysme :
subtil ou atypique
clonique
tonique ou myoclonique
0
1
2
facteur déclenchant :
inconnu
hypocalcémie, hypoglycémie
hémorragie sous arachnoïdienne ou stades 1
Sarnat stade 2
Méningite
Hémorragie stade 3,4
Malformation cérébrale
Sarnat stade 3
EEG :
Normal
Anomalies mineures
Anomalies marquées
Examen neurologique :
Normal
hypotonie modérée, hyperexcitabilité
Hémi syndrome, hyper- hypo – tonie majeure
0
1
1
2
2
2
2
2
0
1
2
0
1
2
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Duration of Anticonvulsant Therapy Guidelines
Neonatal Period
If neonatal neurological examination becomes normal, discontinue
therapy
If neonatal neurological examination is persistently abnormal, consider
the cause and obtain an EEG.
In most such cases:
Continue phenobarbital
Discontinue phenytoin
Reevaluate in 1 month
At 1 Month After Discharge
If neurological examination has become normal, discontinue
phenobarbital
If neurological examination is persistently abnormal, obtain an EEG.
If no seizure activity is noted on the EEG, discontinue phenobarbita
Volpe, Neurology of the Newborn, 5th ed. 2008
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The following and prognosis
of
neonatal convulsions
or seizures
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Outcome
45 % controlled after either phenobarb
or phosphenytoin
 60 % controlled with both
 30% of survivors develop epilepsy
 WORSE: HIE, meningitis, dysplasia
 WORSE: electrographic seizures
 BETTER: hypoCa, BINC, BIFC, stroke

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Prognosis
Two most useful approaches in utilizing outcome

EEG

Recognition of the underlying neurological
disease
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Prognosis of Neonatal seizures in relation to
EEG
EEG BACKGROUND
NEUROLOGICAL SEQUELAE(%)
Normal
Severe abnormalities†
Moderate abnormalities‡
10
90
~50
Based primarily on data reported by Rowe JC, Holmes GL, Hafford J, et al:
Electroencephalogr Clin Neurophysiol 60:183-196, 1985; Lombroso CT: In
Wasterlain CG, Treeman DM, Porter R, editors: Advances in neurology, New
York, 1983, Raven Press; and includes both full-term and premature infants.
†Burst-suppression pattern, marked voltage suppression, and
electrocerebral
Silence.
‡Voltage asymmetries and “immaturity.”
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Complications





Cerebral palsy
Hydrocephalus
Epilepsy
Spasticity
Feeding difficulties
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Consultations

Neurology consult needed for
- evaluation of seizures
- evaluation of EEG and video EEG
monitoring
- management of anticonvulsant
medications
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Further Outpatient Care

Neurology outpatient evaluation
 Developmental evaluation for early
identification of physical or cognitive
deficits
 Orthopedic evaluations if with joint
deformities
 Consider physical medicine/physical
therapy referral if indicated
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