Transcript Neonatal Seizures

I. Neonatal Seizures
II. Conditions That
Mimic Seizures
Seizure
 transient and reversible alteration of behavior
caused by a paroxysmal, abnormal and excessive
neuronal discharge
 attack of cerebral origin
 sudden and transitory abnormal phenomena
motor, sensory, autonomic, or psychic
 transient dysfunction of part or all of the brain
Epilepsy
A paroxysmal brain disorder of various etiologies
characterized by recurrent seizures due to
excessive electrical discharge of cerebral neurons
associated with a variety of clinical and laboratory
manifestations
two or more seizures not directly provoked by
intracranial infection, drug withdrawal, acute
metabolic changes or fever
Neonatal Seizures
• Tonic Seizures—focal or generalized, may mimic
decorticate or decerebrate posturing, primarily seen 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
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
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.
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
Neonatal Seizures
EEG Classification
• Electrical seizures with absent clinical
seizures
– Electrical seizures associated with markedly
abnormal background EEG
– Seen in comatose patients
Epileptic vs Non-epileptic
Neonatal Phenomena
Clinical
Characteristics
Epileptic
Non-epileptic
Increases with
Sensory
stimulation
Suppresses with
restraint
Rare
Common
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Autonomic
Accompaniments
Major Causes of Neonatal Seizures In Relation to Time of
Seizure Onset and Relative Frequency
TIME OF ONSET*
FREQUENCY
Cause
Full Term
Hypoxic-Ischemic encephalopathy
Intracranial hemorrhage
Intracranial infection
Developmental defects
Hypoglycemia
Hypocalcemia
Other metabolic
Epileptic syndromes
0-3 Days
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RELATIVE
>3 Days
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Premature
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Neonatal Seizures
Etiologic diagnosis
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Hypoxic –ischemic encephalopathy
Metabolic
Infections
Trauma
Structural abnormalities
Hemorrhagic and embolic strokes
Maternal disturbances
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
Causes of neonatal seizures
Ages 4 – 14 days
• Infection
• Metabolic disorders
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Hypocalcemia
Diet
Hypoglycemia
Inherited disorder of
metabolism such as
galactosemia,fructosemi
a
– Hyperinsulinemic
hypoglycemia
– Becwith syndrome
• Drug withdrawal
• Benign neonatal
convulsion
• Kernicterus,
hyperbilirubenemia
Causes of neonatal seizures
Ages 2 – 8 weeks
• Infection
• Head injury
– Subdural henatoma
• Inherited disorder of
metabolism
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Aminoacidurias
Urea cycle defects
Organic acidurias
Neonatal ALD
• Malformations of
cortical development
– Lissencephaly
– Focal cortical
dysplasia
– Tuberous sclerosis
– Sturge weber
syndrome
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
Neonatal Seizures
Etiologic diagnosis
• Inborn errors of metabolism
– Serum ammonia  urea cycle abnormalities
– Acidosis + anion gap + hyperammonemia
urine organic acids should be determined
• Unintentional injection of local anesthetic
– Supportive measures
– Promotion of urine output with IV fluids
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
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
Neonatal Seizures
Fifth-day fits –
• 5th day of life
• normal appearing neonates with mulifocal
seizures
• Present for less than 24 hours
• Good prognosis
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
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
Prognosis of Neonatal Seizures:
Relation to Neurological Diseases
Neurological Disease*
Development
Hypoxic-ischemic encephalopathy
Intraventricular hemorrhage
Primary subarachnoid hemorrhage
Hypocalcemia
Early-onset
Later-onset
Hypoglycemia
Bacterial meningitis
Developmental defect
Normal
50%
10%
90%
50%
100%
50%
50%
0%
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
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
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
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
Clinical Scenario 1
F.M. a 36-37 month old baby boy is noted to have
blinking of the eyelids with sucking movements of
the mouth at 30 hours of life. The extremities are
jittery when tactile stimuli is applied.
Maternal history is unremarkable, NSD, G1P1 (1-00-1) no hypertension, no infection. Birth weight is
2.5kg. Apgar 8 and 10 at 1 and 5min.
The blinking of the eyes and jittery movements of the
extremities recur within the next hour.
Clinical Scenario 1
What is your impression?
What work-ups will you request?
Hgt, CBC, Serum Calcium, Electrolytes
What will be your management?
Na Luminal 20mg/g IV at 1mg/Kg/min
infusion, maintain at 3.5 mg/g/day.
Management of Neonatal Seizures
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Na Luminal 20 mg/kg/day IV bolus
Rate of infusion—1 mg/kg/min
Example: Wt is 3 kg, 3 x 20 = 60 mg
Give 60 mg for 20 mins. IV push
Maintenance dose of Na luminal—5mg/kg/day
Example: 3 x 5 = 15 mg
Give 7.5 mg IV q12 hrs
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
Conditions that Mimic Seizures
• Night terrors
– Common in boys
– 5 – 7 years of age
– Sudden onset between midnight and 2:00 am
during stage 3 or 4 of sleep or slow-wave sleep
– Child screams and appears frightened, dilated
pupils, tachycardia and hyperventilation
– Child thrash violently can not be consoled ,
unaware of parents or surroundings
Conditions that Mimic
Seizures
• Night terrors
– 1/3 will have somnambulism
– Emotional disorder should be explored in
patient with prolonged and persistent night
terrors
– Short course diazepam maybe considered
while the family dynamics is investigated
Conditions that Mimic Seizures
• Breath holding spells
– Cyanotic spells
• Provoked by upsetting or scolding an infant
• Brief shrill cry followed by forced expiration and apnea
• Rapid onset of generalized cyanosis or loss of
consciousness may be associated with repeated
generalized tonic jerks, opisthotonos, bradycardia
• EEG: normal
• Rare before 6 months, peak about 2 years & abate by 5
years old
• TX: parent counseling
Conditions that Mimic
Seizures
• Breath holding spells
– Pallid spells
• Initiated by painful experience
• Child stops breathing  loss of consciousness 
pale and hypotonic  tonic seizures
• Bradycardia with asystole for 2 seconds may be
recorded
• EEG: normal
• TX supportive but may give atrophine sulfate at
0.01 mg/kg/24 hr in divided doses with a maximum
dose of 0.4 mg
Conditions that Mimic Seizures
• Syncope
– Simple syncope
• Decreased blood flow  loss of consciousness 
ischemia influences the higher cortical centers to
release inhibiting influence on reticular formation
within the brainstem  brief tonic contractions of
muscles
• Results from vasovagal stimulation precipitated by
pain, fear, excitement , prolonged standing
particularly in a warm environment
• Age : 10 -12 years old, females
Conditions that Mimic
Seizures
• Syncope
– Simple syncope
• Tilt test – effective in producing symptoms
including hypotension
• Tx: oral B adrenergic blocking agents
Conditions that Mimic Seizures
• Syncope
– Cough syncope
• Most common in asthmatic children
• Occurs shortly after sleep and coughing paroxysm
awakens the child
• Patients face become plethoric, perspires,
agitated, frightened
• Loss of consciousness with generalized muscle
flaccidity, vertical upward gaze and clonic muscle
contraction lasting for several minutes
• Urinary incontinence is frequent
Conditions that Mimic
Seizures
• Syncope
– Cough syncope
• Cough causes an increased intrapleural pressure
 decreased venous return to the right side of the
heart  decreased right ventricular output 
reduction of left ventricular filling  rapidly
diminished cerebral blood flow  cerebral hypoxia
 loss of consciousness
• Tx: Prevention of bronchoconstriction
Conditions that Mimic Seizures
• Syncope
– Prolonged QT syndrome
• Sudden loss of consciousness during exercise or
emotional and stressful experience
• Onset late childhood or adolescence
• With cardiac arrhythmias such as ventricular
fibrillation
• ECG: abnormal lengthening of the QT interval
(corrected QT of 0.46 or more)
• May be associated with acquired heart disease
(myocarditis, mitral valve prolapse, electrolyte
abnormalities, drug induced) or congenital forms
Conditions that Mimic Seizures
• Syncope
– Prolonged QT syndrome
• Autosomal recessive trait (Jervell and LangeNielsen syndrome) associated with deafness
• Autosomal dominant (Romano-Ward syndrome) 
mutations in cardiac potassium channel gene
linked to chromosome 11p15.5 LQT1
• LQT2 results from mutation to second potassium
channel gene linked to chromosome 7q35-36
Conditions that Mimic Seizures
• Syncope
– Prolonged QT syndrome
• LQT3 result in mutation in cardiac sodium channel
linked to 3p21-24
• LQT4 linked to chromosome 4q25-27
• Testing include supervised exercise test or Holter
monitoring
• Tx: B adrenergic antagonist drugs
Permanent implantable cardiac pacing or left
thoracic sympathectomy may be considered
if drug is not effective
Parents shoudls be taught CPR
Conditions that Mimic Seizures
• Paroxysmal Kinesigenic Choeoathetosis
– Sudden onset of unilateral or occasional bilateral
choreoathetosis or dystonic posturing of a leg,
arm and facial grimacing and dysarthia
– Precipitated by sudden movements, excitement
or stress
– Rare last for more than 1 minute
– Onset between 8 – 14 years
– Attacks may be daily or intermittent
Conditions that Mimic
Seizures
• Paroxysmal Kinesigenic Choeoathetosis
– NE, MRI and EEG – normal
– Autosomal recessive inheritance is suggested
– Tx: Phenytoin
Conditions that Mimic
Seizures
• Shuddering attacks
– Onset at 4 – 6 months of age
– Sudden flexion of the head and trunk and
shuddering or shivering movements
– May be a precursor to benign essential
tremors
Conditions that Mimic
Seizures
• Benign Paroxysmal torticollis of infancy
– Recurrent attacks of head tilt with pallor,
agitation and vomiting
– Onset : 2 – 8 months
– Spontaneous remission at 2 – 3 years of age
– Abnormalities in vestibular function
– Some patients develop migraine in childhood
Conditions that Mimic Seizures
• Hereditary Chin trembling
– Repeated episodes of rapid 3/sec chin
trembling movements
– Precipitated by stress, anger, frustration
– Autosomal dominant
– NE and EEG - normal
• Narcolepsy and cataplexy
– Narcolepsy begins before adolescence
– Attacks of irrepressible daytime sleep with
transient loss of muscle tone (cataplexy)
Conditions that Mimic
Seizures
• Narcolepsy and cataplexy
– EEG shows recurrent sleep attacks consist of
REM sleep
– Patients are easily aroused
– Tx for narcolepsy Modafinil acetamide 200
mg/day
Conditions that Mimic
Seizures
• Cataplexy
– sudden loss of muscle tone and fall to the
floor precipitated by laughter, stress or
frightening experience
– Tx:
scheduled
naps,
amphetamines,
methyphenidate, tricyclic antidepressant and
counselling regarding occupational safety
Conditions that Mimic
Seizures
• Rage attacks or episodic dyscontrol syndrome
– Sudden and recurrent episodes of violent
behavior with minimal provocation
– Seem to be psychotic at the time of the attack
– EEG: normal
Conditions that Mimic Seizures
• Pseudoseizures
– Occurs typically between 10 – 18 years old
– Lack of cyanosis, normal reaction of pupils to
light, no loss of sphincter tone
– Normal plantar response
– Absence of tongue biting
– Can be persuade to have an attack by the
physician
– EEG-excessive muscle artifact
Febrile Seizures
 3 mo – 6 yrs (peak age of onset 14 – 18
mo)
 Normal Neurological Exam & development
 Occurs with fever (not due to CNS
Infection)
 Most commonly due to viral URTI,
otitis media, Roseola, UTI
Normal EEG
Mapped to Chromosomes 19p and 8q13-21
in some families- Autosomal Dominant pattern
Incidence Rate: 3-4% of young children
Simple Febrile Seizures
• Seizures are Generalized
• Lasts a few seconds, not more than 15 min
• Occurs only once in 24 hours
Complex Febrile Seizures
• Seizures are focal
• Lasts more than 15 min
• More than 2 seizures on the first day, (recurrent)
Factors associated with increased risk of
recurrence
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Age less than 12 mo
A positive family history of febrile seizures
Complex features
Lower temperature before seizure onset
Febrile seizures are not associated with
decreased intellectual performance.
Factors associated with an increased risk of
developing Epilepsy In Children with FS
• Complex type of FS
– focal seizures / post ictal neurological sx
• Positive family history of Epilepsy
• Onset of FS below 12 years
• Delayed milestones / Pre Existing Neurologic
Disorder
Management Of Febrile Seizures
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In an actively convulsing patient:
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Do not put anything in the mouth
Time the event
Don’t restrain the patient
Don’t give anything to drink to the patient
Turn the patient to the side to prevent
choking
6. Put something under the patient’s head to
prevent injury
Management of Febrile Seizures
• In a convulsing patient with seizures lasting
more than 5 min or with recurrent seizures
Diazepam 0.2- 0.4mg per kg IV
– In a patient with just a history of febrile
seizure
– No maintenance anticonvulsant is
recommended
Management of Febrile Seizures
• Careful evaluation of the patient to look
for the cause of the fever
• Antipyretics to lessen discomfort (Have not been
shown to lessen the recurrence of febrile seizures)
• Reassurance and Education of the Parents
• Advise the parents regarding the use of oral
diazepam at the onset of febrile illness
• Oral Diazepam 0.3 mg/kg every 8 hours on the
first day of illness
Use of Maintenance Anticonvulsants
2 AEDs can prevent the recurrence of
febrile seizures:
Phenobarbital and Valproate
However routine use as maintenance
anticonvulsants are not recommended for
Simple Febrile Seizures
Phenobarbital-decreases cognitive function in
treated children
Valproate – May cause hepatotoxicity in children
<2yrs old
Use Of AED’S as prophylaxis in
Preventing Recurrence of Febrile Seizures
• The potential side effects and risks using
Phenobarbital and Valproate do not justify its
use in a disorder with an excellent prognosis
regardless of treatment
(SIMPLE FEBRILE SEIZURES)
• Carbamazepine and Phenytoin do not prevent
febrile seizures
Clinical Practice Guidelines on the First
Simple Febrile Seizure
1. Lumbar Puncture should be performed in
all children below 18 months for a first
simple febrile seizure
2. Neuroimaging studies should not be
routinely performed In children for a Simple
First FS
3. Antipyretic Drugs are used to lower fever
and should not be relied upon to prevent
the occurrence of FS
Summary of Recommendations First FS
4. The use of continuous anticonvulsants are not
recommended in children after a FIRST
SIMPLE FEBRILE SEIZURE .Although
anticonvulsants can reduce the recurrence of
febrile seizures, the adverse side effects of
these do not warrant their use in this disorder.
5. The use of intermittent anticonvulsants are
not recommended for the prevention of
febrile seizures.
Clinical Practice Guidelines (Con,t)
6. Electroencephalogram should not be
routinely requested in children with a first
simple febrile seizure.
Child Neurology Society Philippines
and Philippine Pediatric Society, 2000